NCP Nutrition in Clinical Practice

Volume 33 • Number 1 • February 2018

NUTRITION SUPPORT CHALLENGES

Barriers and Solutions to Delivery of Intensive
Care Unit Nutrition Therapy

Enteral Access Devices: Types, Function, Care,

and Challenges

Chronic Critical Illness: Application of What We

Know

Parenteral Nutrition Safety: The Story Continues

Drug Shortages: Effect on Parenteral Nutrition

Therapy

Nutrition Screening vs Nutrition Assessment:

What’s the Difference?

Graduation Day: Healthcare Transition From

Pediatric to Adult

Peer-reviewed, practical solutions in clinical nutrition wileyonlinelibrary.com/journal/ncp

ISSN: 0884-5336

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 Nutrition in Clinical Practice
Volume 33 Issue 1 February 2018

Editor’s Note 7
Jeanette M. Hasse, PhD, RD, LD, FADA, CNSC

Invited Reviews
Barriers and Solutions to Delivery of Intensive Care Unit Nutrition Therapy 8
Michelle Kozeniecki, MS, RD, CNSC; Heather Pitts, RD, LDN, CNSC; and Jayshil J. Patel, MD
Enteral Access Devices: Types, Function, Care, and Challenges 16
Linda M. Lord, NP, CNSC, ACNP-BC
Chronic Critical Illness: Application of What We Know 39
Martin D. Rosenthal, MD; Amir Y. Kamel, PharmD; Cameron M. Rosenthal, MD; Scott Brakenridge, MD;
Chasen A. Croft, MD; and Frederick A. Moore, MD
Parenteral Nutrition Safety: The Story Continues 46
Phil Ayers, PharmD, BCNSP, FASHP; Joseph Boullata, PharmD, RPh, BCNSP, FASPEN, FACN;
and Gordon Sacks, PharmD, BCNSP, FCCP
Drug Shortages: Effect on Parenteral Nutrition Therapy 53
Beverly Holcombe, PharmD, BCNSP, FASHP, FASPEN; Todd W. Mattox, PharmD, BCNSP;
and Steve Plogsted, PharmD, BCNSP, CNSC
Nutrition Screening vs Nutrition Assessment: What’s the Difference? 62
Maria Isabel Toulson Davisson Correia, MD, PhD
Head and Neck Cancer Tumor Seeding at the Percutaneous Endoscopic Gastrostomy Site 73
June R. Greaves, RD, CSNC, CDN, LD, LDN
Graduation Day: Healthcare Transition From Pediatric to Adult 81
Kelly Green Corkins, MS, RD, CSP, LDN, CNSC; Michelle A. Miller, MS, RD, LDN, CNSC; John R Whitworth, MD;
and Carol McGinnis, DNP, APRN-CNS, CNSC

Reviews
Knowledge of Constituent Ingredients in Enteral Nutrition Formulas Can Make a Difference in Patient Response 90
to Enteral Feeding
Patricia Savino, MBA, RD
Oral Feeding Difficulties in Children With Short Bowel Syndrome: A Narrative Review 99
Judy Hopkins, OTD, OTR/L, CLC; Sharon A. Cermak, EdD, OTR/L, FAOTA; and Russell J. Merritt, MD, PhD
Natural Bioactive Food Components for Improving Enteral Tube Feeding Tolerance in Adult Patient Populations 107
Adam J. Kuchnia, MS, RD, LD, CNSC; Beth Conlon, PhD, MS, RD; and Norman Greenberg, PhD

Invited Commentary
Mid-Upper Arm Circumference Z-Score as Determinant of Nutrition Status: Does Occam’s Razor Apply? 121
Cecelia Pompeii-Wolfe, RD, LDN, CNSC; and Timothy A. S. Sentongo, MD

Clinical Research
Evaluating Mid-Upper Arm Circumference Z-Score as a Determinant of Nutrition Status 124
Karen Stephens, MS, RD, CSP, LD; April Escobar, MS, RD; Erika Nicole Jennison, MS, RD; Lindsey Vaughn, MS, RD;
Rhonda Sullivan, MS, RD; and Susan Abdel-Rahman, Pharm.D.; on behalf of the CMH Nutrition Services Z-Score
Research Team
Monitoring Nutrition in Critical Illness: What Can We Use? 133
Suzie Ferrie, AdvAPD, MNutrDiet, PhD; and Erica Tsang, APD, MNutrDiet
Enteral Feeding Tube Clogging: What Are the Causes and What Are the Answers? A Bench Top Analysis 147
Christopher M. Garrison, PhD, RN CNE
Hang Height of Enteral Nutrition Influences the Delivery of Enteral Nutrition 151
Renee Walker, MS, RD, LD, CNSC, FAND; Lauren Probstfeld, MS, RD, CNSC; and Anne Tucker, PharmD, BCNSP

Letter to the Editor

Determining Efficacy, Safety, and Preparation of Standardized Parenteral Nutrition 158
Chelsea K. Krueger, PharmD; and Todd W. Canada, PharmD, BCNSP, BCCCP, FASHP, FTSHP
Reviewer Acknowledgments 160

Cover Art Note

This issue of NCP highlights topics related to current challenges in providing nutrition support.
Cover art credit: Gary S Chapman 
C Getty Images

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Editor’s Note
Clinical and basic science research on nutrition support has
improved patient outcomes in all settings, from the intensive
care unit (ICU) to the home and in long-term care facilities.
Several advances in nutrition support are described in this
issue of Nutrition in Clinical Practice along with articles that
address continuing challenges related to nutrition support
techniques, formulations, devices, and continuity of care for
patients.
One of the significant nutrition support challenges in
the ICU is ensuring that nutrition support is delivered
as ordered. In the first paper of this issue, Kozeniecki,
Pitts, and Patel address barriers to delivery of enteral
nutrition (EN) including process-related issues, ICU-related
interruptions, EN tolerance, and provider behaviors; they
also propose some solutions to improve EN delivery. In the
next paper, Linda Lord discusses indications and challenges
of various EN tubes. Dr. Kamel and colleagues present
the challenges associated with chronic critical illness and
possible nutrition interventions for a condition termed per-
sistent inflammation, immunosuppression, and catabolism
syndrome (PICS).
Two Invited Reviews focus on parenteral nutrition (PN).
The first by Ayers, Boullata, and Sacks reviews errors that
may occur with PN as well as proposed processes and
guidelines designed to reduce those errors and improve
safety. Dr. Holcombe et al evaluate PN in relation to
common PN component shortages, reasons for shortages,
and strategies to deal with the shortages.
Other challenges relate to nutrition screening, assess-
ment, and continuity of care to emphasize potential gaps in
Nutrition in Clinical Practice
Volume 33 Number 1
February 2018 7

C 2018 American Society for
Parenteral and Enteral Nutrition
DOI: 10.1002/ncp.10066
wileyonlinelibrary.com
meeting patient needs when their medical status and other
factors evolve over time. Specifically, Correia explains the
difference between nutrition screening and assessment and
how these important care steps contribute to the nutrition
care process. Green Corkins and colleagues describe chal-
lenges to the provision of continuity of care as the pediatric
patient grows and graduates to management by healthcare
teams who cover adult patients. These review papers are
complimented by the analysis of Ferrie and Tsang, who
investigated the indicators that can be used to monitor the
adequacy of nutrition support during critical illness. Dr.
Garrison discusses original data for us to better under-
stand the common problem of tube clogging, the causes,
and resolution. June Greaves delves into the unintended
consequences of metastatic gastric deposits that develop at
the percutaneous endoscopic gastrostomy site in patients
with head and neck cancer. These papers are augmented by
Patricia Savino’s review of how patients respond to EN as a
factor of the ingredients of the formulation.
Interdisciplinary nutrition support practitioners will
need to continue to collaborate with those in basic science
and others to evaluate the current process, formulations,
devices, and tools needed to address the challenges we have
outlined in this issue of NCP and advance the scientific basis
and clinical application of nutrition support.
Jeanette M. Hasse, PhD, RD, LD, FADA, CNSC
Editor-in-Chief, NCP
Invited Review

Nutrition in Clinical Practice

Volume 33 Number 1
Barriers and Solutions to Delivery of Intensive Care Unit February 2018 8–15

C 2017 American Society for

Nutrition Therapy Parenteral and Enteral Nutrition

DOI: 10.1002/ncp.10051
wileyonlinelibrary.com

Michelle Kozeniecki, MS, RD, CNSC1 ; Heather Pitts, RD, LDN, CNSC2 ;
and Jayshil J. Patel, MD3

Abstract
Despite recommendations for early enteral nutrition (EN) in critically ill patients, numerous factors contribute to incomplete
delivery of EN, including insufficient nutrition risk screening in critically ill patients, underutilization of enteral feeding protocols,
fixed rate-based enteral infusion targets with frequent EN interruption, and suboptimal provider practices regarding nutrition
support therapy. The purpose of this narrative review is to identify common barriers to optimizing and delivering nutrition in
critically ill patients, and suggest strategies and solutions to overcome barriers. (Nutr Clin Pract. 2018;33:8–15)

Keywords
critical care; enteral nutrition; intensive care; nutritional support; nutrition therapy; parenteral nutrition; patient care management

Introduction Process-Related Barriers

Malnutrition in hospitalized patients is common, occur-
ring in an estimated 30%–50% of patients during their
hospitalization.1,2 Malnutrition is an independent risk fac-
tor for hospital mortality, length of hospital stay, and
increased costs.3 Approximately 1 in 3 patients is malnour-
ished upon admission to the hospital1,4,5 ; however, acquired
malnutrition during intensive care unit (ICU) admission
further compounds preexisting malnutrition and may in
part be due to the numerous barriers standing in the way
of delivering optimal nutrition therapy.6
Numerous observational studies have demonstrated that
enteral nutrition (EN) in critically ill patients is withheld a
mean of 4.8–7 h/d.7,8 The optimal dose and timing of nutri-
tion in critically ill patients is unknown. Regardless, patients
do not receive prescribed calories, with 1 report showing
receipt of approximately 60% of prescribed calories,9 and
some ICUs reporting intake as low as 33% of prescribed
calories.10 Therefore, it is important to identify and over-
come potential barriers that prevent prescribed nutrition,
irrespective of dose. The literature suggests process related
and ICU-related barriers contribute significantly to not
achieving prescribed nutrition dose.6,8,11 The purpose of
this narrative review is to describe common process-related
barriers, ICU-related nutrition interruptions, and provider
attitudes and behaviors that can limit ICU nutrition opti-
mization. Under the premise of mitigating malnutrition, we
will offer solutions and strategies to potentially overcome
common barriers that stand in the way of optimizing ICU
nutrition therapy (Table 1).
Numerous guidelines endorse the provision of early EN in
critical illness because the provision of early ICU nutrition
has been found to reduce mortality12,13 ; however, process-
related barriers can delay early EN initiation. One process-
related barrier may be identifying which ICU patients may
benefit from early EN initiation. All critically ill patients
are not alike, and identifying those who will benefit from
nutrition therapy is likely a key factor in attenuating
nutrition risk, which is the risk for acquiring complica-
tions such as nosocomial infections, muscle weakness, and
chronic ventilatory support that may be associated with
undernutrition. The 2016 American Society of Enteral and
Parenteral Nutrition guidelines for critical care nutrition
support recommend screening ICU patients for nutrition
From the 1 Department of Nutrition Services, Froedtert Hospital,
Milwaukee, Wisconsin, USA; 2 Department of Nutrition Services,
Cone Health, Greensboro, North Carolina, USA; and 3 Department
of Medicine, Division of Pulmonary & Critical Care Medicine,
Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Financial disclosure: None declared.
Conflicts of interest: None declared.
Received for publication September 15, 2017; accepted for publication
November 21, 2017.
This article originally appeared online on December 26, 2017.
Corresponding Author:
Michelle Kozeniecki, Department of Nutrition Services, Froedtert
Hospital, Milwaukee, Wisconsin, USA
Email: Michelle.Kozeniecki@froedtert.com
Kozeniecki et al
Table 1. Summary of Barriers and Solutions to Delivery of
Nutrition Therapy in the Intensive Care Unit.
Barriers Potential Solutions
Process-related r Implement an ICU-specific screening
tool, such as NRS 2002, NUTRIC, or
modified NUTRIC scoring system
r Initiate EN at target infusion rate
r Quicker advancement (eg, increasing
rate every 4 hours instead of every
8 hours)
r Empower registered dietitians or
nutrition support teams to initiate
and manage EN orders
ICU-related r Reduced fasting for tests/procedures,
interruptions including use of small-bowel feeding
tubes when appropriate
r Increasing EN infusion rate to
provide >100% of daily target volume
r Volume-based EN
Real or perceived r Eliminate gastric residual volume
intolerance checking or change to less frequent
checking (eg, every 8 hours instead of
every 4–6 hours)
r Consider short-term use (<5–7 days)
of prokinetic agents when appropriate
r Do not delay initiation of EN based
solely on hypoactive bowel sounds
r Initiate PN in a timely manner based
on nutrition status and nutrition risk
Provider attitudes r Provider education through strong
and behavior multidisciplinary collaboration
r Use of ICU-specific nutrition
protocols, tailored to the
institution/unit
r physicians comply with nutrition team recommendations.
Routine practice audits
EN, enteral nutrition; ICU, intensive care unit; NRS, Nutritional Risk
Screening; NUTRIC, Nutrition Risk in the Critically Ill.
risk.13 Identifying critically ill patients who will benefit from
nutrition therapy can be a challenge.
Two scores, the Nutrition Risk in the Critically Ill (NU-
TRIC) and Nutritional Risk Screening (NRS) 2002, have
been proposed to identify nutritional risk. An NRS score >3
or NUTRIC score >5 indicate nutrition risk. The subjective
global assessment evaluates nutrition status; however, the
NRS 2002 and NUTRIC scores take into account both
nutrition status and disease severity, with higher scores
correlating with higher mortality.13,14 The NUTRIC score
is limited by the need for an interleukin-6 (IL-6) level.
The modified NUTRIC score was developed and excludes
an IL-6 and independently predicts 28-day mortality.15
The modified NUTRIC score can be completed through
chart review and does not require a patient interview or
knowledge of the patient’s weight or nutrition history.16
The NRS 2002, in contrast, requires a weight history and
9
knowledge of nutrition intake before admission, which may
not be available for all ICU patients, limiting its use.
Process-related barriers to identify nutrition risk may
include local implementation of NUTRIC and/or NRS
2002 scores and utilization of scores to optimize nutrition
prescription in those identified to be at nutrition risk.
Challenges in score implementation may include inability to
access components of the score. For example, the sequential
organ failure assessment (SOFA) requires the worst of
physiologic and laboratory variables over 24 hours, whereas
the Acute Physiology and Health Evaluation II (APACHE
II) scores require physiologic and laboratory variables in
the first 24 hours of ICU admission. Identification of these
variables and calculating the overall scores can be time
consuming to calculate if the scores are not readily available
through the electronic medical record (EMR). Implementa-
tion of an EMR-based program to calculate APACHE II
and SOFA scores may allow for timely nutrition screening
and expedite the identification of critically ill patients who
would benefit most from nutrition therapy.
Delays in nutrition order placement and provider un-
derprescribing may be additional process-related barriers in
some ICUs. Traditionally, the registered dietitian (RD) will
provide recommendations for the type of enteral formula,
starting rate, goal rate, and advancement rate. A licensed
independent practitioner is ultimately responsible for plac-
ing the order in many settings. This current paradigm can
lead to delays because recommendations for EN initiation
may be given a lower priority as compared with other
ICU interventions, not ordered, or are ordered without
advancement instructions. Franklin et al17 found 40% of
Furthermore, several studies suggest physicians underpre-
scribe EN. In an observational study of 51 hospitalized
patients, physicians presribed 22.0 ± 8.6 kcal/kg mean daily
calories without a specified method of calculation, whereas
the mean daily caloric requirement was 28.1 ± 4.7 kcal/kg
using the Harris–Benedict equation and a stress factor of 1.2
or 1.5. Thus, only 78.3% of predicted caloric requirements
were prescribed. Similarly, Quenot et al18 showed an average
of 75% of predicted calorie requirements (assuming optimal
calorie intake of 25 kcal/kg/d) were prescribed among 203
patients during the first week of ICU stay. In another study,
physicians prescribed 65.6% of the estimated caloric needs
(using 25–35 kcal/kg/d) in 44 ICU patients.19
In a study of medical ICU patients, the process for
EN initiation and advancement was the primary reasons
for inadequate delivery of prescribed EN volume, despite
adequate calorie prescription.8 Delays in EN initiation and
slow initiation/advancement may be reduced by initiating
EN at the target infusion rate. In 2008, Desachy et al20
compared the initial efficacy and tolerability of early EN
with immediate vs gradual introduction of optimal flow
rate. Both regimens were implemented using an early EN
10
protocol and were started within 24 hours after mechanical
ventilation. One hundred patients received a 1 kcal/mL
formula administered via a gastric tube by use of a vol-
umetric pump. In the immediate optimal flow group, EN
was initiated at the optimal flow rate corresponding to
25 kcal/kg/d (average of 75 mL/h). In the incremental group,
EN was initiated at a flow rate of 25 mL/h and increased in
increments of 25 mL/h every 24 hours until the optimal flow
rate corresponding to 25 kcal/kg/d was reached (average
of 76.5 mL/h). The immediate optimal flow group received
95% of estimated calories (1715 kcal/d) compared with 76%
of estimated calories (1297 kcal/d) in the gradual group
(P < .0001). There were no episodes of aspiration pneumo-
nia in either group. At least 1 episode of a gastric residual
volume (GRV) >300 mL was observed in 18 patients, 5
of whom were in the gradual group and 13 of whom
were in the immediate optimal flow group (P = .04). The
frequency of diarrhea was similar in the 2 groups. The
authors concluded that EN can be introduced at the optimal
dose regimen in shock-free patients receiving mechanical
ventilation, provided that standard precautions are taken to
reduce the risk for aspiration.20 For ICUs unable to initiate
EN at the goal infusion rate, a more rapid advancement
(eg, increase rate every 4 hours instead of every 8 hours)
may achieve similar outcomes without increased risk to the
patient; however, studies evaluating advancement rates are
lacking.
ICU-Related Interruptions
EN delivery in critically ill patients is interrupted up to 7
hours per patient per day.7,19,21,22 Many ICU-related EN
interruptions are avoidable. Nursing cares, such as bathing,
are the most frequent reason for EN interruption but
account for a small percentage of time without EN.22 Other
nursing cares such as wound dressing changes, bed linen
changes, and exchanging empty infusion bags also lead to
EN cessation. Traditional practices of placing patients nil
per os (NPO) at midnight or 8 hours before a scheduled
procedure reduce EN delivery and are not always supported
by demonstration of harm. Interrupting EN for proce-
dures, in preparation for surgery, and for interventional
radiology procedures are less frequent causes but account
for a much larger percentage of time off EN.22 Examples
of procedures where EN is withheld include endoscopy,
bronchoscopy, wound care, fixation of orthopedic fractures,
tracheostomy and/or percutaneous gastrostomy placement,
transesophageal echocardiography, and central venous or
arterial line placements. Holding EN for anticipated extuba-
tion is also commonly reported, with a median interruption
time of 3 hours in 1 study.8 Finally, “other reasons” for EN
interruption include ICU transfer, high blood sugar, high
bilirubin, observed or perceived intestinal gas, dialysis, and
equipment/formula problems.6,19
Nutrition in Clinical Practice 33(1)
The most intuitive solution to mitigating interruptions
is defining the minimum length of time to hold EN before
each interruption without increasing risk to the patient and
ensuring that all clinicians follow recommended practice.
Pousman et al23 implemented a reduced fasting protocol
that allowed patients undergoing selective operative and
nonoperative procedures to receive EN up until the time of
the procedure if the patient was receiving small-bowel feeds,
or 45 minutes before the procedure if receiving gastric feeds.
There were no differences in the incidence of infectious
complications, including ventilator-associated pneumonia,
suggesting continuing EN up until the time a procedure
was safe. Similarly, continuing EN up until extubation for
those receiving small-bowel feeding through a nasojejunal
tube or aspirating gastric contents just before extubation of
the patient is fed gastrically may reduce EN interruption,
although a paucity of data exist for best EN practices
during the peri-extubation period.24 In critically ill pediatric
patients, 1 study demonstrated that EN delivery to the small
bowel during extubation was possible and safe, as compared
with the traditional practice of holding EN for 4 hours
before and after extubation.25
Unfortunately, reduced ICU fasting time may not be a
feasible solution because of logistical complexities of each
ICU, patient acuity, the variety of tests, and the coordi-
nation between personnel and departments required. In 1
study, despite rigorous education of reduced fasting, 36% of
patients in the reduced fasting group inadvertently received
no nutrition before their procedures.23 Several different
approaches to compensatory feeding have been described by
way of proactively overprescribing the hourly EN infusion
rate assuming that EN will be interrupted or by reactively
increasing hourly EN infusion rate, after the interruption, to
achieve a daily target volume26-30 (summarized in Table 2).
The latter is known as volume-based feeding (VBF).
Lichtenberg et al27 hypothesized that a compensatory,
higher calculated EN infusion rate would decrease the daily
caloric deficit in enterally fed ICU patients. Hourly infusion
rates were established for the control group by dividing the
target volume by 24 hours, and for the intervention group by
dividing the target volume by 20 hours, based on historical
average delays/interruptions in their ICU. A total of 268
patient days in 37 patients were evaluated, with 110 days in
the control group and 158 days in the intervention group.
Mean daily volume received in the intervention group was
97.3% of target volume compared with 79.7% in the control
group (P < .001).27
In recent years, a paradigm shift to VBF has been pro-
posed, which includes prescribing EN based on total volume
of formula to be delivered in 24 hours and empowering
the nurse to alter the rate of EN delivery to compensate
for time off of feeds. In other words, if EN was held for a
procedure for 5 hours, the EN rate would be increased to
a higher rate to ensure that the goal volume was infused
Kozeniecki et al 11

Table 2. Compensatory Feeding Strategies.

Examples to Provide 1800 kcal/d

Strategy Description with a 1 kcal/mL EN Formula Considerations

Traditional 24-hour Divide target volume by 1800 kcal ÷ 1 kcal/mL ÷ 24 h/d = r Increased risk for
rate-based EN 24 hours to determine goal 75 mL/h underfeeding
hourly infusion rate.
Increased EN Prescribe daily EN volume 1800 kcal × 120% = 2160 kcal ÷ r Increased risk for
infusion rate 20% higher (120%) than 24 h/d = 90 mL/h overfeeding
target volume.
or
Divide target volume by 1800 kcal ÷ 1 kcal/mL ÷ 20 h/d =
20 hours to determine goal 90 mL/h
hourly infusion rate.
Volume-based EN Prescribe EN based on total 1800 kcal ÷ 1 kcal/mL ÷ 24 h/d = r May not be appropriate
volume of formula to be 75 mL/h for patients at risk for
delivered in 24 hours and If EN is held for 6 hours, divide refeeding syndrome
empower the RN to alter the volume of formula r Concern in patients who
the rate of EN delivery to remaining by the number of require vasopressor
compensate for time EN is hours left in the day: support
held. 1350 mL of formula remains r Maximum hourly
÷ 12 hours left in the day = infusion rates may need
increase rate to 112.5 mL/h to be specified for both
for the rest of the day gastric and small-bowel
After 24 hours, reset EN at the feeding to prevent
24-hour infusion rate and potential intolerance or
repeat malabsorption
Concomitant r Use of promotility agents when deemed appropriate
therapies r Early introduction of enteral protein modulars
r Adjusting and/or liberalizing GRV practices by increasing the threshold at which EN is held,
reducing the frequency with which GRV is checked, or eliminating GRV checking
r Placement of a small-bowel feeding tube
r Consider use of (S)PN if unable to meet estimated needs enterally

EN, enteral nutrition; GRV, gastric residual volume; PN, parenteral nutrition; SPN, supplemental parenteral nutrition.

by the end of the day. Beginning the next day, the target
shifts back down to the 24-hour calculated rate. Several
investigators have demonstrated an effective increase in the
percent of prescribed calories and protein delivered by using
VBF,9,28-31 although the degree to which delivery increased
has varied. Surgical ICU patients receiving VBF received
a smaller proportion of prescribed calories, as compared
with medical ICU patients on the same protocol32 and ICUs
with baseline poor performance in providing prescribed
calories.31 The individual institution’s VBF protocol, use
of promotility agents, protein modulars, EN initiation rate,
maximum hourly infusion rate, EN product used, and
GRV thresholds may have affected EN intake. Despite
differences in the characteristics of each VBF protocol used,
patients in each group experienced similar rates of emesis,
regurgitation, aspiration, and pneumonia, suggesting VBF
was safe.9,28-31 In 1 study, there was a slight increase in
diarrhea (P = .046).29 VBF is an aggressive strategy to
optimize prescribed calories and may not be appropriate
for certain patient populations, such as those patients who
are hemodynamically unstable or at high risk for refeeding
syndrome. The maximum hourly infusion rate may also
need to be specified for both gastric and small-bowel feeding
to prevent potential intolerance or malabsorption issues.
Real or Perceived Intolerance
EN intolerance may be a real or perceived barrier to
optimizing nutrition therapy and support. The definition of
“intolerance,” however, remains debated, and the percep-
tions, beliefs, and misinformation regarding what actually
constitutes EN intolerance may contribute to inadequate
EN provision.33 The presence or absence of bowel sounds,
“elevated” GRV, nausea, vomiting, aspiration, abdomi-
nal distention, bloating or abdominal discomfort, bowel
movements, and results of abdominal radiologic studies
are commonly used to evaluate for gastrointestinal (GI)
function. Feeding intolerance has also been described as a
general term and should be considered if EN is stopped
for any clinical reason other than tests or procedures,
including GI bleeding, enterocutaneous fistula, and imme-
diately postoperatively.34 Unfortunately, no single marker
12
of GI function is sensitive enough for assessing EN
tolerance.34,35 In addition, evaluating EN intolerance in the
ICU setting can pose a greater challenge because many
patients are unable to verbalize symptoms, eliminating the
clinician’s ability to utilize markers such as nausea and
abdominal discomfort. GI dysmotility is reported in up to
60% of critically ill patients36 ; therefore, it is important for
clinicians to understand alternative causes and limitations
of GI dysmotility to ensure EN delivery can be optimized
and not inadvertently halted.
Hypoactive bowel sounds have been assumed to correlate
with ileus, causing providers to withhold or interrupt EN;
however, the presence or absence of bowel sounds does
not necessarily translate to mucosal integrity or absorptive
capacity. In fact, ileus may be accompanied by absent,
hypoactive, or high-pitched bowel sounds and may be prop-
agated by withholding EN37 ; therefore, the recommended
solution to attenuate dysmotility and minimize the period of
ileus is to start EN as soon as possible after ICU admission
and/or surgery.13
In 1 study, GRV was the most common reason for
EN discontinuation, and nearly 45% of patients for whom
EN was discontinued had a GRV <200 mL nearly half
of the time.19 A perception that elevated GRV translates
into complications such as aspiration has been refuted in
the literature. In 1 study, GRV threshold of 400 mL was
not associated with an increased risk for complications.38
Even GRV thresholds up to 500 mL have not increased
incidence of vomiting, regurgitation, or pneumonia, as
compared with thresholds of 150–250 mL.39-41 Several
studies have compared not checking GRV with checking
GRV and have demonstrated less intolerance in the group
that did not monitor GRV.42-44 One trial showed signifi-
cantly more vomiting when GRVs were not checked (P =
.002).43 In ICUs that continue to monitor GRVs, a GRV
threshold of 500 mL with monitoring every 8 hours (as
opposed to every 4–6 hours) can be utilized. Furthermore,
prokinetic agents, such as metoclopramide or erythromycin,
may also be considered when clinically appropriate to help
manage elevated GRV, although these medications are not
approved by the U.S. Food and Drug Administration for
management of EN intolerance and may be associated with
serious side effects.45 In 2014, a European regulatory agency
recommended limiting the duration of prokinetic use to
no more than 5 days, lowering the maximum daily dose,
and avoiding their use in patients with chronic conditions
such as gastroparesis to minimize the risk for neurologic
and cardiac adverse reactions.46,47 Alternative strategies
to promote gastric emptying include achieving adequate
blood glucose control to prevent gastroparesis, promot-
ing regular bowel movements, and minimizing the use of
opioids.
PN should not be initiated based on medical diagnosis
or disease state alone, but instead a thorough evaluation
Nutrition in Clinical Practice 33(1)
including clinical factors and a physical examination should
be completed to determine its appropriateness.13,48 For ICU
patients who are determined to be severely malnourished
or at high nutrition risk with an EN contraindication,
guidelines suggest PN be initiated as soon as possible.13,48 A
meta-analysis by Braunschweig et al49 showed no nutrition
therapy in malnourished patients was associated with a
significantly higher risk for mortality than exclusive PN
(relative risk 3.0; 95% confidence interval, 1.09–8.56; P <
.05). In well-nourished or low nutrition risk ICU patients,
exclusive PN can be withheld for the first 7 ICU days.13,48
However, supplemental PN (SPN) on day 7 can be consid-
ered for low or high nutrition risk patients not achieving
at least 60% of energy and protein requirements through
EN alone.50 In a meta-analysis by Elke et al,51 4 trials
demonstrated significantly higher caloric provision using
PN compared with EN, whereas 9 trials demonstrated a
nonstatistically significant difference in calorie provision in
groups receiving EN or PN.
Older studies demonstrating harm with PN may be
a perceived barrier to utilizing it as an energy source
in patients who are receiving inadequate or no nutri-
tion support.52-55 These older studies demonstrated hy-
perglycemia with PN, which may have been related to
hyperalimentation. Similarly, a recent meta-analysis showed
an increased incidence of infectious complications in groups
receiving PN compared with groups receiving EN. When
aggregated according to caloric intake, increased infectious
complications were also seen when the PN group received
a significantly higher caloric intake than the EN group;
however, no difference was seen when caloric intake was
similar between the EN and PN groups.51 In a recent large
randomized controlled pragmatically designed study, 2388
critically ill adults were randomly assigned to early EN or
PN. Early PN was associated with a significant decrease in
hypoglycemia (P = .006) and vomiting (P < .001). There
were no differences in treated infectious complications or
90-day mortality between groups.54 In a recent randomized
controlled pilot trial, adult ICU patients with acute res-
piratory failure whose body mass index was <25 or ࣙ35
were randomized for EN alone or SPN and EN.56 Over the
first 7 days, SPN increased delivery of calories and protein
by 26% and 22%, as compared with EN alone. Surgical
ICU patients receiving SPN and EN were found to have a
38% increase in delivered kilocalories and 35% increase in
protein, as compared with an 18% increase in kilocalories
and 13% increase in protein among medical ICU patients
(P < .05). There were no significant differences in outcomes
between groups; however, this pilot trial was not powered for
measured outcomes. The findings from the aforementioned
studies suggest reduced hesitation to utilize SPN in critically
ill patients.
Kozeniecki et al
Provider Attitudes and Behavior
Provider attitudes and behaviors are ultimately the
factors that determine successful delivery of ICU
nutrition. Large gaps have been identified between
what is recommended by societal guidelines and actual
practice.57,58 Implementing strong evidence-based guideline
recommendations into clinical practice may take up
to a decade, with 1 study suggesting up to 20 years
before implementation.59 Resistance to changing an
established practice has been identified as one of
the main barriers to implementing nutrition guideline
recommendations.11 Inertia of previous practice (ie, “This
is how I’ve always done it.”), fear of adverse events due to
aggressive feeding (ie, poor outcome expectancy), lack of
awareness or familiarity with current guidelines, lack
of self-efficacy, and reduced protocolization are examples
of provider-related behavior that may prevent adequate
feeding in the ICU.10,11,60,61 Cabana et al60 have suggested
clinicians’ lack of barriers knowledge may be an
impediment to changing practice and without knowledge
of such barriers, any interventions or guideline recom-
mendations aimed at improving practice are unlikely to be
successful.
A promising solution to mitigating provider-related bar-
riers is the assembly of a multidisciplinary nutrition support
team composed of dietitians, physicians, pharmacists, and
nurses with a stake and knowledge in nutrition support.
A systems-based process to utilize a multidisciplinary team
to optimize nutrition support may gain more traction
than an individual-based effort. Use of an ICU-specific
nutrition protocol is an example of a systematic approach
to standardizing nutrition therapy and guiding provider
decision making in a standardized way. EN management
protocols have been shown to increase EN usage, de-
crease time to feeding, increase the adequacy of calories
and protein provided, delay inappropriate PN initiation,
and decrease the number of ventilator days and risk for
mortality.28,32,62-64 Yeh et al,30 through implementation of
an aggressive EN protocol, have demonstrated fewer late
surgical ICU infections. Use of such a protocol has demon-
strated EN optimization without increasing harm through
complications such as vomiting, regurgitation, aspiration,
and pneumonia.28 Heyland et al28 described the bene-
fits of implementing an EN protocol in an international,
prospective, observational cohort study that included 5497
ICU patients from 269 ICUs in 28 countries. Sites using
an EN protocol had quicker EN start time (41.2 hours
after admission to the ICU, as compared with 57.1 hours
in those without an EN protocol; P = .0003), achieved
greater nutrition adequacy from EN and PN (61.2% of kcal
requirements vs 51.7% in those without an EN protocol; P =
.0003), and nutrition adequacy from EN alone (45.4% kcal
requirements vs 34.7% in those without an EN protocol;
13
P < .0001).28 For best individual health system results, the
feeding protocol must be tailored to meet the unique needs
of the system.29 After implementation, routine practice
audits can be implemented to monitor the effectiveness of
nutrition interventions, the results of which can be used
to determine future protocol calibration. This checks and
balances approach has been described in surgical ICU
nutrition support, and the framework can be extrapolated31
to a variety of practice areas as long as the interventions are
tailored appropriately to each.
Conclusion
Numerous ICU processes, interruptions, and provider atti-
tudes and perceptions contribute to barriers in delivering
optimal ICU nutrition support. Reduced nutrition support
can have lasting implications for patients, particularly those
at high nutrition risk. Creating a multidisciplinary team to
foster nutrition support awareness and continued education
may improve providers’ perception of nutrition. Although
it is unrealistic to assume all ICU-related interruptions
can be avoided, a more detailed analysis may be required
to identify strategies to compensate for interruptions. For
enterally fed critically ill patients, an evidentiary basis is
forming to support the use of reduced-fasting protocols,
compensatory increased enteral feeding goal rates, imme-
diate initiation of target flow rate, and 24-hour volume-
based enteral feeding in attempts to achieve target EN
volume. These particular strategies demonstrate an overall
trend toward increased EN intake and appear to be feasible,
safe, and well tolerated. More research is required, however,
to identify the optimal amount of calories and protein to
prescribe, specifically in the first week of critical illness.
Lastly, improving multidisciplinary awareness and educa-
tion regarding nutrition may improve physician prescription
of target nutrition goals, reduce inappropriate cessation of
EN for perceived intolerance, and increase the use of SPN.
Such strategies are recommended within the context of the
individual organization, its population, and resources for
feasibility and implementation. Further studies to identify
the impact of such strategies on patient-centered outcomes
are needed.
Statement of Authorship
Michelle Kozeniecki, Heather Pitts, and Jayshil J. Patel con-
tributed to the conception and design of the review. Michelle
Kozeniecki and Heather Pitts drafted the manuscript; Michelle
Kozeniecki and Jayshil J. Patel critically revised the manuscript.
All authors agree to be fully accountable for ensuring the
integrity and accuracy of the work, and read and approved the
final manuscript.
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Invited Review

Nutrition in Clinical Practice

Volume 33 Number 1
Enteral Access Devices: Types, Function, Care, February 2018 16–38

C 2018 American Society for

and Challenges Parenteral and Enteral Nutrition

DOI: 10.1002/ncp.10019
wileyonlinelibrary.com

Linda M. Lord, NP, CNSC, ACNP-BC

Abstract
Enteral access feeding devices are placed in patients who have a functional and accessible gastrointestinal (GI) tract but are not
able to consume or absorb enough nutrients to sustain adequate nutrition and hydration. For many individuals, enteral nutrition
support is a lifesaving modality to prevent or treat a depleted nutrient state that can lead to tissue breakdown, compromised immune
function, and poor wound healing. Psychological well-being is also affected with malnutrition and dehydration, triggering feelings
of apathy, depression, fatigue, and loss of morale, negatively impacting a patient’s ability for self-care.1 A variety of existing devices
can be placed through the nares, mouth, stomach or small intestine to provide liquid nutrition, fluids, and medications directly to
the GI tract. If indicated, some of the larger-bore devices may be used for gastric decompression and drainage. These enteral access
devices need to be cared for properly to avert patient discomfort, mechanical device–related complications, and interruptions in the
delivery of needed nutrients, hydration, and medications. Clinicians who seek knowledge about enteral access devices and actively
participate in the selection and care of these devices will be an invaluable resource to any healthcare team. This article will review
the types, care, proper positioning, and replacement schedules of the various enteral access devices, along with the prevention and
troubleshooting of potential problems. (Nutr Clin Pract. 2018;33:16–38)

Keywords
enteral access; enteral nutrition; feeding tube; gastrostomy

Introduction with gastroparesis, chemotherapy agents, gastric outlet or

Enteral access feeding devices are placed in patients who
have a functional and accessible gastrointestinal (GI) tract
but are not able to consume or absorb enough nutrients to
sustain adequate nutrition and hydration. The provision of
nutrition through these devices can be a lifesaving modality
to prevent or treat the dangers of a depleted nutrient
state: tissue breakdown, compromised immune function,
and poor wound healing.1-4 Enteral nutrition (EN) sup-
port can also promote psychological well-being because
malnutrition and dehydration have been shown to produce
feelings of apathy, depression, fatigue, and loss of morale,
negatively impacting a patient’s ability for self-care.5 A
variety of existing devices can be positioned through the
nares, mouth, stomach, or small intestine to provide liquid
nutrition, fluids, and medications directly to the GI tract.
Enteral access feeding devices may be used short term to
provide nutrients for optimal functioning through periods
of illness, trauma, or arduous medical therapies. Long-
term enteral access feeding devices can provide nutrients
through extended periods of medical need and lifelong, if
indicated. Gastrostomy tubes and gastric ports of dual-
lumen tubes may also be used for gastric decompression
and drainage to avert nausea and vomiting that can ensue
intestinal obstructions, or other conditions. Enteral access
devices need to be cared for properly to prevent patient
discomfort, mechanical device–related complications and
interruptions in the delivery of needed nutrients, hydration,
and medications. Clinicians who seek knowledge about en-
teral access devices and actively participate in the selection
and care of these devices will be an invaluable resource
to any healthcare team. This article will review the types,
care, proper positioning, and replacement schedules of the
various enteral access devices, along with the prevention and
troubleshooting of potential problems.
From the University of Rochester Medical Center, Rochester, New
York, USA.
Financial disclosure: None declared.
Conflicts of interest: None declared.
Received for publication July 3, 2016; accepted for publication August
6, 2017.
Corresponding Author:
Linda M. Lord, NP, CNSC, ACNP-BC, University of Rochester
Medical Center, Rochester, NY 14642, USA.
Email: linda_lord@urmc.rochester.edu
Lord
Figure 1. Feeding tube in stomach. 
C Nestlé Health Science,
reprinted with permission.
Figure 2. Feeding tube in small bowel. 
C Nestlé Health
Science, reprinted with permission.
Nasally Placed Feeding Tubes: Types,
Indications, and Key Components
Nasally placed feeding tubes are short-term enteral ac-
cess devices with distal tips positioned in the stomach
(Figure 1) or small intestine (Figure 2). They are commonly
used in the inpatient setting for temporary EN support,
up to about 4–6 weeks, because they can be placed at
the bedside by appropriately trained clinicians and are
easily removed when no longer necessary. They are gener-
ally available in 3.5–12 French (Fr), which describes their
outer diameter. Some practitioners use larger-bore 14–18 Fr
nasogastric tubes manufactured for gastric decompression
and drainage as a vehicle for tube feeding administration.
These tubes may not clog as readily as smaller tubes, and
gastric residual volumes (GRVs) may be easier to obtain.
However, clinicians need to check their state public health
laws because using larger-bores tubes for feeding may be
17
prohibited unless medically necessary, as in the case of New
York State.6 These larger-bore, stiffer tubes are not ideal
as feeding tubes because they are uncomfortable and may
increase the risk for sinusitis and pressure ulcers.
Placement of a tube into the stomach is the initial
option unless small-bowel tube position is needed for
anatomical reasons (gastrectomy, gastric outlet obstruc-
tion) or to provide nutrients beyond a proximal fistula,
obstruction, or bowel leak. Clinicians may also prefer small-
bowel feeding tube placement for those patients who are at
high aspiration risk. This includes patients with decreased
level of consciousness, diminished cough or gag reflex,
impaired lower esophageal sphincter, neurologic deficits,
severe gastroesophageal reflux disease, severe gastroparesis,
elevated GRVs, and emesis. Dual-lumen tubes can provide
simultaneous gastric decompression and drainage, along
with small-bowel tube feeding.
Patients who have had recent nasal surgery, nasal frac-
tures, or severe trauma to the midface should not have a
feeding tube placed nasally. Additional patients considered
high risk for nasally placed feeding tubes are those with
significant coagulation abnormalities, severe esophageal
varices or stricture, or alkaline ingestion, and those who
have undergone recent esophageal banding.7 Upper GI or
head and neck cancers may preclude feeding tube placement
through the esophagus. Enteral tubes can also be placed
orally for short-term gastric access in intubated and sedated
patients, such as those with altered nasal anatomy or nasal
trauma, sinusitis, or facial fractures, but otherwise oral
gastric tubes are not advised because of patient discomfort.8
Most tubes are approximately 36 inches, long enough for
small-bowel passage, but lengths are available up to 45–55
inches for tall adults and further small-bowel advancement
beyond the ligament of Treitz. Small-bore feeding tubes
tend to be of a soft material, polyurethane or silicone,
so many contain a temporary metal stylet or guidewire
within the lumen to stiffen the tube for ease of insertion
(Figures 3 and 4). The stylet is subsequently removed
after proper tube position is confirmed and should not be
reinserted unless the manufacturer has deemed it safe per
its specific guidelines. Stylet reinsertion risks include tube
perforation or exit through the outflow port potentially
perforating the esophagus or GI tract. Some manufacturers
may allow reinsertion of the stylet into their particular
feeding tube, to assist in positioning it into the small
bowel or repositioning if it has moved out of a desired
location. This ability can minimize radiograph exposure
and patient discomfort. The clinician should check the
integrity of the stylet, follow the manufacturer’s instructions
carefully, and only reinsert the stylet that was originally
provided with the feeding tube. The tip of feeding tubes may
contain a weighted material, like tungsten (Figure 5), but
nonweighted tips are also available (Figure 6). It is thought
that the weight may help maintain tube position in the
18 Nutrition in Clinical Practice 33(1)

Figure 3. Weighted feeding tube with stylet.

Figure 5. Weighted feeding tube tip.

Figure 4. Unweighted feeding tube with stylet.

GI tract; however, studies have not confirmed this. Non-

weighted tip feeding tubes tend to be easier to insert through
the nares and have been shown to pass more readily into
the small bowel, compared with weighted tip feeding tubes,
after administration of intravenous (IV) metoclopramide9
and an equally high rate of small-bowel passage after IV
erythromycin.10
In addition to single lumen feeding tubes, there are
dual-lumen tubes where the outlet holes of one lumen
are positioned in the stomach and the alternate lumen
continues to the small intestine. With dual-lumen tubes, the
gastric lumen is often used for either decompression and
drainage of the stomach or medication administration. The
small-bowel lumen, often referred to as the jejunal lumen,
is typically used for tube feeding delivery. Alternatively, Figure 6. Unweight feeding tube tip.
a larger-bore nasogastric tube can be placed in 1 nares
temporarily for gastric decompression and drainage, and a
Lord
separate small-bore feeding tube positioned in the alternate
nares for small-bowel tube feed administration.
Nasally Placed Feeding Tubes: Placement
Nasally placed gastric and small-bowel feeding tubes are
typically inserted at the bedside either blindly or with the
aid of a manufactured device to enhance patient safety. For
blind tube placements, radiographic film should be obtained
to determine tube tip location before the instillation of
feedings or medications. If inserted blindly, predicted length
of tubing required to reach the stomach is predetermined
for each patient. Clinicians commonly follow the nose-ear-
xiphoid method, where the measurement starts at the tip of
the nose to an earlobe to the bottom of the xiphoid process.
The accuracy method of this was tested, along with other
variables, in adult patients undergoing esophageal motility
procedures.11 The ideal feeding tube tip position for gastric
placement was identified as being between 3 and 10 cm past
the distal lower esophageal sphincter. The nose-ear-xiphoid
method was found to be accurate 72.4% of the time. In
this investigation, a more accurate method to achieve ideal
gastric placement was described as a 3-variable model using
gender, weight, and a nose-to-umbilicus measurement while
the patient’s head is lying flat on the bed. The accuracy rate
of having the tube positioned 3–10 cm into the stomach
rose to 85.3%. The tubes outside this intended position were
placed too proximal in half of the cases and too distal in the
other half. This regression model uses nomograms, one for
male and one for female, where a line is drawn from the nose
to umbilicus measurement located on the left column to the
body weight measurement located on the right column, and
the predicted gastric tube insertion distance is determined
at the cross-sectional point.
One of the most hazardous risks of feeding tube inser-
tion is inadvertent tube placement into the bronchial tree.
It has been reported that between 1% and 2% of blind
feeding tube placements result in passage into the bronchi,
and some of these will cause pulmonary injury and even
death.12 Pulmonary intubation of a feeding tube can lead
to pneumothorax, pneumonia, and empyema.13-15 Feeding
tubes also have the potential of perforating the esophagus,16
and intracranial placement has been reported.17-20 Risk
factors for inadvertent bronchopulmonary intubation of
feeding tubes include altered mental status, sedation, pres-
ence of a tracheostomy or endotracheal tube, absence of the
cough reflex, difficulty with tube placement, and anatomic
abnormalities.12 If the tube is placed blindly, it should be
withdrawn immediately if there are any signs of respiratory
distress, like dyspnea, choking, or coughing, or if the patient
is unable to talk. If the patient is alert, sips of water taken
while the tube is inserted and advanced will help guide it in
appropriately through the esophagus.
19
Figure 7. Grassy green feeding tube aspirate.
Once the predetermined length has been inserted, as-
piration of fluid from the tube should be used initially
to help determine tube tip location, reducing the number
of radiographic films needed to verify placement. A 30-
to 60-mL syringe is used to instill 30 mL of air to clear
the tube and then aspirate fluid.21 This can be attempted
twice and if unsuccessful, reposition the patient and try
again.22 The aspirate volume, color, and pH measurement (a
drop of aspirate can be placed on a colorimetric pH strip)
can be assessed. If the aspirate is cloudy and grassy green
(Figure 7), clear and colorless, tan or off-white, or bloody
or brown, and has an acidic pH of ࣘ5.5, gastric placement
is highly likely especially if it is a large volume.23-26 Small-
bowel aspirates tend to be smaller volumes and are brownish
green or light to dark golden yellow (bile colored).22 Pleural
fluid is typically watery, pale yellow, or straw colored, and
tracheobronchial secretions are usually tan or off-white
fluid of mucous consistency, and either can be tainted with
streaks of blood. A pH value >6 can be associated with
gastric, small-bowel or respiratory placement, so this higher
value is not reliable for determining tube tip location. The
use of gastric acid suppressants and continuous drip tube
feedings can increase the gastric pH levels.26-29
Abdominal auscultation over the epigastrium by stetho-
scope while instilling air through the tube does not let
the clinician know the location of the tube tip.25,30,31 The
inability to instill air, however, may identify a kinked tube.
Esophageal placement may be suspect if the air is “burped”
back by the patient, but hearing the air bubble by auscul-
tation does not determine esophageal, gastric, small-bowel,
or bronchopulmonary placement.
If the tube is inserted blindly, it is highly recommended
that a radiographic film be obtained that identifies the entire
route of the tube to the distal tip, before instilling tube
feedings or medications.32 Inadvertent bronchial placement
needs to be ruled out, but additionally the tube tip could
be positioned near the gastroesophageal junction or in the
esophagus if insufficient length is inserted or the tube could
loop back from the stomach upwards placing the patient is
at high risk for aspiration of the infused fluids. The tube tip
20 Nutrition in Clinical Practice 33(1)

may also end up in another unintended position, such as

duodenal placement of an intended gastric tube.
Some techniques to reduce the risk for pulmonary place-
ment include listening for air exchange at the end of the tube
after 25 cm tube length has been inserted,22 carbon dioxide
calorimetry,33-36 and tube placement check by radiograph.37
Fluoroscopic and endoscopic guidance for feeding tube
placement have been utilized, and placement is verified
during tube placement.12,38,39
There are also ongoing efforts by industry to promote
the safe and proper placement of feeding tubes. There are
manufactured small = bore feeding tubes that contain real-
time imaging techniques such as electromagnetic tracking,
where a signal is transmitted and tracked by a receiver
that is placed on a patient’s chest and a graphic display is
visualized on a monitor during tube advancement40-43 or
the integration of a tube with a 3-mm camera where the
anatomy is visualized along the tube’s course and displayed Figure 8. Nasal bridle. Image courtesy of Applied Medical
on a monitor.44 With the advent of these technologies for Technology, Inc.
safe feeding tube passage, blind feeding tube placement
in patients at high risk for inadvertent bronchopulmonary
intubation should be avoided.12
If small-bowel placement is desired, the tube tip ideally
should be eased past the pylorus, through the 12 inches
of duodenum, curved beyond the ligament of Treitz and
into the jejunum to minimize retrograde reflux of the tube
feeding formula45-47 and lower the risk for tube migration
back into the stomach. Prokinetic agents, like metoclo-
pramide and erythromycin, can facilitate this progression
and have shown the most benefit if administered before
the insertion of nonweighted tip feeding tubes.9,10 One ret-
rospective analysis of critically ill, mechanically ventilated
patients showed that aspiration was significantly lower in
the small bowel compared with placement in the stomach,
and aspiration decreased significantly the farther the feeding
tube was into the small bowel.48 Aspiration was 11.6% Figure 9. Incremental markings.
lower just past the pylorus, 13.2% lower in the second/third
portions of the duodenum, and 18% lower in the fourth
portion of the small bowel and beyond. This analysis also pull at their tubes or who have facial wounds or burns
reported that pneumonia occurred significantly less often preventing adhesive securement of their tubes49 (Figure
when the feeding was positioned at the second portion of 8). A recent meta-analysis has shown them to be superior
the duodenum or beyond. to adhesive tape for tube securement and prevention of
tube dislodgement.50 Nasal bridles are also less invasive
compared with the suturing of feeding tubes to the nose.
Nasally Placed Feeding Tubes: Securement
Tubes can potentially slip through any type of securement,
Once the tube tip is properly positioned in the stomach or so it is imperative that there be some method to detect tube
small intestine, it must be immediately secured to the nose migration inward or outward. The tube can be marked with
or cheek with tape, adhesive strips, a transparent physiologic indelible ink where it enters the nose or mouth, or if the tube
dressing, or securement device per the institution’s protocol. has incremental markings (Figure 9), the marking at the
It is beneficial to provide some slack and attach a more distal mouth or nose can be recorded. The length of visible tubing
portion of tube to the cheek with some type of adhesive could also be measured, recorded, and compared with
as an added securement. These tubes may cause distress future position checks (Figure 10). One of these methods
in confused patients who may then attempt to dislodge should be chosen and utilized so that any tube movement
them. Nasal bridles have been used in patients who may can be dealt with promptly.
Lord
Figure 10. Tape measure.
Nasally Placed Feeding Tubes: Site Care
and Replacement
Skin checks around the nose, or mouth if placed orally,
should be performed routinely and skin should be inspected
whenever the tape or securement device is replaced. The tube
should be positioned so that it is not pulling on the nares
or mouth as this may lead to pressure injury or ulceration.
The tape or securement device should be examined to be
sure that it is adequately holding the tube in position and
should be changed as per the institution’s policy. Nasally
placed feeding tubes should be replaced routinely following
manufacturers recommendations, monthly is generally an
accepted guideline.
Stomal Feeding Tubes: Types, Indications,
and Key Components
Longer-term devices are placed when patients require en-
teral access for >4–6 weeks. These are tubes placed di-
rectly into the stomach or small intestine surgically, la-
paroscopically, endoscopically, or radiographically; they are
referred to as stomal or percutaneous tubes.38 Gastrostomy
(G) tubes, jejunostomy (J) tubes, and gastrojejunostomy
(G/J) tubes fall under this category. The term percuta-
neous endoscopic gastrostomy (PEG) is sometimes used as
a generic term for G tube, but they are one type of G
tube: the type that is inserted endoscopically and typi-
cally contains an internal plastic dome-shaped funnel. If a
patient requires longer-term enteral access and is already
scheduled for surgery or a laparoscopic, a radiographic,
or an endoscopic procedure, then placing the enteral ac-
cess device at the same time should be considered. Before
placement, the abdominal wall needs to be inspected for
suitable condition (note surgical scars, ostomies, fistulae,
drainage tubes, or open wounds), the patient needs to be
21
assessed for the ability to undergo anesthesia, and coag-
ulopathies need to be corrected. Some G tubes can be
placed using IV conscious sedation with local anesthesia
administered in the abdomen where the tube is to be
inserted.
The indications for gastric and small-bowel access are
similar to those for nasally inserted feeding tubes. In ad-
dition, stomal feeding tubes may be used for nutrition
and hydration in palliative care and dementia but war-
rant careful individual assessment before the institution
of this therapy.51 Patients who are terminally ill may not
experience hunger and thirst, and an enteral access device
with forced nutrition may promote abdominal discomfort
and fullness, nausea, emesis, fluid retention, and increased
risk for aspiration and pneumonia. Advanced dementia is
also considered a terminal disease. Hand feeding should be
considered initially because it provides social stimulation,
direct human touch, and nurturing. Swallowing studies
should be obtained and dysphagia diets utilized whenever
possible.
G Tubes
G tubes are positioned in a gastric stoma for the delivery
of liquid feeding formulas, fluid, and liquid medications
into the stomach. They can also be used for gastric de-
compression and drainage. In general, G tubes are less
likely to clog compared with nasally placed feeding tubes
because they have larger diameters and are shorter in
length.52 G tubes that are secured to the abdominal wall
under clothing are typically more acceptable to patients
than nasally placed tubes that are visible on the face and
produce the sensation of a foreign body in the pharynx. G
tubes are manufactured of either a polyurethane or silicone
material. Although silicone material is softer and more
comfortable than polyurethane, the internal diameters are
narrower due to thicker walls, and one prospective investi-
gation showed increased material deterioration (dilatation
and bubbling) and tube obstruction associated with fungal
colonization in silicone tubes compared with polyurethane
tubes.53
G tubes are identified:
r by the French size (12 –30 Fr);
r by the internal retention device: balloon (inflatable
internal balloon) or nonballoon (plastic dome or
mushroom-shaped funnel); or
r as standard (visible tube exiting abdomen) or low-
profile (skin level tube flush with abdomen; stoma
length also needs to be identified).
Standard G tubes. Manufactured standard G tubes have a
plastic external retention device (referred to as a bolster,
disc, bumper, phalange, or anchor) that is movable along the
22 Nutrition in Clinical Practice 33(1)

Figure 12. Gastrostomy tube in situ. 

C Nestlé Health Science,

reprinted with permission

Figure 11. External retention device.

tube and fitted snug to the skin to prevent inward migration

of the tube (Figure 11). The proper position of this external
retention device is a dime’s width from skin. It can be either
circular, star-, or rod-shaped depending on the brand. The
grip of this device varies depending on the brand. For those
with a looser grip or if the grip loosens over time, a zip
tie can be applied on or just above the movable external
retention device to secure it in position, being careful not
to tighten it so much that the tube lumen or balloon port (if
present) obstructs.
Foley catheters with an inflatable balloon and Malecot Figure 13. Balloon gastrostomy tube.
winged nonballoon catheters are not recommended as G
tubes because they do not contain a movable external reten-
tion device and, therefore, require sutures or some alternate
tube attachment device to prevent inward migration of the
tube. They will not connect to enteral bags or syringes
with the new ENFit design (see later Enteral Connections
section).
Standard G tubes also contain an internal retention
device to prevent tube migration outward and potential
dislodgment (Figure 12). This internal retention device is
either an inflatable balloon (balloon G tubes) or nonballoon
plastic dome or mushroom-shaped funnel (nonballoon G
tubes). It is the tension between the internal and external
retention devices that prevents tube migration inward or
outward.
Balloon G tubes are easier to remove and replace, but
they require more frequent replacements compared with
nonballoon G tubes. The balloon G tube contains an
internal balloon that is filled with water (Figures 13 and
14). It can easily be identified because it contains a balloon
port where the water can be instilled or withdrawn from the
internal balloon. Sterile or distilled water is recommended
because the minerals in saline or tap water may precipitate Figure 14. Balloon gastrostomy tube: internal balloon.
Lord
Figure 15. Nonballoon gastrostomy tube.
Figure 16. Nonballoon gastrostomy tube: internal.
and cause blockage of the balloon port. Balloon G tubes
are placed transabdominally as an initial G tube or a
replacement G tube and require replacement every 3–4
months to prevent balloon fatigue and rupture. If it is placed
as the initial device, a gastropexy technique is used with
temporary T-fasteners or dissolvable sutures that hold the
stomach to the abdomen until it affixes to the abdominal
wall.54
Nonballoon G tubes contain an internal funnel, referred
to a bolster, disc, bumper, mushroom, or dome (Figures 15
and 16). They may stay in place for 6–12 months. These
tubes are usually placed transorally down the esophagus and
through the stomach. Tubes placed endoscopically, referred
to as PEG tubes, are nonballoon G tubes.55
Most manufactured G tubes have incremental markings
on the tube that indicate the distance from the stomach wall
and signify the length of the stomal tract. The nonballoon
23
Figure 17. Low profile balloon gastrostomy tube.
type usually contains a clamp on the tubing to prevent
the backflow of gastric fluids when uncapping tube. The
balloon G tube does not contain a clamp because it could
damage the internal tubule that carries the water between
the balloon port and the internal balloon. If a clamp is not
present, the tubing needs to be pinched when uncapping the
tube.
Low profile G tubes. There are also low profile or skin-level
G tubes, commonly referred to as “button” G tubes, where
the visible portion of the tube is rod shaped with a cap
closure and is premeasured to be flush to the abdomen.
The stomal tract length needs to be measured (in cm) for
the appropriate low profile tube shaft length to be placed.
There are manufactured stomal measuring devices, but the
clinician can also look at the incremental markings on
the existing G tube to determine the stomal tract length.
Low profile G tubes are identified by both a Fr size and
shaft length (in cm). Currently, they are available in shaft
lengths from 0.8 to 6.0 cm. The internal retention device
may be a water balloon requiring replacement every 3–
4 months (Figure 17) or a nonballoon mushroom-shaped
dome (Figures 18 and 19) requiring replacement every
6–12 months. Low profile G tubes contain an antireflux
valve to prevent leakage of gastric contents when uncapping
the device. A separate extension tubing is plugged into low
profile G tubes for infusions and then removed when the
infusion is complete (Figures 20 and 21).
Compared with the standard G tubes (Figure 22), low
profile G tubes are less visible and lighter, have fewer
24 Nutrition in Clinical Practice 33(1)

Figure 20. Extension tube for low profile balloon gastrostomy

tube.

Figure 18. Low profile nonballoon gastrostomy tube.

Figure 21. Extension tube low profile non-balloon

gastrostomy tube.

Figure 19. Low profile nonballoon gastrostomy tube. Image

courtesy of Applied Medical Technology, Inc.

restrictions on mobility, do not require tape to secure excess

tubing to skin, and are less likely to dislodge by getting
caught on something (Figure 23). Another advantage to
the low profile G tube is the antireflux valve so if the cap
should open, there would not be the gastric fluid leakage
that could occur if the standard G tube cap became loose
and inadvertently opened. Low profile G tubes are well
established in the pediatric population, but they can provide Figure 22. Standard gastrostomy tube. Courtesy Halyard
all these same benefits for adults, who may also appreciate Health.
this option.
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Figure 23. Low-profile gastrostomy tube. Courtesy Halyard
Health
Patient and caregiver preference should be considered
when offering a low profile tube because, in some cases, they
may prefer not to deal with the extension tubing attachment
and are content with the standard G tube. Some medical
facilities are not properly trained to attach the extension
tubing. Also, in obese individuals, the gastric stoma tract
length may be longer than the commercially available low
profile tube shaft lengths.
Janeway Gastrostomy
A Janeway gastrostomy is a surgical procedure where a
tunnel is created within the stomach that is brought out
through the abdomen to form a permanent stoma.56 A
catheter or feeding tube is inserted into the stoma, ap-
proximately 6 inches, to administer infusions and medica-
tions into the stomach. The catheter or tube is removed
when not being used to allow the stoma to close and
prevent leakage between feedings. A Janeway gastrostomy
is useful for patients who may pull at and dislodge their
tubes.
G/J and J Tubes
Jejunal ports of G/J tubes and J tubes are positioned in the
small bowel for the delivery of liquid feeding formulas, fluid,
and possibly liquid medications for the same indications
as outlined for nasally placed small-bowel feeding tubes.
Jejunal ports of G/J tubes and J tubes are more likely to
clog compared with G tubes due to their longer length and
smaller diameter. Patient and caregiver education should
highlight techniques for preventing and treating tube clog-
ging because G/J tubes and newly placed J tubes require
fluoroscopy or endoscopy for replacement.
25
Figure 24. Standard transgastric balloon G/J tube. Courtesy
Halyard Health
G/J and J tubes are identified:
r by the Fr size: G/J tubes (14–24 Fr), J tubes (5 – 16
Fr);
r by the internal gastric retention device, if present:
balloon (inflatable internal balloon) or nonballoon
(plastic dome or mushroom shaped funnel);
r as standard (visible tube exiting abdomen) or low
profile (skin-level tube flush with abdomen; stoma
length also needs to be identified); or
r by length, if G/J tube (15–95 cm).
Transgastric G/J tubes. Transgastric implies that the tube
enters and is guided through the stomach for ultimate
entry into the small bowel. One option for small-bowel
access is to thread a jejunal catheter through an existing
G tube. In this scenario, the gastric port of the G tube is
blocked to gain access into the small bowel. There are also
manufactured transgastric G/J tubes that contain 2 separate
lumens for gastric and small-bowel access or transgastric
J tubes that contain 1 lumen only for small-bowel access.
These are available as balloon (Figure 24) or nonballoon
and as standard (Figure 24) or low profile (Figure 25)
tubes as described earlier. When small-bowel access is
needed via a gastric stoma, postinsertion tube placement
is verified radiographically, endoscopically, or surgically to
ensure appropriate position of the tube tip. Transgastric
small-bowel tubes may malposition back to the stomach, so
obtaining residual checks for volume, color, and pH value
through the gastric port (if available) and jejunal port may
give the clinician some information on tube tip location.
J tubes. Instead of accessing the small bowel by the trans-
gastric route, a tube could be placed directly through a
surgically created jejunal stoma to avert gastric malposition,
thereby lowering the risk for aspirated tube feeding formula
26
Figure 25. Low profile transgastric Balloon J tube.
and fluids. In addition, direct J tubes can potentially be
replaced in a home or clinic setting, without radiographic
guidance, once the stoma tract has matured. The Witzel
jejunostomy is a surgically created serosal tunnel into the
small bowel, and the J tube is inserted into it. The tube
should be at least 6 inches into the tunnel to prevent back-
flow and site leakage of the formula, fluid, or medications.
There are commercially available J tubes that have a Dacron
cuff that is embedded within the skin layers (Figure 26);
some contain a small internal water balloon to prevent
tube displacement (3–7 mL), and others require securement
with either sutures or some type of external anchoring
device. A needle catheter jejunostomy involves inserting a
needle obliquely through the small bowel; then a Seldinger
technique is used to insert a very small-bore feeding tube (5
Fr) into the small bowel.57 The commonly used urethral red
rubber catheter, as a jejunal feeding tube, will not connect
to enteral bags or syringes with the new upcoming ENFit
design (see later Enteral Connections section).
Stomal Feeding Tubes: Securement
Strategies can be employed for patients who tend to pull
at their stomal tubes, such as tucking the tube away under
clothing or applying an abdominal binder, which is a wide
elastic wrapped around the abdomen and secured with
Velcro. Care must taken that a binder is not too tight,
causing pressure or trauma to the tube site. For stomal
tubes that do not contain an external retention device,
tube securement can be achieved with manufactured tube
attachment devices that are secured to the abdomen with
adhesive, Steri-Strips, tape, or sutures.
Nutrition in Clinical Practice 33(1)
Figure 26. J tube.
Stomal Feeding Tubes: Site Care
Newly placed stomal tubes have a split gauze dressing
inserted either underneath or above the external (bolster,
disc, bumper, phalange, anchor) that can be removed after
24 hours. Afterward, the site can be left open to air, or
a new split-gauze dressing can be applied daily and as
needed for excessive site drainage. If the gauze is placed
underneath the external retention device, be sure it is not
causing excessive tension to the site. Some patients like
the padding a gauze provides around the site or under the
external (bolster, disc, bumper, phalange, anchor). The site
should be washed gently with soap, followed by a water
rinse and patted dry, including underneath the external
(bolster, disc, bumper, phalange, anchor). Harsh agents such
as hydrogen peroxide should not be used for routine cleaning
because they can inhibit wound healing and irritate the skin.
Hydrogen peroxide may be used to lift crusty drainage if
needed, but it should be followed immediately by a water
rinse. Keeping the site as dry as possible will help lower the
risk for skin breakdown and hypertrophic or granulation
tissue growth. The external (bolster, disc, bumper, phalange,
anchor) should ideally be about a dime’s width from the
skin. Patients may take tub baths or swim after 2–6 weeks
depending on provider’s instructions.
Stomal Feeding Tubes: Replacement
Stomal tubes may eventually tear, malposition, or dislodge,
so they should be periodically replaced to avoid emergency
department visits and the potential for missed nutrition,
fluids, and medications. The balloon volume of balloon
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G and J tubes tends to shrink over time, or the balloon
may rupture and spring a leak, leading to tube malposition
and dislodgement. Balloon G tubes should generally be
replaced every 3–6 months, depending on manufacturer’s
guidelines and patient history of tube malfunction and
dislodgements. Nonballoon G tubes (includes PEG tubes)
should be replaced every 6–12 months, depending on manu-
facturer’s guidelines. With nonballoon G tubes, the internal
(bolster, disc, bumper, mushroom, or dome) may deteriorate
and separate either while in situ or when removing the
entire tube through the abdominal wall by the traction pull
technique.
Tube Patency
To keep feeding tubes patent and avoid sludge buildup
and clogs, they need to be flushed regularly with water
(Figure 27), pump alarms need to be responded to quickly,
viscous solutions and slow flow rates need to be avoided, and
medications should not be mixed with each other or with the
tube feeding formula.
According to the American Society for Parenteral and
Enteral Nutrition (ASPEN) 2017 Safe Practices for Enteral
Nutrition Therapy, feeding tubes should be flushed with at
least 30 mL pf water every 4 hours during continuous tube
Figure 27. Water flush. 
C Nestlé Health Science, reprinted
with permission.
27
feedings, before and after intermittent feedings, and after
GRV checks.58 They also should be flushed with at least 15
mL of water before, after, and in between each medication.
In hospital and clinic settings, sterile water is generally used
for water flushes, medication dilution, and reconstitution of
powdered formulas. In the home setting municipal tap water
can be used for routine water flushes; however, distilled
or sterile water is recommended for powdered formula
reconstitution, medication dilution, and flushes before and
after medication delivery. These solutions are free of heavy
metals and other contaminants that can cause untoward in-
teractions and alter the pharmacodynamics of administered
drugs.59 Because sterile water is not generally covered by
insurance in the home setting, distilled water is acceptable.
Juices or sweetened sodas should not be used for flushes
because their acidic nature can coagulate the protein in
feeding formulas and form clogs.60-62
Medication Delivery Through Feeding Tubes
Medications administered through feeding tubes should
be given in liquid form or, if allowed, crushed to a fine
powder and dissolved completely in water. Crushed and
dissolved tablets in water are preferred as the liquid forms
of medications are manufactured for oral consumption
and contain added sugars and flavoring agents, making
them more viscous and hypertonic. Some liquid medi-
cations contain sorbitol, which has a laxative effect and
may cause diarrhea, bloating, and gas. As noted earlier,
medications should be diluted with sterile water, or in the
outpatient setting distilled water may be used. Delayed-
released, enteric-coated, or microencapsulated medications
cannot be crushed because it alters the drug bioavailability.
Medications should not be mixed with each other or with
the tube feeding formula, and the tube feeding may need
to be held around the administration time of some med-
ications. Administering each medication separately with
at least a 15 mL of water flush in between prevents
physical and chemical incompatibilities that can alter the
actions of the drugs and can cause clumping and tube
clogging.58,59,63 Medications should be administered via G
ports if possible. If a small-bowel port needs to be used for
medication delivery, be sure that the solution is intended for
immediate-release systemic absorption, that it is not too
viscous or hyperosmolar, that the drug is not meant for
direct action in the stomach or require the acidity of the
stomach, and that the alkaline environment of the small
bowel does not inhibit drug absorption. It would be prudent
to consult with a pharmacist for any concerns related to
medication administration via feeding tubes.
Tube Declogging
One complication that interferes with the timely delivery
of the nutrition formula, free water, and medications is the
28
clogging of the feeding tube. Nasoenteric feeding tubes and
J tubes are more likely to clog than G tubes because of
their longer lengths and narrow diameters. The initial rec-
ommendation regarding tube declogging is to work on the
clog as soon as possible. The longer the wait, the less likely
the tube declogging technique will be successful.64 Address
pump alarms and reported difficulties with infusions as soon
as possible. Initially an attachment of a water-filled syringe
and plunger movement back and forth can be used to help
loosen up a clog and encourage clog withdrawal from the
tube’s lumen.65 If it does not clear, water penetration66,67
may be initiated while supplies are gathered for the selected
tube declogging procedure. Pancreatic enzymes activated
with baking soda and water have been shown to dissolve
clogs more effectively compared with solutions such as
sugared sodas, cranberry juice, or meat tenderizer.68 The
following subsections provide some suggested techniques.
(Note: If any of these techniques are successful in loosening
a clog, the clog should be withdrawn if able and the tube
flushed immediately afterward with at least 30 mL water.)
Initial Water Flush
Withdraw all fluid from the tube so that the water to be
instilled is in closer proximity to the clog; then attach a 30-
to 60-mL syringe of water and use a back-and-forth motion
to loosen the clog and then attempt to withdraw the clog.
Water Penetration
Withdraw all fluid from tube so that the water to be instilled
is in closer proximity to the clog; then attach a 30- to 60-
mL syringe of water, instill as much water as the tube will
allow under mild pressure, and use a back and forth motion
to loosen then clog, then leave in place 30–60 minutes.
Periodically move syringe back and forth during this period.
Try to withdraw; repeat if needed.
Activated Pancreatic Enzyme65-71
Activated pancreatic enzyme uses the same technique
for water penetration described earlier but substitutes a de-
clogging solution: Dissolve a crushed 650-mg non-enteric-
coated sodium bicarbonate tablet or ¼ tsp baking soda in
10 mL of warm water. Add the contents of an opened
12,000-U pancrelipase capsule (Creon) or a crushed 10,440-
U pancrelipase tablet (Viokace) and allow to dissolve (may
take 20–30 minutes). Withdraw all fluid from tube so that the
declogging solution is in closer proximity to then clog and
then follow the water penetration technique. The declogging
solution can be repeated once, but if unsuccessful the tube
will likely need to be replaced. This solution can also be used
as a prophylactic lock to prevent sludge buildup in the high-
risk tubes.72 A short-term periodic lock such as a 1-hour
instillation once weekly, not continuous, would be prudent
Nutrition in Clinical Practice 33(1)
to avoid any potential interactions between the solution and
the material composition of the tube.73
Commercial Declogging Devices
Commercial declogging devices are those manufactured by
industry to declog feeding tubes.
r Enzyme cocktail in preloaded syringe: patented pow-
der containing α-amylase, papain, cellulase, enzyme
enhancers, and antibacterial agents preloaded in a
syringe that is activated with water. The solution
is then instilled through a narrow-bore applicator
tube that is inserted in the feeding tube for closer
proximity to the clog. It remains in the tube for 30–60
minutes to exert its declogging action. It can be used
in all enteral tube types. A company trial states 100%
success rate on the first or second try in 17 patients
with formula clogs.74,75
r Machine-operated declogger: a flexible wire encased in
a sheath that is attached to a machine that causes a
rapid back-and-forth motion to mechanically break
up clogs.76 It can be used with nasally inserted G
and J feeding tubes. The advantage of this method,
according to the company, is the average procedure
time of 2.8 minutes compared with water penetration
and enzymatic methods that can take 30–60 minutes.
r Corrugated plastic rod: A long, flexible plastic rod
with corrugations that is inserted into the tube and
twists into a clog to mechanically break it up. This
can only be used for larger-bore G and J tubes, and
the length to be inserted needs to be predetermined
so as not to exceed the length of the tube.77
Tube Position
Most enteral access devices have incremental markings on
the tube that identify the length of tubing beginning from
the tip, or for stomal tubes from the point just above
the internal retention device, continuing to the distal end
(Figures 28 and 29).
Documentation of the incremental marking on the tube
at the exit site (nares, mouth, or stoma) just after initial
insertion can assist in determining tube migration inward or
outward. The tube could also be marked with an indelible
marker at the exit site, but these markings fade so the initial
marking should be periodically redrawn. For nasoenteric
feeding tubes, standard G tubes, standard G/J tubes, or
J tubes, the visible tube length can also be measured and
documented for future comparison.
GRV and Small-Bowel Residual Volume Checks
For patients who are unable to communicate symptoms
of GI upset, the aspiration of GRVs from feeding tubes
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Figure 28. Weighted feeding tube with incremental markings.
Figure 29. Balloon G tube with incremental markings.
with a syringe has been an age-old and widely accepted
method to help determine tolerance to EN support. Enteral
tube feedings have been held ࣙ1 hour for a variety of
GRVs ranging from 50 mL or twice the hourly rate, to
more recent recommendations allowing values as high as
200–500 mL. Standardized GRV protocols were not estab-
lished with their widespread use because GRV measure-
ments and the subsequent holding of tube feedings were
not investigated for the ability to prevent aspiration or as-
piration pneumonia until recently. Researchers over the last
couple of decades have begun to compare different levels
of GRV used to hold enteral formula delivery with the inci-
dence of aspiration and aspiration pneumonia, percentage
of “goal” formula delivered, and associated GI symptoms
29
in the intensive care unit (ICU) patient population. There
was a recent review by Elke et al78 of these randomized
controlled trials and various observational studies related
to GRV monitoring. This group advised examining patient
characteristics and the delivery strategy of the EN support
when developing protocols for the use or nonuse of GRV
checks. They noted that a multicenter trial of critically ill
patients on a ventilator that showed no benefit of adjusting
EN for GRV checks >250 mL on nosocomial pneumonia
rates had enrolled 93% medical ICU patients.79 In this
investigation, surgical and trauma patients, who are at
higher risk for aspiration pneumonia, were not fully eval-
uated. In addition, they noted that in trials where feedings
continued despite GRVs, strict protocols were applied to
prevent gastric reflux and aspiration of contaminated oral
secretions including head of bed (HOB) elevation, regular
oral decontamination, and use of prokinetic agents.
In an investigation using an aspiration risk protocol by
Metheny et al,80 it was found that the combination of HOB
elevation (by medical order and hourly documentation
in the medical record) and bedside insertion of small-
bowel feeding tubes for patients determined to be at high
aspiration risk, decreased aspiration prevalence rate from
88% to 39% and pneumonia from 48% to 19%. GRVs
were obtained, and only 3 patients (2%) in the study group
using the aspiration risk protocol had a residual volume of
ࣙ200 mL.
EN Delivery Schedules
The traditional tube feeding delivery strategy is the gradual
increase of the hourly infusion rate until reaching the goal
rate. The goal rate is determined by dividing the total vol-
ume to be infused per day by 24 hours. However, when the
feeding is interrupted, less formula is infused and the goals
frequently are not met. Newer, more aggressive approaches
have been suggested, and some may initiate feedings at goal
rates, use promotility agents, or allow for higher hourly
rates to make up lost infusion times.81-85 Elke et al78 have
suggested that those patients who are undergoing these
more aggressive schedules are more likely to benefit from
GRV checks because higher amounts of formula are being
infused more swiftly and may not be tolerated as well.
Although not all elevated GRVs will lead to a clinically
significant aspiration, it has been shown that the probability
of aspiration is higher when GRVs are elevated.86
Guidelines for GRV Checks
Published guidelines for GRV checks generated by various
countries have not been identical in their recommendations.
The National Guidelines for the Provision and Assessment
of Nutrition Support Therapy in the Adult Critically Ill
Patient submitted in February 2016 by the Society of
Critical Care and the ASPEN suggest that GRVs not be
30
used as part of routine care to monitor ICU patients
receiving EN.87 They also state that for those ICUs where
GRVs are still utilized, holding EN for GRV <500 mL
in the absence of other signs of intolerance should be
avoided. The Canadian Practice Guidelines suggest a GRV
threshold of 250–500 mL and contend that abandoning
GRV checks or using a 500-mL threshold was premature
and questioned the external validity of the current trials.88
The German Nutrition Society suggests abandoning GRV
checks in medical ICU patients provided that the medical
team has the ability to adjust the enteral infusion, such
as when vomiting occurs.89 However, in the surgical ICU
patients, they suggest obtaining GRV checks and adjusting
the EN delivery rate with a threshold of 200 mL. The
“2006 ESPEN (European Society for Parenteral and Enteral
Nutrition) Guidelines on Enteral Nutrition: Intensive Care”
do not address GRVs except that “IV administration of
metoclopramide or erythromycin should be considered in
patients with intolerance to enteral feeding e.g. with high
gastric residuals.”90
Notably, published guidelines are based upon investiga-
tions of nasally inserted feeding tubes with tips ideally well
into the stomach, but do not address G tubes situated in
the anterior portion of the stomach. It would appear that a
given GRV from a G tube would be more worrisome and,
therefore, should have lower GRV limits.
GRV: Discard or Reinstill?
A randomized, prospective clinical trial was conducted in an
adult medical-surgical ICU of a public university hospital
comparing various outcomes of patients randomized to
the discarding vs the reinstilling of GRV (up to 250 mL,
remaining volume discarded).91 They were identified as the
discard and return group. The return group surprisingly
had a significantly lower incidence of subsequent high GRV
(>350 mL), and the authors suggested that the reinstilling
of the GRV may have some effect at maintaining GRV
at “closer physiological levels.”91 There was a statistically
higher frequency of hyperglycemia episodes in the return
group. There was no difference in obstruction of the nasally
placed feeding tubes, enteral feeding delays (defined as
>20% difference between prescribed and amount admin-
istered per day), intolerance episodes (nausea, vomiting,
diarrhea, and abdominal distention), discomfort episodes,
or hypokalemic episodes. The authors also stated that
there was no difference in pulmonary aspiration between
groups; however, the definition of this was not well defined.
It appears that they checked blood glucose in tracheal
aspirates to determine the aspiration of glucose-containing
formula. This method has been shown not to correlate with
aspiration of formula, but has a correlation with blood
glucose levels and, therefore, is not useful for detection of
tube-feeding formula aspiration.92 Notably, all patients had
Nutrition in Clinical Practice 33(1)
HOB elevated ࣙ30 degrees, were on continuous tube feeding
schedules, and received 40 mg of omeprazole per day. These
practices have been shown to lower GRVs, and study results
showed only a 2.3% incidence rate of GRV >250 mL in
the return group and a 4.1% incidence rate of GRV >250
mL in the discard group. The GRVs were <150 mL in 93%
of the return group and 88% of the discard group. This
study gives some evidence that reinstilling up to 250 mL of
GRV poses no additional risk for increased accumulation of
gastric fluid levels, GI intolerance, or hypokalemia, but did
not address the incidence of pulmonary aspiration between
groups.
Minimizing Aspiration Risk
This leaves institutions still in a quandary of what GRV
amount warrants holding EN and for how long. The prac-
tice of GRV checks is time consuming, may increase the
risk for contamination and tube clogging, and may pro-
mote the holding of EN unnecessarily. Institutions should
examine these various guidelines and research investigations
closely, and develop protocols or algorithms based on their
patient population and EN delivery schedules. It should
also be noted that oropharyngeal and gastric secretions
also contribute to aspiration risk. Protocols to minimize
aspiration risk should not weigh heavily on GRVs but
include measures that prevent the movement of enteral
feedings and contaminated secretions into the lung.
Protocol or algorithm development geared toward min-
imizing aspiration risk in hospitalized tube-fed patients
should consider the following:
r HOB elevation 30–45 degrees with documentation
at least every 4 hours. If HOB is contraindicated,
consider reverse Trendelenburg position.87,93,94
r Routine oral care with chlorhexidine twice
daily87,94,95
r Performance of oropharyngeal suctioning when han-
dling of secretions is difficult, before the HOB is
lowered, before the endotracheal tube cuff is deflated,
and prior to extubation
r Use continuous tube feedings by pump instead of
bolus feedings for patients at high aspiration risk81,83
r GRV frequency, 4-hour intervals are suggested in
critically ill patients92,96
r GRV levels at which to:
o hold tube feedings and for how long
o perform a GI review of systems and an ab-
dominal examination
o consider a promotility agent87
o convert to a small-bowel feeding tube87
r Guidelines for volume of GRV to reinstill back to the
patient91
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r Assess for position of enteral access device: noting
that the initial marking on tube is still positioned at
the exit site or that the premeasured external tube
length is the same, 4-hour intervals are suggested.96
Tube position should also be checked if the patient
has emesis, retching, or a coughing episode, tube has
been tugged on, or tube length appears too long or
short.
r Frequency of GI review of systems that includes
presence of nausea, emesis, reflux, feelings of full-
ness, abdominal discomfort, pain, or cramping: 4-
hour intervals are suggested96
r Frequency of abdominal assessments that
include evidence of distention and abnormal or
absence of bowel sounds, and tracking of bowel
movements/ostomy outputs: 4-hour intervals are
suggested96
r Utilization of minimal sedation techniques
Discontinuation of GRV checks
When patients become alert and communicative, they can be
questioned on GI symptoms to determine tolerance to EN.
They can report their feelings of fullness, nausea, bloating,
and abdominal discomfort, and it can be noted if they
are having regurgitation or emesis. These interventions can
be used instead of GRV checks to assess adequate gastric
emptying of EN infusions.
Residual Volume Checks From Small-Bowel
Feeding Tubes
Clinicians may want to check residual volumes from nasally
placed small-bowel feeding tubes or the J port of a G/J
tube in patients who are at high risk for aspiration, having
reflux, vomiting, or having shortness of breath to detect
potential tube-tip malposition back into the stomach. The
clinician may detect a significant increase in the volume
and change in color of the aspirate. These checks may also
help determine whether there may be a distal obstruction,
because small-bowel residuals should typically be of a low
volume. However, it is especially important that J tubes be
flushed with water before and after these checks to maintain
tube patency because they can clog easily and require a
higher level of skill to replace.
Enteral Connections
Enteral access devices require connection to a syringe or
feeding bag to administer the feeding formula, medication,
or water to the patient. Misconnections between unrelated
delivery systems need to be avoided because deleterious out-
comes have occurred when, for example, enteral feeding for-
mulas have been inadvertently infused into IV catheters.97
The Stay Connected initiative was created by GEDSA
31
Figure 30. ENFit design. Image from stayconnected.org
website.
(Global Enteral Device Supplier Association) to help in-
troduce new small-bore connectors in medical devices to
prevent misconnections between unrelated delivery systems.
The Stay Connected initiative is assisting in the gradual
introduction of new standard connectors for delivery of spe-
cific liquids and gases, starting with enteral access devices.
With the new ENFit design, enteral feeding containers,
enteral syringes, and the distal end of extension sets (low
profile devices) will contain the female connector end, and
enteral access devices will contain the male connector end
(Figure 30). This new ENFit design will not allow enteral
delivery system connections to IV catheters, IV solutions,
respiratory equipment, neuraxial analgesia/anesthesia, or
limb cuff inflation devices. Information and updates on the
initiative can be found at http://StayConnected.org.98
Tube Complications
Tube Malposition
A tube can malposition anytime after tube placement when
the tip of the nasally placed feeding tube migrates from
the small bowel to the stomach, or from the stomach to
either the esophagus or small bowel. The tube is unlikely to
malposition to the bronchial tree once positioned properly
in the GI tract.22 If a small-bowel tube advances farther
into the small bowel over time, this is generally considered
desirable because it would further decrease the aspiration
risk. Malposition may be detected by a change in length
of visible tubing or movement of a predetermined marking
on the tube; however, the tube may also malposition up
and down the GI tract without any evidence of shifting on
the outside.22 The small-bowel lumen of a transgastric G/J
tube or a transgastric J tube may also migrate back into the
stomach without any visual changes in the position of the
tube on the abdomen. Placement of a G tube directly into a
32
gastric stoma or a J tube via a jejunal stoma lowers the risk
for tube malposition.
Visualization and pH testing of tube aspirates may
help determine the tube tip location Once continuous drip
tube feedings are initiated, the appearance and pH of the
aspirates change because creamy tan formulas will obscure
the color, and the higher pH (>6.0) will affect the pH of
the aspirate.23,99 Gastric aspirates will tend to be curdled
formula, off-white with sediment, green, brown, or bloody,
whereas small-bowel aspirates could be clear golden yellow
thicker than water, yellow-brown or greenish brown, or
either could emerge like unchanged formula. If the patient is
receiving intermittent feedings, an aspirate check just before
a feeding for visualization and pH check may help determine
gastric vs small-bowel placement. One investigation showed
that the use of 3 indicators for tube position resulted in
the ability to determine tube location 81% of the time in
critically ill patients on continuous tube feeding schedules in
either the stomach or small bowel.99 These were observing
for tube length changes and the volume and color of the
aspirates, 5 times daily. They also observed for pH values;
however, 98.4% of patients studied were receiving either an
H2 receptor antagonist or a proton pump inhibitor. The
pH value was significantly lower in the gastric compared
with small-bowel aspirates, but the means were 6.4 vs 6.8,
respectively. Despite the use of gastric acid inhibitors, in
about 50% of the cases where the tube malpositioned from
the small bowel to the stomach (11/23), the pH value
decreased from 6–7 to ࣘ5.5. In the remaining patients, the
pH remained 7 in both locations.
Observation of a substantial increase in the volume of
aspirate from a tube originally positioned in the small bowel
may indicate malposition of the tube tip into the stomach.
Of concern is a tube tip that malpositions from the stomach
upward near the gastroesophageal junction or into the
esophagus, or a small-bowel tube that malpositions in the
stomach because these can increase aspiration risk. When
a patient vomits or refluxes formula, the mouth should be
checked for excess tubing, and if the tube is not visibly
malpositioned, tube-tip location should be checked by ra-
diographic film before restarting the tube feeding infusion.
Alternatively, if a gastric tube malpositions into the small
bowel, an intermittent drip or bolus feeding schedule could
cause dumping syndrome, as evidenced by abdominal pain
and bloating, diarrhea, dizziness, flushing of the skin, and
diaphoresis.
Exit Site Issues
Nasally inserted feeding tubes. Nasoenteric tubes may cause
skin breakdown and ulcerations at nares or mouth. Other
complications surrounding these tubes include otitis media,
epistaxis, or sinusitis. Sinusitis may occur because of the
tube blockage of normal sinus drainage and can present
Nutrition in Clinical Practice 33(1)
as nasal pain or pressure, redness, edema, fever, and/or
purulent discharge. One investigation showed as many as
16% of surgical ICU patients had fever of unknown etiology
due to sinusitis that resolved after drainage.100 Larger-
bore 18 Fr nasogastric tubes have been associated with an
increased incidence of middle-ear effusions in intubated
patients.101
Stomal tubes.
Site drainage. Stomal tubes may have site drainage that
could be normally clear, tan, cloudy, yellow, green, and
brown. If the drainage is excessive, then tube position and
internal balloon volume, if present, should be checked.
If the external (bolster, disc, bumper, phalange, anchor)
is positioned more than a dime’s width from the skin,
then it should be repositioned by an experienced clini-
cian/individual. If excess leakage continues despite proper
tube positioning and balloon volume fluid content, the
clinician could consider transitioning a G tube to a G/J
tube instilling formula and fluids distally, allowing heal-
ing of the G tube site with good site care (see later).
Proton pump inhibitor therapy should be considered to
prevent or treat site irritation from excessive acidic gastric
leakage.
Skin breakdown and site infection. If there is redness or
excoriation at the exit site, zinc-based products, such as
diaper rash creams or absorptive powders, can be applied
and the site covered with a split-gauze dressing. If there
is excessive site leakage, a dressing that is manufactured to
wick away moisture is preferable to gauze. Nonalcohol skin
barrier films or skin barrier wafers can be used.102 If there
are scattered reddened raised papules spreading from the
stoma outward, a fungal infection is suspected. This can be
treated with a topical antifungal such as nystatin powder
or cream applied directly and a zinc oxide cream coating
covered with a split-gauze dressing, twice daily. A wound
consult can be obtained and should be if these first-line
treatments are ineffective.
To evaluate for a stomal-site infection, observe for red-
ness, induration, edema, pain, and sometimes fever. The
color of the site drainage does not determine an infection
because normal gastric fluid can be a variety of colors
including green. If an infection is suspected, a thin layer of
an antibiotic ointment can be applied, or if severe, a broad-
spectrum antibiotic may be warranted.
Site pain. Excessive pain at stomal tube sites may be caused
by an external (bolster, disc, bumper, phalange, anchor) that
is positioned too tight, tube dislodging, skin breakdown, or
a site infection.
Hypertrophic or granulation tissue growth. Over time, there
may be the development of reddened, lumpy, moist, shiny
Lord
Figure 31. Granulation tissue.
tissue growth protruding from the stoma site of stomal
tubes. This is called hypertrophic or granulation tissue, some-
times referred to as “proud flesh,” and may emerge from
the internal stoma because of moisture and tube movement
(Figure 31). The presence of this excess tissue usually leads
to increased site drainage as the seal around the tube is
compromised and continued drainage provides more mois-
ture for continued tissue growth. The treatment involves
dissolution, commonly with silver nitrate applicators, and
continued treatment with a topical corticosteroid that can be
applied with a cotton tip applicator as needed.103 Mometa-
sone furoate 0.1% can be used once daily or triamcinolone
acetonide 0.1% 3 times daily. Care must be taken not to
apply the corticosteroid on healthy skin because it will cause
thinning of the skin over time. As a last resort, surgical
removal of granulation tissue can be undertaken, but should
be performed only by a skilled clinician because it can
bleed easily and a thorough assessment is needed to rule
out malignancy.104 Prevention of granulation tissue growth
around a stomal tube consists of keeping the site as dry
as possible, securing the tube to prevent movement, and
ensuring that the movable external attachment device or
low profile tube is positioned about a dime’s width from
skin.
Tumor implantation and metastasis at PEG tube site. A
rare but potential complication in patients with throat
cancer appears to be the shearing of cancer cells during
PEG tube placement and subsequent tumor seeding at the
abdominal wall and PEG tube site.105 In 1 report of 218
patients with head and neck cancer with active disease and
a viable tumor in the oropharynx or hypopharynx at the
time of PEG placement, 2 patients (0.92%) experienced
PEG site metastasis.106 This can be treated with palliative
radiation or resection, but prognosis is poor.105 Because
this complication has for the most part been reported
33
Figure 32. Buried bumper syndrome. 
C Nestlé Health Science,
reprinted with permission.
with endoscopically placed G tubes using the transoral
approach, alternate methods of tube placements, such as
radiologic percutaneous tubes using the transabdominal
approach, could be considered in patients with head and
neck cancer, and an overtube technique has also been
suggested.105,107,108
Buried bumper syndrome. At times, the internal (bolster,
disc, bumper, dome) of stomal tubes may embed into the
gastric wall from excessive traction and become buried
(Figure 32). This may occur with nonballoon stomal tubes
but is not likely with balloon stomal tubes. Symptoms
of this syndrome include pain during infusions, resistance
to infusions, and inability to rotate G tube 360 degrees.
Transgastric G/J tubes should not be rotated because the J
tube portion could malposition. Treatment is tube removal.
This untoward event can be prevented by rotating G tubes
360 degrees daily and loosening the external (bolster, disc,
bumper, anchor) slightly if it is determined to be too tight
to the skin.
Leaking or broken caps of G tubes. The distal caps of G
tubes may lose their grip over time and begin to leak or may
begin to rip off the tube. Some tubes have replacement Y
connector caps, so the faulty cap may be exchanged with
a new cap. These are available for nonballoon G tubes
and some balloon G tubes. In balloon G tubes where the
balloon port is congruent with the tube’s lumen, the distal Y
connector cap cannot be replaced because severing the end
of the tube would deflate the internal balloon (Figure 33).
The distal Y connector replacement caps are only available
for balloon G tubes where the balloon port is positioned
beyond the Y connector (Figure 34).
Stomal tube dislodgement. Early dislodgement of a G tube
is a medical emergency because the stomach lining can
34
Figure 33. Y connector congruent with tube.
Figure 34. Y connector separate from tube.
separate from the abdominal wall, leading to internal gas-
tric leakage into the peritoneum and peritonitis.109 Pa-
tients usually need to go to the emergency department
for replacement under the appropriate visual guidance. If
tubes are blindly replaced before complete healing, the new
tube could potentially malposition outside the stomach
or intestine and also cause peritonitis. The maturity of a
stomal tract depends on tube type, insertion method, and
provider discretion. Balloon G tubes that have gastropexy
sutures (retention sutures or T-fasteners) applied initially
securing the stomach to the peritoneum develop a mature
or established stomal tract in about 4–6 weeks. Nonbal-
loon G tubes without the gastropexy suture securement
Nutrition in Clinical Practice 33(1)
are dependent solely on the pressure between the external
(bolster, disc, bumper, phalange, anchor) and the internal
(bolster, disc, bumper, dome), and it may take 6 weeks up
to 3 months before it is considered mature or established.
J tube stoma tract maturity also takes up to 3 months.
Once a tract is considered mature or established and the
tube dislodges, a new tube may be inserted at the bedside
or in a clinic setting by a credentialed provider or trained
caregiver.
Healthcare facilities should establish policies that ad-
dress who can replace stomal tubes and the designated wait
period for tract maturity. Clinicians who replace G and
J tubes should be credentialed for this procedure. In our
medical facility, we wait 8 weeks for necessary balloon G
tube replacements at the bedside or in a clinic setting in the
adult patient population. For the nonballoon PEG and J
tubes that do not have the added securement of gastropexy
sutures, we wait a full 3 months for needed tube replacement
at the bedside.
Stoma tracts may begin to narrow and close within a
few hours when a stomal tube dislodges, even in a mature
tract. Clinicians who are not credentialed may consider
placing a temporary Foley (balloon deflated) or red rubber
urethral catheter of the same Fr size as the original tube
to prevent closure. This temporary tube should not be
used until a replacement G or J tube is safely placed by a
credentialed clinician. If a patient’s caregivers are trained
on tube replacement in a mature stoma tract, they should
replace tubes only in the individual on which they were
trained. A G or J tube also should not be replaced blindly if
there are signs of infection at the site.
Tube replacement generally does not require analgesia
but does benefit from either a topical water-soluble lu-
bricant or anesthetic jelly to ease the new tube through
the stoma tract. The new tube should be of the same
Fr size and the same centimeter shaft length if a low
profile tube unless it has been determined that an alternate
shaft length would be more appropriate. Shaft lengths
may change if a patient’s abdominal girth decreases or
increases.
After blind insertion of a new G tube, placement could
be checked by an attempt to aspirate fluid, but this may not
always be possible because typically patients who undergo a
planned procedure have been instructed to have no food or
tube feedings for at least 4 hours beforehand. In addition,
the position of a G tube on the anterior surface of the
stomach is not conducive for access to GRVs. A water flush
should be instilled through the tube after placement to be
sure there is no resistance or discomfort. There should be the
ability to rotate the G tube a full 360 degrees. J tubes should
not be rotated because this could cause tube malposition.
If any difficulty occurs with tube insertion, resistance to
a water flush afterward, or pain with infusions, confirm
placement with radiographic film.
Lord 35

Nasally Inserted Tube Removal

Nasally inserted tube removal involves placing a towel
across the patient’s chest and providing tissues and an
emesis basin. The tape or securement device is removed.
The patient is instructed to take a deep breath and exhale
slowly. As the patient exhales, the tube is slowly but evenly
withdrawn and covered with a towel as it emerges.

Stomal Tube Removal

For stomal tube removal, a patient should be NPO, except
for sips of water and medications, for 4 hours beforehand.
A standard or low profile balloon G, transgastric G/J, trans-
gastric J tube, or J tube removal is accomplished by placing
a towel across the patient’s abdomen, lubricating the stoma
with either a water-soluble lubricant or anesthetic jelly, with-
drawing the fluid from the balloon port (if present), pressing
a flat hand against the abdomen for countertraction, and
gently pulling the tube out with the other hand.
Nonballoon standard G tubes, transgastric G/J tubes,
and transgastric J tubes are more difficult to remove and
cause some discomfort for the patient if removed by traction
pull. There is an internal (bolster, disc, bumper, dome,
mushroom) that deconforms as it passes through the gastric
stoma. A towel is placed across the patient’s abdomen, the Figure 35. Low profile nonballoon G tube removal. Image
stoma is lubricated with either a water-soluble lubricant or courtesy of Applied Medical Technology, Inc.
anesthetic jelly, and one flat hand is pressed against the
cautioned that this procedure will be uncomfortable during
abdomen for countertraction; the other hand has a firm
tube removal because the stoma tract dilates for a few
grasp on the tube close to the abdominal wall and the tube
seconds, but the discomfort usually resolves quickly as the
is firmly pulled out. The traction pull technique can only
stomach muscles relax afterward. A nonballoon tube can
be used with nonballoon G tubes that have a collapsible
also be removed endoscopically.
internal (bolster, disc, bumper, mushroom, or dome). If not,
Patients are allowed only sips of water and no food for
the nonballoon G tube will require endoscopic removal.
4 hours after tube removal as the stoma closes, and the site
In some facilities, the “cut and push” technique is used
should be kept dry and covered with a gauze dressing for
when the nonballoon G tube is not collapsible. The external
24 hours. On occasion, the stoma tract may not close spon-
portion of the tube is cut close to the skin, and the remaining
taneously, and a leaky gastrocutaneous fistula tract forms.
internal (bolster, disc, bumper, mushroom, or dome) is
There are various endoscopic clipping, suturing, plugging,
pushed into the stomach. When the detached remnant
and banding techniques115,116 or surgical intervention, for
(bolster, disc, bumper, mushroom, or dome) is allowed to
fistula closure. Before undergoing one of these procedures,
remain the stomach, it is assumed that it would pass with
the clinician could try applying a thick zinc oxide paste
stool. However, there have been reports of trapping of the
to the opening covered with a pressure dressing utilizing a
remnant piece in the pylorus or intestinal wall, obstruction
gauze roll secured with a transparent adhesive. This should
of the intestine, or upward migration of the remnant leading
be reapplied daily or when drainage begins to leak through
to esophageal obstruction.110-114 In these cases, retention of
the gauze. Administration of acid blocking and gastric
the remnant piece has led to untoward GI symptoms, res-
emptying agents may also be helpful.117
piratory symptoms, need for further endoscopic or surgical
procedures, and at times death. To avoid these untoward
complications with the traction pull technique, endoscopic
Summary
retrieval of the internal (bolster, disc, bumper, mushroom, Knowledge gained about enteral access devices can assist
or dome) should be immediately attempted if it is noted to clinicians in being able to identify the various tube types
be missing. Nonballoon low profile G tubes are removed and determine whether the tube or tube port exits in the
by inserting a metal obturator through the tube to stretch stomach or small bowel for appropriate delivery of nutrition
it taut before removal (Figure 35). Patients should be formulas, water flushes, and medications. Clinicians could
36
better ensure optimal delivery of nutrients and medications
by seeing that tubes are positioned correctly and secured
properly. Clinicians could recommend appropriate water
flushes needed to prevent tube clogging, suggest methods to
declog tubes, and ensure that medications are not mixed to-
gether or with tube feeding. Methods to prevent aspiration
in the enterally fed patient could be used that include some
type of protocol or algorithm to deal with residual volume
checks. Potential abnormal tube and tube site issues could
be recognized and treatment modalities applied. Clinicians
could educate patients and caregivers on feeding tube and
site care, the frequency of tube changes, and the rationale
and details of the new global ENFit design. There is a
knowledge gap in many healthcare facilities surrounding
enteral access devices. Clinicians who familiarize themselves
with the functionality of these devices could provide a
valuable service to patients, caregivers, and other healthcare
professionals.
Acknowledgment
I would like to thank Christopher S. Brown for taking high
resolution images of the many various enteral access devices
portrayed in this manuscript.
Statement of Authorship
L.M. Lord, as sole author, drafted and revised the
manuscript; contributed to the acquisition, analysis, or
interpretation of the data; agrees to be fully accountable for
ensuring the integrity and accuracy of the work; and read
and approved the final manuscript.
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109. O’Rear JM, Prahlow JA. Early percutaneous endoscopic gastrostomy
tube dislodgement. Am J Nurs. 2015;115(6):26-31.
110. Agaba AE, Sarmah SS, Victor Babu BA, et al. Small bowel ob-
struction caused by intraluminal migration of retained percutaneous
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2007;89(6):W1-W5.
111. Brown JN, Borrowdale RC. Small bowel perforation caused by a
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PEG tube replacement: implications to daily clinical practice. Surg
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Invited Review

Nutrition in Clinical Practice

Volume 33 Number 1
Chronic Critical Illness: Application of What We Know February 2018 39–45

C 2018 American Society for

Parenteral and Enteral Nutrition

DOI: 10.1002/ncp.10024
wileyonlinelibrary.com
Martin D. Rosenthal, MD1 ; Amir Y. Kamel, PharmD2 ; Cameron M. Rosenthal, MD3 ;
Scott Brakenridge, MD1 ; Chasen A. Croft, MD1 ; and Frederick A. Moore, MD1

Abstract
Over the last decade, chronic critical illness (CCI) has emerged as an epidemic in intensive care unit (ICU) survivors worldwide.
Advances in ICU technology and implementation of evidence-based care bundles have significantly decreased early deaths and have
allowed patients to survive previously lethal multiple organ failure (MOF). Many MOF survivors, however, experience a persistent
dysregulated immune response that is causing an increasingly predominant clinical phenotype called the persistent inflammation,
immunosuppression, and catabolism syndrome (PICS). The elderly are especially vulnerable; thus, as the population ages the
prevalence of this CCI/PICS clinical trajectory will undoubtedly grow. Unfortunately, there are no proven therapies to prevent
PICS, and multimodality interventions will be required. The purpose of this review is to: (1) discuss CCI as it relates to PICS, (2)
identify the burden on healthcare and poor outcomes of these patients, and (3) describe possible nutrition interventions for the
CCI/PICS phenotype. (Nutr Clin Pract. 2018;33:39–45)

Keywords
critical illness; intensive care unit; inflammation; immunosuppression; metabolism; multiple organ failure

Introduction 6 eligible clinical conditions (prolonged acute mechanical

Critical illness phenotypes continue to evolve as mortality
from acute critical illness has dramatically decreased, es-
pecially when discussing severe sepsis and septic shock.1,2
Nevertheless, patients who survive the acute phase of crit-
ical illness continue to linger much longer in the intensive
care unit (ICU), developing a much more chronic phase.
The term chronic critical illness (CCI) was first coined by
Girard and Raffin3 in 1985 when discussing acutely ill
patients requiring ongoing support in the ICU setting. In
the late 1990s, reports continuing to describe CCI emerged
under a variety of descriptive terms, including “neuropathy
of critical illness,” “myopathy of critical illness,” “ICU
acquired weakness,” and most recently, “post intensive care
unit syndrome.”4 These reports largely originated from
medical ICUs and included a rather heterogeneous mixture
of admission diagnoses. A common thread among most
reports describing CCI seemed to have an acute exacerba-
tion of chronic diseases and need for prolonged mechanical
ventilation. Thus, persistent low-grade organ dysfunction
appears to be a common thread linking most causative
factors of CCI.
A clinical definition of CCI as a prolonged mechanical
ventilation support for >21 days for at least 6 h/day or
patients who require tracheostomy within the course of
their ICU admission was described in 2005.5 Kahn and
colleagues6 used a combined quantitative and qualitative
measure to define CCI: >8 days in an ICU with 1 of
ventilation, tracheotomy, stroke, traumatic brain injury, sep-
sis, or severe wounds). In the search to define persistent in-
flammation, immunosuppression, and catabolism syndrome
(PICS), Vanzant et al7 defined CCI as >14 days in ICU
with organ dysfunction. CCI and PICS both represent pa-
tients with aberrant immunology where homeostasis is not
achieved and dysfunction persists. These patients with CCI
experience ongoing immunosuppression (eg, lymphopenia),
inflammation (eg, neutrophilia with elevated acute-phase
response proteins), and significant lean muscle mass wasting
associated with catabolism.8-10
From the 1 Department of Surgery, Division of Acute Care Surgery
and Center for Sepsis and Critical Illness Research, University of
Florida College of Medicine, Gainesville, Florida, USA;
2 Department of Pharmacy, UF Health, University of Florida College
of Pharmacy, Gainesville, Florida, USA; and 3 Department of
Pediatrics, University of Florida, Gainesville, Florida, USA.
Financial Disclosures: None declared.
Conflicts of Interest: None declared.
Received for publication August 21, 2017; accepted for publication
November 8, 2017.
Corresponding Author:
Martin D. Rosenthal, MD, Department of Surgery, Division of Acute
Care Surgery, University of Florida College of Medicine, PO Box
10019, Gainesville, FL 32610-0019, USA.
Email: martin.rosenthal@surgery.ufl.edu
40
Unfortunately, PICS is the consequence of optimal
evidence-based ICU care, and currently the therapies to
prevent or treat CCI and PICS are limited. Given the
complex and persistent nature of the underlying dysregu-
lated immunity, multimodality treatment will be required
that will need to be extended beyond hospitalization to
enhance rehabilitation. The purpose of this review is to: (1)
discuss CCI as it relates to PICS, (2) identify the burden
on healthcare and poor outcomes of these patients, and (3)
describe possible nutrition interventions for the CCI/PICS
phenotype.
The CCI/PICS Clinical Trajectory
CCI, as discussed earlier, is organ dysfunction that persists
>14 days in an ICU patient. This is surprisingly common
in surgical ICUs. Originally, it was thought that the leading
risk for CCI was age >65 years, chronic comorbidities,
and admission to the ICU.7-9 Recently, in accordance with
previous thoughts, new evidence suggests that after major
torso trauma, CCI occurs in roughly 20%, whereas after
sepsis the incidence rate approaches 50%.11,12 These patients
with CCI compared with patients who rapidly recover are
typically older (>55 years), have poorer premorbid health
status, and have sustained more severe trauma or septic
insults.7,13-17 Mira, Brakenridge, and colleauges11 concluded
that CCI is a common trajectory of critically ill polytrauma
survivors and is associated with poor long-term outcomes.
In this recent review of patients with major torso trauma,
the multivariate analysis revealed age 55 years, systolic
hypotension 70 mm Hg, transfusion 5 units packed red
blood cells within 24 hours, and Denver multiple organ
failure (MOF) score at 72 hours as independent predictors
of CCI (area under the curve 0.87, 95% CI: 0.75, 0.95).11 In
contrast, a recent review of surgical patients with sepsis re-
vealed that of the 145 patients with sepsis who were enrolled,
19 (13%) died during their hospitalization and 71 (49%)
experienced development of CCI based on the definition of
CCI as >14-day ICU length of stay and persistent organ
dysfunction.12
Several other ICU pathophysiologic states are either
similar in nature or are part of the CCI spectrum. Among
these entities are ICU-acquired weakness (ICUAW), di-
aphragm dysfunction associated with prolonged mechanical
ventilation, and PICS.10 Most of these patients, if not
all, were observed to lose tremendous amounts of lean
body mass despite optimal nutrition, causing profound
weakness (catabolism), suffer from recurrent nosocomial
infections (immunosuppression), typically develop decubi-
tus ulcers, have poor wound healing, have sepsis recidivism,
and ultimately experience poor long-term outcomes.8-10,18
A recent report by Puthucheary et al19 demonstrated the
basis of ICUAW associated with CCI. In this prospective
Nutrition in Clinical Practice 33(1)
observation trial of 63 critically ill patients with an average
APACHE II (Acute Physiology and Chronic Health Eval-
uation II) score of 23.5, the authors found that the rectus
femoris cross-sectional area (CSA) decreased on average
17.7% by day 10, and the ratio of protein to DNA de-
creased by 29.5%.19 They also observed that with increasing
organ failure the muscle breakdown and decrease in CSA
were more significant despite adequate nutrition. In fact,
“leg protein breakdown remained elevated throughout the
study with the pattern of intracellular signaling supporting
increased breakdown and decreased synthesis.”19 The novel
observation of the study was that 40% of these patients had
evidence of muscle necrosis associated with inflammatory
cell infiltrate on serial muscle biopsies. This provocative
observation indicated that the muscle is likely a target of
the dysregulated immunity related to CCI/PICS and may
explain why early, aggressive nutrition may be ineffective
in preventing the progressive muscle loss seen in these
patients.19 In addition, patients with CCI tend to be or
become frail and suffer from significant levels of pain,
dyspnea, psychological distress, thirst, fatigue, delirium,
and distress related to impaired communication.20-25 These
symptoms not only stem from the protracted course of
their hospital stay, but are associated with their exposure
to ICU interventions that cause distressing symptoms as
well.20,21,24,26 Ultimately, patients with CCI and PICS have
poor long-term quality of life; suffering from depression,
cognitive impairment, complex physiologic abnormalities,
organ dysfunction, neuroendocrine deficits, and immuno-
logic dysfunction.13,14,24,27-32
Although the underlying mechanism for these devas-
tating ICU syndromes is undoubtedly multifactorial, the
laboratory work of Moldawer, Efron, and colleagues33 using
chronic murine models of sepsis and trauma have identified
the expansion of myeloid-derived suppressor cells (MDSCs)
to explain the persistent immune dysregulation observed
in CCI/PICS. A recent focused translational study of 67
surgical patients with severe sepsis confirmed the clinical
relevance of these laboratory observations. It showed that
the numbers of MDSCs rapidly increase after sepsis and
are persistently elevated out to 28 days.33 Importantly, these
MDSCs were shown to suppress T lymphocyte proliferation
and decrease the release of TH1 and TH2 cytokines. More-
over, MDSC expansion correlated with adverse outcomes
including: (1) early increased expansion was associated with
early mortality, (2) persistent expansion was associated with
prolonged ICU stays, and (3) persistent expansion was a
strong independent predictor of nosocomial infections and
poor postdischarge disposition.33 These data provide the
theoretical basis for the use of immune stimulants that
modulate MDCSs similar to what has been successfully uti-
lized in advanced malignancies to achieve durable response
rates.
Rosenthal et al
Burden on Healthcare and Poor Outcomes
Now that patients with CCI/PICS are surviving and being
discharged from ICUs, healthcare costs reflect this strug-
gling patient population and places significant burden on
their caretakers. In fact, Kahn et al6,34 estimated that 5%–
7.6% of patients admitted to the ICU experience CCI,
accounting for >380,000 cases, 107,000 in-hospital deaths,
and >$26 billion in healthcare expenses. Iwashyna et al35
also demonstrated that despite CCI accounting for only
5% of ICU admissions, patients that experience develop-
ment of CCI have >30% of ICU utilization. Both authors
report that these patients are less likely to be discharged
home and have higher inpatient mortality.6,35 In fact, of
the patients who ultimately experience CCI, Cox et al36
found that only 10% will achieve enough functional ca-
pacity to independently live at home within 1 year of
discharge.
In new data discussed earlier, Mira, Brakenridge, and
colleagues11 demonstrate that CCI patients are more likely
to be discharged to a long-term care setting (56% vs
34%; P = 0.008) than to a rehabilitation facility or home.
In addition, patients with CCI at 4 months had higher
mortality rates (16.0% vs 1.9%; P < 0.05) compared with
survivors scoring lower in general health measures (P <
0.005).11 In another recent report, patients with CCI were
more likely to be discharged to long-term acute care
facilities (32% vs 3%; P < 0.0001), whereas those with
rapid recovery were more often discharged to home. The
6-month mortality rate was significantly higher in CCI as
compared with a rapid recovery cohort (37% vs 2%; P <
0.01).12 These 2 studies only affirm that patients with CCI
have reduced rehabilitation potential and poor discharge
disposition.
Ultimately, these patients with CCI live through the acute
illness only to have an exuberant financial toll on health-
care systems13,34,37 and caregivers (strained relationships,
depressed mood, adverse psychological responses, and un-
derlying stress).38,39 To revisit Kahn et al,6 these authors
published that the in-hospital mortality rate for a patient
with CCI was 30.9%, and that the overall population-based
prevalence was 34.4 per 100,000. Extrapolating these data
to the entire United States, for the year 2009, Kahn et
al6 estimated a total of 380,001 cases of CCI, 107,880
in-hospital deaths, and $26 billion in hospital-related
costs.
The U.S. Census Bureau estimates that between 2000 and
2025 the elderly population will grow by 80%; thus, the
incidence of CCI and PICS are likely increase as well.40
Thus, a P50 grant award to the University of Florida,
Health Sepsis and Critical Illness Research Center (UF
SCIRC) will continue to research CCI, frailty in surgery, and
PICS through the grant by NIGMS entitled, “PICS: A New
Horizon for Surgical Critical Care”.
41
Possible Nutrition Interventions
The persistent smoldering inflammatory and catabolic state,
hormonal elaboration, and perpetual downward spiral of
CCI produce a “cachexia” phenotype for which current ICU
nutrition interventions are relatively ineffective. Current
literature surrounding supportive care for patients with CCI
is unified by 2 crucial strategies: early mobilization and
anabolic nutrition. In this section, the role of protein and
anabolic supplements, immunonutrition, and specialized
pro-resolving mediators (SPMs) will be reviewed.
Protein and Anabolic Supplements
In reviewing the literature on sarcopenia, a slower, yet
similar pathologic state to CCI, Fiatarone et al41-43 rec-
ommended resistance exercise and anabolic nutrition. The
authors stressed the need for high-resistance exercise (early
mobilization of ICU patients) coupled with supplemen-
tal nutrition to maintain lean muscle mass. Reinforcing
Fiatarone’s claim, Paddon-Jones et al44-46 established that
daily protein consumption of 0.8–1.5 g/kg/d of daily protein
and dietary-derived amino acids (AAs) potentially slows or
prevents muscle protein catabolism. In addition, Morley et
al and the Society for Sarcopenia, Cachexia, and Wasting
Disease47 recommended >1.5 g/kg/d of protein, as well
as in combination with exercise and supplemental leucine
and creatine. Leucine is an AA that can stimulate the
mammalian target of rapamycin (mTOR) pathway, increase
protein synthesis, and inhibit protein breakdown.
More recently, however, The Protein Summit met to
reestablish new recommendations for nutrition guidelines.
Historically, critically ill patients were recommended to
receive >1.2 g/kg/d protein supplementation.8,48,49 As the
literature evolves, an understanding has emerged that the
old recommendation may be underfeeding protein. During
periods of physiologic stress, the body tends to catabolize
large amounts of protein.50 In sepsis and blunt trauma,
Plank, Monk, and colleagues51-53 showed that resting energy
expenditure peaks at about 4–5 days, can continue for up
to 12 days, and can lose up to 16% of total body protein.
Similarly, in burn patients, “the hypermetabolic response to
major burn injury is associated with increased energy ex-
penditure, insulin resistance, immunodeficiency, and whole
body catabolism that persists for months after injury.”54
This has led Herndon and Tompkins55 to recommend 2
g/kg/d protein supplementation for appropriate compen-
sation of the catabolic insult. Nevertheless, the current
guidelines have raised the recommendation to >1.5 g/kg/d
protein supplementation to provide adequate nutrients for
the critically ill, catabolic patient. However, the following
question remains: Is 1.5 g/kg/d enough for patients with
CCI?
42
Starting around 2010, studies have emerged showing
clear benefit to delivery of protein calories over nonprotein
supplements. Weijs et al49,56 showed that early high-protein
delivery had survival benefit, yet energy overfeeding was
linked to increased mortality. Allingstrup et al57 echoed
Weijs et al’s49,56 findings, adding that a higher provision of
protein (>1.46 g/kg/d vs 1.06 or 0.79 g/kg/d) and AAs was
associated with lower mortality.
Importantly, Compher et al58 showed that increased
protein delivery had a significant survival benefit in nu-
tritionally high-risk patients based off the Nutrition Risk
in the Critically Ill (NUTRIC) score >5. Compher et al58
concluded that greater nutrition and protein intake is asso-
ciated with lower mortality and faster time to discharge alive
in the high-risk, longer-stay patients, but not significantly
so in nutritionally low-risk patients. These are the patients
with CCI. The ones who “are high risk and longer stay pa-
tients.” Moreover, in 2013, Deutz and Wolfe59 described an
“anabolic response” where higher protein supplementation
suppresses endogenous protein breakdown. The anabolic
response is a measure of fractional synthetic rate minus
the protein breakdown, and it was even more positive with
higher amounts of protein provided.59 This has inordi-
nate implications for patients with CCI/PICS to combat
catabolism and potentially feed them with increasing doses
of protein. Unfortunately, there is a paucity of literature
prescribing large doses of protein in the CCI/PICS patient
population, and at this time only inferences can be made
based on the body of literature we currently have.
In addition to protein delivery, there are increasing
supplements that intensivists could provide to help trig-
ger anabolism or use as an anticatabolism agent. Among
these agents, Herndon et al54,60-65 described in the pedi-
atric burn population the use of: (1) growth hormone,54
(2) intensive insulin therapy,60,61 (3) oxandrolone,62,63 (4)
propranolol,64 and (5) exercise programs.65 These hormones
and medications have a net ability to be “potent anabolic
agent and salutary modulator of posttraumatic metabolic
responses.”54 The conclusion was that they can increase
lean muscle mass, bone mineralization, and strength, and
attenuate the hypermetabolic response to burn. In doing so,
patients would have shortened recovery.60,61,66
Immunonutrition
Protein and AAs are not only beneficial for this patient
population, but also are intriguing because they can serve
a dual purpose with the capability for immunomodulation.
Arginine is a conditional AA whereby endogenous pro-
duction is insufficient during periods of metabolic stress
(such as sepsis) and requires supplementation to restore
maximal function of the immune system.67 With regard
to the immune system, arginine has 2 important roles:
production of nitric oxide (NO) and lymphocyte function.
Nutrition in Clinical Practice 33(1)
Three isoforms of NO synthase (endothelial, inducible, and
neuronal) transform arginine into systemic NO.8,68-76 NO
has been shown to be an intracellular signaling molecule,
influencing a multitude of mammalian organ systems.
NO is also responsible for improved bactericidal action
in macrophages. Arginine also has a potent modulatory
role on the immune system via its effects on lymphocyte
proliferation and maturation, as well as lymphocyte and
macrophage differentiation.77-86
Thus, arginine deficiency or unavailability leads to T
lymphocyte suppression and lack of proliferation.77,80,83
Consequently, T cell dysfunction leads to reduced circulat-
ing CD4 cells, increased interleukin-2, increased interferon-
γ production, and loss of T cell receptor complex called
the ζ -chain peptide rending the receptor incapable of rec-
ognizing antigen.67,69,83,87 Limited arginine coupled with a
loss of T cell receptor function results in multilevel impaired
immune function and response. This immune incompetence
is believed to contribute to an increased infectious morbidity
in critically ill patients.83 Controversy exists as to the supple-
mentation of arginine during sepsis, but the patients with
CCI/PICS are typically outside their initial septic insult.
Thus, theoretical benefit would be derived by repleting this
conditional AA in this patient population to restore some
of the immunosuppression.
Specialized Pro-Resolving Mediators
A relatively new agent that shows promise in treating and
preventing CCI is fat mediators collectively called SPMs, of
which resolvins have the most potential. SPMs are purified
fish oil that promote resolution of the aberrant inflamma-
tory cascade. Serhan et al88,89 identified that SPMs decrease
inflammation by cessation of leukocyte infiltration and ac-
tivation, and “pro-resolve” inflammation through enhanced
macrophage clearance of debris, bacteria, and apoptotic
cells. Further research is needed, but these molecules could
potentially attenuate the systemic inflammatory response
syndrome/septic response, allowing for early recovery back
to functional status in our critically ill patient population.
Conclusion
CCI is a pathophysiologic state, much like PICS, that is
very difficult to treat. Identifying who is going to acquire
CCI is of utmost importance to starting various thera-
peutic strategies early to hopefully stop the potentiation
to PICS. Breaking this downward spiral is going to take
a multimodal approach combating the malnutrition and
ICUAW/neuropathy and restoring anabolism. Further re-
search is needed at the cellular level to control MDSC
proliferation, and in the outcomes arena to clinically deter-
mine which nutrition strategies have impact. High-protein
supplementation has been shown to work, but now we need
to determine how much is best for patient with CCI. Finally,
Rosenthal et al
SPMs could hold the future for attenuating the overly robust
and persistent immunosuppressive, inflammatory, catabolic
nature patients with CCI have with the ultimate goal to re-
gain muscle mass, increase the possibility of rehabilitation,
and regain baseline function/independence once discharged
from the ICU.
Acknowledgments
The investigators acknowledge the contribution of the Center
for Sepsis and Critical Illness Award P50 GM-111152 from the
National Institute of General Medical Sciences.
Statement of Authorship
A. Kamel, M. Rosenthal, and F. Moore wrote the manuscript
and helped edit the manuscript. S. Brakenridge and C. Croft
provided feedback and edited the manuscript. M. Rosenthal
and C. Rosenthal provided final edits for submission.
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Invited Review

Nutrition in Clinical Practice

Volume 33 Number 1
Parenteral Nutrition Safety: The Story Continues February 2018 46–52

C 2018 American Society for

Parenteral and Enteral Nutrition

DOI: 10.1002/ncp.10023
wileyonlinelibrary.com
Phil Ayers, PharmD, BCNSP, FASHP1 ; Joseph Boullata, PharmD, RPh, BCNSP,
FASPEN, FACN2 ; and Gordon Sacks, PharmD, BCNSP, FCCP3

Abstract
Parenteral nutrition (PN) is an important therapeutic modality used for a variety of indications in adults, children, and infants.
PN is a complex, high-alert medication that requires appropriate education and ongoing competency assessment to ensure a safe
process. PN is not recognized by many organizations as a medication, which leads to underreporting of errors. This article will
provide important insight and recommendations to promote a safe PN process. (Nutr Clin Pract. 2018;33:46–52)

Keywords
parenteral nutrition; safety; electronic health records; medication errors; nutritional support

Introduction and Drug Administration Safety Alert released in 1994

Parenteral nutrition (PN) is an important therapeutic
modality used in a variety of settings for a number of
indications in adults, children, and infants. PN is a complex,
high-alert medication that requires appropriate education
and ongoing competency assessment to ensure a safe pro-
cess. The Institute for Safe Medication Practices (ISMP)
recognizes PN as a high-alert medication because significant
patient harm may occur when provided in error or outside
of accepted best practices.1 Despite this ISMP classification,
a recent publication noted that only 58% of organizations
have precautions in place to prevent errors and harm to pa-
tients who are receiving PN.2 This article will provide insight
regarding the types of PN errors that can occur, describe
processes to reduce errors, and introduce opportunities to
promote PN safety.
Perspective on PN Safety
Soon after the introduction of PN into clinical practice,
the potential for associated complications was noted.3,4
Included were both clinical complications and process-
related complications. The metabolic and access-related
clinical complications were addressed in large part by the
contributions of nutrition support teams involved in di-
rect patient care.5-7 Guidance for PN compounding began
to address process-related complications (i.e., medication
errors) culminating with the U.S. Pharmacopeia (USP)
chapter <797> (“Pharmaceutical Compounding—Sterile
Preparations”).8-11 These latter hazards exist because of
poor practices throughout the entire PN process (i.e., PN
prescribing, order review, compounding, administration)
and not just at the compounding step. The U.S. Food
in response to the hazards of PN precipitate formation
highlighted early concerns with safe PN administration.
The U.S. Food and Drug Administration Safety Alert was
specifically issued in response to reports of 2 deaths and at
least 2 cases of respiratory distress associated with the ad-
ministration of PN admixtures thought to contain a calcium
phosphate precipitate. Diffuse microvascular pulmonary
emboli containing calcium phosphate were confirmed on
patient autopsies.12 Formed in 1978 to help optimize the
nutrition support of patients, the American Society for
Parenteral and Enteral Nutrition (ASPEN) spearheaded
efforts to create guidance documents for practitioners in-
volved with PN.13 The first PN publication focused on safety
appeared in 1998 and has been subsequently revised.14,15
Those narrative documents were followed by a PN safety
summit and a pair of articles that provided practice
recommendations for PN that addressed specific, clinically
relevant questions at each step in the PN use process.16-18
Another document using a similar approach of clinically
relevant questions provided practice recommendations on
From the 1 Mississippi Baptist Medical Center, Jackson, Mississippi,
USA; 2 Hospital for the University of Pennsylvania, Philadelphia,
Pennsylvania, USA; and 3 Auburn University, Auburn, Alabama,
USA.
Financial Disclosure: None declared.
Conflicts of Interest: None declared.
Received for publication September 15, 2017; accepted for publication
November 8, 2017.
Corresponding Author:
Phil Ayers, PharmD, BCNSP, FASHP, 1225 N. State Street, Jackson,
MS 39202, USA.
Email: payers@mbhs.org
Ayers et al
appropriate indications for PN.19 Subsequent publications
provided standardized competencies for each major step in
the PN process.20,21 More recently, the USP has advanced
its commitment by proposing a dedicated chapter on PN
safety. The chapter is being drafted by a task force as-
signed by the USP Healthcare Quality and Safety Expert
Committee.
Safe practices involve an interplay among individual
healthcare providers or teams of providers, their respective
departments, and their administrative organizational struc-
tures that enable a patient-focused safety culture.
PN Errors
PN historically has not been considered a medication by
many healthcare institutions; thus, PN errors may have
been underreported. A national survey of nutrition support
providers revealed 44% of organizations do not track or are
unaware of medication errors related to PN.2 A recent publi-
cation highlighted the ISMP’s Medication Errors Reporting
Program for PN errors and potential errors from 2006–
2016.22 A review of these data encompassing 10 years of
voluntary reporting noted compounding/dispensing as the
most common errors reported, followed by administration,
order review, and prescribing.
A large children’s hospital reviewed PN error data over
a 7-year period and found an error rate of 2.7 per 1000
PN prescriptions compounded (0.27%).23 A prospective
observational study over 1.5 years, designed by Sacks et al,24
noted an error rate of 15.6 per 1000 PN prescriptions (1.6%).
The majority of the errors in Sacks et al’s24 study occurred
during the PN administration phase. In this study, 9.1% of
errors were associated with temporary harm and none with
permanent harm.
A recent review of home PN discrepancies was con-
ducted between prescriptions written by a pediatric home
PN program and PN formulations compounded by 13
home infusion companies. In a 4-month period of the
100 PN compounds reviewed, 46 (46%) contained at least
1 discrepancy affecting 56% of the patients in the study.
None of the discrepancies caused patient harm, but this is
an alarming figure in this fragile patient population.25 Al-
though time intensive, the PN order review and preparation
steps are critical to patient safety and require competent
practitioners.21
Pharmacists can play a key role in preventing harm
from prescribing errors associated with pediatric patients
receiving PN. In a study conducted at a large German
university hospital in pediatric patients admitted to a
neonatal and pediatric intensive care unit (NICU/PICU),
investigators evaluated the impact of a clinical pharmacist
on the incidence, type, and severity of errors in pediatric
PN orders.26 The pharmacist was granted access to the
computerized physician order entry (CPOE) system and
47
performed a review on all PN orders over a 19-month pe-
riod. Order verification included review of patient data; PN
ingredients; appropriate dose for age, weight, and clinical
condition; adherence to maximum formulation osmolarity
for administration route; and compatibility and stability
before preparation. The pharmacist contacted the respon-
sible physician for any identified errors and corrected these
prior to PN preparation; thus, no errors actually reached
any patients in this study. Overall, 118 prescribing errors
were identified in 111 of 3012 PN orders for an error rate
of 3.9% (95% confidence interval: 3.2–4.6). The highest
number of errors occurred in the category “concentration
range,” which was attributed to orders of calcium glu-
conate concentration ࣙ0.4% in PN formulations intended
for infusion via a peripheral venous catheter. High calcium
concentrations in PN formulations increase the risk for
peripheral vein damage and tissue necrosis in the event of
extravasation. The second most common error type was
associated with nutrient “dosages,” followed by “indication”
errors. Most dosage errors were related to incorrect amounts
of water-soluble vitamins and trace elements, whereas all
indication errors would have resulted in an omission of a
PN component even though the component was indicated.
The potential for severity of each PN error was assessed
independently by 3 experts using the National Coordinating
Council for Medication Error Reporting and Prevention
index. The majority of the errors were considered categories
C and D (“error reached the patient but no harm”), whereas
only 12% of errors were classified as category E, which may
have contributed to or resulted in temporary patient harm.26
Thus, clinical pharmacists can be very effective in detecting
and preventing PN errors that CPOE systems may fail to
identify.
Data from the United Kingdom also support the valu-
able role that pharmacists may play in a medical team to
improve PN safety and prevent any adverse events. The
U.K. National Aseptic Error Reporting Scheme has been
collecting information on pharmacy compounding errors,
including errors that do not reach the patient (i.e., near
misses) since 2003. In a cumulative report analyzing data
from January 2004 to December 2007, approximately 19%
(895/4691) of all errors with injectable medications were as-
sociated with adult and pediatric PN formulations.27 Error
categories included transcription, calculations, expiration,
final volume, dose/strength, and labeling. Pharmacists were
identified as the most likely personnel to detect errors
(45.3%), followed by technicians (38.9%) and nurses (5.5%).
More than half (56.2%) of the errors associated with adult
PN and 41% of pediatric PN errors occurred mostly at
the first order review stage in the compounding area. The
complex process of PN preparation associated with the
numerous additions of nutrient and/or drug components
to the final container is thought to contribute to the
high rate of errors. Furthermore, errors with pediatric PN
48
formulations were associated with greater levels of perceived
patient harm than other intravenous preparations. This may
be related to the fact that errors with pediatric PN were de-
tected in clinical areas during or after administration (1.7%)
compared with all other intravenous products (ࣘ0.9%).27
Pharmacists must adhere to strict standards for the
preparation and handling of PN, such as USP chapter
<797>, which details the conditions and practices that
minimize risks for contamination. Failure to do so can
result in catastrophic events like the 2011 outbreak of
Serratia marcescens in 19 patients receiving PN outsourced
to a single compounding pharmacy.28 In October 2010, the
pharmacy began compounding and filter-sterilizing amino
acid solutions for adult PN using nonsterile amino acid
powders. The powders were mixed with 80–100 L of sterile
water in a large mixing container that was cleaned with de-
tergent and tap water from a non-aerator-containing faucet.
It was later identified that the pharmacy tap water faucet
was the source of the introduction of S. marcescens. Because
the amino acid powders were slow to dissolve into solution,
the personnel allowed the amino acids to sit in the water 1–2
days before filtration, and this may have facilitated bacterial
overgrowth. Based upon current USP standards, steriliza-
tion of water-containing compounded sterile preparations
should occur within 6 hours of compounding. Although
the amino acid solution was sterilized by passing it through
a 0.2-μm capsule filter, a larger upstream (i.e., prefilter)
was not used to reduce the bioburden of bacteria or
remove excessive particulate matter visible in the solution.
Also, pharmacy staff noted that particulate matter in the
prefiltered solution frequently caused a reduction in flow
across the filter membrane, and this required replacement of
the filter 1–5 times during the sterilization step. Replacement
of the filter likely contributed to contamination because of
a break in the sterile filling system. Although the pharmacy
set aside 25-mL aliquots of filtered amino acid solutions
to be tested for sterility, the amino acids were routinely
incorporated into PN solutions and administered to patients
before the sterility results were obtained within 10–14 days.
USP chapter <797> requires that all preparations com-
pounded from nonsterile powders in batches >25 containers
be tested for sterility, and testing of larger volumes (i.e.,
liters) as opposed to 25 mL might have led to a greater
likelihood of identifying contamination. These breaches
in mixing, filtration, and sterility testing emphasize the
importance of ensuring that personnel are appropriately
trained and are compliant with compounding standards.28
PN Process
The PN use process (Figure 1) is modeled in general after
the medication use process. It describes the process within
which PN is used. It includes a number of broad, yet critical
patient-focused steps: from the initial patient assessment
Nutrition in Clinical Practice 33(1)
Figure 1. Parenteral nutrition (PN) use process.
and recommendation to use PN, to the prescriber’s order,
the pharmacist’s review of the order, the preparation of
the PN, the administration of the PN, and back to routine
patient monitoring and reassessment. A significant amount
of readily available documentation may be required at each
step to include all transitions in care. It becomes apparent
that the process will necessarily involve multiple clinicians
from different departments and perhaps different physical
locations working together to provide safe nutrition care.
For this reason, excellent communication between practi-
tioners, with a high degree of competence in their respective
roles, plus significant standardization within the process, is
valuable and can serve as a risk-management strategy.17
Researchers have used various techniques focused on
critical processes, like PN use, as a means of identifying
which steps are most prone to experiencing errors. One pop-
ular method is failure mode and effects analysis (FMEA),
which was introduced into the hospital environment in the
1990s.29 A FMEA is a technique conducted prospectively
by a team to prevent the occurrence of an error or adverse
event. The Joint Commission requires accredited hospitals
to perform at least 1 prospective risk assessment each
year, and the ISMP recommends using FMEA to prevent
medication errors.30 FMEA has successfully identified po-
tential errors in the various stages of PN preparation for
neonates that resulted in corrective measures to improve
the detectability of errors. Using FMEA, Arenas and col-
leagues detected 82 potential areas for failure through-
out the various stages in the PN use process. Similar to
Sacks et al’s24 study, the transcription phase was identified
as having the highest number of possible errors (22 failures),
followed by the preparation phase of PN (18 failures).
In response to these failures, a checklist was created to
enable greater control in detecting errors. This tool created
a framework for systematic review of all phases of the
PN process and facilitated the detection of errors before
reaching the patient.31 ASPEN has created checklists for
Ayers et al
prescribing and communicating the PN order, PN order
review and verification process, PN compounding, and
PN administration to assist healthcare practitioners with
decreasing errors in the most critical aspects of the PN
process. The ASPEN PN Safety Toolkit may be found on
the organization’s website.32
PN Guidelines and Recommendations
In 2014, ASPEN published Clinical Guidelines: Parenteral
Nutrition Ordering, Order Review, Compounding, Labeling
and Dispensing, as well as the Parenteral Nutrition Safety
Consensus Recommendations.17,18 The guidelines rated the
quality of evidence by applying the concepts from the
Grading of Recommendations, Assessment, Development
and Evaluation (GRADE) to support the recommenda-
tions. The Consensus Recommendations were developed
using expert opinion to answer questions related to PN
where evidence was not sufficient to support the use of
GRADE methodology.
This pair of documents together provided guidance and
recommendations in all aspects of the PN process to assist
in the provision of safe PN. Appropriate policies and proce-
dures should be developed and followed in all steps of the
PN process.17 Highlights of recommendations are listed in
Tables 1–4. The overarching theme is that standardization,
Table 1. Prescribing.17 .
Standardized process for PN management
Comprehensive PN education and competency assessment
Appropriate indication and access
Goals for protein and energy documented
Standardized PN order form, electronic preferred
Clinical decision support electronic order
PN ingredients ordered as amounts per day in adults and
amounts per kilogram per day in pediatric and neonatal
patients
Home PN order template
PN, parenteral nutrition.
Table 2. Order Review/Verification.17 .
Prescribe PN using a computer prescriber order entry system
fully integrated with an automated compounding device.
Verbal and telephone orders should be avoided.
Transcribed data should be double-checked by an independent
process.
Pharmacist should be skilled and knowledgeable in PN.
Compare PN formulation with previous day’s order.
Review for compatibility and stability.
Outsourced PN should undergo the same standardized
pharmacy review and verification.
Quality improvement programs should be in place to report,
track, and analyze errors.
PN, parenteral nutrition.
49
Table 3. Compounding.17 .
Compliance with U.S. Pharmacopeia chapter <797>
Provision of in-depth training focusing on compounded sterile
preparations
Certification of pharmacy technicians
Annual competency assessments of pharmacists and
pharmacy technicians
Maximizing automation and technology
Soft and hard limits for parenteral nutrition ingredients
Restricting automated compounding device change privileges
to well-trained personnel
Use of checklists or sign-off sheets
Table 4. Administration.17 .
Education and competency assessment for nurses, patients,
and/or caregivers
Interdisciplinary quality improvement programs for analysis
of PN errors
Policies addressing extravasation
Polices prohibiting the use of PN prepared for home or in
subacute or long-term facilities
Protocols for safe operation of infusion pumps
Verifying PN label against PN order and independent
double-check of infusion pump settings
Polices for selection, insertion, care, and maintenance of
vascular access device
Policies for tubing change and appropriate filters for
administration
PN, parenteral nutrition.
communication, and competency need to be built into an
organization’s policies, procedures, and practices.
Electronic Health Record and PN
In 2015, a work group was formed consisting of members
from ASPEN, the Academy of Nutrition and Dietetics,
and the American Society of Health-System Pharmacists
(ASHP). This work group, consisting of experts in PN,
electronic health record (EHR) functionality, and health
information technology (HIT) standards, identified areas
of opportunity for optimizing the EHR in the PN process.
The work group developed a consensus recommendations
document. The group is awaiting approval of the ASPEN,
Academy of Nutrition and Dietetics, and ASHP boards
of directors with plans to publish in each organization’s
respective journal.
The goals of the work group were:
r Increase the awareness of EHR vendors of consen-
sus recommendations and guidelines for safe PN
ordering.
r Recommend to EHR vendors opportunities to im-
prove PN process functionality and clinical decision
support (CDS).
50
r Encourage HIT standards for PN across the contin-
uum of care.
r Publish a joint white paper on PN and EHR best
practices.
This consensus recommendation document will serve to
identify the best practices to date for electronic ordering of
PN using HIT. As HIT standards become more prevalent
in the infrastructure of health systems, it is assumed that
these best practices will be integrated into evolving and
mature HIT standards, and that the incorporation of these
standards into work practices, policy, and design/build of
EHR technology will result in safer processes for ordering,
administering, and managing PN therapy.
The consensus recommendations document addresses
5 areas for EHR functionality. EHRs should include the
following PN therapy functionalities:
1. Use standardized and validated PN order and label-
ing templates as recommended by ASPEN.
2. Design PN orders to facilitate ordering based on
ASPEN recommendations and incorporate CDS to
guide the prescribers on requirements and maximal
limits for macronutrients and micronutrients for
adult, pediatric, and neonatal patients.
3. Analyze workflow from patient-specific PN ordering
to administration to the patient, and document de-
livered PN admixtures in such a way as to minimize
manual human transcription or double documenta-
tion and provide appropriate CDS support in all of
these steps.
4. Include the functionality to order cyclic PN with
and without taper up and/or taper down rates of
infusion.
5. Include the functionality to transition from hospital
PN orders to home PN orders and vice versa.
Future Directions
The changing healthcare environment will dictate that fu-
ture PN practices be fiscally responsible and deliver a safe,
effective, and efficient product. Commercially available, 2-
chamber PN formulations have been available for many
years, but a 3-chamber bag has been recently introduced into
the U.S. market. The 3-chamber bag contains all 3 macronu-
trients, dextrose, protein, and fats, in separated compart-
ments that are “activated” to a single-chamber product
preceding patient administration. Theoretically, these prod-
ucts will lessen the potential for errors observed during
the ordering, transcription, and compounding phases of
the PN process. However, to date, no prospective studies
have confirmed that these products are any safer than
PN formulations extemporaneously compounded in the
institutional setting.
Nutrition in Clinical Practice 33(1)
As stated previously, personnel must undergo rigorous
training in sterile compounding and demonstrate ongoing
competency through written examinations, media-fill tests,
and observation audits of compliance with all required steps
in the sterile compounding process. Historically, personnel
often slow down and are more thorough and deliberate
about completing each step in the compounding process
when they know their technique is being observed during
an in-person competency assessment. A recent report
has described the use of video footage captured through
cameras mounted in the compounding area ceiling to record
personnel in each phase of compounding, from entering the
anteroom and preparing supplies to appropriate donning of
garb and final product preparation.33 Pharmacy managers
randomly selected a time when personnel prepared sterile
preparations to review the footage. Compliance rates
during the compounding process improved from an initial
mean score of 74.4% (range 47.5%–97.5%) to 86.4% (range
70%–100%) after retraining and a period of 3–4 weeks
had passed. The use of emerging technologies, such as
equipment that detects breaks in sterile technique during
the actual compounding activity, will continue to evolve
and reduce the risk for physical contamination.
Clinical information systems can also be applied to
the safe management of PN. Recent efforts have focused
on the use of CDS systems and electronic prescription
programs, which can integrate protocols for practitioners,
jointly manage the clinical and laboratory tests for follow-
up of patients, and provide alert systems. Capability to
calculate the correct amount of different components in the
formulation is also included in these systems, which can
reduce preparation time and any potential for errors. In
the home care environment, these systems can be used to
control any issues associated with transportation, storage,
and recovery of PN products. Clinical information systems
contain features for a repository of all records associated
with the PN process, allowing for evaluation of variables at
any time or phase in the process. Thus, computer technology
can easily facilitate implementation of FMEA in a real
practice setting, with the aim of ensuring quality and
minimizing any risks associated with PN therapy.34
Conclusion
PN is a complex medication and requires an interdisci-
plinary approach to promote safe use. Institutions should
recognize PN as a medication and encourage error reporting
and analysis to improve the safety of PN. The functionality
and interoperability of EHR is a key component in working
toward the goal of safe delivery of PN.
PN Research Opportunities
EHR and reduction in PN prescribing errors
PN prescriber education and error reduction
Ayers et al
PN and automated compounding devices functionality
to reduce transcription errors
Transitioning PN from hospital to home using EHR
functionality
PN Resources
ASPEN Parenteral Nutrition Safety Toolkit: https://www.tn
uritioncare.org/Guidelines_and_Clinical_Resources/
Toolkits/Parenteral_Nutrition_Safety_Toolkit/
Standardized Competencies for Parenteral Nutrition
Prescribing
The American Society for Parenteral and Enteral Nu-
trition Model Nutrition in Clinical Practice Guenter P,
Boullata JI, Ayers P, et al. Standardized competencies for
parenteral nutrition prescribing: the American Society for
Parenteral and Enteral Nutrition model. Nutr Clin Pract.
2015;30(4):570-576.
Standardized Competencies for Parenteral Nutrition Or-
der Review and Parenteral Nutrition Preparation, Including
Compounding the ASPEN Model
Boullata JL, Holcombe B, Sacks G, et al. Standardized
competencies for parenteral order review and parenteral
nutrition preparation, including compounding: the ASPEN
model. Nutr Clin Pract. 2016;31(4):548-555.
The A.S.P.E.N. Parenteral Nutrition Workbook: Cases
and Worksheets for Adult, Pediatric, and Neonatal Patients
Ayers P, Guenter P, Holcombe B, Plogsted S, eds.
A.S.P.E.N. Parenteral Nutrition Handbook. 2nd ed. Silver
Spring, MD: American Society for Parenteral and Enteral
Nutrition, 2014.
Statement of Authorship
All authors equally contributed to the conception and design of
the research; contributed to the acquisition, analysis, and inter-
pretation of the data; drafted the manuscript; critically revised
the manuscript, agree to be fully accountable for ensuring the
integrity and accuracy of the work; and read and approved the
final manuscript.
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15. Mirtallo J, Canada T, Johnson D, et al. Safe practices for parenteral
nutrition. JPEN J Parenter Enteral Nutr. 2004;28:S39-S70.
16. Mirtallo JM. Consensus of parenteral nutrition safety issues and
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17. Ayers P, Adams S, Boullata J, et al. A.S.P.E.N. parenteral nutrition
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2014; 38(3):296-333.
18. Boullata JI, Gilbert K, Sacks G, et al. A.S.P.E.N. clinical guidelines:
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appropriate? JPEN J Parenter Enteral Nutr. 2017;41:324-377.
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21. Boullata JL, Holcombe B, Sacks G, et al. Standardized competen-
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tion, including compounding: the ASPEN model. Nutr Clin Pract.
2016;31(4):548-555.
22. Guenter P, Ayers P, Boullata JI, Gura KM, Holcombe B, Sacks GS.
Parenteral nutrition errors and potential errors reported over the past
10 years. Nutr Clin Prac. 2017;32(6):826-830.
23. MacKay M, Anderson C, Boehme S, et al. Frequency and severity of
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24. Sacks GS, Rough S, Kudsk KA. Frequency and severity of harm
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large university teaching hospital. Pharmacotherapy. 2009;29(8):966-
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25. Raphael BP, Murphy M, Gura KM, et al. Discrepancies between
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Nutr Clin Pract. 2016;31(5):654-658.
26. Hermanspann T, Schoberer M, Robel-Tillig E, et al. Incidence and
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inpatients at a neonatal and pediatric intensive care unit. Front Pediatr.
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27. Bateman R, Donyai P. Errors associated with the preparation of aseptic
products in UK hospital pharmacies: lessons from the national aseptic
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28. Gupta N, Hocevar SN, Moulton-Meissner HA, et al. Outbreak of
serratia marcescens bloodstream infections in patients receiving par-
enteral nutrition prepared by a compounding pharmacy. Clin Infect Dis.
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29. DeRosier J, Stalhandske E, Bagian JP, Nudell T. Using health care
failure mode and effect analysis: the VA national center for patient
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30. Cohen MR, Senders J, Davis NM. Failure mode and effects analysis: a
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31. Arenas V, Gomez SA, Nieto GM, Faus FV. Using failure mode and
effects analysis to improve the safety of neonatal parenteral nutrition.
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32. ASPEN PN safety toolkit. https://www.nutritioncare.org/Guidelines_
and_Clinical_Resources/Toolkits/Parenteral_Nutrition_Safety_
Toolkit/. Accessed September 21, 2017.
33. Connor TK, Lim JH, Hinton TM. Auditing sterile compound-
ing competency with video observation. Am J Health Syst Pharm.
2017;74(16):1218-1219.
34. Gabarron JM, Sanz-Valero J, Wanden-Berghe C. Information sys-
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Invited Review

Nutrition in Clinical Practice

Volume 33 Number 1
Drug Shortages: Effect on Parenteral Nutrition Therapy February 2018 53–61

C 2018 American Society for

Parenteral and Enteral Nutrition

DOI: 10.1002/ncp.10052
wileyonlinelibrary.com

Beverly Holcombe, PharmD, BCNSP, FASHP, FASPEN1 ;

Todd W. Mattox, PharmD, BCNSP2 ; and Steve Plogsted, PharmD, BCNSP, CNSC3

Abstract
Drug shortages continue to be a threat to the health and welfare of numerous patients in the United States. For patients who
depend on parenteral nutrition (PN) for survival, these shortages pose an even greater threat. Almost 75% of active drug shortages
are sterile injectables, which includes PN components. Providing PN therapy is particularly challenging for clinicians because this
is a complex medication and may contain 40 or more individual ingredients, of which multiple components may simultaneously be
in limited supply. The availability of PN components must be considered during every step of the PN use process from ordering
the PN prescription to administering this therapy to a patient. Alterations to a standardized process can lead to medication errors
that can adversely affect patient outcomes and consume healthcare resources. (Nutr Clin Pract. 2018;33:53–61)

Keywords
drug shortages; parenteral nutrition; adverse events; drug compounding; patient safety; risk management

Shortages of medications, including parenteral nutrition
(PN) components, are a significant threat to public health
and safety and affect healthcare in the United States.
Shortages can result in delayed or compromised therapy,
cause providers to prescribe an alternative therapy, result
in medication errors, adversely affect patient outcomes, and
consume healthcare resources.1,2 In the United States, it
has been estimated that annual labor costs associated with
managing shortages and the additional costs to procure
substitute drugs exceeds 400 million dollars.3,4
Almost 75% of the active drug shortages are sterile
injectables, which includes ingredients used in PN therapy
(verbal communication, Erin R. Fox, PharmD, BCPS, Di-
rector, University of Utah Drug Information Service, May
2, 2017). Providing this therapy is particularly challenging
for clinicians because PN is a complex medication and may
contain 40 or more individual ingredients, of which multiple
components may simultaneously be in limited supply. The
availability of PN components must be considered during
every step of the PN use process from ordering the PN pre-
scription to administering this therapy to a patient. Unlike
antibiotics, there are no therapeutic alternatives for missing
PN components. Adults, neonates, and pediatric patients
who need this life-sustaining therapy have no alternatives if
there is a shortage of one or more of the critical components
in the PN.
This article will review the history and factors
contributing to shortages of PN components, efforts
of the U.S. Food and Drug Administration (FDA) and
manufacturers to prevent and mitigate shortages, the status
of shortages, the effect of shortages on patient care and
patient outcomes, and resources and strategies for managing
shortages. This article includes reports and statistics on drug
shortages from various sources. Each report is a snapshot
in time of shortages, and they fluctuate depending on that
scope of time and the measures used to monitor shortages.
With that said, the general picture of the types and trends
in the number of shortages should be the focus of the
reader.
Factors Contributing to Sterile Injectable Drug
Shortages
Shortages of PN components are not new to healthcare
professionals who care for patients receiving this impor-
tant medical therapy. Clinicians have been managing PN
component shortages for almost 3 decades beginning with
From the 1 American Society for Parenteral and Enteral Nutrition,
Silver Spring, Maryland, USA; 2 Moffitt Cancer Center, Tampa,
Florida, USA; and 3 Nationwide Children’s Hospital, Columbus,
Ohio, USA.
Financial disclosure: None declared.
Conflicts of Interest: None declared.
Received for publication September 2, 2017; accepted for publication
November 27, 2017.
Corresponding Author:
Beverly Holcombe, American Society for Parenteral and Enteral
Nutrition, 8401 Colesville Rd, Suite 510, Silver Spring, MD, 20910,
USA.
Email: beverlyholcombe@yahoo.com
54
Parenteral Nutrition Components in Short Supply Since 2010*
Amino acids L-Cysteine hydrochloride
Ascorbic acid Potassium acetate
Calcium chloride Potassium chloride
Calcium gluconate Potassium phosphate
Chromium (chromic chloride) Selenium (selenious acid)
Copper (cupric chloride) Sodium acetate
Cyanocobalamin (B12) Sodium chloride
Dextrose 70% Sodium phosphate
Folic acid Sterile water for injection
IV lipid emulsion Thiamine hydrochloride
Magnesium sulfate Vitamin A
Multivitamins Zinc chloride
Multi-trace elements Zinc sulfate
*In short supply, at least once
Figure 1. Parenteral nutrition components in short supply
since 2010.
a shortage of intravenous adult multivitamins in 1988
and another shortage of intravenous adult and pediatric
multivitamins in 1996. These shortages were intermittent
and usually short lived. However, since 2010, almost every
component used in the preparing PN admixtures (Figure 1)
has been in short supply at least once. The time frame in
which these shortages resolved has varied and some product
shortages that have occurred and were resolved reoccurred
while other shortages lasted for months to years.
According to the FDA, from 2006–2011 the number of
new drug shortages reported increased from 56 to 251, an
increase of almost 350%. At the same time, the number
of reported new shortages of sterile injectables increased
almost 800% (Figure 2). Many of these sterile injectables are
generic medications that have been commercially available
for decades.5 PN components such as electrolytes, trace min-
erals, vitamins and dextrose fall into this category. Classes of
drugs commonly in short supply include anesthesia medica-
tions, antibiotics, pain medications, nutrition and electrolyte
products, and chemotherapy agents. PN components such
as electrolytes, trace minerals, vitamins and dextrose fall
into this category. The reasons for drug shortages can result
from many factors, including regulatory, natural disasters,
voluntary recalls, issues with raw materials, increase in
demand, discontinuation, loss of manufacturing site, and
quality issues. Some firms made the business decision to
discontinue an older medication to produce a newer, more
profitable medication. As for shortages of generic sterile
injectables, a small number of manufacturers produce these
medications and have a limited production capacity, espe-
cially for older products. Furthermore, the production of
sterile injectables is a complex, complicated process with
Nutrition in Clinical Practice 33(1)
300
250
200
150
Sterile Injectables
All Forms
100
50
0
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016
Figure 2. New United States drug shortages per year.
Courtesy CAPT. Valerie Jensen, U.S. Food and Drug
Administration, Center for Drug Evaluation and Research
Drug Shortages.
long lead times. Any production problems or quality issues
will likely result in a shortage.6
A series of events contributed to the 2011 drug shortage
crisis. In the early 2000s there was a market consolidation
in the pharmaceutical industry so that a small number
of manufacturers acquired a relatively large percentage of
the market. Another contributing factor to the market
consolidation was the Medicare Modernization Act, which
reduced the reimbursement paid by Medicare for many
generic sterile injectables administered in nonhospital set-
tings. Thus, manufacturers were hesitant to increase prices
or to invest capital to upgrade manufacturing capabilities.5
In 2008, a worldwide recall of heparin occurred. Scien-
tists determined that the raw material for heparin processed
in China contained a contaminant that was responsible
for numerous deaths and adverse events. This incident
prompted increased and more meticulous inspections of
pharmaceutical manufacturers by the FDA. Subsequently
there was an increase in the number of warning letters
sent to manufacturers documenting noncompliance with
manufacturing standards and serious quality issues. Some
of the quality issues identified were mold, metal particles,
contaminants, and insects as well as manipulating data such
as altering analytical test results. Between 2009 and 2010,
the number of warning letters issued increased by 42% and
the following year an additional 156% increase.5 Some man-
ufacturers who received warning letters agreed to take their
manufacturing off-line to address the quality concerns. In
some situations, more than 1 manufacturer of generic sterile
injectables halted manufacturing for remediation, leaving no
one in the market to increase production as an effort to
avoid or minimize shortages. The simultaneous shutdown
decreased the production of generic sterile injectables from
Holcombe et al
1 billion units per year to 700 million units per year, a 30%
decrease in capacity.5
The reasons for drug shortages were addressed in the
2014 and 2016 U.S. General Accounting Office (GAO)
reports on drug shortages. The GAO found that many
shortages of sterile injectable drugs were supply disruptions
caused by a manufacturer slowing or stopping production to
address quality issues. Other identified potential underlying
causes of shortages of the generic sterile injectable drugs
were economic issues such as low profit margins limiting
capital for investment in infrastructure improvements, lead-
ing some manufacturers to completely exit the market.7,8
The International Society for Pharmaceutical Engineering
conducted a survey of its membership and found that com-
pliance, together with manufacturing and product quality
issues, represented the single most important factor leading
to drug shortages.9
FDA Safety and Innovation Act (FDASIA)
The 2011 drug shortage crisis prompted the President of the
United States to sign an Executive Order giving the FDA
more authority to combat drug shortages. This authority,
which was codified into law in the FDASIA of 2012, has
enabled the FDA to work with manufacturers to restore
the production of many life-saving therapies.6 FDASIA
requires pharmaceutical manufacturers to notify the FDA
of a potential shortage or a permanent discontinuance or
interruption in the production of prescription medications
that are life-saving, life-sustaining, or intended for use
in the prevention or treatment of a debilitating disease
or condition. These early notifications give the FDA and
manufacturers more time to collaborate and initiate actions
aimed at preventing supply disruptions from turning into
shortages and mitigating the impact of shortages, should
they occur. Early notifications, along with an increase in
FDA resources, have resulted in progress toward decreasing
the number of new drug shortages (Figure 2). Furthermore,
since 2011 the FDA has collaborated with manufacturers
to avert more than 1000 drug shortages, and of these
approximately 75% were sterile injectables. Although sig-
nificant progress has been made in preventing and avoiding
shortages, there are currently 174 active and ongoing drug
shortages (verbal communication, Erin R. Fox, PharmD,
BCPS, November 6, 2017).
FDASIA also requires the FDA to issue a noncom-
pliance letter to manufacturers who fail to comply with
the drug shortage notification requirements. Last, FDASIA
directed the FDA to develop a strategic plan on preventing
and mitigating drug shortages. There are 2 underlying goals
of this strategic plan. The first is to further mitigate drug
shortages through improving and streamlining its processes
for mitigating existing or potential shortages. The second
is to develop long-term strategies for preventing shortages
55
by focusing on the root causes of shortages as an effort to
predict drug shortages.10 FDASIA does not give the FDA
the authority to require a manufacturer to produce a drug,
increase production of a drug, or change the distribution of
a drug.6
Pharmaceutical manufacturers have taken actions to
prevent drug shortages. One initiative is the International
Society for Pharmaceutical Engineering Drug Shortage Pre-
vention Plan. The goal of this plan is to assist pharmaceu-
tical and biopharmaceutical manufacturers in identifying
the causes of drug shortages that result from manufactur-
ing and quality issues and use this information to avoid
shortages.11
Status of Drug Shortages
A recent report from the U.S. GAO used data collected from
the University of Utah Drug Information Service (UUDIS)
from 2010–2015 to characterize the current state of all drug
shortages in the United States.8 The number of new drug
shortages has generally decreased since 2011, although the
number of ongoing shortages remains high. A total of
136 new shortages occurred in 2015. However, 291 or 68%
of the total shortages (427) were ongoing shortages that
began in a prior year. These figures are slightly different
from those reported by the UUDIS (142 new shortages in
2015) and substantially different from a recent report from
the FDA’s Center for Biologics Evaluation and Research
and Center for Drug Evaluation and Research database. A
total of 21 new drug and biological product shortages were
identified from January 1–September 30, 2016.12 A total
of 48 ongoing shortages were reported. These figures are
similar to those reported for calendar year 2015.13 A total of
22 new shortages and 48 ongoing shortages were identified.
The difference in the number of shortages reported
by the UUDIS and the FDA is striking. However, there
are clear differences in the reporting systems that likely
affect the data.14 For example, each defines drug shortage
differently. The FDA uses the definition from FDASIA,
whereas the UUDIS definition is used by the GAO (Table
1). The American Society of Health Systems Pharmacists
(ASHP) is another resource for information regarding drug
shortages. The ASHP also adapted the UUDIS definition
for reporting shortages, so the information reported by the
ASHP is frequently different than that reported by the
FDA.14 The intended audience for the ASHP is healthcare
practitioners, whereas the FDA website is targeted to the
public.14 The purpose of the ASHP shortage information
is notification of new shortages and the status of ongoing
shortages and to provide drug shortage management re-
sources. The purpose of the FDA shortage information is
to provide information obtained from manufacturers about
a current shortage, including the estimated duration of
the shortage as well as any product discontinuations. The
56 Nutrition in Clinical Practice 33(1)

Table 1. Summary of FDA and UUDIS Processes for Identifying and Resolving Drug Shortages.

FDA UUDIS

Definition of a shortage
How notified of shortage
Standards for
determining whether a
shortage exists
Criteria for resolving
shortage
A period of time when the demand or
projected demand for the drug within the
United States exceeds the supply of the drug.
Manufacturers are required to notify FDA of a
discontinuance or interruption in the
production of a life-saving drug.a In
addition, the public and the American
Society of Health-System Pharmacists
voluntarily file reports on drug availability.
The FDA also works closely with and
regularly communicates with UUDIS.
All manufacturers cannot meet current market
demand for the drug based on information
provided by manufacturers and market sales
research.
Shortage is occurring nationwide.
Shortage is determined by the supply of the
drug at the market level based on
information from manufacturers and IMS
Health.
One or more manufacturers are in production
and able to meet full market demand.
A supply issue that affects how pharmacies
prepare and dispense a product or that
influences patient care when prescribers must
choose an alternative therapy because of
supply issues.
Voluntary reports from practitioners, patients,
pharmaceutical industry representatives, and
others. UUDIS also works closely with and
regularly communicates with the FDA.
Shortage is verified with manufacturers and it
affects how a pharmacy prepares or
dispenses a product; or the use of alternative
drugs is required because of the shortage,
which may affect patient care.
Shortage is occurring nationwide.
Shortage is determined by the supply of a drug
by national drug code based on information
from manufacturers and providers,
according to a UUDIS official.
All manufacturers of the drug restore all
strengths and package sizes to full
availability or discontinue their products.b

Source. The U.S. Food and Drug Administration (FDA) and the University of Utah Drug Information Service (UUDIS). GAO-16-595.8
a 21U.S.C. § 356c. The law defines a life-saving drug as one that is life supporting, life sustaining, or intended for use in the prevention or treatment
of a debilitating disease or condition. (https://www.gpo.gov/fdsys/pkg/USCODE-2012-title21/pdf/USCODE-2012-title21-chap9-subchapV-partA-
sec356c.pdf. Accessed December 29, 2017.)
b For example, UUDIS could be notified of a shortage involving 3 manufacturers: Manufacturer A has no product available; Manufacturers B and

C still do, but have limited supply of certain package sizes. According to a UUDIS official, UUDIS would consider the shortage to be resolved (1)
when Manufacturers A, B, and C all have all strengths and package sizes back in stock; (2) if Manufacturer A decides to discontinue its product,
when Manufacturers B and Manufacturer C both have all strengths and package sizes back in stock; or (3) when UUDIS obtains other
information indicating that a shortage has been resolved, such as the FDA notifying UUDIS that Manufacturers B and C have increased supply
and all market need has been met.

FDA shortage information also provides information about
the FDA’s and any other stakeholders’ roles in addressing
and preventing future shortages. The scope of the FDA
shortage list includes all drugs that are confirmed to be a
national shortage by the FDA, whereas the ASHP reports
all drug and biologic shortages reported and confirmed by
the manufacturer that have a national impact. In general,
the ASHP website lists more shortages than the FDA
website.14
Summary reports of drug shortages agree that sterile in-
jectable medications such as anti-infective and cardiovascu-
lar drugs have been severely affected by drug shortages.8,12,13
According to the UUDIS, almost three-quarters of the
active drug shortages are sterile injectables, which includes
PN components. A recent report of medications used by
critically ill adults confirms these reports.15 Of the to-
tal drug shortages reported from 2001–2016, 51% were
medications used in critical care settings. Approximately
25% were considered medications used for high acuity
conditions such as vasopressors, antiarrhythmics, and anes-
thesia/sedative agents. However, shortages of medications
classified as fluid, electrolytes, and nutrition were also
reported. Although the number of shortages tended to
be relatively lower than the other therapeutic categories,
the median shortage time was 8.1 months (interquartile
range 6–13.9 months). This report is consistent with other
previous reports that almost all injectable products used for
compounding PN have been intermittently in short supply
since at least 2010.15-17
The effects of PN product shortages can affect each
step of the PN use process including procurement, man-
agement, prescribing, order review, compounding and dis-
pensing, administration, and monitoring as well as patient
outcomes.16 Shortages of PN components have a significant
Holcombe et al
effect on healthcare organizations and patients. Some of
these consequences are staff time consumed to develop
contingency plans, inability to meet patients’ macronutrient
and micronutrient needs, and suboptimal patient outcomes,
including nutrient deficiencies, increased length of stay,
and mortaility.18 The effects of shortages have been illus-
trated by reports of altered practice in response to product
shortages.17,19-22 In an attempt to address necessary changes
in practice caused by a lack of PN products, practitioners
have reevaluated the criteria for PN use as well as timing
for providing certain macronutrients such as lipid injectable
emulsion (previously referred to as intravenous fat emul-
sion), trace elements, and multivitamin injections.17,19,20
Others have reported changes in their routine PN process
by restricting computerized prescriber-order-entry of PN
orders to trained practitioners and implementing the use of
standardized, commercially available PN products (some-
times referred to as multichamber bag or premix PNs).20-22
PN product shortages have affected the automated com-
pounding of PN procedures as well. For example, injectable
electrolytes in severe shortage have been removed from the
automated compounding device for manual addition to
the PN admixture to minimize waste associated with the
automated compounding device, which increases the risk
for compounding errors and contamination.16,19 Although
some altered practices have resulted in improved care, many
have had more negative results, and in some cases have
caused patient harm. For example, Kaur et al20 reported
improved PN utilization and the enforcement of PN prod-
uct restrictions after reexamining the criteria for PN use
and restricting initial computerized prescriber-order-entry
PN order entry to trained practitioners.20 However, others
have reported increased costs associated with increased fre-
quency of laboratory monitoring for electrolyte abnormali-
ties and increased use of intravenous piggyback electrolytes
associated with use of standardized, commercially available
PN products to conserve crystalline amino acids.19,21
Inadequate provision of intravenous nutrients because
of PN component shortages has also resulted in patient
harm.23 Case reports of anemia as a result of copper
deficiency, hyposelenemia, and severe dermatitis in prema-
ture neonates associated with zinc deficiency have been
reported.23 Others have reported electrolyte abnormalities
or difficulty in treating electrolyte abnormalities directly
related to a lack of individual injectable electrolytes.16,22
Other non-PN component drug shortages have negatively
affected PN patients as well. For example, a severe short-
age of ethanol resulted in recurrent catheter-related blood
stream infections in patients requiring home PN therapy.24
More serious reports are those that have associated deaths
with PN product shortages such as thiamine deficiency
and administration of PN contaminated with improperly
sterilized extemporaneously prepared crystalline amino acid
injection.25 In an effort to further explore the effect of
57
drug shortages on PN errors, Storey et al26 conducted a
retrospective study of PN related errors reported to the
U.S. Pharmacopeia Medication Errors Reporting Program
and the MedMARx system (Institute for Safe Medication
Practices, Horsham, PA). Data from May 2009–April 2010
(control period: relatively less number of shortages) was
compared with data collected May 2010–April 2011 (rel-
atively higher number of shortages). Most of the 1312
errors that were reported from May 2009–April 2011 were
ranked in categories that did not result in patient harm.
A total of 19 errors were associated with patient harm;
however, only 13 errors were associated with the shortage of
a PN component. Most were associated with lipid injectable
emulsion, and none were associated with patient harm.
Their conclusion was that there was no correlation of drug
shortages with the frequency of PN errors. In view of the
numerous reported problems associated with PN product
shortages, the authors speculated that the limitations of
the MedMARx system for reporting errors may contribute
to the inability to demonstrate a significant correlation be-
tween PN product shortages and PN related errors. Guenter
and colleagues reviewed error reports from the Institute
for Safe Medication Practices that were associated with the
PN use process from 2006–2016 and identified errors in
prescribing and PN order review that were associated with
shortages of PN components.27
Strategies and Resources for Managing Drug
Shortages
PN components should be included in a healthcare organi-
zation’s plan for managing drug shortages. An interprofes-
sional team and interdepartmental collaboration on policies
and procedures related to shortages of PN components and
optimizing the safety and quality of PN therapy during
a shortage is crucial. Every step of the PN use process
(procurement, prescribing, order review, compounding, la-
beling, and administration) must be considered when using
a substitute product. Substitute PN components must be
carefully evaluated for compatibility and stability with other
ingredients in PN admixtures. Furthermore, changing from
a compounded PN admixture system to using standardized,
commercially available PN products (e.g., multichamber
bag) may require changes to how PN is administered to
patients, including the administration set and filter.
The institution’s information technology department
needs to be involved and work closely with members of the
nutrition support service/team and pharmacy department
to develop contingency plans for shortages. Furthermore,
when a shortage occurs clinicians and information tech-
nology staff work together to update the computerized
prescriber-order-entry system, including clinical decision
support when substitute components or products must be
used. With thoughtful and thorough planning orders for
58
Table 2. Resources for Managing Shortages of Parenteral Nutrition Components.
Organization
U.S. Food and Drug Administration
American Society of Health-System Pharmacists
American Society for Parenteral and Enteral Nutrition
The Joint Commission
The Center for Medicare and Medicaid Services
PN can be adapted quickly to reflect shortages of macronu-
trients, electrolytes, minerals, vitamins, and trace elements
while maintaining the safety and quality of PN therapy.28
The ASHP has developed guidelines for managing drug
shortages in hospitals and healthcare systems.1 The guide-
lines include a process for making decisions about procuring
the drug and the therapeutic implications of the shortage.
The drug shortage management plan has 3 phases. Phase
1, which is typically the responsibility of a pharmacy
purchasing agent, is to verify a shortage exists and assess
the potential effects of the shortage.
The second phase of the plan is preparation and in-
cludes identifying therapeutic equivalents, communicating
information about the shortage to clinical staff, prioritizing
patients, and managing inventory to avoid stockpiling. The
American Society for Parenteral and Enteral Nutrition
(ASPEN) shortage resource materials should be referred to
when dealing with shortages of PN components. ASPEN
provides strategies for managing shortages of individual
PN components, including amino acids, lipid injectable
emulsion, electrolytes and minerals, trace elements, vita-
mins, and L-cysteine. Each shortage management consider-
ation provides recommendations specific to the individual
PN component as well as general strategies for manag-
ing shortages of PN components.29-34 The 2014 ASPEN
Parenteral Nutrition Safety Consensus Recommendations
include guidance for every step of the PN use process to
improve the safety of PN therapy during shortages of PN
components.35
The final phase is the contingency plan and includes
guidelines for managing a complete outage of a drug or if
the drug is only available from compounding pharmacies or
nontraditional sources such as the gray market or from a
foreign manufacturing source.
During an extreme shortage, the FDA may look for a
manufacturer that is willing and able to redirect product into
the U.S. market. Prior to the product coming to the United
States, the FDA evaluates the product to ensure its safety
and efficacy as well as the quality of the manufacturing
site. The FDA may then permit the temporary importation
of the drug from the foreign manufacturing source. These
products have been used safely and successfully in the
Nutrition in Clinical Practice 33(1)
Drug Shortage Resources
https://www.fda.gov/Drugs/DrugSafety/DrugShortages/default.htm
https://www.ashp.org/Drug-Shortages
https://www.nutritioncare.org/public-policy/product-shortages/
http://www.jointcommission.org/assets/1/18/Revision_to_
MM.02.01.01_HAP_20111222.pdf
https://www.cms.gov/Regulations-and-Guidance/Guidance/
Manuals/downloads/som107ap_a_hospitals.pdf
foreign market, but have not sought official approval for
use and distribution in the United States. Imported products
have generally been sterile injectables and have included PN
components such as sodium glycerophosphate, multitrace
element products, and amino acids. If such products are
imported and used in the United States, practitioners should
thoroughly familiarize themselves with the prescribing in-
formation located in the product’s package insert. For
imported sterile injectables, data such as compatibility and
stability or aluminum content may not be available because
of differing legal requirements between the countries.
The practitioner’s role in reporting problems with obtain-
ing PN components is important to managing shortages and
outages. Several options are readily available for reporting
product shortages. The FDA has an email address to allow
an easy method of notifying them of a PN product shortage
(drugshortages@fda.hhs.gov). Along with the FDA, the
clinician should consider notifying ASHP and ASPEN.
The management of shortages should include surveil-
lance for adverse events and suboptimal patient outcomes
associated with shortages. Types of adverse events associ-
ated with shortages of PN components were discussed pre-
viously. These events are considered medication errors and
should be reported to the Institute for Safe Medication Prac-
tices Medication Error Reporting Program (https://www.
ismp.org/errorReporting/reportErrortoISMP.aspx). This is
a confidential national voluntary reporting program that
provides expert analysis of the system causes for medi-
cation errors and disseminates recommendations for pre-
vention. Adverse events should also be reported to FDA
MedWatch (ttps://www.fda.gov/Safety/MedWatch/HowTo
Report/default.htm).
There are several resources available on the internet free
of charge to assist clinicians with identifying and managing
drug shortages (Table 2).
ASHP
The ASHP provides extensive resources and information
on drug products, their availability, and shortage manage-
ment (https://www.ashp.org/Drug-Shortages). It maintains
a page of current shortages (https://www.ashp.org/Drug-
Holcombe et al
Shortages/Current-Shortages). Information regarding dis-
continued drugs, drugs that are no longer available, and re-
solved shortages is provided as well. This page also features
links to the FDA’s drug shortage information section, drug
shortage statistics, a section where drug shortages may be
reported, and a section where frequently asked questions are
posted. A link to a shortage resources section provides best
practices, tools, guidelines, and publications related to drug
shortages.
FDA Drug Shortage Program
The FDA Drug Shortage Program (https://www.fda.gov/
drugs/drugsafety/drugshortages/default.htm) site provides
valuable resources and links to other organizations and
resources. The FDA’s drug shortage database allows one
to check the status of a drug by searching by the drug’s
generic name or the active ingredient. In addition, one can
also search for discontinued medications and the status of
drugs by therapeutic category. The FDA offers an email
subscription service that sends notifications to subscribers
when there is new or updated information about a drug
shortage. In addition, there is a link to download the FDA
drug shortage app for the Android R
-based and Apple R
- shortages and outages, which shall include notifying the
based mobile devices. This page also includes news items
such as announcements of extended expiration dates for
sterile injectables and the portal for manufacturers to re-
port a shortage. There are numerous links to other FDA
resources, including frequently asked questions about drug
shortages and a drug shortage infographic as well as a link to
the ASHP Drug Shortage site. Each year the FDA reports to
Congress the state of the drug shortages, which summarizes
the major actions taken by the FDA to prevent or mitigate
drug shortages. Links to these reports are provided on this
page. The FDA Drug Shortage page offers many resources,
and readers are encouraged to explore this page.
ASPEN
ASPEN is an active stakeholder in providing timely
updates and helpful guidance on how to cope with PN
component shortages. Their Product Shortages website
(https://www.nutritioncare.org/public-policy/product-short
ages/) provides access to the latest information on PN
component shortages and contains links to both the
ASHP and FDA Drug Shortage websites, if further
information is needed. There are also links to report
PN component shortages and to report adverse events
associated with shortages. There are links to periodic
publications specifically addressing recommendations for
managing shortages of lipid injectable emulsion, amino
acids, electrolytes and minerals, vitamins, trace elements,
and cysteine.29-34 These publications do not offer specific
clinical recommendations on how to manage a patient but,
59
rather, items to consider when dealing with a shortage along
with appropriate references for the clinician to review.
The Joint Commission
The Joint Commission addresses shortages and outages
through standard MM.02.01.01 (http://www.jointcommis
sion.org/assets/1/18/Revision_to_MM.02.01.01_HAP_201
11222.pdf), which states that a hospital must have a
process in place to communicate medication shortages
and outages to the all staff who participate in medication
management. Hospitals are also required to develop and
approve medication substitution protocols.
The Center for Medicare and Medicaid Services
(CMS)
CMS addresses shortages and outages through Appendix
A of the State Operations Manual (https://www.cms.
gov/Regulations-and-Guidance/Guidance/Manuals/downl
oads/som107ap_a_hospitals.pdf). Similar to The Joint
Commission standard, the CMS states that hospitals
should have processes in place to address medication
prescribing staff, developing drug substitution protocols,
educating healthcare professionals about substitution
protocols, and obtaining medications in the event of a
disaster.
Resolution of PN Component Shortages
Although the number of drug shortages, especially sterile
injectables, continues to be significant and affect patient care
and safety, some drug shortages do resolve. A drug shortage
is considered resolved when the product is available through
the normal supply chain. Furthermore, there is a sufficient
supply of the product so that allocations, direct orders, and
drop shipments are not necessary. Finally, the FDA and/or
ASHP/UUDIS declare the shortage resolved and remove
the drug from the list of current drug shortages to the list of
resolved shortages. The resolution of a drug shortage may
not be associated with a reduction in price of the product to
the cost prior to the shortage.
Once the PN component shortage is considered re-
solved, all rationing and conservation strategies should be
suspended as these are intended to be used only during
shortages. It is important to return to providing the full
dosing of the PN components and sufficient quantities
should be purchased to provide those full daily components
to all patients requiring PN therapy. The lack of observed
adverse events or deficiencies during rationing of a PN
component and the potential cost savings associated with
“partial” dosing should not be the impetus to continue less
than optimal dosing.
60
Summary
Drug shortages continue to be a significant threat to public
health and safety and affect healthcare in the United States.
Shortages can result in delayed or compromised therapy,
cause providers to prescribe an alternative therapy, result
in medication errors, adversely affect patient outcomes,
and consume healthcare resources. Drug shortages became
a national crisis in 2011 when 251 new drug shortages
were reported to the FDA, and of these 183 were sterile
injectables. There are many reasons for drug shortages, but
the primary reasons for shortages of sterile injectables are
manufacturing and quality issues.
In response to the 2011 drug shortage crisis, FDASIA
was signed into law in 2012 and has enabled the FDA to
work with manufacturers to restore production of many
life-saving therapies. The number of reported new drug
shortages has generally decreased since 2011. Only 136 new
drug shortages were reported in 2015. However, the number
of ongoing shortages exceeded 400.
Almost 75% of the active drug shortages in the United
States are sterile injectables, which includes ingredients
used in PN therapy. Providing this complex therapy that
can contain more than 40 ingredients can be particularly
challenging when multiple PN components are concurrently
in limited supply. The effects of PN product shortages
can affect each step of the PN use process, including
procurement, management, prescribing, order review, com-
pounding and dispensing, administration, and monitoring
as well as patient outcomes.
Managing drug shortages, including PN components,
requires a plan and an interprofessional team to provide
input into developing the plan and to implement the plan
during a shortage or outage. ASHP has published guidelines
for managing drug shortages in hospitals and healthcare
systems. ASPEN has published resources materials, includ-
ing strategies for managing shortages of PN components,
and these should be referred to when developing a plan to
manage such shortages. Other resources are available for
identifying and managing drug shortages include the FDA,
The Joint Commission, and the CMS.
Statement of Authorship
All authors contributed to all aspects of the manuscript. All
authors critically revised the manuscript, agree to be fully
accountable for ensuring the integrity and accuracy of the
work, and read and approved the final manuscript.
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Invited Review

Nutrition in Clinical Practice

Volume 33 Number 1
Nutrition Screening vs Nutrition Assessment: February 2018 62–72

C 2017 American Society for

What’s the Difference? Parenteral and Enteral Nutrition

DOI: 10.1177/0884533617719669
wileyonlinelibrary.com

Maria Isabel Toulson Davisson Correia, MD, PhD1,2

Abstract
Screening and assessment imply different processes, with the former indicating risk factors for a deprived nutrition condition and
the latter providing the nutrition diagnosis. Both should be routinely performed at hospital admission according to recommended
guidelines; however, this is not the reality worldwide, and undernutrition remains highly prevalent in the hospital setting. Therefore,
the objective of the current review is to delve into the principles leading to nutrition status deficiencies and how they should be
addressed by screening and assessment. A critical appraisal for the reasons associated with the misunderstanding between screening
and assessing is proposed without further discussing the many available screening tools while approaching some of the assessment
instruments. (Nutr Clin Pract. 2018;33:62–72)

Keywords
nutrition screening; nutrition assessment; hospitalization; nutritional status; malnutrition

The nutrition status of an individual is a determinant of
body composition and functional status. Deficient states
negatively affect patients’ outcomes, increasing morbimor-
tality, time spent in the hospital, and readmission rates as
well as costs, while decreasing quality of life.1,2 Therefore,
screening for risk factors associated with deficiencies and,
when indicated, assessing an individual’s nutrition status
should be part of the evaluation of a patient. Unfortunately,
this is not a worldwide mandatory process in most health-
care institutions.
Professional society guidelines recommend routine nu-
trition screening at hospital admission and, if indicated,
nutrition assessment,3-5 but they differ in how these pro-
cesses are defined. The European Society of Parenteral
and Enteral Nutrition5 states, “The purpose of nutritional
screening is to predict the probability of a better or worse
outcome due to nutritional factors, and whether nutritional
treatment is likely to influence this.” The American Society
for Parenteral and Enteral Nutrition (ASPEN)3,4 refers
to screening as “a process to identify an individual who
is malnourished or who is at risk for malnutrition to
determine if a detailed nutrition assessment is indicated.”
Furthermore, there is a discrepancy between what expert
societies recommend and what it is practiced in the real
world, which is somehow difficult to explain. The Nutrition
Care in Canadian Hospitals Study reported an absence of a
systematic approach related to nutrition care in the hospital
setting.6 The authors suggest that to improve care processes
and strategies and promote nutrition care culture, it is of
utmost importance to adopt a multilevel approach in which
patients and families, together with staff, are part of the
whole knowledge translation pathway.
This lack of a systematic approach to nutrition screening
and assessment is certainly not due to a lack of information
on the subject. The importance of the nutrition status on the
overall well-being of the individual has been documented
since the Minnesota experiments carried out by Ancel Keys
in the mid-1940s.7-14 Nonetheless, nowadays, deficiencies
in the nutrition status—undernutrition—are still the most
prevalent conditions in the hospital and outpatient settings
in the world, with rates ranging from 20%–80%, based
on the group of patients evaluated or the method used
to provide the diagnosis.15-23 Thus, the question lies on
what reasons might justify such abysm between scientific
knowledge and the real clinical world.
Screening and assessment are different processes, which
were extremely well presented and discussed in a paper by
From the 1 School of Medicine, Universidade Federal de Minas
Gerais, Belo Horizonte, Brazil; and 2 Nutritional Therapy Team,
Instituto Alfa de Gastroenterologia, Hospital das
Clı́nicas–Universidade Federal de Minas Gerais, Belo Horizonte,
Brazil.
Financial disclosure: None declared.
Conflicts of interest: None declared.
This article originally appeared online on December 14, 2017.
Corresponding Author:
Maria Isabel Toulson Davisson Correia, MD, PhD, School of
Medicine, Universidade Federal de Minas Gerais, Av Carandaı́ 246
Apt 902, Belo Horizonte, MG 30130-060, Brazil.
Email: isabel_correia@uol.com.br
Correia
Charney24 in 2008, who stressed that nutrition screening and
assessment encompass variables related to identify nutrition
problems. According to the author, there is a wide variety
of tests used by different societies and experts to identify
nutrition risk factors. In this regard, the author recommends
that such tools have acceptable reliability and validity while
being cost-effective and providing rapid results. However,
assessment allows the clinician to gather more information
and conduct a nutrition-focused examination to determine
if there is truly a nutrition derangement, to name it, and to
indicate the severity of this problem. However, despite the
long time that has gone by, the doubt still seems to exist, and
societies have tried to address this, as well as the definition
of other practiced important terminologies in the practice
of clinical nutrition.25
The objective of the current review is to delve into the
principles leading to nutrition status condition and how
they should be addressed by screening and assessment.
The reasons associated with the misunderstanding between
screening and assessing are proposed without further dis-
cussing the many available screening tools while approach-
ing some of the assessment instruments. In fact, it would
almost be an impossible task to cover all of them, given that
there are >200 articles in PubMed referring to “nutrition
screening” in adults, 63 in the last 5 years, and >5000 when
the search phrase is “nutrition assessment,” 1865 in the last
5 years.
Nutrition Status
Nutrition status is the balance between an organism’s de-
mands for physiologic functioning and its intake and use
of nutrients. If for any reason, mostly as a consequence of
famines or disease states, there is an inadequacy of nutrients
to meet needs, then undernutrition/malnutrition develops.
There have been many definitions for the undernutri-
tion/malnutrition syndrome. According to Jellife,26 it is “a
morbid state secondary to a deficiency or excess, relative
or absolute, of >1 essential nutrients.” However, in clin-
ical practice—whether discussing children, adults, or the
elderly—malnutrition has mostly been used to characterize
a deficient nutrition status condition. Because of its many
terminologies, the search for an ideal, clear, and adequate
definition has led several experts and various associations to
try to better characterize the status of those with nutrition
derangements.25,27-32 In fact, undernutrition may be a better
term than malnutrition to define a deficient nutrition status
(the prefix under meaning “less, lower”), as malnutrition
also encompasses obesity (the prefix mal meaning “bad,
wrongful”).
Undernutrition is a consequence of insufficient intake,
increased demand for nutrients, or a disorder in the absorp-
tion/use of nutrients. Unintentional loss of body weight is
the basic characteristic of undernutrition, which is usually
63
caused by decreased food intake resulting from lack of
appetite, alone or with inadequate utilization of nutrients
or increased losses as well as requirements. The main risk
factors leading to undernutrition include any disease state
per se (chronic or acute), alone or in conjunction with social
segregation (eg, elderly individuals, those with psychological
diseases), low economic status, lack of medical aware-
ness, and longer hospitalizations. Functional decline, which
is often linked with undernutrition,33 may precede body
composition alterations, which are often underdiagnosed,
mostly as a consequence of the worldwide pandemic of
obesity.34
In the early stages of undernutrition, muscle is pro-
tected, as energy and protein requirements are met by
use (and, therefore, loss) of liver glycogen and body fat
associated with the mobilization of labile protein stores
from the viscera. It is in this phase that functional alterations
occur while body composition changes might not yet be
identified.33 As time progresses, loss in muscle and fat
compartments increases, leading to severe undernutrition.
Simultaneous imbalance of micronutrients also occurs.
Although terms such as “protein-energy” and “protein-
caloric” malnutrition/undernutrition are recognized by the
International Classification of Diseases, “overall” undernu-
trition encompasses micronutrients.
The many available terms in the medical literature
encompassing nutrition derangements have led an inter-
national committee of experts to propose the following
nomenclature for undernutrition diagnoses: “starvation-
related malnutrition,” when there is chronic starvation with-
out inflammation; “chronic disease-related malnutrition,”
when inflammation is chronic and of mild to moderate
degree; and “acute disease or injury-related malnutrition,”
when inflammation is acute and of severe degree.35 Inflam-
mation and the nutrition status are directly linked since the
increased production and/or expression of proinflammatory
mediators leads to protein breakdown and increased resting
metabolic rate, while protein requirements are increased to
produce acute phase proteins.
Other terms have been used to define alterations in the
nutrition status, such as cachexia and sarcopenia. Cachexia
derives from the Greek words kakos and hexis, which
mean “bad condition,” and it has often been considered
an advanced undernutrition state, especially in patients
with cancer. However, cachexia affects not only those with
neoplastic diseases but also patients with wasting diseases,
such as chronic obstructive pulmonary disease, cardiac
failure, and AIDS, among others. According to experts,
the syndrome is a consequence of negative protein and
energy balance driven by the combination of reduced food
intake and abnormal metabolism.32 The term sarcopenia
has been differently defined by the various societies and
authors.36-38 It is derived from the Greek words sarx (flesh)
and penia (poverty). The Society of Sarcopenia, Cachexia
64
and Wasting Disorders36 coined it as “a person with muscle
loss whose walking speed is ࣘ 1 m/s or who walks < 400 m
during a 6-minute walk, and who has a lean appendicular
mass corrected for height squared of 2 standard deviations
or more below the mean of healthy persons between 20
and 30 years of age of the same ethnic group.” Muscle
and functionality loss is also related to the nutrition status,
as undernourished individuals present with decreased body
compartments, of which the muscle is mostly affected in the
acute inflamed patient.
On the other extreme of undernutrition lies obesity, an
unhealthy accumulation of fat mass, defined as a body
mass index (BMI) >30 kg/m2 . Obesity is a global pandemic
that is also associated with increased morbimortality with
diminished quality and length of life while dramatically
increasing individual, national, and global health costs.39 It
is important to stress the fact that many obese individuals
may often present with deficits of their nutrition status and
that sarcopenia—sarcopenic obesity—per se is associated
with adverse effects,34,40 placing them at higher risk of
complications when sick.41,42 Therefore, it is of utmost
importance to raise awareness to the fact that sick obese
individuals are, as well as the other patients, at higher risk
of undernutrition. However, this condition frequently goes
underdiagnosed43,44 due to the lack of routine nutrition
screening and assessment.
In summary, several terms have been used to charac-
terize the nutrition status of an individual, and a call
for unanimity has been raised by different experts from
nutrition societies.45 Nonetheless, there is no doubt that
unintentional weight loss and decreased food intake, with
disease, which may further affect nutrient absorption and
utilization, lead to a decline in overall body function, placing
the individual at risk of increased morbimortality.1,46-49
Thus, the importance of identifying risk factors for under-
nutrition (screening) and, when indicated, further assessing
the nutrition status (assessment) is fundamental to the
best holistic approach of any sick individual. The disease
per se may lead to undernutrition, and undernutrition
alone affects disease outcomes in a vicious circle. So,
screening and assessment—2 different processes to iden-
tify the nutrition status (Figure 1)—should be routine in
healthcare.
Nutrition Screening
The etymology of the word screen seems to date from
medieval Europe: Escren, from Old North French; Escran,
from Old French, “a screen against heat”; Scherm, either
from Middle Dutch or Frankish, “screen, cover”; Skrank,
whose origins are unattested to a written source, “barrier.”50
The word was initially a noun, meaning a physical object of
protection (apparently, against fire), and only in the late 15th
century did it seem to evolve to a verb with a complementary
Nutrition in Clinical Practice 33(1)
Figure 1. Nutrition screening versus assessment. Most people
can carry it out, including the patient and family.
meaning as a “contrivance for warding off the heat of a
fire or a draught of air.” Thus, as a verb, “to screen” has
associations to the physical act of protection. According to
Bravo,50 “screen as a verb cannot be defined without first
defining screen as a noun. Because of the dual nature of
the word screen it becomes a complicated word to define.
Yet screen, be it noun or verb, is always a medium with
a message.” The latter definition certainly applies to its
role in terms of nutrition screening, being then the act of
identifying risk factors against the integrity of the nutrition
status of an individual.
There are many nutrition screening tools currently being
used in the hospital and the community, some more sophis-
ticated and others simpler,5,51-57 encompassing the general
patient or more specific disease-related populations5,54,56-61
and supported by clinical nutrition societies.3,5,62 In thesis,
the ideal screening tool should be easy and quick to use and
have high sensitivity and specificity, with good accuracy
in detecting the nutrition risk while identifying nutrition-
related outcomes. However, statisticians have shown that
to reach high sensitivity and specificity with accuracy is
almost impossible.63-65 In this regard, the majority of the
techniques used to put together most of the nutrition
screening tools seem not to have utilized either uniform
or adequate methods aiming at this purpose. However,
those constructed under these principles should be
used.
The attribution of a score to each question related as a
risk factor to undernutrition has often been utilized, and the
final addition of all these indicates the risk of a deficient
Correia
nutrition status or poor outcome.66 This approach could
represent a bias by prejudging the effect of a variable over
the other and thus negatively affecting the adequacy of the
tool. Few screening tools have been adequately evaluated by
employing multivariate statistical models. These models are
alternative approaches that take into account the relevance
and impact of independent variables related to the risk
of the outcome variable—in this case, undernutrition—
therefore validating the adequacy of the instrument.67
Van Bokhorst-de van der Schueren et al68 carried out a
systematic review to assess the validity and predictive valid-
ity of nutrition screening tools, in different languages, for
the general hospital population. They identified 83 studies
(32 screening tools), in which 42 presented data on construct
or criterion validity versus a reference method and 51 evalu-
ated the tools based on predictive validity on outcomes such
as length of stay, mortality, and complications. According to
the authors, “none of the tools performed consistently well
to establish the patients’ nutrition status.” The same authors
evaluated, in another study, those tools being used among
the elderly population in nursing homes, and they identified
24 papers using 20 instruments.69 Seventeen studies reported
on criterion validity and 9 on predictive validity. Four of
the tools had been designed for use in long-term settings.
None of them, not even those designed for the nursing home
environment, performed (on average) better than “fair” in
providing the “residents’ nutrition status” or in predicting
inadequate nutrition status–related outcomes. This led the
authors to conclude that “not one single screening or assess-
ment tool is capable of adequate nutrition screening as well
as predicting poor nutrition related outcome. Development
of new tools seems redundant and will most probably not
lead to new insights.”
Given all the above drawbacks, as well as the principle
of screening, which is to identify risk factors other than
provide a diagnosis, it seems reasonable that the best tool
to use should preferentially be easy enough to be applied
by anyone in the healthcare system or even answered by
the patient or a member of the family. In this regard,
most of the screening tools have in common 2 queries: (1)
unintentional recent weight loss, usually around 5%–10%,
and (2) inadequate food intake in the last 1 or 2 weeks (these
cutoffs have been a matter of discussion among experts).70
A positive answer to any of them should indicate a need for
further and deeper evaluation. This should be performed by
a trained healthcare professional (dietitian, doctor, nurse)
using whatever tool is the protocol in the institution. This
certainly would favor against time constraint–related prob-
lems faced by most healthcare providers in the different
settings, who are overloaded with tasks, while providing the
attending physician the indication for the need to evaluate
the nutrition status of the sick individual. In summary,
making screening easy would probably help increase overall
awareness to the nutrition condition.
65
Nutrition Assessment
Nutrition assessment differs from nutrition screening in the
depth of the information obtained by the individual in
relation to his or her nutrition conditions, which will allow
the clinician to formulate a diagnosis. Thus, by nutritionally
assessing a person, one is going to be able to confer if there
is undernutrition or not and determine the severity of the
condition to better plan the most appropriate intervention
and mostly follow up the effectiveness of the feeding therapy
regimen.
Several methods for nutrition assessment have been
used throughout time. While some techniques are very
sophisticated and expensive, others are less complicated and
available in most hospitals. Each has clinical advantages and
disadvantages. However, the gold standard tool should (1)
be sensitive and specific enough to predict outcomes related
to nutrition status and (2) be able to show changes in the
status of the individual after any nutrition intervention.
The latter is certainly the most difficult aspect, since there
is an intertwined relation between nutrition status and
disease, which hampers the current tools to evaluate the
role of each in the patient’s outcome. Maybe the first big
challenge lies exactly on the ideal definition for undernutri-
tion, as previously discussed. Nonetheless, several nutrition
assessment tools have been well associated with prognosis,
mortality, and costs—in particular, Subjective Global As-
sessment (SGA),1,42,47,48,71 which should be considered when
choosing a tool for use in any institution.
Anthropometry is still the most used criterion, in par-
ticular by dietitians. No doubt, body weight is a simple
measure of total body mass, which—when compared with
previous weight (usual weight) or ideal weight (based on the
weight of healthy populations)—provides insights into the
patient’s nutrition status. Weight loss >10% of usual body
weight is strongly indicative of undernutrition and is related
to higher morbidity and mortality.71-73 A loss of more than
one-third of the original weight was linked with imminent
death in a classic study by Nightingale et al, who combined
3 methods to detect undernutrition: percentage weight loss,
mid arm muscle circumference, and BMI. According to the
authors, for those who cannot be weighed or have edema,
mid arm muscle circumference could help improve the
diagnosis.74 Also, weight loss might be difficult to determine
in some individuals due to lack of information, illiteracy, or
mental disorientation. Morgan et al75 showed that weight
loss accuracy by patient report was 0.67 and its power
of prediction was 0.75. These data indicate that 33% of
those patients who had lost weight would have been missed
and 25% of those with stable weights would have been
diagnosed as having lost weight. This scenario may even be
worse, such that weight loss could be perceived positively by
the physicians, the patients, and the families, in particular
in the current obesity pandemic, thus declining clinicians’
66
sensitivity to it. Also, weight change alone may not have any
nutrition significance, since it is influenced by confounding
factors, mainly related to the hydration status.
Weight and height provide the BMI, which, according to
population studies, has been shown to be associated with
significant mortality rates when values are between 14 and
15 kg/m2 .76 Nonetheless, with the obesity pandemic, it has
become extremely difficult to rely solely on BMI as a prog-
nostic tool for declined nutrition status. A Canadian group
recently published a classification system incorporating the
prognostic significance of BMI and percentage of weight
loss for patients with cancer, showing that those with lower
BMI and a higher percentage of weight loss had decreased
survival.76
Skin folds and arm circumferences are body compart-
ment measurements of muscle and adipose tissue, which
suffer from the interference of obesity and edematous
states and which are influenced by intraobserver and in-
terobserver errors. Furthermore, the patients’ measures are
compared with those in tables derived from healthy pop-
ulations. Jellife’s26 and Frisancho’s77 standard tables for
triceps skinfold and mid arm muscle circumference are the
most commonly used in clinical practice. Both of these are
questionable in regard to the used methods. Jellife collected
data by measuring European male military personnel in
service in Greece and low-income American women. Fri-
sancho derived tables from measurements of white men
and women who had participated in the 1971–1974 U.S.
Health and Nutrition Survey. Thuluvath and Triger crit-
ically assessed these tables and indicated that 20%–30%
of healthy controls would be diagnosed as malnourished
based on the standards of these tables.78 Furthermore, these
authors found an inadequate correlation between the Jellife
and Frisancho standards. Thus, these measures are certainly
rather controversial to be routinely used in clinical practice,
in particular alone.
Currently, more sophisticated body composition meth-
ods have been used as nutrition assessment tools for healthy
and sick populations as well as athletes, in the clinical
setting and in research. Tools such as computed tomography
(CT), ultrasound, nuclear magnetic resonance, whole body
conductance and impedance, dual-energy x-ray absorptiom-
etry, neutron activation, hydrodensitometry, and others are
good examples of these instruments. However, many of
them are difficult to use in the hospital setting, especially
with the bedridden severely ill patient; they also expose the
individual to high radiation (CT) and are rather expensive.
Nonetheless, CT and ultrasound have been shown to in-
dicate important losses of muscle mass and subcutaneous
tissue, as well as the presence of intermuscular adipose
tissue. All of these findings are associated with loss of func-
tionality and increased risk of adverse outcomes in patients
with cancer as well as those with other diseases.40-42,79-82
However, it is of utmost importance to bear in mind that
Nutrition in Clinical Practice 33(1)
CT is an examination of convenience; that is, nobody
will demand such assessment only for body composition
purposes.
Biochemical hepatic markers, such as serum albumin
level, transferrin, retinol binding protein, and prealbumin,
have been used by physicians to provide the nutrition
diagnosis. When low, serum albumin level (one of the
most extensively studied proteins) has been associated with
increased morbidity and mortality.82-86 However, serum
albumin level represents an equilibrium among hepatic
synthesis, serum albumin level degradation, and losses
from the body. In fact, serum albumin level reflects the
balance between intravascular/extravascular compartments
and water distribution. Two-thirds of the serum albumin
level pool are in the extravascular compartment and one-
third in the intravascular. The half-life of serum albumin
level, when released into the plasma, is about 21 days. A
total of 10.5–14.0 g (200 mg/kg) of serum albumin level
is synthesized and degraded every day in a steady state.
Therefore, a deficient nutrition status will hinder serum
albumin level production as a consequence of the lack of
nutrients that are essential to its synthesis. However, in
chronic malnutrition states, the plasma serum albumin level
concentration is often normal because of the compensatory
effect (lower degradation and a shift from the extracellular
compartment to the intracellular).87,88 However, in acute
stress situations, such as those related to infection, surgery,
and polytrauma, serum albumin levels are generally very
low as a consequence of decreased synthesis, increased
degradation, transcapillary losses, and fluid replacement,89
which are undoubtedly also risk factors for the deterio-
ration of the nutrition status. Therefore, serum albumin
level might be altered due to factors other than undernu-
trition, as in hepatic disorders, protein losses (in fistula,
peritonitis, nephrotic syndromes, etc), and acute infection
or inflammation—once again, risk factors for a deprived
nutrition status.
In the same way that serum albumin level is influenced by
the above-mentioned phenomena, so are the other hepatic
proteins, which confer them as questionable markers of
nutrition status when used alone. Similar acute conditions
may also affect the creatinine height index. This is obtained
by measuring a 24-hour urinary creatinine excretion, and
the results are compared with standard values for a given
height. Any other factor that might interfere with creatinine
excretion, such as age, renal disease, stress, and diet, may
affect its interpretation.90 The same applies to nitrogen
balance.
As a consequence, nutrition indexes using the aforemen-
tioned markers/tools are doomed to imply serious diag-
nostic bias, as each measurement has its own restrictions.
However, when they were put together to assess surgical
populations, it was possible to predict with increased sen-
sitivity major morbidity.82,91
Correia
Other relevant assessment tools—such as handgrip dy-
namometry and exercise testing for heart rate variability,
as well as respiratory muscle strength, fiber quality, and
functionality—may be ways to detect earlier muscle loss
and provide a better evaluation of nutrition repletion. They
have not been fully given their importance in the clinical
setting, probably because of their difficulty in assessing se-
vere acutely ill patients. Handgrip dynamometry, ergometer
workup with heart rate changes during maximal exercise,
as well as respiratory muscle strength seem to earlier detect
muscle loss, fiber quality, and functionality while providing
a better evaluation of nutrition repletion after therapy.92-97
As multiple elements of lean tissue (water, minerals, nitro-
gen, and glycogen) are incorporated after feeding, intra-
cellular potassium is increased, and membrane potential is
enhanced. This suggests that cell ion uptake happens earlier
than protein synthesis during nutrition therapy.94,95 Thus,
muscle and cell energetics are closely associated, and the
nutrition status may be rapidly impaired in the presence
of sepsis, trauma, renal failure, and drug administration
by direct impact on skeletal muscle function. However,
for dynamometry—the most practical of all the functional
tests—the absence of standardized equipment and proto-
cols has limited its usage. Also, this tool is not feasible for
patients in the intensive care unit, owing to their clinical
conditions (eg, intubation, hypercapnia, hypoxia, intrinsic
muscle disorders) as well as the use of muscle relaxants
and other drugs. However, muscle functionality could be
assessed by the contraction of the adductor pollicis muscle
in response to an electrical stimulus of the ulnar nerve at the
wrist. This tool could be used for the assessment of nutrition
status and as an indicator of nutrition improvement under
these conditions.98 In this regard, another method that
could help assess nutrition repletion is calorimetry, which
measures energy expenditure. The latter is dependent on
muscle mass, as this is the metabolically active tissue and
major determinant of energy expenditure.99,100 However,
the metabolic status of the individual, the presence of fever,
changes in ambient temperature, and the thermic effect of
food and activity may influence calorimetry, hampering its
use alone to provide the nutrition diagnosis. Furthermore,
a steady state is mandatory for accurate calorimetry results,
and throughout the day, at least 3–5 measurements should
be done to achieve more precise data, in severely ill patients
in particular.
In routine clinical practice, the use of most of the above-
discussed instruments alone may be hampered as related
to the drawbacks of each, the costs, and the availability.
Therefore, it is of utmost importance to rely on clinical
judgment supported by assessment tools, especially among
critically ill patients.
SGA, as described by Detsky et al,101,102 and the in-
strument detailed in the Academy of Nutrition and Dietet-
ics/ASPEN (AND/ASPEN)103,104 statements are very simi-
67
lar clinical tools of assessing the nutrition status of patients,
which individually include nutrition risk variables. They
cover various aspects of a patient’s nutrition history, from
body weight changes to functional capacity alterations. This
information can be provided by the patient or a relative with
good accuracy. SGA provides the nutrition diagnosis based
on gathered information regarding loss of weight, changes
in food intake, gastrointestinal symptoms/signs (vomiting,
diarrhea, anorexia), the stress imposed by the disease, and
a physical examination that evaluates loss of muscle and
fat mass as well as the presence of edema. AND/ASPEN
considers that if ࣙ2 of the following 6 characteristics are
present, the patient is malnourished: insufficient energy in-
take, weight loss, loss of muscle mass, loss of subcutaneous
fat, localized or generalized fluid accumulation that may
sometimes mask weight loss, and diminished functional
status as measured by handgrip strength. In addition,
several authors have compared these 2 tools with other
used instruments that provide the diagnosis and predict
morbidity, mortality, length of stay, and costs.17,47,48,71,105-111
Recently, a multicenter cohort study assessed different
nutrition indicators to predict outcomes of hospitalization
and readmission rates. After controlling for age, sex, and di-
agnosis, severely malnourished patients (by SGA) and those
with impaired hand grip strength stayed in the hospital
longer and had increased 30-day readmission.109 A potential
advantage of AND/ASPEN over SGA is that the former
is an objective method while the latter relies completely on
the interviewer’s capacity to (1) collect information from
the patient or members of the patient’s family and then (2)
interpret these and provide the patient’s diagnosis based on
his or her expertise. It is therefore mandatory that all of
those willing to perform SGA undergo a process of training
to decrease the chances of bias. Furthermore, SGA was
developed to provide the diagnosis within 48 hours after
hospital admission, but it has also been used at different
time frames, still with good prognostic results.1,101,102,112
Nonetheless, its useful to assess nutrition status evolution
and interventions has been questionable. However, a new
study from the Canadian group,73 whose objective was to
assess factors associated with nutrition decline in medical
and surgical wards, used SGA at admission and discharge.
It showed that 37% of the patients had in-hospital changes
in SGA: 19.6% deteriorated and 17.4% improved. Thus, the
SGA role as a marker of adequate nutrition repletion should
further be tested in other studies, since, as previously stated,
nutrition status changes usually occur at molecular and
cellular levels before reaching functional or body composi-
tion improvements.94,95 Variations of SGA, such as Patient-
Generated Subjective Global Assessment113,114 or Scored
Global Assessment,115 have been described and used in
cancer populations with good outcome associations.110,116
Considering the similarity of SGA and the
AND/ASPEN tool, with the former having potential
68
drawbacks, in particular among nonexperts—that is, it
relies on clinician interpretation, while the latter is more
objective—it would certainly be important to adopt
widespread use of the AND/ASPEN instrument.
Conclusion
A deficient nutrition status (undernutrition) is still an under-
diagnosed condition among sick and vulnerable individuals
(particularly the elderly), placing them at higher risk of
morbimortality, increased hospital stay, and readmissions
with associated higher costs.2,22,117-119 Nutrition screening
and assessment are 2 approaches that utilize risk factors
to identify at-risk individuals (the former) and help make a
nutrition diagnosis (the latter). Nutrition screening should,
in general, be a quicker tool that any healthcare professional
can carry out. However, in clinical practice, some screening
instruments are rather time and labor complex.68,120,121
Nonetheless, nutrition assessment must encompass vari-
ables that will not only help provide the nutrition diagnosis
but also confer adequate follow-up of the patients after
nutrition therapy. The latter, unfortunately, is still a more
controversial issue, and many tools currently fail to ade-
quately provide such a characteristic.
Screening and assessment both predict outcomes related
to the nutrition status. Nutrition assessment, a more com-
plex approach, would be expected to perform better. How-
ever, this has been a matter of discussion in the literature,
with results indicating that both can be used59,110,120,122-124
and with similar predicting capacity.110,120 Therefore, given
that strong evidences have shown the link between risk
of nutrition-associated factors and increased morbimor-
tality, length of hospital stay, and costs,1,48,73,97,125,126 if
in most healthcare settings, for different reasons, only
screening can be carried out, this would certainly help
narrow the gap between what it is recommended and what
it is performed.4,5 However, it is important to stress that
well-structured and scientifically developed tools should be
adopted.68,69
Ultimately, enrolling the patient and the families in the
process of screening the nutrition status might be useful,
especially in places where the overload of work hampers
healthcare professionals to routinely carry out screening
or assessment. According to Straus et al,127 “failures to
use evidence from research to make informed decisions
in healthcare are evident across all groups of decision
makers, including healthcare providers, patients, informal
caregivers, managers and policy-makers.” Such failures are
evident worldwide, in primary and specialty care, and by all
disciplines. It is common that well-established recommenda-
tions are not adopted, while certain treatments not proven
to be effective are. This seems to be the case with nutrition-
related actions, with low awareness among physicians who
do not routinely screen and assess their patients, despite all
Nutrition in Clinical Practice 33(1)
the recommendations and the grade of evidence in regard
to undernutrition and worse outcomes.1,86,118,128-130
In summary, nutrition screening and, if indicated, nutri-
tion assessment should be part of the integral care of any
sick individual, with the goal of decreasing nutrition-related
morbimortality. It would probably be recommendable if ex-
perts and societies came to an agreement on how to provide
easy definitions and recommendations45 to facilitate the
implementation of nutrition practices in the clinical setting,
particularly by nonnutrition experts. Raising awareness
around nutrition-related problems by simpler, objective, and
noncontroversial guidelines may positively influence the
physicians’ approach to the nutrition management of their
patients. In a scientific world in which 1000 articles are
indexed in MEDLINE daily,127 physicians, not to mention
administrations, would need a huge amount of time to be
updated. This explains why guidelines have a tremendous
impact on clinical practice and should be systematically and
critically assessed.131
Statement of Authorship
Maria Isabel Correia contributed to the conception/design of
the manuscript and to the acquisition, analysis, or interpreta-
tion of the data. Maria Isabel Correia drafted and critically
revised the manuscript. Maria Isabel Correia agrees to be fully
accountable for ensuring the integrity and accuracy of the
work. The author read and approved the final manuscript.
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Invited Review

Nutrition in Clinical Practice

Volume 33 Number 1
Head and Neck Cancer Tumor Seeding at the Percutaneous February 2018 73–80

C 2018 American Society for

Endoscopic Gastrostomy Site Parenteral and Enteral Nutrition

DOI: 10.1002/ncp.10021
wileyonlinelibrary.com

June R. Greaves, RD, CSNC, CDN, LD, LDN

Abstract
The National Institutes of Health National Cancer Institute estimates that over 13,000 new cases of head and neck cancer (HNC)
will be diagnosed in 2017. Patients with HNC often require enteral nutrition (EN) via gastrostomy tube to provide nutrition
support and hydration because of tumor obstruction of the oropharynx and/or cumulative effects of chemoradiation therapy.
The percutaneous endoscopic gastrostomy (PEG) tube has become the preferred technique for EN access because placement is
considered a minimally invasive procedure. There are 3 methods of PEG placement: Gauderer-Ponsky “pull,” Sachs-Vine “push,”
and Russell “push” method. The Gauderer-Ponsky “pull” method has become the preferred method of PEG placement. It has been
previously reported that the rate of stomal metastasis can be 0.5%–1% of those undergone the Gauderer-Ponsky “pull” method
that is consistent with HNC morphology. Other researchers believe the rate may be as high as 0.5%–3%. This article reviews the
3 methods of PEG placement, as well as all potential complications, including metastatic seeding at the PEG site. In addition, 1
additional case of tumor seeding at the PEG site will be reviewed. Consideration for avoidance of the Gauderer-Ponsky pull method
of PEG placement or other methods of feeding tube placement where the gastrostomy tube has to pass through the oral cavity
before exiting the abdominal wall in patients with squamous cell carcinoma of the head and neck should be considered. (Nutr Clin
Pract. 2018;33:73–80)

Keywords
gastrointestinal access; oncology; enteral nutrition; head and neck neoplasms; gastrostomy; gastrointestinal intubation

Introduction with HNC who is receiving concurrent chemotherapy with

The effects of malnutrition and poor survival rates in the
oncology patient have been well documented. It is estimated
that approximately 50% of patients with head and neck
cancer (HNC) will require alternative means of nutrition
support due to dysphagia resulting from obstructing tu-
mors, tumor compression (arising from thyroid and tracheal
cancers) within the pharyngeal region, and/or the effects of
concurrent chemoradiation therapy. Symptoms of disease
and/or treatment, such as vomiting, mucositis, xerostomia,
dysphagia, and odynophagia, contribute to inadequate oral
intake of nutrition and hydration, leading to weight loss,
nutrition deficiencies, and dehydration. To effectively treat
the patient, nutrition support is essential in arresting and
restoring weight status, correcting nutrition deficiencies,
and maintaining adequate hydration. The decision to place
an enteral feeding tube prophylactically can vary between
cancer treatment facilities based on their protocols and
guidelines. If short term, temporary nutrition support is
needed (defined as 4–6 weeks)1 ; a nasogastric tube (NGT)
can be placed. For purposes of this subject, use of NGT in
this population will not be included.
Feeding gastrostomy tubes have been recognized as ap-
propriate delivery of enteral nutrition (EN) in the patient
radiation therapy and during recovery period. Kwong and
colleagues2 reviewed 16 patients who had a feeding tube
placed in anticipation of treatment side effects that would
prohibit oral intake. The authors note that although pos-
sible side effects of treatment were reviewed with the
patient, along with benefits of prophylactic percutaneous
endoscopic gastrostomy (PEG) placement, the patients did
not fully appreciate how difficult oral intake of food and
hydration would be.2 The authors conducted a survey of
their patients on the benefits of the feeding tube once
treatment was completed. Although the feeding tube was
From the Coram CVS Specialty Infusion Services, Denver, Colorado,
USA.
Financial disclosure: None declared.
Conflicts of interest: None declared.
Received for publication June 27, 2017; accepted for publication
October 10, 2017.
Corresponding Author:
June R. Greaves, RD, CSNC, CDN, LD, LDN, Coram CVS Specialty
Infusion Services, 555 17th Street, Suite 1500, Denver, CO
80202-3900, USA.
Email: june.greaves@coramhc.com
74
viewed an annoyance, all patients viewed the PEG as a
benefit that sustained them during treatment and often
described the feeding as “saved their lives.”2 Benefits noted
included arresting or curtailing weight loss and providing an
alternative means of nutrition and hydration. Participants
responded that they would encourage all future patients to
undergo PEG placement.
van der Linden et al3 studied 240 patients with HNC in
attempts to quantify predictive indicators to design PEG
placement protocols. Of the 240 patients, 202 patients un-
derwent PEG placement, and 195 patients used the PEG for
nutrition and hydration. Of those who did not have a PEG
placed, 12 patients required nutrition support via NGT.
Factors to consider in PEG placement included stage of
tumor advancement, planned treatment, dysphagia/feeding
difficulties before treatment, and the age of the patient.
This study demonstrated the benefits of prophylactic PEG
placement in selected patients, but that further research
is needed to determine predictive factors in feeding tube
placement.
Locher and associates4 studied the relevance of pro-
phylactic PEG placement in patients with HNC. Nutrition
compromise and deficiencies are estimated to occur between
45% and 57% of patients at time of diagnosis.4 The authors
cite side effects and complications of concurrent chemora-
diation therapy: dysphagia, odynophagia, dysgeusia, ulcer-
ative mucositis, fibrosis, salivary gland dysfunction, pain,
xerostomia, dental caries, soft tissue necrosis, osteonecrosis,
bacterial and fungal infections, and nausea and vomiting,
all of which contribute to malnutrition because of the in-
ability to consume adequate nutrition and hydration orally.4
Malnutrition is associated with poor treatment outcomes,
including morbidity and mortality, infections, compromised
immune response, recurrence of disease, and poor quality of
life.4 Severity of nutrition deficiencies and symptoms expe-
rienced during treatment can delay or interrupt treatment,
which is correlated with poor outcomes. Although NGT
may be appropriate, the American Gastroenterological As-
sociation recommends gastrostomy feeding tube placement
in those who will require EN support lasting >30 days.4
Prophylactic PEG tube placement before treatment may
prevent dehydration and nutrition deficiencies often expe-
rienced in patients with HNC.4 Reported benefits of PEG
tubes included arresting or slowing of weight loss, fewer
inpatient hospitalizations, and decreased interruptions in
treatment.
Lucendo and Friginal-Ruiz5 support the benefits of pro-
phylactic PEG placement and early initiation of EN support
in the patient with HNC, which can limit weight loss and
provides nutrition and hydration during chemoradiation
therapy. In contrast to those who required PEG placement
during treatment with weight loss, suffered higher morbid-
ity, compared to those who underwent prophyloactic PEG
placement.5
Nutrition in Clinical Practice 33(1)
With the advancement of gastrostomy tube placement
techniques, patients can undergo gastrostomy tube place-
ment either endoscopically performed by a gastroenterol-
ogist, or by a radiologist in interventional radiology. The
methods of PEG placement are the Gauderer-Ponsky “pull”
method and the Sachs-Vine “push” method. The Russell
“push” method can be placed either with endoscopic guid-
ance by a gastroenterologist or without endoscopic guid-
ance by a radiologist. The Gauderer-Ponsky pull method
has become the most used PEG placement. There are several
published reports on the incidence of cancer tumor cell
seeding at the PEG site for those who have undergone the
Gauderer-Ponsky pull method.
The purpose of this review is to bring heightened aware-
ness to the potential complication of tumor seeding at the
PEG site using the Gauderer-Ponsky pull method.
Methods
A case study will be presented and compared with published
reports of tumor seeding at the PEG site from 1997 to 2017.
Given the rare occurrence of this complication, 35 articles
(33 in English, 2 in German) were cited on a PubMed
library–based search. Additional authors included tumor
seeding as a potential complication in their articles, dis-
cussing adverse effects and complications to enteral feeding
access devices.
To understand how tumor seeding can occur, it is impor-
tant to review the various methods of PEG placement and
theories as to how tumor cells may migrate to the PEG site.
PEG Placement Techniques
There are 3 methods of PEG placement: Gauderer-Ponsky
pull, Sachs-Vine push, and the Russell push method, which
can be placed in interventional radiology, endoscopic suite,
or at the bedside.6-8 In the event that PEG placement is con-
traindicated, a gastrostomy tube can be surgically placed.
Contraindications to PEG placement include obstructing
tumors of the oropharyngeal cavity preventing passage of
an endoscope, ascites, peritoneal dialysis catheter, previ-
ous abdominal surgeries, inability to transilluminate the
abdominal cavity, inability to access the anterior stomach
wall, uncorrectable coagulopathy, portal hypertension with
gastric varices, and colonic interposition.5,7
The Gauderer-Ponsky pull method was first described
in 1980.7-12 The gastrostomy tube is placed via complete
esophagogastroduodenoscopy (EGD). During EGD, the
stomach is filled with air, which pushes the stomach wall
up toward the abdominal wall. The light at the tip of
the endoscope is turned upward, allowing viewing of the
abdominal wall. A needle or catheter is placed through the
abdominal wall into the stomach. After a small incision
is made in the abdominal and gastric walls, a guidewire is
passed through the needle/catheter site and is captured with
Greaves
a polypectomy snare. The endoscope, snare, and guidewire
are pulled out through the stomach, up the esophagus, and
out the mouth, and the gastrostomy tube is attached to the
guidewire. The guidewire is pulled out of the abdominal
wall, pulling the gastrostomy tube from the mouth, down
the esophagus and stomach, and out through the abdominal
incision.8,9,11,13 This technique requires 2 passages of the
endoscope through the oral cavity and 1 passage of the PEG
through the oral cavity. The Sachs-Vine push method, which
was first described in 1983,7 is similar to the Gauderer-
Ponsky pull method, except for use of the guidewire. In
the push method, the PEG is a long, semirigid, tapered
tube with a dilator attached to the proximal end. The
dilator is inserted over a guidewire and advanced into the
mouth, down the esophagus, into the stomach, and out the
abdominal wall through the incision site.7 This technique
also requires 2 passes of the endoscope and passage of the
PEG through the oral cavity. The Russell push PEG, which
requires only 1 pass of the endoscope, was first described
in 1984. With this PEG placement method, the stomach
is filled with air and a needle is placed in the stomach as
in the Gauderer-Ponsky method. A 16 French peel-away
introducer sheath and dilator is pushed over the guidewire
into the stomach and abdominal wall. The dilator and
guidewire are removed, leaving the introducer sheath in
place. A 14 French balloon tip Foley catheter is placed into
the introducer sheath, and the catheter balloon is inflated
and pulled up against the abdominal wall, bringing the
stomach wall into position with the abdominal wall.7 The
advantage of this method is 1 passage of the endoscope
into the oral cavity and no passage of the PEG through the
oral cavity. The disadvantage is that the PEG tube itself is
generally smaller, such as 14 French rather than the standard
PEG of 20–24 French.7
Chadha et al13 found in a retrospective study that a
modified Russell push PEG technique, the Brown-Muller
T-fastener introducer technique, resulted in fewer post
placement infections and occurrences of metastatic cancer
at the PEG site because the PEG is not passed via the oral
cavity. In the Brown-Muller T-fastener introducer place-
ment method, the stomach is pulled up against abdominal
wall nylon anchoring devices, similar to those used to
attach price tags to clothing. The anchoring devices are
back loaded into a needle, which is passed percutaneously
through the abdominal and stomach walls under endoscopic
guidance.7,13 The T-bars are placed in a 4-corner pattern,
and the introducer-dilator is centered in the middle of the
pattern. Following incision, a guidewire is advanced into the
stomach with the assistance of a cannula, and a balloon tip
catheter is inserted. The balloon is inflated in the stomach.
The external portion of the T-fasteners is cut at skin level
approximately 2 weeks after the PEG is placed. The internal
portions of the T-fasteners are excreted via stool.7,13 One
potential complication of this method is ulceration at the
75
T-bar site, which can cause ulceration and necrosis of the
gastric wall.7 Once the T-bars are released, the internal
portion of the T-bar may be imbedded in the abdominal or
gastric wall.7 However, rates of ulceration and necrosis of
the gastric and abdominal wall have been rare.
Syndor et al14 studied 201 patients who underwent PEG
with T-fastener kits. Of those 201 patients, 71 patients
underwent abdominal computed axial tomography (CAT)
scan imaging of the PEG site. In these 71 patients, a total of
153 T-fasteners were deployed. At 4-week follow-up, 5.1%
of fasteners detached and were no longer present; 59.5% had
T-fasteners intraluminal, subcutaneous, or anterior within
the gastric wall; and 35% were found in abdominal wall
musculature. At 3-month follow-up, 48.6% of T-fasteners
detached and were no longer present, 25% were found
intraluminal or within the gastric wall, and 26.4% were
subcutaneous or in the anterior abdominal wall. Syndor et
al14 note that no T-fastener-related complications occurred
(abscesses, fluid collections, or fistulas). In addition, the
T-fastener migration into the abdominal wall occurred
shortly after tube insertion and did not guarantee intact
gastroplexy.
Said et al15 reported 1 case of abdominal wall necrotizing
fasciitis approximately 2 weeks after PEG placement that
resulted in death.
Chadha et al13 studied 356 patients over a 10-year period
and notes the overall complication rates with T-fastener
PEGs as cellulitis 6%, abscess 4%, splenic abscess <1%,
minor bleeding with spontaneous cessation 4%, deaths 0%,
tumor implantation 0%, leaking 8%, and accidental dis-
lodgement 28%. The Gauderer-Ponsky method carries an
overall complication rate of 20%–50%, with 5% mortality
rate in patients with HNC.13
Enteral Feeding Tube Complications
Complications to PEG tube placement include, but are
not limited to, aspiration pneumonia (1%–30%), infec-
tion/cellulitis of the PEG site (5%–38%), necrotizing soft tis-
sue infection (<2%), peritonitis/pneumoperitoneum (40%
endoscopy; 55% radiologic placement), tube dislodgement
(4%–7.8%), bleeding (2.3%–3.3%), gastrocutaneous fistula
(2%–3%), formation of granulation tissue (common; no
statistics available), leaking at the PEG site (1%–2%), ileus
(3%), splenic injury (<1%), colon and small-bowel per-
forations (<3%), puncture of the left lower lobe of the
liver (<3%), tube clogging (35%) pain at the PEG site
(0.3%–2.4%), gastric outlet obstruction (<3%), and death
(<1%).9,13,16 Tumor cancer seeding at the PEG site has been
added to the list of complications.
One specific problem is buried bumper syndrome (BBS),
which is defined as the migration of the internal bumper
of the PEG into the gastric or abdominal wall; it occurs in
approximately 2% of adult PEG patients.9,16-18 BBS can be
76
related to excessive tightening or tension of the bumpers,
characteristics of the internal bumper, malnutrition, weight
gain, and poor wound healing.9,16-18 Excessive tightening or
tension on the external bumper can cause ischemic necro-
sis, which can result in ulceration of the gastric mucosa,
allowing the external bumper and the internal bumper to
be “sandwiched” in the abdominal wall.9,16-18 As the ulcera-
tion heals, the bumpers can be buried into the abdominal
wall.9,16-18 BBS may initially present as increased leaking
around the PEG site, infection of the PEG site, fixation and
immobility of the PEG (unable to rotate in tract), resistance
to feeding, or abdominal pain during feeding.9,16-18 The
incidence of BBS has decreased with improvements in the
design of the internal bumper and softer disk-type designs
that avoid sharp edges.18 Not applying the external bumper
too tightly can aid in preventing BBS.9 The external bumper
can be loosened after the PEG site is well established
(approximately 2 weeks after PEG placement).7 In addition,
periodically pushing the PEG in and out of the stomach
(approximately 1–2 cm) and rotating the PEG can help to
ensure that the internal bumper or tip of the PEG is not
becoming buried into the stomach wall.9 The symptoms of
BBS can mimic those symptoms that have been noted with
stomal seeding.
Tumor Seeding/Stomal Metastasis
The first reported cases of stomal metastasis to the stom-
ach and abdominal wall after gastrostomy placement were
described by Algaratharm et al in 1971. Preyer and Thul
reported the first case of stomal metastasis at the PEG
site in 1989. New cases are identified annually. Although
tumor seeding is a rare complication, reported incidence
rate has been estimated at 0.5%–3%6,9,10,16,19 of patients with
HNC with PEGs. It is also believed that stomal metastasis
is underestimated. An article by Thakore et al10 cites that
Antler et al reported that autopsy findings may be as
high as 9%. Cruz et al20 notes that soft tissue metastasis
was noted in 8% of patients with HNC postmortem, with
distant metastasis and gastric metastasis reported in 0.3%
of patients with HNC.
Cases of metastasis tumor seeding have been found in
patients with stage III/IV squamous cell carcinoma within
1–24 months after PEG placement using the Gauderer-
Ponsky pull method.6,8-14,16,19,21,22 Stomal metastasis has
also been seen in those with stage II/III oropharyngeal
cancers as well.
Tumor implantation, or tumor seeding, is believed to
occur because of multiple, or traumatic, passages of in-
struments, as well as the PEG tube itself, through the oral
cavity. During passes through the esophageal lumen, cancer
cells can adhere to the instruments, the internal bumper,
or the PEG tube and can translocate to the PEG incision
site.6,8-10,12,13,16,19-24
Nutrition in Clinical Practice 33(1)
Other theories of tumor implantation include hematoge-
nous and lymphatic spread as the result of surgical stress,
increasing tumor metastasis because of high concentrations
of circulation cortisol levels.6,8-11,19,20,22-24 This process can
induce morphologic changes in the capillary lumen, al-
lowing tumor cells to implant at the incision site through
the increased circulation, and the environment of the PEG
site.8,10,18,23,24
Ellrichmann et al11 conducted a study of 50 patients with
PEG placement. Brush cytology from the PEG tubing and
incision site was taken immediately after PEG placement
and repeated 3–6 months postprocedure. Forty patients
underwent the pull method, and 10 underwent direct in-
troducer technique. Cytology samples of the PEG tubing
and incision site immediately after PEG placement showed
cancer cells in 22.5% of the patients who underwent the
pull method. For those who underwent the direct introducer
PEG placement, no malignant cells were detected after
immediate placement. At the 3- to 6-month follow-up, 32
patients in the pull method PEG group were reexamined.
Malignant cells were detected on brush cytology in 3
patients. The remaining 29 patients had benign cytology
smears. No macroscopically visible tumors were observed
at follow-up. Of the direct introducer group, 9 patients
completed the 3- to 6-month follow-up. No malignant cells
were found on brush cytology.
Stomal metastasis can be associated with poor prognosis,
with mean reported survival rate of 3–24 months after
diagnosis.8,10-13,18,20 Stomal metastasis is not commonly
considered a complication because the onset of symptoms
often mimics localized infection with redness, induration,
abdominal pain, ulceration of the PEG site, constipation,
and drainage at the stoma site.6,8,10-12,24 Symptoms can
temporarily resolve with antibiotic therapy. Stomal seeding
can be asymptomatic. Fung et al19 reported 5 cases of
stomal seeding, with only 1 case with clinically symptomatic
metastasis, whereas the remaining 4 patients were diagnosed
by radiographic scans. Recurrence of symptoms should be
evaluated, including biopsy of the PEG site, to rule out
stomal seeding.23 Multiple passes through the oral cavity
or esophageal lumen with PEG instruments and the PEG
itself, as in the Gauderer-Ponsky pull technique, is believed
to increase the potential for cancer cells to adhere to the
instruments or PEG, allowing them to translocate at the
PEG site.6-8,10-13,17,19-25 Table 1 lists potential signs and
symptoms of tumor seeding. Table 2 reviews the benefits
and disadvantages of PEG placement.
Reported Cases of Tumor Seeding
Huang et al6 reviewed 4 cases of PEG-site metastasis after
treatment for squamous cell carcinoma of the head and
neck. Two cases will be briefly reviewed. Case presentation
1 was a 69-year-old man with T2N2aMO squamous cell
Greaves 77

Table 1. Potential Signs and Symptoms of Tumor Seeding.
r Induration
r of persistent disease in the right neck. The PEG was
Recurrent infection treatment
r Excessive bleeding
r Ulceration at the PEG stoma
r Excessive pain or discomfort at the PEG stomas
r Excessive purulent drainage
r Masslike growth at PEG stoma
r Progressive granulation tissue formation
PEG, percutaneous endoscopic gastrostomy.
carcinoma of the right pyriform sinus. A PEG was placed
one month before the state of concurrent chemo-radiation
therapy, utilizing the Gauderer-Ponsky pull method. Five
months after completion of chemoradiation therapy, the
patient underwent salvage right neck dissection because
removed postoperatively and the site healed without com-
plication. Fourteen months after neck dissection, a total
of 20 months after chemoradiation therapy and 22 months
after PEG placement, a follow-up whole-body positron
emission tomography scan revealed metastatic disease to
the adrenal glands, liver, and left anterior abdominal wall.6
Biopsies of the abdominal wall were positive for poorly
differentiated squamous cell carcinoma. Eight months after
diagnosis of PEG-site metastasis, the patient died following
a stroke.
Case presentation 26 was a 77-year-old man with a
diagnosis of T3N1M0 squamous cell carcinoma of the right

Table 2. Benefits and Disadvantages of Percutaneous Endoscopic Gastrostomy.

Method of PEG Placement Benefits Disadvantages

Pull method r Minimal pain/discomfort r Requires 2 passes of scope through

r Ability to visualize gastric mucosa during
placement
r Endoscopically, radiologically, or bedside
placement
r Ability to initiate tube feedings within 6–24
hours after placement
r Conscious sedation with local anesthesia
r Short recovery period
r Larger diameter tube 18–28 French
Push method r 1 pass of scope through oropharyngeal cavity
r Endoscopic, radiologic, or bedside placement
r Minimal pain/discomfort
r Short recovery period
r Feeding tube does not pass through
oropharyngeal cavity
r Lower risk for tumor seeding
r Fewer rates of infection
r Technically easier to convert G-tube to J-tube
r Conscious sedation with local anesthesia
T-Fastener r No passage of G-tube or instruments through
the oropharyngeal cavity
r May require 1 passage of the endoscope in the
oropharyngeal cavity to check PEG placement
r Endoscopically, radiologically, or bedside
placement
r Conscious sedation with local anesthesia
r Avoids potential of stomach wall pushing
away from the abdominal wall
oropharyngeal cavity
r Unable to place PEG with obstructing
oropharyngeal tumors
r Contraindicated with ascites, peritoneal
dialysis, peritoneal metastasis
r Increased risk for infection
r Increased risk for tumor seeding the PEG
stoma as feeding tube passes through the
oropharyngeal cavity
r Placement may be challenging in the morbidly
obese
r Guidewire used to facilitate placement can
loop in the stomach
r Smaller diameter tube (14 French)
r Increased risk for tube clogging (because of
smaller diameter tube)
r Possibility stomach may be pushed away
during PEG placement while introducer
dilatator is inserted
r Difficult placement in patient with scarring or
muscular abdominal wall/previous abdominal
surgery
r Contraindicated with ascites, peritoneal
dialysis, or peritoneal metastasis
r Risk for ulceration and abdominal wall
necrosis (rare)
r Smaller diameter tube (14 French)
r Increased risk for tube clogging (because of
smaller diameter tube)
r Contraindicated in ascites, peritoneal dialysis,
or peritoneal metastasis
r Difficult placement in patient with scarring or
muscular abdominal wall/previous abdominal
surgery

PEG, percutaneous endoscopic gastrostomy.

78
supraglottic larynx. The patient underwent PEG using the
Gauderer-Ponsky pull method 1 week before the start of
chemoradiation therapy. Four months after treatment, no
evidence of residual disease was found. Due to dysphagia re-
sulting in hypopharyngeal scarring from radiation therapy,
the patient remained PEG dependent to meet the majority
of his nutrition needs. Fourteen months after treatment, the
patient was admitted to an acute care facility for constipa-
tion and acute renal failure. Upper gastrointestinal series
diagnosed a large gastric ulcer at the PEG site. Biopsies
confirmed squamous cell carcinoma 17 months after PEG
placement. The patient underwent exploratory laparotomy
with planned resection of the gastric mass. Intraoperative
findings of the mass found it to be 8 cm in maximal
diameter with invasion of the colon, mesentery, and pan-
creas with abortion of the planned resection. During the
procedure, the existing PEG was removed with placement of
separate gastrostomy in normal-appearing stomach. Seven
weeks postoperatively, 5 months after diagnosis of PEG-
site metastasis and 20 months after completing chemora-
diation therapy, the patient died while under hospice
care.6
Mincheff 8 reported a case of a 59-year-old man who had
T4N2M0 stage IV squamous cell carcinoma of the right
soft palate, tonsillar fossa, retromolar trigone, and base of
the tongue. He noticed granulation tissue at the PEG site
approximately 1 month after placement. Within 3 months,
the patient had a 4-cm fungating mass around the PEG
site. Three weeks later, the mass had grown to 9 cm in
diameter. Skin biopsy revealed squamous cell carcinoma
that originated from the patient’s HNC. EGD demonstrated
tumor growth around the bumper and mushroom in the
stomach, and computed tomography (CT) scan revealed
a large mass extending through the abdominal wall.8 The
metastatic workup (CT scan of the head, neck, chest, and
abdomen) was negative for metastatic disease, with the
exception of the mass of the abdominal wall and stomach.
The patient underwent localized radiation therapy, resulting
in reduction in the size of the mass.8 Upon completion
of radiation therapy, subsequent CT scan of the abdomen
did not reveal residual disease. The patient underwent en
bloc resection of the abdominal wall at the PEG site, which
included a wedge resection of the stomach with repair to
the abdominal wall with dual mesh. Margins were clear of
neoplastic cells, and no residual tumor was detected.8 On
year 1 of follow-up, the patient experienced development of
local recurrence to the jaw and enrolled in hospice care.
Sinapi et al12 reviewed a case of a 51-year-old man
diagnosed with T4N2bM0 squamous cell carcinoma of
the hypopharynx. Before treatment, a Gauderer-Ponsky
pull method gastrostomy was placed. The patient was suc-
cessfully treated with concurrent chemoradiation therapy.
Within 1 year after completing treatment (and with PEG
still in place), the patient was diagnosed with recurrent
Nutrition in Clinical Practice 33(1)
hypopharyngeal carcinoma. The patient underwent total
pharyngectomy with bilateral neck dissection with pharyn-
geal flap reconstruction. Three months postoperatively, the
patient was able to sustain his nutrition status with oral
nutrition, and the PEG was removed. Five months later,
the patient presented with aphagia. Flexible esophagoscopy
did not show any tumor recurrence but did document
esophageal concentric fibrosis stenosis likely related to
previous radiation therapy, and it was successfully dilated.
Upon examination of the stomach, a gastric submucosal
lesion at the PEG site was found. CT scan confirmed
carcinoma facing the PEG site and infiltrating the anterior
abdominal wall. The patient underwent a successful partial
gastrectomy with en bloc abdominal wall resection. At 8-
month follow-up, no signs of recurrence or residual disease
were found.12
Sinclair et al24 reported a case of a 61-year-old man who
had T2N1 stage III squamous cell carcinoma on the right
side base of the tongue and underwent PEG placement
with the pull method. Approximately 5 days after PEG
placement, he reported mild tenderness and erythema near
the PEG site. The patient was treated for presumed local
cellulitis with oral antibiotics for 1 week, which resulted
in resolution. The PEG was removed 4 months later, but
the patient noted soreness at the PEG site. Sometime later,
the site became erythematous, raised, and indurated, and
the patient received a 1-week course of oral antibiotic
for presumed cellulitis. When no improvement was seen 6
weeks later, clinicians performed a biopsy of the site. The
biopsy was positive for squamous cell carcinoma similar to
the original HNC. EGD demonstrated a 6-cm fungating
mass along the anterior wall of the stomach. The patient
underwent surgical excision of the tumor and subtotal gas-
trectomy, local radiation, and chemotherapy with cisplatin
and 5-fluorouracil. Nine weeks after surgery, biopsy results
of an enlarged left axillary lymph node were positive for
squamous cell metastatic carcinoma.24
Cappell25 reviewed all 44 known cases up to 2007 of
malignant tumor seeding at the PEG site with pharyngoe-
sophageal carcinoma. The mean age of patients was 59.0
± 10 (SD) years; 79% were male. Metastasis was found in
the abdominal wall in 63%, 7% in gastric wall, and 30%
in both gastric and abdominal walls. Mean survival after
diagnosis was 4.3 ± 3.8 months. In 100% of cases, primary
location of the cancer was pharyngoesophageal (0% in other
sites), with 98% squamous cell and 2% adenocarcinoma;
large primary cancer size at diagnosis was mean diameter 4.2
± 2.3 cm. Risk factors for PEG site metastasis included 98%
endoscopic placement and 2% surgical; of the endoscopic
placement, 98% used the pull method and 2% the guidewire
method. Cappell25 concluded that strong risk factors for
PEG site metastasis include pharyngeal as primary cancer,
squamous cell carcinoma, large size tumor, and advanced
cancer staging.
Greaves
Although reported cases are limited, each case shows
common factors:
r Majority of PEGs were placed using the Gauderer-
Ponsky pull technique.
r Majority of patients were diagnosed with stage III/IV
squamous cell carcinoma of the oropharyngeal re-
gion.
r Men seem to have a higher risk stratification than
women.
r Age of the patient was not considered a significant
risk factor.
Case Study
A 68-year-old man who had T2N0M0 squamous cell car-
cinoma of the hypopharynx was referred to the home
care provider for EN support services while undergoing
concurrent chemoradiation therapy. He underwent PEG
placement for EN in November 2009 (the method of PEG
placement was not noted) before initiation of concurrent
chemoradiation therapy. On February 23, 2010, he reported
that the PEG site was red, blistered, and painful, adding
that he had been treated for local infection twice since
PEG placement. He was advised to contact his physician
for biopsy of the site. According to the patient, the physi-
cian was not overly concerned with recurrent infections
and changes to the stoma site. The patient completed
chemotherapy and radiation therapy, and began to transi-
tion to oral intake.
On March 2, 2010, he reported that he had not used
his feeding tube for nearly 1 week, was able to maintain
weight with an oral diet, and was scheduled to have the PEG
removed. However, he added that the PEG site remained red
and raw, with granulating tissue that was bleeding. After the
PEG was removed, the patient reported that the PEG was
beginning to heal and that the breakdown was responding
to antacid liquid applied to the skin for what was diagnosed
as an ulcer at the PEG site. The patient was discharged from
enteral services in March 2010.
The patient suffered a recurrence of pharyngeal cancer
and underwent a total laryngopharyngectomy and right
radical neck dissection on June 9, 2010. A biopsy of the
previous PEG site was performed intraoperatively, and
results confirmed metastatic carcinoma consistent with
hypopharyngeal cancer. The abdominal wall contained a
large mass extending from the skin surface down through
the wall of the stomach. The patient required a subtotal
gastrectomy with sleeve reconstruction of the abdominal
wall, and a tracheoesophageal puncture was performed for
enteral feedings. The patient died of complications of his
illness on March 6, 2011.
79
Conclusion
Clinicians working with patients with HNC should be aware
of all potential complications of PEG placement. Serious
consideration should be given to tumor seeding at the PEG
site if persistent or recurring redness or induration, skin
breakdown, bleeding, or unusual changes are noted to the
skin or stoma site. Biopsies of the PEG site should be
taken with any unusual or unexplained skin changes at the
PEG site. Stomal seeding has been most associated with the
Gauderer-Ponsky pull method; however, it can occur with
the Sachs-Vine push method because of passage of the PEG
tube through the oral cavity. Consideration for avoidance of
the Gauderer-Ponsky pull method PEG placement or other
methods of feeding tube placement where the gastrostomy
tube has to pass through the oral cavity before exiting the
abdominal wall in patients with squamous cell carcinoma
of the head and neck should be considered.
Statement of Authorship
J. Greaves, as sole author, drafted and revised the manuscript;
contributed to the acquisition, analysis, or interpretation of the
data; agree to be fully accountable for ensuring the integrity
and accuracy of the work; and read and approved the final
manuscript.
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access. Nutr Clin Pract. 2002;17:275-283.
2. Kwong JP, Stokes EJ, Poslums EC, Fitch MI, McAdrew A, Vanden-
bussche KA. The experiences of patients with advanced head and neck
cancer with a percutaneous endoscopic gastrostomy tube: a qualitative
descriptive study. Nutr Clin Pract.2014;29(4):526-533.
3. van der Linden NC, Kok A, Leermakers-Vermeer M, de Roos NM, de
Bree R, van Cruijsen H, Terhaard CHJ. Indicators for enteral nutrition
use and prophylactic percutaneous endoscopic gastrostomy placement
in patients with head and neck cancer undergoing chemoradiotherapy.
Nutr Clin Pract.2017;32(2):225-232.
4. Locher JL, Bonner JA, Carroll WR, et al. Prophylactic percutaneous
endoscopic gastrostomy tube placement in treatment of head and neck
cancer: a comprehensive review and call for evidenced-based medicine.
JPEN J Parenter Enteral Nutr. 2011;35(3):365-374.
5. Lucendo AJ, Friginal-Ruiz AB. Percutaneous endoscopic gastrostomy:
an update on its indications, management, complications, and care. Rev
Esp Enferm Dig.2014;106:529-539.
6. Huang, AT, Georgolios A, Espino S, Kaplan B, Neifeld J, Reiter E.
Percutaneous endoscopic gastrostomy site metastasis from head and
neck squamous cell carcinoma: case series and literature review. J
Otolarynol Head Neck Surg. 2013;42(1):20.
7. Vaneck VW. Ins and outs of enteral access. Part 2: long-term access—
esophagostomy and gastrectomy. Nutr Clin Pract. 2003;18:50-74.
8. Mincheff TV. Metastatic spread to a percutaneous gastrostomy site
from head and neck cancer: case report and literature review. JSLS.
2005;9:466-471.
9. Bechtold ML, Mir FA, Boumitri DC, Kiraly LN, Nguyen DL. Long-
term nutrition: a clinician’s guide to successful long-term enteral access
in adults. Nutr Clin Pract.2016;31:737-747.
10. Thakore JN, Mustafa M, Suryaprasad S, Agrawal S. Percutaneous
endoscopic gastrostomy associated gastric metastasis. J Clin Gastroen-
terol. 2003:37(4)307-311.
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11. Ellrichmann M, Sergeev P, Bethge J, et al. Prospective evaluation
of malignant cell seeding after percutaneous endoscopic gastros-
tomy in patients with oropharyngeal/esophageal cancers. Endoscopy.
2013;45:526-531.
12. Sinapi I, Navez B, Hamoir M, et al. Seeding of the percutaneous
endoscopic gastrostomy site from head and neck carcinoma: case report
and review of the literature. Head Neck. 2013;35(7):E209-E212.
13. Chadha KS, Thatikonda C, Schiff M, Nava H, Sitrin MD. Outcomes
of percutaneous endoscopic gastrostomy tube placement using a T-
fastener gastropexy device in head and neck and esophageal cancer
patients. Nutr Clin Pract. 2010;25:658-662.
14. Syndor RH, Scriber SM, Yoon Kim C. T-fastener migration after
percutaneous gastropexy for transgastric enteral tube insertion. Gut
Liver. 2014;8(5):495-499.
15. Said MRM, Abdul Rani R, Raja Ali RA, Chai Soon N. Abdominal
wall necrotising fasciitis: a rare but devasting complication of the
percutaneous endoscopic gastrostomy procedure. Med J Malaysia.
2017;72(1):77-79.
16. Singh A, Gelrud A. Adverse events associated with percutaneous
enteral access. Gastrointest Endoscopy Clin N Am. 2015;25:71-82.
17. Baskin WN. Acute complications associated with bedside placement of
feeding tubes. Nutr Clin Pract. 2006;21:40-55.
18. Kejariwal D, Aravinthan A, Bromley D, Miao Y. Buried bumper
syndrome: cut and leave it alone! Nutr Clin Pract. 2008;23:
322-324.
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nal wall metastasis following percutaneous endoscopic gastrostomy
placement in patients with head and neck cancer. Surg Endosc. 2017;31:
3623-3627.
20. Cruz I, Manel JJ, Brady PG, Cass-Garcia M. Incidences of abdominal
wall metastasis complicating PEG tube placement in untreated head
and neck cancer. Gastrointest Endosc. 2005;62(5):708-711.
21. Thorburn D, Karim S, Soutar DS, Mills PR. Tumour seeding following
percutaneous endoscopic gastrostomy placement in head and neck
cancer. Postgrad Med J. 1997;73(861):430-432.
22. Nevler A, Gluck I, Balint-Lahat N, Rosin D. Recurrent metastasis
spread to a percutaneous gastrostomy site in a patient with squamous
cell carcinoma of the tongue: a case report and review of the literature.
J Oral Maxillofac Surg. 2014;72(4):829-832.
23. Narang T, Ugras S, Pochapin M, Lieberman M. Abdominal wall
metastasis after PEG placement in patients with oropharyngeal cancer.
Pract Gastroenterol. 2009;33:33-38.
24. Sinclair JJ, Scolapio JS, Stark ME, Hinder RA. Metastasis of head and
neck carcinoma to the site of percutaneous endoscopic gastrostomy:
case report and literature review. JPEN J Parenter Enteral Nutr.
2001;25:282-285.
25. Cappell MS. Risk factors and risk reduction of malignant seedings
of the percutaneous endoscopic gastrostomy track from pharyngoe-
sophageal malignancy: a review of all known 44 reported cases. Am
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Invited Review

Nutrition in Clinical Practice

Volume 33 Number 1
Graduation Day: Healthcare Transition From Pediatric February 2018 81–89

C 2018 American Society for

to Adult Parenteral and Enteral Nutrition

DOI: 10.1002/ncp.10050
wileyonlinelibrary.com

Kelly Green Corkins, MS, RD, CSP, LDN, CNSC1 ; Michelle A. Miller, MS, RD,
LDN, CNSC1 ; John R Whitworth, MD2 ; and Carol McGinnis, DNP, APRN-CNS,
CNSC3

Abstract
Because more patients with pediatric-onset chronic conditions are surviving into adulthood, they are graduating from pediatric
healthcare to self-management and adult healthcare. This transfer of care needs to be a process of transitioning medical and
nutrition care. Despite having position statements from professional organizations and several proposed models, issues in the
transition process have been well described, and gaps in transition care persist. Healthcare providers need to be aware of special
needs of emerging adults related to education on chronic condition and self-management skills, emotional support before and after
transition, and legal rights for both the patient and the parent if the emerging adult is not developmentally appropriate to make
his or her own healthcare decisions. Both pediatric and adult providers need to be in active communication with each other and
the patient to develop trusting relationships and actively support the transition of care. This review of literature describes several
models for transitioning, measureable outcomes, insurance provider issues, and legal issues pertaining to healthcare transition.
(Nutr Clin Pract. 2018;33:81–89)

Keywords
transition to adult care; nutritional support; adolescent; needs assessment; enteral nutrition; parenteral nutrition

Introduction insurance provider. Increasing healthcare costs with lower

Improved medical and surgical management of patients
with pediatric-onset chronic conditions (POCC) and ad-
vancements in parenteral (PN) and enteral nutrition (EN)
support have resulted in an increase in the number of
children with special healthcare needs (SHCN) living well
into adulthood. Such patients can then “graduate” from
pediatric-centered care systems to adult-centered care sys-
tems. Graduation for many connotes excitement, antici-
pation, and uncertainty. Excitement stems from a major
accomplishment, such as completing high school. Antic-
ipation may come from moving out of a parent’s home,
starting college, or starting a new job. With graduation
from pediatric care also comes the uncertain transition to
adulthood and the responsibility for healthcare decisions.
Emerging adults with POCC and their parents or caregivers
have added stress associated with this transfer of care.1
Research has shown that quality of life and appropriate
management of their condition are dependent on a smooth
and well-supported transition from both the pediatric and
the adult providers involved.2
Criteria for transition vary from facility to facility.
They may be dictated by age, development, or are spe-
cific to the condition. Sometimes they are dictated by
reimbursement rates and lower quality of life for the patients
supports the need to develop individual hospital and certain
condition-specific protocols for transitioning healthcare
from pediatric providers to adult providers. These protocols
should involve the patient, parents or caregivers, and both
pediatric and adult providers.2
Transition of care is very different from transfer of care.
Synonyms for transition include “change,” “development,”
From the 1 Nutrition Therapy Department, LeBonheur Children’s
Hospital, Memphis, Tennessee, USA; 2 Department of Pediatrics,
Division of Pediatric Gastroenterology, University of Tennessee
Health Science Center and LeBonheur Children’s Hospital, Memphis,
Tennessee, USA; and 3 Sanford USD Medical Center, Sioux Falls,
South Dakota, USA.
Financial disclosure: None declared.
Conflicts of interest: None declared.
Received for publication September 1, 2017; accepted for publication
November 19, 2017.
Corresponding Author:
Kelly Green Corkins, MS, RD, CSP, LDN, CNSC, 50 N Dunlap
Street, 1st floor Research Building, Nutrition Therapy, LeBonheur
Children’s Hospital, Memphis, TN 38103, USA.
Email: kelly.corkins@lebonheur.org
82
and “evolution.”3 Transition is a process that requires
careful planning and ultimately results in the transfer of
care.1,4,5 Adult providers are learning more about POCC
such as type 1 diabetes, cystic fibrosis, congenital heart
defects, specific childhood cancers, solid organ transplants,
sickle cell disease, spina bifida, and inflammatory bowel
disease (IBD) so they can adequately care for adults with
these conditions.6 Although this increased knowledge base
is crucial for lifelong management, the key to adequate
care and autonomy in care for emerging adults with POCC
lies in providing adequate healthcare transition (HCT)
support with 1 person leading and coordinating during
the transition process.7 Without adequate support during
the transition, there is an increased risk for inadequate
follow-up and poor self-management leading to poorer
quality of life for the patient, with increased hospitaliza-
tions, increased rehospitalizations, and increased healthcare
costs.4,6,8
Transition Models for Effective HCT
Various transition models including systems and processes
have been suggested to enhance HCT. Several of these mod-
els are highlighted and compared in Table 1. In 2008, the
Institute for Healthcare Improvement promoted a “Triple
Aim Framework,”9 which highlighted the need to improve
clinical outcomes, improve patient, family, and provider
experiences, and decrease per capita spending. Bensen et
al6 emphasized 3 unmet needs: development of skills for
chronic disease management, enhancement of adult systems
to care for emerging adults with SHCN, and reduction
of lapses in care during transition. In 2002, consensus
statements from the American Academy of Pediatrics, The
American Academy of Family Practice, and the American
College of Physicians10 stressed the importance of provid-
ing high-quality transition care, yet gaps in the process are
still evident in clinical practice. These gaps impact emerging
adults, their families, and their care providers in both
worlds.
One resource with many tools for the transition process
is the Center for Health Care Transition Improvement
model.11 This online resource comes from a cooperative
agreement between the Maternal and Child Health Bureau
and The National Alliance to Advance Adolescent Health.
The 6 Core Elements of Health Transition that are the cor-
nerstones for this model include transition policy, tracking
and monitoring, transition readiness, transition planning,
transfer of care, and transfer completion. See Table 1 for
descriptions of each of the 6 core elements. In addition,
the website (http://www.gottransition.org) provides tools for
measuring transition.11
McManus et al12 described a pilot project for the process
and identifying results of incorporating the 6 Core Elements
of Health Care Transition into a Medicaid managed care
Nutrition in Clinical Practice 33(1)
group plan involving 35 patients, aged 18–23 years, with
complex conditions. Based on this pilot, they suggested that
the process of HCT should begin much earlier than in their
study; it should begin at ages 12–14, as recommended by
the American Academy of Pediatrics, American Academy
of Family Physicians, and Transitions Clinical Report Au-
thoring Group.13
Mahan et al8 discussed that HCT can be divided into
3 stages: (1) setting the stage, initiation of HCT services
and readiness assessment; (2) moving forward, ongoing
provision of HCT services; and (3) reaching the goal,
transfer of care and transition to adulthood. They offered
suggestions to incorporate HCT into the healthcare system
and improve programs through a quality improvement
approach, much like aspects of the 6 Core Elements of
Health Care Transition.
Bensen et al6 provided suggestions to enhance the tran-
sition process, including development of chronic disease
self-management skills and health coaching to develop self-
efficacy and self-advocacy skills. Self-management and self-
advocacy first require the identification of who will be
primarily responsible for future self-management, whether
the patient or a caregiver.6,10-13 Mental health comorbidi-
ties in terms of screening and treatment need to be ad-
dressed and support provided for the emerging adult by
providing links to peer support and mentorship groups.
They suggested identification of the receiving care team
well in advance, thus facilitating communication between
both worlds, and offering means for consultation (eg, via
telemedicine) as indicated.6 They also recommended pro-
viding disease-specific education and support, especially
for rare pediatric conditions and ensuring adequate care
coordination for medically complex patients with SHCN.
They recommended providing guidance to patients and
families as they transfer using clear and transparent policies
and procedures (step 1 of the 6 core elements).6,10 Setting
clear expectations, designating a point of contact through
transition, following a preestablished checklist, and antic-
ipating age-related medical insurance and service changes
were also stressed.6
A position statement by the Society of Pediatric Nurses
described 3 separate components of care related to HCT:
period of extended preparation, transfer of care period, and
period of post-HCT/transfer of care.14 This position state-
ment discusses the need for adequate preparation before
transfer of care, including autonomy, independence, self-
determination, and self-advocacy being integrated into the
principles of care. Preparation should be initiated well be-
fore the intensive period (beginning at age 12 years), prefer-
ably in early adolescence; involve the patient, family, and
team; focus on interests, needs, and preferences; and have
measurable outcomes and benchmarks of achievement.14
The position statement suggested use of a formalized pro-
cess based upon an HCT framework. The assessment tools
 Table 1. Comparison of Healthcare Transition Models During the Adolescent and Emerging Adult Period.

Approximate Center for Health Care Transition Improvement

Age (y) Model’s 6 Core Elements of Health Transition11 Bensen et al (2014)6 Betz (2017)14 Mahan et al (2017)8

12–14 1. Transition r Develop a written policy 1. Develop chronic 1. Extended HCT 1. Setting the stage:
policy on transition by the disease preparation
practice to enhance self-management r Initiation of HCT
agreement of those skills. services
involved in the process. r Readiness Assessment
2. Transition r Establish criteria and a
tracking and process to outline
monitoring progress in the process.
3. Transition r Identify adult providers. 2. Identify and
Readiness r Establish a welcoming support the
and orientation process. receiving care team.
14–18 4. Transition r Facilitate the steps in the 2. Moving forward:
Planning transference process. r Ongoing provision of
◦ Education HCT services
◦ Insurance
resources
◦ Establish legal
surrogate
decision-making
authority, if
needed
5. Transfer of Care r Address concerns of the 3. Provide guidance 2. Transfer of care
emerging adult. to the patient and period (age 18–21
r Clarify approaches. families as they years)
r Conduct self-care move through
assessment. healthcare systems.
r Review priorities.
r Share medical and care
plan information.
18–23 6. Transition r Build collaborative 3. Post-HCT/transfer 3. Reaching the goal
completion partnership of care r Transfer of care
r Continue to tailor care r Transition into
management. adulthood
r Elicit feedback.

HCT, healthcare transition.

83
84
and the transition plan should be fluid and responsive to
needs of the adolescent and the emerging adult. The emerg-
ing adult needs to acquire self-management knowledge
and skill to ensure independence with the treatment pro-
gram. There should be coordinated referrals for education,
housing, transportation, healthcare coverage, and so on.
Guardianship, when needed, should be considered. It is sug-
gested that a discussion occur about the changing dynamics
of the relationship from the parent’s role as primary care-
giver to coach, consultant, and/or organizational assistant
and its implications. This process should be documented in
the patient medical record. Quality improvement, evalua-
tion, and research exploring achievement of outcomes, such
as independence, self-management, adherence, quality of
life, involvement in education, vocation and/or recreation,
and social networks, are important to provide an indication
of success and highlight areas for improvement. The society
recommends that healthcare institutions, community-based
healthcare programs, and schools of nursing use the posi-
tion statement to ensure education, training, resources, and
effective staffing plans.14
Major themes from a 2013 qualitative study by Ritholz
et al15 of 26 emerging adults were designed to give voice to
their perceptions of and insights about their relationships
during transition. Some of these themes included feelings of
loss and gain in provider relationships across the transition,
feelings of sad reluctance that transition is a natural progres-
sion, and feelings of being partners in care vs being on one’s
own, as well as ambivalence over increased independence.
Patients valued how adult providers’ collaborative con-
versations promoted their involvement and accountability
compared with “parent-centric” interactions with pediatric
providers. Participants reported feeling less judged by adult
providers than pediatric providers. The researchers felt
enhanced communication between pediatric and adult
providers may allow patients to feel that all understand
who they are and what they need during this transition.
Patients recommended that pediatric providers actively
promote emerging adults’ autonomy while maintaining
parental support, communication with adult providers,
and follow-up with transitioning patients. Of note was
a finding that patients who did not feel attached to their
pediatric providers reported greater readiness to transfer vs
those who are attached. In addition, hemoglobin A1C levels
seemed correlated in this study and supported by others.
Those with lower A1C levels seemed more reluctant to leave
pediatric providers than those with higher A1C levels.15
Creating a checklist of the important components of
the HCT may be helpful during the process. See Figure 1
for a sample checklist to help organize the process of
HCT. Because the process requires multiple forms to be
completed, institutions should consider using the electronic
forms or note types available in the electronic medical record
systems. An institution-specific checklist can be developed
Nutrition in Clinical Practice 33(1)
and be updated in the electronic medical record, along with
the goals and readiness assessment.
Transitioning PN Support
In surveying gastroenterologists who were members of
BAPEN (British Association of Parenteral and Enteral
Nutrition) about the current practice of HCT of emerging
adults on long-term PN, Kyrana et al16 found that most
frequent concerns were confusion around care routines
and psychological problems at time of transition. They
concluded that a transition pathway and service standards
for adolescents receiving home PN should be developed,
that checklists should be considered for practical aspects
regarding PN administration (eg, pumps), and that key
worker and psychology input should be included to enhance
emotional resilience of the emerging adults and their care-
givers. They concluded that HCT can take up to 2 years and
is greatly facilitated by an identified key healthcare worker.
Psychological issues need to be addressed before transition.
Written information can ensure clarity about all aspects of
care. Communication between pediatric and adult centers
is improved when at least 1 consultant from each center is
present during patient care meetings during the transition
period. In addition, it was suggested that one should aim to
keep the same infusion pump after transition.16
Transitioning the EN Regimen
Patients with conditions that limit oral intake may require
the use of nutrition support and hydration support, either
enterally, parenterally, or both. In some cases, enterally fed
patients may have spent the majority of their lives gaining
nourishment from a pediatric enteral formula. Pediatric
enteral formulas are typically lower in protein than adult
formulas. Pediatric formulas also contain a modified vita-
min and mineral content to meet the needs of patients aged
1–13 years.17 With some transition models recommending
initiating HCT as early as 12 years old, the transition from
a pediatric to an adult enteral formula may be viewed by
some as either a precursor to or an early step in the HCT
process.18-21
Patients and/or their caregivers may view the transi-
tion from pediatric to adult enteral feeding regimens with
some apprehension. Issues with feeding tolerance earlier
in life may make patients or caregivers hesitant to change
formulas. Working as a multidisciplinary team to ease
concerns and transition feeding regimens in a timely manner
can provide patients and caregivers with peace of mind
while continuing to meet patient nutrient requirements and
preventing potential issues with insurance coverage for the
patient’s formula.
Although coverage varies by state and by company, many
insurance plans will cover the use of an enteral feeding
pump in pediatric patients receiving bolus enteral regimens
Green Corkins et al
Figure 1. Sample transition care checklist.
if the bolus is run over an extended time frame. It can
be more difficult for adult patients who do not require
continuous feeds to obtain insurance coverage for enteral
pumps.22,23 Many major enteral formula companies are
typically able to provide assistance navigating coverage
requirements for continued EN support.
Another aspect to consider is the approval by insurance
companies to utilize oral nutrition supplementation to
maintain patient weight and strength. Nutrition supplemen-
tation is not covered under Medicare Part B, and so patients
and providers should work together to apply alternative
strategies to provide sufficient nutrition to the patient within
budgetary constraints.22,23
Case Study
A 23-year-old man presented for a first-time hospitalization
in a facility that provided care for adults after exclusive
care at a pediatric institution. His history included cerebral
palsy with developmental delays. His stature was typical
in build for a person of his age. He did not eat orally
and was receiving EN support via gastrostomy tube. A
85
nutrition support nurse was called to see him regarding his
leaking gastrostomy tube, which had resulted in some skin
breakdown and tenderness at the gastrostomy site. His low
profile tube was quite snug. The nurse assessed his tube size,
then replaced the tube with a longer low profile gastrostomy
for a better fit, which resulted in reduced tenderness, and as
the site healed there was no more leaking.
The nurse discussed the patient’s nutrition regimen with
a dietitian team member. He had been receiving a pediatric
semi-elemental formula via pump during the night and
several small bolus feedings in the day. His mother stated
that this was how they had always done things, and she
indicated a belief that they always would need to follow
this type of regimen. In gaining trust and with ongoing
dialogue, an adult standard polymeric formula was tried and
well-tolerated. Then the patient was transitioned to gravity
bolus feedings during the day that coincided with mealtimes.
Because of his tolerance to this regimen, nocturnal feedings
were discontinued.
The parents appreciated the new regimen because it
allowed them to sleep through the night without having
to respond to the pump alarm if there was a problem or
86
having to add more formula in the middle of the night.
They also were pleased to have a more normal “meal”
schedule. Because of the change to a formula with a profile
more suited to someone of the patient’s age and size, the
supplemental potassium that he received daily could be
discontinued. The change in formula alone resulted in a
$13,000 Medicaid-based savings per year for formula in
addition to reduced delivery supply charges. A guided tran-
sition plan with intentional review of his complex regimen
and discussion with his family about other aspects related
to HCT and changing needs may have been quite helpful in
his care and in the family/provider dynamics in general.
Measuring Transition Outcomes
A common theme in HCT studies is a focus on the program
itself and not on measurable outcomes. Few studies attempt
to validate the effectiveness of an intervention, and even
fewer attempt to compare different transition strategies.
Identifying and following measurable outcomes is the best
way to evaluate the effectiveness of transition interventions.
What to measure, how to measure, and how often to mea-
sure remain undefined for general transition of adolescents
and those with childhood-onset diseases. Data from this
population are difficult to collect because patients move
from one set of providers and medical records to another,
further complicating the identification of the most effective
transition programs. A Cochrane review of 4 randomized
controlled trials evaluating different transition interventions
used for adolescents with various conditions found it hard
to draw conclusions on their effectiveness.24 The outcomes
of a one-on-one, nurse-led intervention, a technology-based
education intervention, a 2-day workshop transition prepa-
ration, and a structured transition program produced only
slight improvements in measures of self-care, general health
behaviors, and transitional readiness. The authors identified
a lack of long-term follow-up needed to validate these
interventions.24 Crowley et al25 also reviewed the evidence
for effectiveness of transition care programs. Six of 10
programs showed statistically significant improvements. All
6 involved the diagnosis of diabetes and measured variations
of hemoglobin A1C , acute and chronic complications, and
rates of follow-up and screening as outcome measures.
The most successful of these programs focused on patient
education and specific HCT clinics. None of the studies
reviewed involved long-term follow-up of morbidity or
mortality.25
In 2016, Coyne reviewed measurable patient outcomes
but concluded significant work remains to define appropri-
ate measurable outcomes.4 Current measures can be divided
into disease-specific outcomes and non-disease-specific out-
comes. The most frequent non-disease-specific measure is
clinic attendance, including the first adult clinic appoint-
ment, frequency of visits (pretransfer and/or posttransfer),
Nutrition in Clinical Practice 33(1)
and missed appointments.4 Patient satisfaction surveys and
the Pediatric Quality of Life Scale are frequently scored.
Disease management and self-efficacy can be assessed
using the Transition Readiness Assessment Questionnaire
(TRAQ) at various times during the transition process.5
TRAQ surveys the emerging adults’ readiness on a scale of
1–5: 1 = not knowing how or when to perform a skill and
5 = consistently performing a skill when needed.26 Also,
pretransfer and posttransfer emergency department visits
and hospitalizations are frequent non-disease-specific mea-
sures. Disease-specific outcomes may include hemoglobin
A1C (diabetes), tacrolimus level and organ rejections (trans-
plantations), hydroxyurea utilization (sickle cell anemia),4
Pediatric Crohn’s Disease Activity Index, Pediatric Ulcer-
ative Colitis Activity Index, number of daily stools, C-
reactive protein, erythrocyte sedimentation rate, serum iron
level, drug metabolites levels (IBD),27 and cystic fibrosis
clinical score.28
Instead of relying on multiple disease-specific transi-
tion strategies, a more generic transition program using a
technology-based intervention has been shown to be effec-
tive and may be a more cost-efficient strategy.28 Fishman
et al29 caution not to set expectations too high for transition-
ing adolescents. A survey of adult patients aged 25–55 years
with IBD found only 57% of them report full independence
with self-management. Also, only 63% of adults could
recall medication doses, 65% recall medication frequency,
and <30% knew of major side effects of the medications.
The authors propose that these findings might be used as
benchmarks for independence and self-management skills
when setting goals and evaluating the effectiveness and
outcomes of adolescent transition interventions.29
Legal Aspects of Transition Care
Pediatric healthcare tends to focus on a family-based ap-
proach toward the patient’s care and treatment. Thanks
to previous statements from the American Academy of
Pediatrics, pediatric patients are accustomed to providing
assent for procedures30,31 ; however, during this life stage,
discussions regarding patient care are usually directed to-
ward surrogate decision makers such as parents. Caregivers
for pediatric patients are responsible for providing informed
permission for treatment plans and ensuring compliance
with the plan of care.31 Once a patient reaches the “age
of majority,” which is considered to be 18 years old in
most states, patients are entitled to full autonomy and
privacy with respect to healthcare decisions. Parents and
legal guardians are no longer entitled to access patient
health information, and the ability to participate in patient
decision making becomes much more limited.32
Transfer of care and responsibility for healthcare de-
cisions can be a major and daunting event for emerging
adults, and parents may fear letting go of some control.33
Green Corkins et al
Parents often underestimate their child’s abilities for self-
management, while the adolescent or emerging adults are
often overconfident and may overestimate abilities and
understanding for self-management.5 The pediatric world
is family centered, focusing as much on the parents as the
children, but the adult sector assumes that the patients have
autonomy and have the capacity to navigate the healthcare
system, shifting from parent to self-managed care.33
With increased survivorship for patients with POCC
comes an increased number of transition patients who lack
the capacity to exercise full autonomy and privacy with
respect to healthcare decisions. Beattie34 highlighted the
need for individualized considerations for those with SHCN
and delayed growth because these may be accompanied by
emotional and intellectual immaturity. Careful attention to
nutrition, emotional, and educational issues are all relevant
in the progression from childhood through adolescence to
adulthood. Parents and caregivers need to be aware that to
maintain the surrogate decision-making authority granted
as a parent/guardian, they must set the legal framework to
become surrogate decision makers in the adult healthcare
system. This position is most commonly referred to as either
a durable power of attorney or a healthcare proxy.31,35
In a collaborative team between the provider and care-
giver this transition would be investigated well before the
patient “ages out” of pediatrics and families find them-
selves unable to make important medical decisions for their
loved ones.
Providers should, as part of transitional care, discuss
legal aspects of medical decision making with patients,
including topics such as assent, consent, surrogate decision
makers (such as guardians, healthcare proxies, or those with
durable power of attorney), and advance directives.31,35 In
addition, providers need to be aware that adolescents are
still maturing emotionally and do not fully understand the
long-term consequences of poor follow-up and poor control
of their chronic condition.1
Provider Issues With Transition
Sharma et al’s36 review of future directions of transition
care highlights the need to integrate transition curriculum
into healthcare provider education. Specifically, internists
report a lack of training as a limiting factor to the care of
adults with POCC. Maintenance of certification activities
covering HCT has been offered by some medical societies
such as the American Board of Pediatrics.36
Insurance and access to care are other recognized bar-
riers to successful transition.27 A survey of LeBonheur
Children’s Hospital’s IBD clinic patients found that 3 of 26
recently transitioned patients aged 18–24 years had failed to
establish care with an adult provider and each had public
insurance (unpublished). This finding is due to limited
available adult subspecialists based on accepted insurance
87
plans at the time of transfer. Two additional emerging adult
patients with Crohn’s disease had to change medications,
from infliximab infusions to adalimumab injections, because
of differences in insurance preferences and lack of available
infusion services following transition. Another patient with
IBD who moved out of state for college was unable to find
an adult provider who accepted the insurance of the patient,
and the pediatric gastroenterologist continued to prescribe
infliximab infusions to be performed at the student health
center with the emerging adult returning to the pediatric
clinic for infliximab when home.
The Patient Protection and Affordable Care Act (ACA)
of 2010 included measures that protect patients during the
transition period.37 Benefits include prohibition of denying
coverage to children younger than 19 based on preexisting
conditions, guaranteed insurance renewals, removing an-
nual and lifetime benefit caps, and extending coverage of
young adults on their parents’ policy to age 26.37 These
protections can be limited to the states that voluntarily
“expanded Medicaid” after 2012.36
New International Classification of Diseases, 10th Revi-
sion (ICD-10) codes for transition services could improve
transition services by providing financial compensation to
providers for their role in planning and coordinating the
transition. The free website Got Transition (http://www.
gottransition.org) provides useful resources and tools for
the provider including a “2017 Coding and Reimburse-
ment Tip Sheet.”11 For example, CPT codes exist (96160,
96161) for the administration, scoring, and documenta-
tion of transition readiness instruments. Thirty minutes of
nonphysician education and training of a patient for self-
management can be coded (98960). Complex chronic care
management taking 60 minutes of physician or clinical staff
time has a code (99487). Finally, facilitating transitional care
with telephone or electronic communications within 2 days
of a patient’s hospital discharge followed by face-to-face
visit also has a code (99495). Ongoing training on the use of
appropriate coding should help facilitate the development
of HCT programs.11
Summary
With improved medical treatments, surgical procedures, and
nutrition support, more patients with POCC are surviving
and thriving well into adulthood. As a result, at some
point they must transfer medical and nutrition care from
pediatric providers to adult providers. Before this transfer of
care occurs, the pediatric providers need to begin the HCT
process.35
Various transition models are described in the literature.
Each one has the same goal of successful HCT providing
adequate support and guidance to the emerging adult with
SHCN. Without consistent markers for success, it is difficult
to determine a successful HCT. In addition, insurance
88
provider issues may prevent a capable emerging adult from
making the transfer of care.
This review revealed that the HCT process should start
early and whatever the criteria, ultimately the pediatric and
adult providers need to work together and build a trusting
relationship with the emerging adult. Teamwork in transi-
tioning can make a critical difference in outcomes. Issues
and focus vary between disciplines, and each professional
can offer specific skills in addressing issues specific to HCT.
In addition to the emotional and self-care issues that
are important for a successful HCT, there are legal factors.
Once a patient reaches “age of majority,” he has full
right to autonomy. Parents need to be prepared and the
patients need to be ready to take this responsibility. It is
important that the pediatric providers begin modeling the
relationship of the adult providers and interact with the
emerging adult independent of his parents.35 If a patient is
not developmentally appropriate to take self-responsibility
for his or her healthcare, the parent must go through the
legal system to maintain decision-making rights.
Statement of Authorship
K. Green Corkins, M.A. Miller, and C. McGinnis contributed
to the outline. K. Green Corkins, M.A. Miller, J.R. Whitworth,
and C. McGinnis contributed to the acquisition, analysis and
interpretation of the articles reviewed, drafted the manuscript,
critically revised the manuscript, and gave final approval. All
authors agree to be accountable for all aspects of the work
ensuring integrity and accuracy.
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AqAAAAAA. Published July 11, 1984. Updated August 27, 2017.
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27. Paine CW, Stollon NB, Lucas MS, et al. Barriers and facilitators
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chronic disease for transition to adult care: a technology program.
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29. Fishman LN, Mitchell PD, Lakin PR, Masciarelli L, Flier SN.
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34. Beattie RM. Symposium 6: young people, artificial nutrition and tran-
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with Crohn’s disease. Proc Nutr Soc. 2010;69:174-177.
35. Davidson LF, Doyle M, Silver EJ. Discussing future goals and legal
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36. Sharma N, O’Hare K, Antonelli RC, Sawicki GS. Transition care:
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Review

Nutrition in Clinical Practice

Volume 33 Number 1
Knowledge of Constituent Ingredients in Enteral February 2018 90–98

C 2017 American Society for

Nutrition Formulas Can Make a Difference in Parenteral and Enteral Nutrition

DOI: 10.1177/0884533617724759
Patient Response to Enteral Feeding wileyonlinelibrary.com

Patricia Savino, MBA, RD

Abstract
Enteral feeding is considered the preferred method for providing a complete or supplemental source of nutrition to patients. Enteral
formulas (EFs) are traditionally assessed from general information provided by the manufacturer such as caloric density, percentage
of macronutrients, and micronutrients to meet the Recommended Dietary Allowance. Sometimes labeling information highlights
particular ingredients to indicate specific properties at a metabolic or nutrition level. However, it is necessary to review the quality
and composition of any enteral formula, since the basic components are responsible for tolerance and nutrition efficacy, and this
should not be overshadowed by the benefit of a single constituent. Intolerance to EF is commonly attributed to individual patient
response or to the means of administration. The objective of this review is to highlight the importance of appraising EFs with
regard to composition and effect on the gastrointestinal tract. (Nutr Clin Pract. 2018;33:90–98)

Keywords
enteral formula; enteral nutrition; nutritional support; formulated food; intolerance

Enteral feeding is the preferred method for providing com-
plete or supplemental nutrition to patients.1 Europe, the
United States, and Latin America each have their own
regulations for enteral nutrition (EN) formulas, which are
classified as “foods for medical purposes.”2-4 Ingredients
used in enteral formulas (EFs) must be carefully appraised
prior to administration as patient response to them may
influence healing and recovery.
EFs are traditionally assessed by general information
such as caloric density and percentage of macronutrients.
However, the value of a particular macronutrient (eg, a
specific carbohydrate) cannot be evaluated solely on the
basis of its caloric contribution, because its composition
may radically differ from other types of carbohydrates.
Moreover, EFs may contain specific added ingredients indi-
cated for particular clinical scenarios, such as the inclusion
of ω-3, glutamine, arginine, or fiber, which are added for
critical care, perioperative care, cancer, or long-term enteral
feeding. EFs may also be classified according to the level of
protein hydrolysis, the indication for a specific disease, and
whether they are designed to be the sole source of nutrition,
a supplement, or a module.5
EFs may also be classified by protein content. The pro-
tein source and level of hydrolysis affect ease of absorption,
gastrointestinal (GI) tolerance, contribution to osmolarity
of the EF, and level of protein utilization.5-10
Fat composition should be considered on the basis of
calorie and fatty acid content and proportion of ω-6 and
ω-3.11-15 This is especially relevant when used by the elderly
or patients with chronic diseases, such as cardiovascular
disease,13 in which prolonged EN is indicated.
Although generally considered innocuous, carbohy-
drates can be a major cause of intolerance that often devel-
ops unnoticed. The presence of fermentable fiber, monosac-
charides, oligosaccharides, disaccharides, and polyalcohols
(known as FODMAPs) can cause intolerance or diarrhea
in susceptible patients.16-20 The addition of fructose as
an energy source can impair GI tolerance, increase blood
glucose response levels, and accumulate in the liver as fatty
acids, and it has recently been shown to be associated with
increased cardiovascular risk.21,22 High-fructose corn syrup
and/or corn syrup are added to several EFs to increase their
From the National Academy of Medicine, Bogotá, Cundinamarca,
Colombia.
Financial disclosure: None declared.
Conflicts of interest: Patricia Savino reports personal fees from
Boydorr Nutrition outside the submitted work.
This article originally appeared online on December 14, 2017.
Corresponding Author:
Patricia Savino, MBA, RD, National Academy of Medicine, Carrera
7a. No. 69-5, Bogotá, Cundinamarca, Colombia.
Email: patricia.savino@gmail.com
This is an open access article under the terms of the Creative
Commons Attribution-NonCommercial License, which permits use,
distribution and reproduction in any medium, provided the original
work is properly cited and is not used for commercial purposes.
Savino
caloric value, improve their flavor, and/or maintain product
stability. However, they have been linked to GI disturbances,
such as bloating and diarrhea.16-20,22 In addition, polyols
such as mannitol and isomalt are also common components
in EN formulas and frequently used as sugar substitutes.17
Fiber is an important component of a normal diet. It can
be classified as fermentable (soluble) or nonfermentable
(insoluble) fiber. Soluble fiber includes nonstarch polysac-
charides, inulin, guar gum, oat, and fructo-oligosaccharides
(FOS). Resistant starch and lignin are considered insoluble
fiber. Elia et al,23 in their systematic review and meta-
analysis, concluded that the inclusion of fiber in EN for-
mulas generates positive physiological effects and clinical
benefits. It also has been hypothesized that fermentable car-
bohydrates may be linked to the development of diarrhea,
since they are part of the FODMAPs.16,18,19 Despite their
benefits, such as being the substrate for microflora in the
large intestine and increasing the GI gut health, intolerance
to FOS may generate bloating, distension, and diarrhea.
Therefore, the inclusion of alternative fiber types in the
EF may improve clinical and nutrition outcomes23,24 ; for
instance, partially hydrolyzed guar gum showed positive
results in several studies,25,26 although its use in critical ill
patients remains controversial.27
Last but not least, micronutrients should be selected
in varying proportions depending on the type of illness
and related deficiencies. Common to all nutrition support
practice, ingredients need to be tailored in accordance with
patient requirements. Particular attention must be paid to
satisfy the complex nutrition needs of the critically ill.
Regulatory Position of EFs
EFs are regulated solely in compliance with Good Manu-
facturing Practice guidelines used for conventional foods.2
Surprisingly, the labeling requirements are less stringent
than those that apply to conventional foods with regard to
nutrition facts.2 In Europe, EN includes all “dietary foods
for special medical purposes” (DFSMP).28 This definition is
taken from the European legal regulation of the commission
directive 1999/21/EC of March 25, 1999.3 In the United
States, the Food and Drug Administration classifies EFs
under the name of “medical foods.”2 The legal definition
comes from the Orphan Drug Act of 1988.29 In Latin
America, regulations are country specific, and EFs are
commonly listed as “foods for medical purposes.”4 Given
that EFs are prescribed to patients with differing levels of
clinical nutrition risk, an accurate and detailed composition
of DFSMP, together with health-related claims, should be
provided by the manufacturer.
Macronutrients in EFs
Macronutrients in EFs vary in chemical forms, molecular
sizes, solubility, and quality. These characteristics can affect
91
the osmolarity, absorption, utilization rate, and tolerance
of the nutrients, which may directly affect patient recovery.
Having eliminated common reasons for EF intolerance such
as microbial contamination, concomitant medications, and
EF temperature, Barrett et al19 considered that formula
composition may be an important causal factor.
Protein, a Crucial Macronutrient
An important overall consideration when selecting an EF is
to establish protein content. Some products continue to be
marketed as high in protein but may not contain amounts
currently considered optimal for patient requirements. An-
other important issue is the quality of the protein in the
formula, which is determined by the relative amounts of
essential and nonessential amino acids demonstrated by
the seminal work of Rose30 60 years ago. The amount of
branched-chain amino acids (BCAAs) also contributes to
amino acid balance and protein quality.6,10,31 In addition,
the origin of protein should be considered since vegetable
protein is not used as efficiently as protein of milk or
egg origin.8,32-34 The efficiency of clinical recovery may
depend on the type of protein administered.35 High-quality
protein derived from animal sources has a protein efficiency
ratio (PER), biological value (BV), net protein utilization
(NPU), and protein digestibility-corrected amino acid score
(PDCAAS) higher than vegetable protein.7,34 These are
methods to assess protein quality.36 Therefore, the origin of
the protein should be determined since it has the potential
to affect not only tolerance but also absorption rate and
protein utilization37-39 (Table 1).
A protein can be administered in various forms. An
EF may provide whole protein, concentrate, isolate or
hydrolysate, and free amino acids, even when originating
from the same protein source. The selection of protein form
as an ingredient in EF depends on various factors, including
cost, improvement of the BV, and manufacturing processes.
Soy protein is less expensive than whey protein, but soy as
an ingredient also affects protein quality and utilization.33,48
Consequently, to improve its quality, it has to be mixed with
animal protein such as casein or whey. Another example is
collagen, which is an inexpensive animal protein but has low
BV, an incomplete amino acid profile (lacks of tryptophan),
and meager amounts of essential amino acids.49 Therefore,
to compensate for these deficiencies, it is mixed with a high-
protein value source such as casein, whey, or even soy.
Protein from the same source can therefore be present in EF
in different forms that modify the amino acid profile and
the presence of other nutrition components. This will lead
to different rates of digestion, absorption, and utilization.
The relative content of some ingredients varies from
one EF to another. For example, whey concentrate has a
higher content of cholesterol and lactose, whereas isolates
are almost exempt from both50 (Table 2). It is also important
92 Nutrition in Clinical Practice 33(1)

Table 1. Comparison of Protein Quality According to Its Origin.

Protein Biological Net Protein True % Leucine

Protein Efficiency Ratio Value Utilization, % PDCAAS Digestibility, % DIAAS, % (g/100 g of Food)

Whey isolate 3.240 ࣙ10049 9249 1.1–1.741 NA 999 11.7–12.042

Whey concentrate 1.1–1.541 9949 95–979 ࣘ6.442
Egg 3.840,43 10040 9440,43 1.040 9849 919 1.0740
Whole milk 3.140,43 9140 8240,43 1.2341 9544 969 0.3240
Collagen NA NA NA 0.0845 NA NA NA
Beef 2.940,43 8040 7340,43 1.042 9844 NA NA
Casein 2.79 7749 72.149 1.049 9944 959 8.6844
Soy isolate 2.349 72.849 61.449 1.042 9844 92–989 6.7846
Soy concentrate 0.9440 9544 NA ࣘ4.946
Beans NA 5347 NA 0.6840 8144 74–789 NA
Soy 2.341,43 7341,43 6141,43 NA 9044 689 0.9346

DIAAS, digestible indispensable amino acid score; NA, not available; PDCAAS, protein digestibility-corrected amino acid score.

Table 2. Composition of Whey Protein in Different Formsa .

Type Protein,b % Lactose,b % Fat,b % Cholesterol,c mg

Whey protein concentrate 25–89 4–52 1–9 150

Whey protein isolate 90–95 0.5–1 0.5–1 0
Whey protein hydrolyzed 80–90 0.5–10 0.5–8 0
a Product composition may vary slightly by manufacturer.
b Modified from Whey Protein Institute (http://www.wheyoflife.org/facts/wheyproteintypes).
c Davisco (Eden Prairie, MN).

to specify if the protein and its subproducts are derived
from whole milk, casein (80%), or whey (20%)50 (Figure 1).
Similarly, the total protein content is higher in soy isolate
(>90%) than in soy concentrate (66%–70%).51 Whey pro-
teins contain all the essential and nonessential amino acids
and are rich in BCAAs (valine, leucine, and isoleucine),
particularly leucine, a key amino acid for protein synthesis.
It is also high in sulfur-containing amino acids (cysteine
and methionine) that contribute antioxidant properties and
enhance immune function.52 These protein characteristics
may potentially influence patient recovery and therefore
length of hospital stay.
Osmolarity must also be taken into account19 since it
is significantly increased by the level of protein hydrolysis
in the formula; the smaller the molecule, the greater the
osmolarity. The extent of hydrolysis can modify osmo-
larity, flavor, absorption, and tolerance depending on the
molecular weight distribution, the peptide profile, and the
amino nitrogen (AN) to total nitrogen (TN) ratio.53 In
Table 3, hydrolysate type 1 is more hydrolyzed since 82.3%
of the protein has a molecular weight <1,000 Daltons while
hydrolyzed protein type 2 has 40.5%.
Prior to administration, the proportion, the source (an-
imal or vegetable), and the level of hydrolysis of the EF
must be appraised together with the individual amino acids
content. These features may change both formula tolerance
and cost of the raw ingredients. It is incumbent upon
clinicians managing patients to be aware of the protein
composition and proportions of an enteral clinical formula.
Although it is difficult to know this without chemical
analysis, osmolarity can provide a clue to the level of
protein hydrolysis present.19 For example, formulas with low
osmolarity cannot contain extensively hydrolyzed protein
or substantial quantities of free amino acids unless the
total protein content is low, is mixed, or has a low level
of hydrolysis. Manufacturers are required to provide this
information as part of the nutrient profile of the EF.
In the past, it was thought that the absorption of
amino acids was faster than dipeptides, tripeptides, or whole
protein and that this would be beneficial, and as such,
amino acids were included in the EF.54 Optimal utilization
of amino acids occurs when digestion and absorption lead
to a low but protracted appearance in the portal vein.
This allows the liver and other organs to make optimal
use of these amino acids for protein synthesis and other
metabolic functions such as the synthesis of purines and
pyrimidines. Consequently, the indication for hydrolyzed
protein or amino acids is limited to severe pancreatic in-
sufficiency and small bowel malfunction.55,56 Even in these
situations, the benefit of predigested protein is uncertain.
Moreover, some EFs that contain hydrolyzed protein or
amino acids are more expensive, without providing the
desired clinical benefit. In a pilot study that compared
standard vs a high-protein peptide-based formula in critical
Savino 93

protein accretion better than casein in the elderly,39 and

in young men, HWP stimulated skeletal muscle protein
synthesis better than casein and soy protein.58 In a ran-
domized controlled trial comparing the use of whey protein
and glutamine, a comparable effect on improved intestinal
permeability and integrity of the gut mucosal cells was
observed in patients with Crohn’s disease.59 HWP was also
compared with casein in a double-blind randomized trial in
elderly patients with acute ischemic stroke.60 Patients in the
HWP group had higher levels of serum albumin (P < .01)
and glutathione (P = .03) and lower levels of interleukin-
6 (IL-6) (P = .03), suggesting decreased inflammation and
increased antioxidant defenses in this group of patients. In
a comprehensive review by Alexander et al,56 the use of
HWP in various diseases was shown to improve health and
nutrition outcomes.

Fat: More Than Just Calories

Years ago, fat was considered to have 2 main purposes:
caloric provision and providing essential fatty acids (EFAs).
Figure 1. Scheme for the production of whey and by- Burr and Burr11 described EFA deficiency in 1929, when rats
products. Whole milk is processed into curd or whey. Whey were fed without fat in their diets and developed dermatitis,
protein concentrate or whey protein isolate contains intact hair loss, wasting, and even death. Linoleic acid, when
proteins, but nutrient profiles vary after each filtering step. supplied as a minimum of 1% of the total calories, prevents
Hydrolysis facilitates protein absorption and increases EFA deficiency, but an optimal dosage is recommended to a
osmolarity and cost. Whey protein blends have the properties range of 3%–4% of total calorie intake. In a 1500-kcal diet,
of its major components.
the minimum amount of linoleic acid required is between
1.7 and 6.7 g/d.61 The view that EFAs are necessary led to
the notion that total fat intake should be from vegetable oils,
Table 3. Molecular Weight Distribution of 2 Hydrolyzed
Whey Proteins. such as safflower, sunflower, soy, and corn, based on the ra-
tionale that the provision of these fat sources would benefit
Hydrolyzed Protein Hydrolyzed Protein the patient. However, because these fatty acids are primary
Daltons Type 1, %a Type 2, %a sources of ω-6 fatty acids, their administration in excess is
harmful due to proinflammatory and immunosuppressive
>20,000 1.28 17.0
5000–20,000 2.41 15.6 effects.12,62 Current knowledge suggests that the composi-
1000–5000 14.00 26.7 tion of fat included in an EF should limit but not totally
<1000 82.30 40.5 exclude ω-6 fatty acids, provide monounsaturated fatty
AN/TN 26.00 12.5 acids, reduce saturated fats, avoid trans fats, and provide ω-3
fatty acids (docosahexaenoic and eicosapentaenoic).13,14,62
AN/TN, amino nitrogen/total nitrogen. The premise that “if something is good, more is better”
a Modified: Hilmar whey protein hydrolysate.53
is therefore not supported by current research. Moreover,
“less is better” when assessing the nutrition requirements
care patients, the results suggested that the latter EF could of certain critically ill patients,63 a concept that can also
be associated with a statistically significant reduction of be applied to avoid excess use of ω-6 fatty acids that, in
adverse events.57 Unfortunately, the EF had important the absence of ω-3 fatty acids, may lead to an unbalanced
differences from the composition of other macronutrients proinflammatory effect.62
that could affect patient tolerance and outcome, such as the The inclusion of structured fats, which were developed
amount of carbohydrates and the type of fats, hindering the in the mid-1980s and contain mixtures of long-chain fatty
interpretation attributed to the effect of hydrolyzed whey acids (LCFAs) from the ω-3 family and medium-chain
protein (HWP).57 triglycerides (MCTs) with 8–10 carbons in length, have
In addition to the degree of hydrolysis, the source of shown better fatty acids absorption, reduction of infection
protein may also have an impact on digestion kinetics. rates, and improvement of hepatic, renal, and immune
Whey protein was shown to stimulate postprandial muscle function.64,65 Structured fats are absorbed and clarified
94
more efficiently, but cost-benefit and contribution to os-
molarity by the MCTs to the EF require further clinical
studies.66,67 Safe doses of ω-3 are between 3 and 5 mg/d,68
and excess intake may suppress immune function and in-
crease bleeding time.69 It may also produce an unpleasant
taste, nausea, heartburn, gastric intolerance, headache, di-
arrhea, and odoriferous sweat.70
Carbohydrates, Good and Bad
Glucose is a rapid energy source and the only circulating
carbohydrate in the body. In a regular diet, carbohydrates
should provide 40%–50% of daily calorie intake. It is
commonly thought that, with the exception of lactose,
carbohydrates are easily tolerated and have no GI side
effects. In general, this is true, but lactose intolerance can
be present in a substantial part of the population, especially
those of Asian, South American, and African descent.71
Poor absorption of lactose, a well-known FODMAP, can
lead to bloating and diarrhea and is generally omitted from
EF. Gibson and Shepherd72 in 2005 provided evidence that
restriction of FODMAPs prevented intolerance symptoms
in patients with functional GI disorders. The presence of
carbohydrates, corn syrup, solid corn syrup, FOS (fructans),
galacto-oligosaccharides (raffinose), fructose, inulin (higher
content with a higher degree of polymerization), and polyols
(maltitol) present in some artificial sweeteners16,18 may
inadvertently augment the content of FODMAPs in an EF.
Sucrose (also called saccharose) is a disaccharide con-
taining 1 molecule of glucose and 1 molecule of fructose.
Some EFs contain up to 25% of the total amount of
carbohydrates as sucrose. As a FODMAP, sucrose can be
poorly absorbed with similar symptoms to those produced
by lactose intolerance. Corn syrup (glucose syrup), corn
syrup solids, and high-fructose corn syrup are other ex-
amples of FODMAPs. Corn syrup and corn syrup solids
are frequently used as the major carbohydrate source in
EFs, since they generate a very sweet flavor, do not change
the viscosity, and are resistant to high temperatures.19,73,74
Corn syrup and corn syrup solids can have different
proportions of fructose and glucose depending on the
manufacturer, and therefore precise detail of composition
should be obtained before use. The high content of ei-
ther of these components can produce negative GI and
metabolic effects.16-20 Monosaccharides, disaccharides, and
trisaccharides have high dextrose equivalents (DEs) and
therefore high fermentability.75 In some patients, GI effects
such as distension, bloating, and diarrhea are linked to
FODMAPs due to their small molecular size and their high
osmolarity.19,20
Short-chain polysaccharides that are poorly absorbed
in the human intestinal tract such as FOS, galacto-
oligosaccharides (GOS), and inulin17 are very common in-
gredients added to EFs to provide fiber, without increasing
Nutrition in Clinical Practice 33(1)
thickness and viscosity.17,18 These fiber sources are also
FODMAPs that can trigger GI symptoms.
Polyols such as maltitol and isomalt are added to some
EFs and, when given simultaneously with fructose, can
worsen the tolerance for an EF.16-18 In some cases, fructose
is supplied as an individual ingredient, but in others, it is
part of the corn syrup or corn syrup solids composition.19
Fructose used to be considered a substitute for glucose, since
the first step in its degradation is not insulin dependent.
However, this premise was proven false when subsequent
steps in its metabolism were shown to require insulin.21,76
Although fructose intolerance with GI symptoms is only
seen in those patients with fructose malabsorption, Barrett
et al77 reported that a third of 82 healthy volunteers could
not absorb a fructose load (assessed by breath hydrogen test-
ing), even in the absence of prior GI symptoms, indicating
that intolerance to an EF can be due to the presence of
fructose in addition to other FODMAPs.
FODMAPs have been shown to produce diarrhea, pain,
nausea, and bloating in patients with irritable bowel syn-
drome (IBS) or with inflammatory bowel disease.17 The re-
moval of FODMAPs in the diet of these patients led to im-
provement of GI symptoms.72,78-82 EFs have FODMAPs as
common ingredients, which are rarely considered a cause of
GI intolerance.83 Research done at the Monash University84
revealed that when comparing a regular Australian diet
with EFs, the latter could be 3–7 times more concentrated
in FODMAPs.85 A retrospective study in 160 patients by
the same institution further showed that the incidence
of diarrhea significantly correlated with the amount of
FODMAPs in the EF.16 Yoon et al20 studied the effect of
3 EFs with different levels of FODMAPs in a randomized,
multicenter, double-blind, clinical trial. Low-FODMAP EF
was significantly associated with improvement of diarrhea
(reduction in King’s Stool scores) relative to moderate-
FODMAP and high-FODMAP EF (P < .05). The low,
moderate, and high formulas contained 0.320 g, 0.753 g,
and 1.222 g total FODMAPs per 200-mL can, respectively.
Patients were classified depending on their final condition
after the intervention: unimproved, normal maintenance,
diarrhea improved, constipation improved, and recurrent
diarrhea/constipation improved. In those patients with im-
proved GI symptoms, particularly in whom diarrhea was
reduced, a significant improvement was observed for the
short-term nutrition markers prealbumin and transferrin.
This may indicate that a low-FODMAP formula could
improve nutrition status and facilitate prompt recovery, al-
though prealbumin and transferrin may also be considered
markers of inflammation.86-88 Halmos18 also considered
that a lower content of FODMAPs in the EF could reduce
the incidence of diarrhea.
Negative metabolic effects are related to the conse-
quences of high carbohydrate consumption and the gen-
eration of nonalcoholic fatty liver. The World Health
Savino
Figure 2. Dextrose equivalents present in nutritive
sweeteners.93 The different carbohydrates used as sweeteners
in enteral formulas can be classified by the amount of dextrose
equivalents. Enteral formulas with ingredients with high
dextrose equivalents are more likely to generate
gastrointestinal intolerance or diarrhea.
Organization (WHO) and the American Heart Association
(AHA) have recommended that the total consumption of
free sugars should not be greater than 10% or even below
5% of the energetic intake of a healthy diet.89,90 This means
that no more than 100 kcal (25 g) for women and 150
kcal (37.5 g) for men per day should come from added
sugars. Although not specifically recommend by the WHO
or AHA, these guidelines should also be followed in patients
with chronic illness who are being fed at home or on long-
term hospitalization to avoid the effects of an unbalanced
diet high in simple carbohydrates. Kearns et al,91 in their
clinical review, have linked the effect of added sugar on
multiple coronary heart disease (CHD) biomarkers and
disease development. In their study, they suggest “that the
sugar industry sponsored its first CHD research project
in 1965 to downplay early warning signals that sucrose
consumption was a risk factor in CHD” and “because CHD
is the leading cause of death globally the health community
should ensure that CHD risk is evaluated in future risk
assessments of added sugars.” Carbohydrates constitute the
largest energy source in EF, representing between 40% and
60% of the daily total calorie value. Therefore, the type of
carbohydrate selected may affect the metabolic profile of the
patient.
Maltodextrin, a polysaccharide commonly used in EFs,
is classified by DEs ranging from 3 to 20.55 Maltodextrins
with low DEs have longer chains of glucose molecules
and are less sweet and more soluble than those with a
high DE (Figure 2). Their osmolarity is 5 times lower
95
than that of glucose. Intolerance to maltodextrins is rare
and is dependent on maltase or isomaltase activity at the
intestinal brush border as well as by small bowel function.55
Up to now, negative effects of maltodextrin have not been
reported. However, high-grade DEs increase osmolarity
and the risk of diarrhea given that delivery of water and
fermentable substrates to the colon have been shown to be
increased by poorly absorbed short-chain carbohydrates.17
The clinician should seek information on DEs from the EF
manufacturer.
It is my personal view that EFs with high amounts
of corn syrup, corn syrup solids, sucrose, and sometimes
fructose should be reformulated with other carbohydrate
sources (eg, maltodextrins) or alternatively by increasing the
amounts of other macronutrients such as protein. The refor-
mulated EF may be better suited to vulnerable populations
with a propensity for metabolic diseases such as the elderly,
patients with noncommunicable diseases, or when used for
long periods.
Vitamins and Minerals: Just the
Recommended Daily Intake?
Commonly, information pertaining to the content of vi-
tamin and minerals in EFs confirms that they meet the
Recommended Daily Intake (RDI). To provide the RDI,
the patient has to be fed a minimum amount of EFs
that in general contain between 1200 and 1500 kcal. Few
formulas contain the RDI in 1000 kcal. Unfortunately, those
that provide the RDI in 1 L are calorically dense (>1.2
kcal/mL) due to an increment in carbohydrates, mainly
from corn syrup, corn syrup solids, and sugar. Therefore,
formula tolerance may be impaired and sometimes the
total desired volume, and thus the RDI, difficult to attain
even after several days of EN administration; moreover,
micronutrients are not provided in adequate quantities.
Patients should receive amounts depending on the most
common deficiencies generated by their particular condition
and supplemented in some cases. According to Berger,92
patients with major trauma and burns can benefit from mi-
cronutrients supplemented by parenteral infusion. Enteral
feeding formulas may not contain sufficient micronutrients
to compensate patient losses or are poorly absorbed during
the early phase of injury.93,94
EF as a Cause of Diarrhea
Thibault et al95 reported a 14% incidence of diarrhea in
a mixed population of patients during the first 2 weeks
after admittance to a tertiary referral intensive care unit
(ICU). They concluded that diarrhea could occur when
>60% of the energy target was given by EN in addition to
administering antibiotics or antifungal medications. Since
they only used fiber-enriched EFs, they questioned whether
96
the number of calories administered could be increased by
using fiber-free EFs. They considered further studies were
warranted to better understand the causes of diarrhea.
The inclusion of fiber as FOS may be an important cause
of formula intolerance. Inclusion of fiber was originally
suggested by Homman et al25 to improve GI function in in-
tensive care patients. Nevertheless, the inclusion of insoluble
fiber in critically ill patients is currently questioned,27 and
new fiber blends for use in EFs to prevent and treat diarrhea
are under investigation.24
Assessment of the different types of diarrhea in the
hospitalized patient is mandatory; de Brito-Ashurst et al96
classified them as dysmotility, inflammatory or exudative,
malabsorptive, osmotic, and secretory. The composition of
the EF is rarely taken into account as a causal factor of diar-
rhea, since detailed labeling information of the formulation
of EF products is scarce or unknown in many cases. Ingre-
dients in EF, such as substantial amounts of FODMAPs,
can cause malabsorptive/osmotic diarrhea. This situation
may be aggravated by an increase in the amount of formula
and thus FODMAPs. For example, 1 cup of milk may be
tolerated in the presence of mild lactose intolerance, but
on drinking 2 or 3 cups of milk per day, GI symptoms of
intolerance may become evident.
As diarrhea can be multifactorial in origin, its etiology
should be established, including investigation of the EF
composition. Thereafter, a treatment protocol can be ini-
tiated to improve EF tolerance; prevent dehydration, elec-
trolyte disturbances, and malnutrition; and reduce length of
hospital stay and cost.97
Conclusions
The selection of an EF should be a conscientious process
based on a number of factors, including the patient’s clinical
and medical status. The ingredients need to be carefully
evaluated in their quality and quantity as they may affect
recovery. The content and type of carbohydrates should
follow the daily amounts recommended by the WHO.
FODMAPs in particular should be assessed since these
may be the cause of GI intolerance. Animal protein should
be preferred over vegetable sources since utilization and
absorption are higher. A balance in the levels of ω-6 and ω-3
fatty acids in the EF may favorably affect the inflammatory
response. Additional administration of vitamins and min-
erals may be required when the volume of the EF supplied
does not provide the required daily intake. The selection of
an EF should not be determined solely on the basis of the
instructions for use provided by the manufacturer; it must
result from a judicious appraisal by the clinical team.
Acknowledgments
The author wishes to thank Santiago Uribe-Lewis and Jennifer
Uribe for editorial assistance.
Nutrition in Clinical Practice 33(1)
Statement of Authorship
P. Savino contributed to the conception and design, drafted the
manuscript, gave final approval, and agrees to be accountable
for all aspect of work ensuring integrity and accuracy.
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78. Gearry RB, Irving PM, Barrett JS, et al. Reduction of dietary poorly
absorbed short-chain carbohydrates (FODMAPs) improves abdominal
symptoms in patients with inflammatory bowel disease—a pilot study.
J Crohns Colitis. 2009;3(1):8-14.
79. Gibson PR, Muir JG. Non-nutritional effects of food: an underutilized
and understudied therapeutic tool in chronic gastrointestinal diseases.
J Gastroenterol Hepatol. 2013;28(suppl 4):37-40.
80. Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG. A diet
low in FODMAPs reduces symptoms of irritable bowel syndrome.
Gastroenterology. 2014;146(1):67-75.e65.
81. Hou JK, Lee D, Lewis J. Diet and inflammatory bowel disease: re-
view of patient-targeted recommendations. Clin Gastroenterol Hepatol.
2014;12(10):1592-1600.
82. Rao SS, Yu S, Fedewa A. Systematic review: dietary fibre and
FODMAP-restricted diet in the management of constipation and
irritable bowel syndrome. Aliment Pharmacol Ther. 2015;41(12):1256-
1270.
83. Thomas JR, Nanda R, Shu LH. A FODMAP diet update: craze
or credible? Nutrition issues in gastroenterology, series #112. Pract
Gastroenterol. 2012;36(12):37-46.
84. Shepherd S, Gibson P. The Monash University Low FODMAP Diet. 4th
ed. Melbourne, Australia: Monash University; 2012.
85. Halmos EP, Liels KL, Rosella O, et al. Enteral and oral nutritional sup-
plement formulas deliver laxative doses of FODMAPs which cannot be
predicted by ingredients lists. J Gastroenterol Hepatol. 2011;26(suppl
4):73.
86. Ingenbleek Y, Bernstein LH. Plasma transthyretin as a biomarker of
lean body mass and catabolic states. Adv Nutr. 2015;6(5):572-580.
87. Raguso CA, Dupertuis YM, Pichard C. The role of visceral proteins
in the nutritional assessment of intensive care unit patients. Curr Opin
Clin Nutr Metab Care. 2003;6(2):211-216.
88. Shenkin A. Serum prealbumin: is it a marker of nutritional status or of
risk of malnutrition? Clin Chem. 2006;52(12):2177-2179.
89. World Health Organization. Sugars intake for adults and chil-
dren guideline. http://www.who.int/nutrition/publications/guidelines/
sugars_intake/en/. 2015. Accessed May 11, 2017.
90. Johnson RK, Appel LJ, Brands M, et al. Dietary sugars intake and
cardiovascular health: a scientific statement from the American Heart
Association. Circulation. 2009;120(11):1011-1020.
91. Kearns CE, Schmidt LA, Glantz SA. Sugar industry and coronary
heart disease research: a historical analysis of internal industry doc-
uments. JAMA Intern Med. 2016;176(11):1680-1685.
92. Berger MM. Antioxidant micronutrients in major trauma and burns:
evidence and practice. Nutr Clin Pract. 2006;21(5):438-449.
93. Ben-Hamouda N, Charriere M, Voirol P, Berger MM. Massive copper
and selenium losses cause life-threatening deficiencies during prolonged
continuous renal replacement. Nutrition. 2017;34:71-75.
94. Heidegger CP, Berger MM, Graf S, et al. Optimisation of energy pro-
vision with supplemental parenteral nutrition in critically ill patients: a
randomised controlled clinical trial. Lancet. 2013;381(9864):385-393.
95. Thibault R, Graf S, Clerc A, et al. Diarrhoea in the ICU: respective
contribution of feeding and antibiotics. Crit Care. 2013;17(4):R153.
96. de Brito-Ashurst I, Preiser JC. Diarrhea in critically ill patients: the role
of enteral feeding. JPEN J Parenter Enteral Nutr. 2016;40(7):913-923.
97. Reintam Blaser A, Deane AM, Fruhwald S. Diarrhoea in the critically
ill. Curr Opin Crit Care. 2015;21(2):142-153.
Review

Nutrition in Clinical Practice

Volume 33 Number 1
Oral Feeding Difficulties in Children With February 2018 99–106

C 2017 American Society for

Short Bowel Syndrome: A Narrative Review Parenteral and Enteral Nutrition

DOI: 10.1177/0884533617707493
wileyonlinelibrary.com

Judy Hopkins, OTD, OTR/L, CLC1 ; Sharon A. Cermak, EdD, OTR/L, FAOTA2 ;
and Russell J. Merritt, MD, PhD1

Abstract
Children with short bowel syndrome (SBS) with associated intestinal failure may be unable to absorb sufficient nutrients to
sustain life. Improvements in the medical management of SBS, including use of parenteral nutrition, has significantly increased
life expectancy. Independence from parenteral nutrition further improves quality of life. However, children living with SBS often
develop oral aversions and feeding difficulties. There is limited research and information on which to base interventions that will
preserve and develop oral motor and feeding skills. The aims of this article are to explore what is known about children with SBS
who exhibit oral aversion/feeding difficulties and to suggest research for possible future interventions that could help these children
overcome oral aversion, eat orally, and increase participation and satisfaction in mealtimes. This review explores the complexity
of feeding children with SBS. Three underlying themes emerged: physical, developmental, and social aspects of eating and
mealtimes. Interdisciplinary teams are needed to effectively address these complex oral feeding problems. Accurate identification the
underlying issues will allow healthcare providers to develop interventions to improve feeding outcomes for children with SBS. Future
research should focus on evaluating the effectiveness of interventions that address each of the underlying issues. (Nutr Clin Pract.
2018;33:99–106)

Keywords
short bowel syndrome; short gut syndrome; oral aversion; parenteral nutrition; feeding and eating disorders; feeding behavior;
sensory sensitivity

Pediatric intestinal failure has been defined as the inabil-
ity of the bowel to absorb sufficient nutrients and fluids
required for adequate growth.1,2 Short bowel syndrome
(SBS), the most common form of pediatric intestinal failure,
has been defined as residual small bowel length <25% of
that predicted or the need for parenteral nutrition (PN)
for >42 days after intestinal resection.3 Others have chosen
less bowel resection (>50%)4 or longer periods (60 days) of
PN dependence.5 SBS has an estimated incidence of 24.5
per 100,000 births per year,3 and it results from congenital
intestinal anomalies and the surgery necessary to correct
them or postnatal events, most commonly necrotizing en-
terocolitis in premature infants.6,7 Children with SBS may
progress to full enteral feeding, remain PN dependent,
undergo intestinal transplantation, or succumb to the un-
derlying disease and complications of its therapy.5
Children with SBS-associated intestinal failure can be
nutritionally supported through PN, which can help them
grow and develop appropriately as the bowel adapts.5,8,9
However, PN has significant risks, which include liver fail-
ure, line infections, and sepsis.10 Introduction of fat restric-
tion, fish oil–based fat emulsion, and intestinal rehabilita-
tion teams have led to dramatic improvements in survival
and a decrease in pediatric intestinal transplantation, in part
by preventing progressive liver failure.11,12 This allows for
a longer period for intestinal adaptation when the bowel
undergoes functional and structural changes to increase
absorptive capacity. Increased time for these changes allows
more children to be weaned from PN.13
Intestinal adaptation is improved with early oral and
enteral feedings.9,14 Oral feedings are offered even when
they do not provide much nutrition value, due to a positive
effect of stimulating gut hormones, growth factors, and
digestive secretions that promote intestinal growth.15 In
addition to the physiologic benefits, families of children with
SBS find oral feeding a significant factor in their quality of
From the 1 Children’s Hospital Los Angeles, Los Angeles, California,
USA; and the 2 Division of Occupational Science and Occupational
Therapy, Herman Ostrow School of Dentistry, University of
Southern California, Los Angeles, California, USA.
Financial disclosure: None declared.
Conflicts of interest: None declared.
This article originally appeared online on December 14, 2017.
Corresponding Author:
Judy Hopkins, OTD, OTR/L, CLC, Children’s Hospital Los Angeles,
4650 Sunset Blvd, Los Angeles, California, 90027
Email: jhopkins@chla.usc.edu
100
life.16 Despite the benefits of oral intake on the underlying
condition and quality of life, many children with SBS take
or receive little oral feeding and develop oral aversion with
resistance to oral feeding.10,16
This article reviews the literature on oral feeding in
SBS and seeks to identify factors that may contribute to
the development of oral aversion and subsequent poor
feeding outcomes. Understanding these factors will allow
healthcare providers to develop interventions to improve
feeding outcomes for children with SBS.
Method: Literature Review
A qualitative analysis (ie, not systematic review) was per-
formed to identify pertinent literature. Electronic databases
included the Cochrane Library, PubMed, Medline, and
Ovid, as well as EBSCO Discovery Service to locate relevant
literature published in English in peer-reviewed journals.
Databases were searched from January 1, 2005–January
1, 2016 (11 years). Search terms used alone or in combi-
nation included oral aversion, short bowel syndrome, short
gut syndrome, quality of life, oral feeding, enteral feeding,
occupational therapy, developmental outcomes, tube feeding,
chronically ill, psychosocial, total parenteral nutrition, nu-
trition status, food mealtime, feeding, diet, adaptation, co-
occupation, bonding, and intestinal failure. Reference lists of
the articles obtained were manually searched for additional
references. The resultant 667 article abstracts and/or titles
were reviewed by the first author. All articles that appeared
relevant to feeding outcomes in children with SBS were
obtained and reviewed by the author, which led to the
inclusion of 40 articles. Articles determined to meet the
criteria of feeding children with SBS were included but not
graded, as our aim was mainly to outline the scope of the
issue.
Review of the articles revealed the primary theme of
the complexity of orally feeding children with SBS. Within
this theme, 3 underlying issues were identified: physical,
developmental, and social aspects of eating and mealtimes.
See Table 1 for primary citations related to each aspect.
Physical
Lack of Positive Oral Feeding Experiences
Adequate nutrition is essential, and many children with
SBS require nutrition support via PN and/or enteral feeding
tubes. Reliance on intravenous and tube feedings means
that they miss out on pleasurable aspects of oral feeding.16
Normal infants are exposed to a variety of sensory inputs
during oral feeding. The pleasant aspects of touch, taste,
smell, and temperature are reinforced by having hunger
satiated.17 Many children with SBS are at risk to develop
oral aversions, due to exposure to aversive oral stimuli,
including prolonged airway management, nasogastric tubes,
Nutrition in Clinical Practice 33(1)
and airway and upper gastrointestinal tract suctioning.18
When an infant’s oral experiences are tube insertion, oral
hygiene, and suctioning, the infant may be conditioned to
believe that oral stimuli are stressful or painful. When oral
feeding is initiated, it may trigger the conditioned response
of feeding avoidance.
It has been hypothesized that long-term use of a naso-
gastric tube for feeding leads to altered sensory perception,
with the pharyngeal area being suppressed to withstand
the trauma inflicted on the mouth and pharynx.16 Because
pleasant oral, facial, and sensory interventions could have
demonstrable effects on feeding skills,19 occupational ther-
apists working in neonatal intensive care units use oral
and nonoral sensorimotor interventions to improve the
transition from tube feedings to oral feedings.20 Oral motor
stimulation interventions may include stroking and positive
stimulation of perioral and intraoral structures (ie, gums,
hard palate, and tongue). Sensorimotor interventions may
include stroking of head, neck, back, and extremities.21
Range of motion of arms and legs and auditory, tactile,
and vestibular programs have been found to be effective in
promotion of oral motor and feeding skills. Multisensory
interventions that include auditory (female voice), tactile
(touch or massage of extremities), visual (eye contact),
followed by vestibular stimulation (rocking) improved alert-
ness and suck strength and organization.21 However, a
recent study that examined early medical and social fac-
tors that were associated with later feeding problems in
premature infants failed to find a correlation among pro-
longed ventilation, oral intubation, and number of days of
nasogastric/orogastric tube feeding and feeding outcomes
at 2 years of age.19 The investigators hypothesized that
this may have been due to improved medical care that has
reduced time on respiratory support, or it may be that
factors other than early exposure to noxious oral stimuli
contribute to later feeding difficulties.
Hunger Satiety Patterns
Children with SBS who receive most of their feeding via
enteral feeding tubes or PN will not experience normal
hunger satiety patterns.16 The practice of scheduled gastric
tube feedings could prolong dependence on tube feedings in
children with SBS, not only because they entail a delay in
oral feeding, but also because they interrupt hunger satiety
patterns that are important learning experiences.22 If the
child is receiving PN, especially when delivered continuously
over 24 hours, it similarly negatively affects sensations of
hunger and satiety.23
Although there are many medical reasons for a child to
remain dependent on PN and tube feedings, it is important
for healthcare professionals and caregivers to consider the
impact of this disruption on hunger satiety patterns. If
caregivers are unaware of the potential impact of appetite
Hopkins et al 101

Table 1. Informative Publications on Feeding Domains.

Aspect of Feeding Primary References

Physical Cole C, Kocoshis S. Nutrition management of infants with surgical short bowel
• Early oral experiences syndrome and intestinal failure. Nutr Clin Pract. 2013;28(4):421-428.
• Hunger satiety patterns Crapnell T, Rogers C, Neil J, Inder T, Woodward L, Pineda R. Factors associated
with feeding difficulties in the very preterm infant. Acta Paediatr.
2013;102(12):e539-e545.
Eneli I, Tylka T, Watowicz R, Hummel J, Ritter J, Lumeng J. Targeting feeding and
eating behaviors: development of the feeding dynamic intervention for caregivers
of 2- to 5-year-old children. J Obes. 2015;2015:1-8.
Developmental Edwards S, Davis A, Ernst L, et al. Interdisciplinary strategies for treating oral
• Critical windows aversions in children. JPEN J Parenter Enteral Nutr. 2015;39(8):899-909.
• Parent-child relationship Cooke L, Fildes A. The impact of flavour exposure in utero and during milk feeding
on food acceptance at weaning and beyond. Appetite. 2011;57(3):808-811.
Treyvaud K, Anderson VA, Howard K, et al. Parenting behavior is associated with
the early neurobehavioral development of very preterm children. Pediatrics.
2009;123(2):555-561.
Dudek-Shriber L. Parent stress in the neonatal intensive care unit and the influence
of parent and infant characteristics. Am J Occup Ther. 2004;58(5):509-520.
Mennella JA, Trabulsi JC. Complementary foods and flavor experiences: setting the
foundation. Ann Nutr Metab. 2012;60(suppl 2):40-50.
Social Winston K. Feeding a child with mealtime challenges: a mother’s work. Work.
• Mealtime experiences 2015;50(3):443-450.
• Quality of life Fiese B, Foley K, Spagnola M. Routine and ritual elements in family mealtimes:
contexts for child well-being and family identity. New Dir Child Adolesc Dev.
2006(111):67-89.
Absolom S, Roberts A. Connecting with others: the meaning of social eating as an
everyday occupation for young people. J Occup Sci. 2011;18(4):339-346.
Evans J, Rodger S. Mealtimes and bedtimes: windows to family routines and rituals. J
Occup Sci. 2008;15(2):98-104.
Winkler M, Wetle T, Smith C, Hagan E, Maillet J, Touger-Decker R. The meaning of
food and eating among home parenteral nutrition-dependent adults with
intestinal failure: a qualitative inquiry. J Am Diet Assoc. 2010;110(11):1676-1683.
Olieman J, Penning C, Poley M, Utens E, Hop W, Tibboel D. Impact of infantile
short bowel syndrome on long-term health-related quality of life: a cross-sectional
study. J Pediatr Surg. 2012;47(7):1309-1316.

dysregulation, they may have unrealistic expectations of the
amount that the child can take orally. This can lead to the
parent pressuring the child to take more by mouth, and the
child may respond by refusing food. This may prolong the
child’s dependence on tube feedings.22,23 To avoid this de-
pendence, parents will benefit from education on responsive
feeding, food exploration, and positive mealtimes. Even a
single session of parent education on positive interactions
during mealtimes has been shown to improve the feeding
outcomes and mealtime behaviors of children with feeding
problems.24
Developmental
Critical Windows
Deprivation of feeding experience contributes to develop-
mental delay in feeding, oral motor, and sensory processing
skills.25 In addition to the effect of decreased feeding
experiences, there are sensitive periods, or critical windows
of opportunity, for establishing normal suck-and-swallow
patterns.26,27 This critical window is a period in development
when the plasticity of the brain facilitates the learning of
sucking and swallowing skills required for early feeding.
Sensory and motor experiences help develop this skill.
Deprivation of these experiences may delay acquisition of
optimal feeding skills.28 Transition to a solid food diet is
another important stage in development and nutrition. Al-
tered early development may affect food choices throughout
childhood.29 Mennella and Trabulsi found that when infants
were introduced to solid foods at age ࣙ10 months, they ate
fewer foods of all types and were less likely to eat table food
at 15 months of age.30
Another study involving the introduction of lumpy solids
suggested that early exposure to a variety of textures and
flavors is important not only for later food choices but
also for feeding development.30,31 If the child’s medical
condition does not allow oral feeding during these critical
102
periods, the child may display oral motor, sensory, and
developmental feeding problems when attempts are made
to start oral feeding at a later age.32
Interventions can be used during these sensitive windows
to help develop functional feeding skills. Oral motor and
sensory motor interventions have been used to promote oral
motor skills in medically complex infants, including those
with prematurity, SBS, and cardiac conditions.33 The oral
motor and sensory interventions can include nonnutritive
and nutritive interventions.
Nonnutritive interventions include skin-to-skin contact
with mother or father, oral motor exercises, and nonnutri-
tive sucking.20 A study by Fucile and colleagues demon-
strated that combination interventions—oral motor (intrao-
ral stimulation with stroking of gums, tongue, and lips)
and sensorimotor (stroking of head, trunk, and extremities,
followed by range of motion of the extremities)—not only
helped to develop oral motor and feeding skills but also
facilitated gross motor skills. Optimized gross motor skills
in turn led to improved stability of the trunk that supported
respiration and oral motor and feeding skills.19
Introducing solids to infants with SBS at developmen-
tally appropriate times may improve chewing and swallow-
ing skills and increase oral intake.15 Taking a proactive
stance may help prevent future feeding difficulties for med-
ically complex children, including those with SBS.34
Parent-Child Relationship
Two social interaction factors known to influence child
development are the caregiving behaviors of parents and
the quality of the early parent-child relationship.35 Feeding
is a time when parents interact with their infant. Feeding
influences children’s social and emotional growth. Feeding
interactions give parents a chance to learn about their in-
fant’s needs, and by successfully meeting them, attachment
between the parent and the infant develops.36 Diminished
feeding opportunities affect this relationship and disturb
bonding. Additionally, early attachment processes may be
disrupted by lengthy hospitalization, invasive medical pro-
cedures, and the parents’ inability to be at the hospital.37
Children with SBS often require multiple operations and
may experience a prolonged hospitalization after birth with
frequent hospitalizations during the first year of life.38
When the child is hospitalized, the parents’ ability to hold
and interact with the infant may be limited by medical
equipment and procedures. These factors contribute to
parental stress, uncertainty, and fear and impair the bonding
process.39 Parents’ concern regarding the health of the criti-
cally ill infant is significantly related to maternal depression,
which impairs bonding and attachment.40,41
In a systematic review, Howe and Wang concluded that
“parent-directed and educational interventions for children
with feeding problems are moderately to strongly effective
Nutrition in Clinical Practice 33(1)
in improving children’s physical growth and development,
increasing the feeding competence of children and their pri-
mary caretakers and improving parent-child interaction.”20
In addition to feeding, parents should be reassured that
caregiving activities such as rocking, bathing, playing, and
communicating with their infant build a reciprocal rela-
tionship and attachment behaviors. To promote healthy
parent and child relationships, a multidisciplinary team that
includes occupational therapists, nurses, psychologists, and
social workers can provide interventions that encourage
parents to participate in their children’s care.42 The parents
can be reassured that they retain the capacity to positively
influence their children’s development.43
Social
Mealtime Experiences
For the healthy child, feeding typically occurs at meal-
times, and these experiences happen within a social context
wherein a parent reads and responds to a child’s feeding
cues.43 The mother’s ability to read cues helps her respond
by modifying her behavior and the environment to allow
the child’s full engagement in the feeding process.44 Addi-
tionally, this caregiver support provides a foundation for
the child’s participation in the social-emotional facet of
mealtime.45 This increases the enjoyment and satisfaction
of feeding and assists the child in building bonds with his
parents.46
Participating in the regular family meals is challenging
for caregivers of children with SBS because the primary
means of nutrition is often via PN and/or feeding tube. Tube
feedings and line care frequently take additional time orga-
nizing and planning to facilitate participation in mealtime.47
Medical conditions can disrupt the family mealtime expe-
rience. Parents who have children with medical needs have
additional responsibilities managing medical appointments,
hospitalizations, and advocating for their children.48 The
child with SBS may not be able to eat orally or may eat
only small amounts of food due to lack of hunger, lack of
feeding experiences, or the clinician’s concern about adverse
consequences of oral feeding.49 This decreases the child’s
full engagement and participation in family mealtimes.
Reduced participation in family mealtimes reduces exposure
to typical cultural and social aspects of mealtimes.50,51
Family meals are often more than a time to nourish
the body. Fiese and colleagues found that family meal-
times increased family identity and provided opportunities
to communicate directly and solve problems together.51,52
Meals and special foods are often included in celebrations
of milestones such as birthdays and weddings, and they
are part of holiday traditions. These rituals may bring a
sense of comfort, promote feelings belonging, and provide
a break from daily stressors.53 Participation in meals can
Hopkins et al
offer a regular and positive context for parents to connect
with children emotionally and to convey family values
and expectations, which directly cultivates children’s well-
being.53 Other shared parent-child time or activities may
not have the same potential for regularity, ritual, or focused
family time.
When the child’s medical needs adversely affect meal-
times, families miss out on the sense of connectedness
and lose a valuable opportunity for social contact.54,55 To
improve the social aspects of mealtimes and family life, all
care, including intravenous feeding, should transfer rapidly
to the home, where the child can develop within his or her
natural family and social environment.56 As clinicians, we
can help parents develop mealtime routines that include
everyone in the family, regardless of the amount of food that
the child with SBS is able to eat.
Quality of Life
Absolom and Roberts found that that social eating is a
valued and meaningful everyday activity in the lives of
adolescents aged 12–16 years. For participants, sharing
food with peers offered valuable opportunities to build
connections and friendships. They also recognized that this
time is used as a way to plan social and leisure activities
outside the school setting.55 Quality-of-life research with
adults and children receiving home PN for intestinal failure
indicates that the ability to eat and enjoy food is directly
linked to quality of life.15 Families report that they feel
helpless and frustrated because of their inability to help the
affected individual eat.56 The study participants voiced the
difficulty of socializing because of the tendency for family,
community, and holiday gatherings to be food related.
Similarly, the limited diet of children with SBS, either
medically or self-imposed, has an impact on quality of life
and the ability to participate fully in social activities such as
eating lunch at school.
Interdisciplinary Teams
Some of the articles reviewed discussed the importance
of an interdisciplinary team in the evaluation and man-
agement of children with SBS and their complex feed-
ing disorders.6,57 Most teams include physicians, nurses,
dietitians, and social workers as core members.58 Some
teams also include occupational therapists, psychologists,
and physical therapists.59 Each team member provides a
unique and valuable role. Physicians take responsibility
for the overall health of the child and manages changes
in medications, PN, and tube and oral feedings. Nurse
practitioners identify and address issues involving central
venous access and enteral feeding devices. They also assess
if the child would benefit from referrals to address oral
feeding and developmental problems. Registered dietitians
determine appropriate calories and promote a variety of
103
foods to optimize nutrition, fluid, and oral intake.60 Oc-
cupational therapists assess various facets of mealtimes,
including sensory, oral motor, swallowing, socioemotional,
and developmental aspects.61 Speech language pathologists
can assess oral motor and swallowing concerns related to
oral feeding.62 Social workers facilitate access to resources
as well as provide emotional support to families to improve
communication between the child and their parents.60 Psy-
chologists can develop behavioral interventions and train
parents and team members in the implementation of the
individualized programs. Team care has the potential to
provide comprehensive patient education that can improve
a child’s eating, which will have an impact on overall quality
of life for the child and family.62 Given these findings,
intestinal rehabilitation teams should assess social aspects
of feeding and implement intervention strategies to improve
regarding life satisfaction and ameliorate stress. Addressing
quality-of-life needs may decrease frustrations around eat-
ing and support participation in positive mealtime activities.
Discussion and Conclusion
Improvements in the medical management of SBS in chil-
dren has significantly increased life expectancy.6 Achieving
independence from PN improves quality of life.61 Transition
to oral feeding is a key goal for these patients and is best
addressed by interdisciplinary teams. Teams should take a
holistic approach to address not only the physical aspects of
oral feeding but also the developmental and social aspects.62
Although full oral feeding is the goal, when this is not
possible the team should provide interventions that support
the physical, developmental and social aspects for successful
oral feedings and quality of life.
This literature review highlights 3 central aspects of
oral feeding in children with SBS: physical, developmental,
and social. Physical aspects of feeding include oral facial
trauma from procedures such as intubation, nasogastric
tube placement, and suctioning.11 This is compounded by
diminished opportunities to experience the normal orofacial
pleasure of eating and hunger satiety patterns.63 Occupa-
tional therapists can intervene during an infant’s initial
hospitalization by providing positive oral facial experiences
and sensorimotor interventions.19,21 Initiating oral feeding
as soon as the infant is medically stable may provide oppor-
tunities for oral motor skill development and ensure that
critical windows of feeding development are not missed.7
As a child gets older, therapists ensure that developmentally
appropriate tastes and textures are offered to continue oral
motor skill development.27
Developmental aspects of feeding include not only oral
motor skills development but also sensory and socioemo-
tional development.44 Interventions designed to support the
parents’ ability to hold and interact with the infant while
hospitalized may decrease fear and increase the parent-child
104
connection.48 This may help to improve the parents’ com-
petence and self-efficacy in caring for their child and will
support the development of healthy relationships.64
The third aspect identified in this review is the social
aspect of oral feeding and mealtimes. Families of children
with SBS have fewer mealtime experiences, and this can
diminish quality of life and decrease opportunities for so-
cial interactions.65 Proposed interventions include helping
families recognize and respond appropriately to their child’s
feeding cues, setting up mealtime routines, and providing
strategies to address social isolation in these children and
their families.51 The mealtime interventions ensure regular
opportunities for socialization among family members that
improves sense of belonging and nurtures the child’s well-
being. Feeding group interventions could provide a sense of
social connectedness for the children and the parents while
addressing feeding concerns.66
Implications for Practice
Early introduction of oral feedings could help prevent oral
aversion and feeding problems. This may be best addressed
by having the neonatologist and neonatal registered dieti-
tian round with the intestinal rehabilitation team as soon as
it has been determined that the infant will likely need long-
term nutrition support.
Interdisciplinary teams are best to take a holistic ap-
proach. Team members bring unique perspectives, the sum
of which provides a more complete approach to addressing
the child’s needs. Interventions can then be designed to
integrate this broader perspective to improve the quality of
life for the child and his or her family. Potential interventions
are outlined in Table 2.
Recommendations for Future Research
Future research is needed to better identify early events
that predict feeding problems in patients with SBS. Trials
of interventions that address these events and behaviors
can then be implemented. There is still much to learned
about the role of various nonoral feedings on concurrent
feeding behavior later feeding outcomes. The potential for
group interventions for such patients that involve parents
as part of a therapeutic and supportive network remains to
be explored. In light of the small number of patients cared
for at a single medical center, research studies will need to
be coordinated across multiple centers to enroll sufficient
numbers of children and help ensure the generalizability of
the lessons learned.
Statement of Authorship
All authors equally contributed to the conception and design
of the research; and J. Hopkins and R. J. Merritt contributed
to the acquisition, analysis, and interpretation of the data.
All authors drafted the manuscript; critically revised the
Nutrition in Clinical Practice 33(1)
Table 2. Interventions for Each Domain.
Aspect of
Feeding Interventions
Physical r Early feeding when medically
appropriate15
r Nonnutritive oral motor exercises19
r Sensorimotor interventions21
Developmental r Offer developmentally appropriate
foods when medically appropriate29
r Support family in holding and
interacting with baby during initial
hospitalization40
Social r Encourage participation in family
mealtime rituals and routines54
r Feeding groups for children and their
parents66
r Adapt schedule of parenteral
nutrition or enteral feeds to allow
child to participate in school
activities6
r Encourage the child to eat with peers
at school55
manuscript; agree to be fully accountable for ensuring the
integrity and accuracy of the work; and read and approved the
final manuscript.
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Review

Nutrition in Clinical Practice

Volume 33 Number 1
Natural Bioactive Food Components for Improving Enteral February 2018 107–120

C 2017 American Society for

Tube Feeding Tolerance in Adult Patient Populations Parenteral and Enteral Nutrition
DOI: 10.1177/0884533617722164
wileyonlinelibrary.com

Adam J. Kuchnia, MS, RD, LD, CNSC1 ; Beth Conlon, PhD, MS, RD2 ;
and Norman Greenberg, PhD2

Abstract
Tube feeding (TF) is the most common form of nutrition support. In recent years, TF administration has increased among patient
populations within and outside hospital settings, in part due to greater insurance coverage, reduced use of parenteral nutrition, and
improved formularies suitable for sole source nutrition. With increasing life expectancy and improved access to TFs, the number of
adults dependent on enteral nutrition is expected to grow. However, enteral TF intolerance (ETFI) is the most common complication
of TFs, typically presenting with at least 1 adverse gastrointestinal event, including nausea, diarrhea, and constipation. ETFI often
leads to reductions in TF volume with associated energy and protein deficits. Potentially ensuing malnutrition is a major public
health concern due its effects on increased risk of morbidity and mortality, infections, prolonged hospital length of stay, and higher
healthcare costs. As such, there is a need for intervention strategies to prevent and reduce ETFI. Incorporating whole foods with
bioactive properties is a promising strategy. Emerging research has elucidated bioactive properties of whole foods with specific
benefits for the prevention and management of adverse gastrointestinal events commonly associated with TFs. However, lack of
evidence-based recommendations and technological challenges have limited the use of such foods in commercial TF formulas. This
review addresses research gaps by discussing 5 whole foods (rhubarb, banana, curcumin, peppermint oil, and ginger) with bioactive
attributes identified through literature searches and clinical experience as having substantial scientific rationale to consider their
application for ETFI in adult populations. (Nutr Clin Pract. 2018;33:107–120)

Keywords
enteral nutrition; enteral formulas; tube feeding; dietary supplements; digestive signs and symptoms

Summary for the prevention and management of adverse GI events

Tube feeding (TF) is the most common form of nutrition
support. In recent years, TF administration has increased
among patient populations within and outside hospital
settings, in part due to greater insurance coverage, reduced
use of parenteral nutrition (PN), and improved formula-
ries suitable for sole source nutrition. With increasing life
expectancy and improved access to TFs, the number of
adults dependent on enteral nutrition (EN) is expected to
grow. However, enteral TF intolerance (ETFI) is the most
common complication of TFs, typically presenting with
at least 1 adverse gastrointestinal (GI) event, including
nausea, diarrhea, and constipation. ETFI often leads to
reductions in TF volume with associated energy and protein
deficits. Potentially ensuing malnutrition is a major public
health concern due its effects on increased risk of mor-
bidity and mortality, infections, prolonged hospital length
of stay, and higher healthcare costs. As such, there is
a need for intervention strategies to prevent and reduce
ETFI. Incorporating whole foods with bioactive properties
is a promising strategy. Emerging research has elucidated
bioactive properties of whole foods with specific benefits
commonly associated with TFs. However, lack of evidence-
based recommendations and technological challenges have
limited the use of such foods in commercial TF formulas.
This review addresses research gaps by discussing 5 whole
foods (rhubarb, banana, curcumin, peppermint oil, and
ginger) with bioactive attributes identified through literature
searches and clinical experience as having substantial scien-
tific rationale to consider their application for ETFI in adult
populations.
From the 1 Department of Food Science and Nutrition, University of
Minnesota–Twin Cities, Saint Paul, Minnesota, USA; and 2 Nestlé
Nutrition R&D Centers Inc, Bridgewater, New Jersey, USA.
Financial disclosure: None declared.
Conflicts of interest: None declared.
This article originally appeared online on December 14, 2017.
Corresponding Author:
Adam J. Kuchnia, MS, RD, LD, CNSC, University of Minnesota,
225 Food Science and Nutrition, 1335 Eckles Avenue, St Paul,
MN 55108-6099, USA.
Email: kuchn001@umn.edu
108
Background
Increased dietary variety is recommended by major public
health organizations as part of a healthy lifestyle due to
its association with reductions in overall mortality and
chronic diseases, including obesity, cancer, stroke, and car-
diovascular disease.1-3 Dietary variety emphasizes an overall
healthy eating pattern rich in diverse types of fruits, veg-
etables, grains, legumes, nuts, seeds, meat/poultry, fish, and
oils/fats.1 Dietary variety is largely lost in people dependent
on EN support, where the sole source (or majority) of
nutrition is provided via commercially available, highly
purified TF formulas. Although understudied, the long-
term health of predominantly tube-fed individuals may be
compromised as a result.
It is estimated that a half-million people in the United
States are reliant on TFs and approximately 10% of hospi-
talized patients require some form of nutrition support.4-6
With the increasing aging population7 and reported benefits
of enteral feeds, this number is expected to rise over the
next 5 years.5 Development of ETFI is the most common
complication of TFs, estimated to occur in up to 33%
of all hospitalized patients4 and up to 75% of critically
ill patients.8,9 Although there is no universally accepted
definition, ETFI typically involves high gastric residual
volumes and various degrees of nausea, vomiting, diar-
rhea, constipation, abdominal distention, and bloating.4,8
High gastric residual volume, nausea and vomiting, and
diarrhea10,11 ranked as the most prevalent side effects
among patients in the intensive care unit (ICU)8 and
otherwise.4 Although the 2016 Society of Critical Care
Medicine and American Society for Parenteral and Enteral
Nutrition adult critical care guidelines12 suggest that gastric
residual volumes not be used as part of routine care to
monitor enterally fed patients in the ICU, they remain
of concern to healthcare professionals and caregivers due
to gastroparesis and the potential increase in aspiration
risk.
Unfortunately, there is no consensus for treatment of
ETFI, but interventions typically consist of reducing rate
or volume or postponing or stopping TFs altogether.4,13,14
Medication management is also frequently attempted15 ;
however, many first-line medications cause unwanted side
effects that may complicate medical course.15 As a re-
sult of postponing or stopping TFs, the deleterious ef-
fects of malnutrition ensue. Malnutrition is a promi-
nent driver of increased mortality, hospital length of
stay, hospital costs, overall healthcare costs, and reduced
quality of life (QOL).16-18 An estimated 4–19 million
patients in the United States are undiagnosed and un-
treated for malnutrition each year.19 Identifying, prevent-
ing, and treating malnutrition is a priority quality im-
provement initiative among hospitals.20 However, despite
the clinical and economic consequences of malnutrition
Nutrition in Clinical Practice 33(1)
resulting from ETFI, effective treatment strategies remain
elusive.4
The addition of whole foods with bioactive properties
to TF formulas may improve ETFI and subsequently re-
duce malnutrition. Bioactive properties of whole foods are
attributed to components in foods or dietary supplements—
other than those needed to meet basic human nutrition
needs—that are responsible for changes in health status.21
Key bioactives consist of phytochemicals (eg, flavonoids,
polyphenols, terpenoids, alkaloids, and sulfur containing
compounds) and nucleotides.22 Commonly known bioactive
components include lycopene (tomatoes), long-chain ω-3
fatty acids (fatty fish), and epigallocatechin gallate (green
tea).21 While many bioactives have antioxidant activities
that protect the body against various oxidative stresses and
inflammation,23 recent studies have positioned additional
food components, such as prebiotics and probiotics, as
bioactives due to their therapeutic or prophylactic effect on
human health. Bioactive food components are most effec-
tive when consumed as whole foods because of naturally
occurring synergistic effects among phytochemicals and
nucleotides. For example, several reviews have summarized
clinical trials showing that turmeric extracts and curcumin
potentially protect the GI tract through anti-inflammatory
effects,24 which may safely and effectively help maintain re-
mission in patients with ulcerative colitis (UC).25 However,
most large-scale, commercially available TF formulas are
devoid of these potentially beneficial components. Reasons
for this may be twofold: (1) there is a lack of evidence-
based recommendations for how to use bioactive food com-
ponents in chronically TF patients, and (2) technological
challenges make it difficult to preserve the bioactivity of
foods in commercial TFs.26 Despite these challenges, the
addition of bioactive food components may benefit TF
regimens and play an important role in patient care.
Methods
We conducted literature searches using PubMed and Sco-
pus. Pertaining to bioactive efficacy, the search was limited
to randomized controlled intervention trials published in
the English language and retrievable as full text (Table 1).
Although the adult patient population is the focus of
this review, pediatric studies were included as supportive
evidence when adult intervention studies were lacking to
help explain the mechanistic action of various whole foods.
Preclinical, animal, and in vitro studies were investigated
in support of efficacy and for discussion of the safety
and mechanistic action of the bioactive attributes. With
the aim of informing new clinical recommendations for
patients, the following discussion highlights 5 whole foods
and their bioactive components that may improve ETFI
symptoms (Table 2) and the health of patients dependent
on TFs.
Kuchnia et al
Table 1. Clinical Trials on Bioactive Food Components Alleviating Adverse Gastrointestinal Symptoms.
Sample
Intervention: Study Design
Rhubarb
Randomized controlled trial
Randomized controlled trial
Ginger
Randomized controlled trial
Randomized, double-blind,
placebo-controlled, crossover trial
Randomized, double-blind,
placebo-controlled, crossover trial
Randomized, double-blind,
placebo-controlled trial
Randomized, double-blind,
controlled, crossover trial
Randomized, double-blind,
placebo-controlled trial
Randomized, placebo-controlled
trial
Banana
Randomized, double-blind,
controlled trial
Randomized controlled trial
Randomized, double-blind,
controlled trial
Randomized controlled trial
Randomized controlled trial
Peppermint oil
Randomized, double-blind,
placebo-controlled trial
Randomized, double-blind,
placebo-controlled
109
Size Outcome Reference
94 Rhubarb decoction (50 mL), given enterally, was as good as 27
standard prokinetic agents for advancement of feeding tubes
into small bowel (P = .916).
126 EEN in combination with rhubarb powder (15 g) significantly 26
improved gastrointestinal function vs EEN or PN regimens
alone (P < .001).
60 Ginger powder (500 mg) mixed with yogurt significantly 56
reduced nausea severity and frequency when compared with
the control group (P > .05).
48 Ginger powder (1 g) added to standard antiemetic treatment 58
showed no advantage in reducing nausea and vomiting over
placebo.
36 Ginger powder (Zintoma; 1 g) added to standard antiemetic 59
treatment had no additional benefits beyond placebo in
prevalence, severity, or duration of nausea and vomiting.
576 Supplementation with 0.5, 1.0, and 1.5 g of ginger extract 48
significantly improved acute nausea severity vs placebo
(P = .003).
50 Ginger powder alone (1 g) is as effective as metoclopramide, 62
but not ondansetron, in controlling nausea and vomiting
episodes.
100 Ginger powder capsules (1 g) added to standard ondansetron 63
therapy significantly reduced postoperative nausea and
vomiting vs placebo (P < .05).
106 Ginger powder capsules (Zintoma; 750 mg) were effective for 65
relief of mild to moderate nausea and vomiting (P < .001).
57 Green banana–derived (250 g/L) resistant starches significantly 72
improved intestinal permeability and diarrhea by way of
reduced lactulose:mannitol ratio (P < .05).
40 Dehydrated banana flakes (6 g/lb/d) provides an improved 74
method for reduction of diarrhea symptoms vs standard
hydration therapy.
62 Green banana supplementation (250 g/L) effectively reduced 79
stool frequency, weight, and amount of rehydration fluids
when compared with the control diet (P < .05).
80 Supplementation with a green plantain (50 g) mixture 76
significantly reduced stool frequency, volume, and weight
and improved weight gain vs a yogurt-based diet (P < .002).
31 Dehydrated banana flakes (1–3 tbsp every 8 h) was as good as 78
medical management at reducing diarrhea severity and
frequency and trended toward significance for improving
nutrient delivery vs control.
72 Triple-coated microsphere PO (two 180-mg capsules TID) 81
supplementation for 4 wk significantly reduced total IBS
symptoms scores vs placebo (P = .03).
65 PO (brand unspecified; 2 mL TID) supplementation for 6 wk 102
significantly improved abdominal pain vs placebo (P < .001).
(continued)
110 Nutrition in Clinical Practice 33(1)

Table 1. (continued)

Sample
Intervention: Study Design Size Outcome Reference

Randomized, double-blind, 90 Compared with placebo, PO supplementation (Colpermin; one 85

placebo-controlled
Randomized, double-blind,
placebo-controlled
Randomized, double-blind,
placebo-controlled
Randomized, double-blind,
placebo-controlled
Curcumin
Randomized, double-blind,
placebo-controlled trial
Randomized, double-blind,
placebo-controlled trial
Randomized trial, partially blinded
Randomized, double-blind,
placebo-controlled trial
0.2-mL [187 mg] TID capsule for 8 wk) significantly reduced
abdominal pain (P < .001) and improved quality of life
(P < .01).
57 PO (MintOil; two 225-mg capsules BID) supplementation for 101
4 wk was more effective than placebo at improving total IBS
symptoms score (P < .0090). Benefits lasted 1 mo after
discontinuing therapy in >50% of treated patients.
110 PO (Colpermin; one 0.2-mL [187 mg] capsule TID or QID) for 103
4 wk significantly improved IBS-related symptoms, including
pain, abdominal distension, and stool frequency, vs placebo
(P < .05).
40 Compared with hyoscyamine (Egazil; 0.2 mg), patients 99
supplementing with PO (Colpermin; one or two 0.2-mL
[187 g] capsules TID) for 2 wk reported significant
therapeutic improvements in IBS symptom scores (P < .001)
with less side effects (P < .001).
89 Curcumin supplementation (2 g/d), in combination with 115
standard therapy, showed significant improvements in UC
remission maintenance as compared with placebo (P = .04).
50 Curcumin extract capsules (Cur-Cure; 3 g/d), consumed in 112
combination with standard therapy, was superior to therapy
and placebo in inducing clinical and endoscopic UC
remission (P = .01 and P = .43, respectively).
207 IBS symptom prevalence significantly decreased in a 120
dose-response manner between baseline and after treatment
with 2 doses of curcumin extract (72 or 144 mg; P < .001).
45 Curcumin extract preparation (NCB-02 enema; 140 mg) in 130
combination with standard therapy did not significantly
reduce UC disease activity or remission rates vs placebo.

BID, twice daily; EEN, early enteral nutrition; IBS, irritable bowel syndrome; PN, parenteral nutrition; PO, peppermint oil; QID, 4 times daily;
TID, 3 times daily; UC, ulcerative colitis.

Rhubarb for Constipation and GI Motility
Overview. Rhubarb, a plant in the Polygonaceae family,
has been used for centuries as a traditional Chinese herbal
remedy and as a therapeutic compound throughout the
world.27,28 The pharmacologic effects of rhubarb are due
to its active constituents of anthraquinone glycosides—
specifically, rheinanthrone, aloe-emodin, and physcion.29
These compounds exert therapeutic effects that stimu-
late peristalsis of the GI tract28,30 and may alleviate
constipation.30,31 Anthraquinones found in rhubarb are
found in other stimulant laxatives.32 As EN becomes an
increasingly more integral component of patient care,
improvements in the prevention of aspiration and con-
stipation, via improved gastric motility, warrant close
attention.33 Rhubarb may present a new natural bioactive
that may help normalize GI motility to ultimately improve
nutrient delivery.
Mechanisms. The ability of rhubarb to induce a purgative
and laxative effect is thought to be, at least partially,
due to its anthraquinone glycoside content.29 Specifically,
sennoside A is metabolized into rheinanthrone by intestinal
bacteria and reaches the colon, where it exhibits its stim-
ulatory effect.34,35 Water channels in colon mucosal cells,
particularly aquaporin 3, play a role in water absorption
and expulsion. Kon and colleagues34 in 2014 showed a
downregulation of colon epithelial aquaporin 3 in rats
given rhubarb extract. Downregulation of aquaporin 3 may
inhibit water transfer to the vascular side of the colon,
causing a laxative effect due to water localizing in the
lumen of the colon.35 Subsequently, an oral dose of rhubarb
intervention increased stool output with an 8-fold increase
in fecal water content when compared with controls.34
Efficacy. Preclinical data from Chen and Ran36 in 1996
investigated the effect of rhubarb intervention in rats with
Kuchnia et al 111

Table 2. Foods and Their Bioactive Food Components prokinetic medications, alluding to the need for develop-
Proposed to Alleviate Specific ETFI Symptoms. ment of new prokinetic agents.15
Furthermore, Wang et al4 recently showed that delayed
Main Bioactive ETFI Symptoms
Food Components Targeted gastric emptying or gastroparesis, as measured by increased
gastric residual volume, was the most frequently observed
Rhubarb Anthraquinone glycosides Constipation ETFI (63%) in hospitalized patients (n = 754), followed
(rheinanthrone, Gastroparesis by nausea and vomiting (36%). Delayed food delivery to
aloe-emodin, physicon) Reflux the small intestine has the potential to compromise the
Ginger Gingerols Nausea rate and magnitude of absorption in critically ill patients41
Shogaols Vomiting and, likely, all clinical populations. Such gastric pertur-
Zingerones bations have proven problematic due to the lack of fat42
Paradols and glucose43,44 absorption as a result of delayed nutrient
Banana Resistant starches/SCFAs Diarrhea transit. Thus, delayed gastric emptying may directly relate
Peppermint oil Menthol GI pain to underfeeding. The extent to which hypocaloric feeding
Menthone GI spasms with inadequate protein provisions negatively affects patient
Isomenthone outcomes has been thoroughly documented,14,16 putting
Menthyl acetate paramount importance on the development of natural
Menthofuran interventions, such as rhubarb formulations, to promote the
1,8-cineol recovery of GI motility and nutrient delivery.
Curcumin/ Curcuminoids (curcumin, Inflammation In 2014, Wan and colleagues27 investigated the effect of
turmeric demethoxycurcumin, (indirectly rhubarb supplementation with early EN on GI function
bidemethoxycurcumin) affects TF in 126 critically ill patients with severe acute pancreatitis.
tolerance)
The combination of early EN, infusion starting 1 day
ETFI, enteral tube feeding intolerance; GI, gastrointestinal; SCFAs, postadmission, and 15 g of rhubarb powder mixed with
short chain fatty acids; TF, tube feed. 100 mL of water resulted in faster recovery of gastric
motility when compared with early EN or PN regimens
alone. Subsequently, the intervention group had a reduction
necrotizing pancreatitis (n = 17). Compared with controls, in disease severity, inflammatory markers, and ICU and
1.5 mL of a rhubarb decoction given over 8 hours sig- hospital length of stay.27 In the future, such interventions
nificantly increased intestinal motility. This improvement may promise an improved level of patient care and a
in motility was accompanied by a significant decrease in reduction in healthcare costs.
mesenteric lymph node tissue endotoxin levels, illustrating
a decrease in bacterial translocation in the rhubarb group.36 Safety and technical challenges. Rhubarb preparations did
A recent prospective randomized controlled trial by Li not directly elicit any adverse effects in the trials described,
et al28 underscored the potential clinical importance of potentially due to the short duration of these studies.
rhubarb in a group of 94 critically ill patients needing Conversely, in an individual case report presented in 2006,
small bowel feeding tubes. Researchers found that, when Kwan and colleagues45 reported on the acute renal fail-
compared with prokinetic agents metoclopramide and ery- ure of a young woman after prolonged use of a natural
thromycin, 50 mL of an enteric rhubarb decoction infusion Chinese herbal slimming pill containing rhubarb-extracted
(solution obtained from boiling 50 g of raw rhubarb in anthraquinone derivatives. It was suggested that renal
100 mL water and discarding undissolved residue) was as failure was exacerbated by concomitant intake of other
good, if not better, at improving immediate advancement nonsteroidal anti-inflammatory drugs, such as diclofenac.45
of a feeding tube into the jejunum. Success rates in the Although a causal relationship was not established, intake
rhubarb, erythromycin, and metoclopramide intervention of herbal remedies should be taken under clinician super-
groups were 91%, 90%, and 87%, respectively. The study vision, with knowledge of various potential medication in-
demonstrated rhubarb’s ability to serve as an effective proki- teractions and disease comorbidities. Moreover, foods high
netic agent by stimulating gastric and intestinal motility.28 in oxalic acid, such as rhubarb, have been suggested to con-
Such results indicate substantial clinical importance, as tribute to kidney stone formation.46 Taylor and Curhan47
historical use of prokinetic medications to improve peristal- found, however, that dietary oxalate impact on urinary
sis has shown adverse events, such as reduced absorption oxalate levels appears low, but caution should be taken with
and tachyphylaxis, eliciting concern among clinicians.37-39 individuals who are susceptible to stone formation. Further
A meta-analysis by Lewis et al40 paints an ominous picture investigations on dose and duration should be considered
of uncertainty when describing potential adverse events of for prolonged use,28 but acute usage of a 50-mL decoction
pneumonia, mortality, and length of stay with the use of appears safe and effective. However, there is currently no
112
commercial preparation of a rhubarb decoction, which will
impede clinical usage. Once formulations are commercially
available, bioactive concentration and efficacy testing need
to be conducted.
Ginger for Nausea and Vomiting
Overview. Ginger is 1 of the most widely consumed spices
worldwide and has been used for medicinal purposes in
Asian countries for centuries.48 It is an underground stem
of the perennial plant Zingiber officinale and is cultivated
in most regions of the world.49 Ginger contains an ar-
ray of bioactive compounds, including gingerols, shogaols,
zingerones, and paradols,49,50 which have been investi-
gated for their beneficial effects on nausea and vomiting,51
inflammation,52 and metabolic perturbations.53,54 However,
ginger has most notably been studied for its ability to
combat morning sickness, postoperative nausea and vom-
iting, and chemotherapy-induced nausea and vomiting.52
A retrospective cohort study involving chart review of 754
hospitalized patients by Wang et al4 estimated that 36%
of hospitalized patients receiving TFs experience nausea
and vomiting. Similarly, a multicenter, prospective study of
298 hospitalized adults by Bloechl-Daum and colleagues55
reported clinically relevant symptoms in up to 60% of
patients undergoing chemotherapy, many of whom required
TF support.
Mechanisms. Despite improvements in antiemetics, nausea
and vomiting still affect up to 60% of patients.55 It has been
proposed that ginger may support serotonin type 3 (5-HT3 )
receptor antagonism.56 These receptors are expressed in the
central nervous system in regions involved in gag reflex
and vomiting.57 Receptor antagonists, such as ondansetron,
are used as a standard of care postoperatively and in
controlling chemotherapy-induced nausea and vomiting.50
Moreover, 5-HT3 receptors have been linked to peristaltic
activity in the GI tract, as shown by antagonism altering GI
motility in vitro.56,58 Ginger’s efficacy and clinical relevancy
in reducing ETFI, however, have yet to be completely
elucidated.52,59
Efficacy. A review of 9 clinical trials and 7 reviews by
Marx and colleagues52 investigated the clinical efficacy
of various ginger formulations in regard to all-cause
nausea and vomiting. They concluded that ginger is a
promising treatment for nausea and vomiting in a va-
riety of clinical applications. Common limitations were
noted within the literature, which included poorly con-
trolled studies and small sample sizes, warranting future
investigations.52
In 2015 in a randomized controlled trial, Arslan and
Ozdemir60 investigated the ability of ginger to reduce
Nutrition in Clinical Practice 33(1)
nausea and vomiting in 60 women undergoing treatment
for breast cancer. When added to adjuvant antiemetic
treatment, 500 mg of ginger powder, mixed with yogurt
and taken just prior to chemotherapy, further reduced
nausea severity and vomiting episodes.60 However, the study
was unblinded and likely introduced bias. Two randomized
crossover double-blind studies by Manusirivithaya et al61
and Fahimi et al62 examined similar endpoints but with
differing results when compared with those of Arslan and
Ozdemir. In both studies (n = 48 and n = 36, respectively),
1 g/d of ginger added to standard antiemetic treatment
showed no acute benefits in nausea or vomiting when
compared with placebo among patients with various cancer
diagnoses undergoing cisplatin-based chemotherapy.61,62
Small sample sizes and heterogeneity within groups may
have contributed to the differing results.
It is important to consider the prevalence and severity
of a range of symptoms that occur with the initiation of
chemotherapy, including nausea, vomiting, and retching.
While ginger supplementation often improves at least 1
of these symptoms, it does not always improve all symp-
toms simultaneously.51,63 Furthermore, supplementation
does not always alleviate symptoms throughout the entire
intervention period, often showing benefits in the short or
long term but typically not both. In 2012, Ryan et al51
conducted a large double-blind multicenter controlled trial
investigating the effect of increasing doses of ginger extract
capsules (0.5–1.5 g) added to standard antiemetic treatment
in 576 adults receiving chemotherapy. Study results showed
improvements in acute nausea severity when compared with
placebo on day 1 of treatment for all intervention groups,
with the best outcomes shown in the intervention groups
receiving 0.5 and 1.0 g of ginger.51 Despite improvements
in acute chemotherapy-induced nausea and vomiting, de-
layed and follow-up ginger supplementation did not show
significant improvements. Although the benefits of ginger
supplementation in this group is sometimes murky, the
majority of studies favor usage.64
While results vary when ginger is used as adjuvant
therapy for cancer, it has been shown to be as effec-
tive as some drugs when it is taken in place of stan-
dard antiemetics. In a heterogeneous cancer population
(n = 50), Sontakke and colleagues65 investigated the abil-
ity of 1 g of daily ginger (capsule format) to combat
chemotherapy-induced nausea and vomiting in a random-
ized crossover double-blind trial. The antiemetic efficacy of
ginger was found to be equal to metoclopramide but not
ondansetron.65
Ginger supplementation has been shown to benefit pa-
tient populations beyond those undergoing cancer treat-
ment. In a 2014 prospective double-blind randomized con-
trolled study, Mandal and colleagues66 examined the ef-
fects of adjuvant ginger therapy in patients undergoing
surgery (n = 100). Episodes of postoperative nausea and
Kuchnia et al
vomiting were assessed hourly, up to 18 hours after surgery,
following intake of a 1-g capsule of ginger powder. Re-
searchers concluded that the combination of an antiemetic
with ginger was superior to an antiemetic and placebo
and significantly reduced the incidence of postoperative
nausea and vomiting.66 Earlier studies corroborate these
findings in surgery patients.67 Furthermore, a meta-analysis
by Thomson et al49 critically examined 6 clinical trials
to evaluate the effects of ginger on prevention of nausea
and vomiting in early pregnancy. While acknowledging
limitations in existing clinical studies, the authors concluded
that ginger is significantly better than placebo.49 Similarly,
Saberi et al68 investigated if a ginger intervention alone
could relieve symptoms of mild to moderate nausea and
vomiting in pregnant women (n = 106). Participants were
block randomized to 1 of 3 groups: 750-mg/d ginger capsule,
lactose capsule placebo, or control. After a 7-day study
period and 4 days of intervention, researchers found a
significant decrease in nausea and vomiting when compared
with placebo and control. Similar research has supported
these benefits.69
Safety and technical challenges. At this point, few studies
have reported adverse events with ginger supplementation.
A meta-analysis by Viljoen and colleagues70 sought to assess
the safety of oral ginger supplementation in nausea and
vomiting associated with pregnant women. A comprehen-
sive analysis of 12 randomized controlled trials, comprising
1278 pregnant women, were included. Researchers found
no adverse events, side effects, or spontaneous abortion
with supplementation of ginger powder/extract (600–2500
mg/d).70 Conversely, Ryan et al51 found a total of 9 ad-
verse events out of 576 patients undergoing chemotherapy,
which resulted in withdrawal from the study. Adverse events
included heartburn, bruising/flushing, and rash and were
thought to be directly related to the study drug (0.5–1.5 g
of ginger extract). Studies reviewed here primarily involved
oral administration of either powder or extract, typically
in capsule form, but also included other forms (eg, yogurt
snack). Ginger is generally recognized as safe by the Food
and Drug Administration with little to no adverse effects
reported when taken at a dose of 1–2 g/d. Whether supple-
mented alone or in combination with standard antiemetic
treatment, ginger has potential to alleviate nausea and vom-
iting with little risk and may reduce risk of aspiration due
to vomiting and other harmful signs of ETFI. Randomized
controlled trials in various populations receiving enteral
TFs and standard antiemetic treatment are needed.
Banana for Diarrhea
Overview. Banana is a popular fruit grown in >130 coun-
tries worldwide and belongs to the genus Musa from the
113
family Musaceae. Like many other fruits and vegetables,
bananas contain a plethora of bioactive compounds with
vast nutrition and medicinal value, including phenolics,
carotenoids, biogenic amines, and phytosterols.23 Pharma-
cologic benefits target the GI tract, specifically the colon,
where it has been studied for its ability to ameliorate 1 of the
most prevalent ETFI symptoms—diarrhea.4 Diarrhea has
a reported prevalence of 2%–68% in hospitalized patients
and up to 95% in critically ill patients on TFs.10,71 This wide
range in reported incidence is namely due to the lack of
a standardized definition in the clinical setting. Diarrhea,
although acknowledged, is greatly underappreciated in re-
gard to overall recovery and nutrition status.10 For instance,
it was demonstrated that increased stool weight >350 g/d
can be used as a surrogate for energy loss and intestinal
energy malabsorption,72 leading to increased complications
and detrimental outcomes.14
Mechanisms. Antidiarrheal effects of banana are thought
to be facilitated by its high content of resistant starches. The
bioactive properties of resistant starches are attributed to
their prebiotic effect.73 Resistant starches pass into the colon
undigested, where they undergo bacterial fermentation.
This reaction, largely attributed to unripe, green bananas,
generates short chain fatty acids, which stimulate colonic
absorption of water, salts, and electrolytes.74,75 Beyond
salvaging fluid losses in the colon, green bananas also
improve mucosal function and hasten recovery in aberrant
pathologies.76 Moreover, in 2004 Rabbani and colleagues75
showed that banana has more systemic benefits by im-
proving small bowel mucosal permeability, as shown by a
reduction in lactulose:mannitol ratio in patients affected
with diarrhea.75
Efficacy. Traditionally, green bananas and dehydrated ba-
nana flakes have been used to treat many digestive disorders
in pediatrics77-79 but have more recently been speculated
to improve diarrhea induced by disease80 and by the ini-
tiation of TFs.81 An important historical study conducted
in 1950 by Fries and colleagues77 examined the effects
of dehydrated banana flakes in 40 infants suffering from
nonspecific diarrhea. Infants in the intervention group
received 6 g of dehydrated banana flakes per pound of body
weight per 24 hours over 3 days. Water was used to dilute
the banana flakes, and the total dose was divided into 9
feedings given throughout the day. The intervention was
considered successful, or “good,” if infants responded to
therapy within 72 hours with formed stools, with no more
than 3 or 4 stools per day. Authors concluded that banana
flakes appropriately ameliorated symptoms of diarrhea,77
which corroborated the proposed beneficial effects of
banana.
Rabbani et al82 examined the therapeutic effects of
green banana supplementation in children with persistent
114
diarrhea. In a double-blind randomized controlled fashion,
62 infants were given a rice-based diet, containing 250
g/L of cooked green banana, 4 g/kg of pectin, or a rice
diet alone for 7 days. Significant benefits were observed
by day 3 in both intervention groups, and by day 4, 82%
and 78% of children recovered from diarrhea in the pectin
and green banana groups, respectively. This was compared
with only 23% recovery in the control group. Green banana
and pectin were shown to significantly reduce stool fre-
quency and weight, oral rehydration fluids, and intravenous
(IV) fluid administration.82 In 2009, Álvarez-Acosta et al79
took a similar approach to evaluate the effects of a green
plantain–based diet when compared with a yogurt-based
diet among 80 children with persistent diarrhea. In this
randomized controlled trial, children in the intervention
group were fed 50 g of green plantain in a mixture prepared
with egg white, corn oil, glucose, water, and electrolytes
for 1 week. The plantain-based intervention group had
significantly improved responses of diminished stool fre-
quency, volume, weight, duration, and improved weight
gain.79
Early investigations in pediatrics paved the way for a
more recent investigation examining ETFI in adults. Emery
et al81 investigated whether 7 days of dehydrated banana
flakes, when compared with routine medical treatment,
could alleviate diarrhea in a group of 31 critically ill
tube-fed patients. Intervention consisted of 1–2 tbsp of
banana flakes every 8 hours and potentially increasing to
3 tbsp, pending clinician judgment. Both groups, inter-
vention and standard therapy, showed reduced severity of
diarrhea, and even though the banana flake group had
a threefold increase in Clostridium difficile toxin, it still
had less diarrhea at the end of the study period, thereby
allowing for delivery of more adequate nutrition support.
An additional benefit of banana flakes is that they are not
contraindicated for use in patients with C difficile diarrhea,
since it does not reduce GI motility. Banana flakes, as
added to an enteral TF regimen, constitute an efficacious
and cost-effective treatment for diarrhea and should be
considered for first-line management in critically ill tube-fed
patients.
Safety and technical challenges. Banana flakes and whole
banana administration is advocated by various medical
groups, including the Cleveland Clinic,83 for its ability to
normalize bowel movements. No adverse events have been
documented in any of the referenced information, and it use
appears to be safe for adults and children. Although it is
seemingly safe and cost-effective, optimal dosage should be
determined by clinical judgment. Moreover, green bananas
contain higher amounts of resistant starch than more
ripe bananas. Thus, supplementation should contain high
proportions of green banana/flakes as compared with ripe
banana/flakes.
Nutrition in Clinical Practice 33(1)
Peppermint Oil for GI Spasms and Pain
Overview. Peppermint oil (PO; Mentha piperita L), a nat-
ural oil obtained by steam distilling fresh leaves of the
peppermint plant,84 is a perennial herb commonly found
across North America and Europe. PO been associated
with reduced GI spasms85 and gastric pressure,86 decreased
frequency and severity of abdominal pain,87-89 stimulated
bile flow,90 and antibacterial properties.91,92 The antispas-
modic and GI-soothing effects of PO have made it a
common herb in complementary and alternative medicine
for ailments that include irritable bowel syndrome (IBS),
dyspepsia, nausea, and general abdominal discomfort and
cramping.93 It is estimated that IBS affects up to 11% of the
global population,94 lending public health importance to
the development of medical and complementary/alternative
medicine interventions for it.
Mechanism. The antispasmodic and GI-soothing effects
of PO are mostly attributed to the presence of monoter-
penes and, to a lesser extent, sesquiterpenes (<2% of
composition).95,96 Menthol is the predominant monoter-
pene, making up 30%–50% of PO’s composition, followed
by menthone (14%–32%), isomenthone (1.5%–10%), men-
thyl acetate (2.8%–10%), menthofuran (1.0%–9.0%), and
1,8-cineol (3.5%–14%).84,97,98 In vitro data suggest that
menthol relaxes colonic smooth muscle mechanical activity
by blocking calcium influx through sarcolemma L-type cal-
cium channels.86 This mechanism corroborates the reported
activity of menthol capable of relaxing stomach, intestinal,
and colonic motility.86,99
Efficacy. Findings of several recent systematic100,101 and
nonsystematic reviews87,102 support the safe and effective
use of enteric-coated PO for attenuating GI spasms and pain
in adult populations (ࣙ18 years) with IBS87,100,101 for doses
up to 1200 mg/d.103 In 2014, PO received a positive evalua-
tion from the American College of Gastroenterology Task
Force,104 citing 5 randomized controlled trials (involving
482 patients) supporting the finding that “PO is superior to
placebo in improving IBS symptoms.” Collectively, studies
support the use of enteric-coated PO to improve total IBS
symptoms score105 and symptoms of IBS (most commonly
pain) with minimal adverse effects. Studies have mixed
findings regarding QOL, with results supporting significant
improvement89 and no change.106
The majority of studies (n = 5) assessed the effects of
enteric-coated, delayed-release PO under the brand name
Colpermin89 or MintOil on IBS symptoms. Liu et al107
found that 4 weeks of PO supplementation (187 mg, 3 or 4
doses per day) resulted in greater improvements in patient-
reported IBS symptoms than the placebo group, including
abdominal pain, distension, and stool frequency. Capello
and colleagues105 similarly observed that consumption of
Kuchnia et al
PO (225 mg, twice daily) for 4 weeks significantly reduced
the total IBS symptoms score at 4 weeks vs placebo. Benefits
of PO supplementation lasted 1 month after therapy in
>50% of patients. Merat and colleagues89 conducted a
double-blind, placebo-controlled trial that examined the
effects of enteric-coated PO (Colpermin, 0.2 mL [187 mg],
3 times per day before meals) when compared with placebo
in 60 adults with clinically confirmed IBS. Consumption
of PO significantly reduced IBS symptoms and improved
several measures of QOL over 8 weeks.89 Carling et al103
published the only clinical trial with an active comparator
(l-hyoscyamine; Egazil, one or two 0.2-mg tablets per day)
in a double-blind crossover study.87 Enteric-coated PO
(Colpermin, one or two 0.2-mL capsules per day), but not
l-hyoscyamine, significantly improved IBS symptoms and
patient-reported therapeutic effect at the end of the treat-
ment period. Side effects were greater with l-hyoscyamine,
whereas PO had side effects comparable to placebo.
In a randomized controlled trial, Alam and colleagues106
compared daily supplementation with PO (2 mL; brand
unspecified) with placebo for 6 weeks among patients with
diarrhea-predominant IBS. Abdominal pain significantly
improved vs placebo, but indicators of QOL did not.
The authors reported benefits of PO supplementation af-
ter the discontinuation of therapy (measured at 2 weeks
postintervention), similar to the findings of Cappello and
colleagues.105
Two earlier clinical trials, published by Nash et al108 and
Lawson et al,109 did not find improvement of IBS symptoms
with PO supplementation. Limitations included a small
sample size and poor adherence to study protocols. Law-
son and colleagues109 selected individuals with prominent
colonic-type symptoms and postulated that enteric-coated
capsules might release PO in the small bowel rather than the
colon, attenuating the effect of PO on the colon. Moreover,
in a recent double-blind, placebo-controlled clinical study,
Cash and colleagues85 assessed the effects of PO delivered as
a novel triple-coated microsphere formulation that provided
sustained release of PO in the small intestine in 72 pa-
tients (mean age, 40.7 years) with mixed-symptom IBS and
diarrhea-predominant IBS. After 4 weeks of intervention,
PO significantly reduced total IBS symptoms score by
40% from baseline, and this decrease significantly differed
from the 24.3% decrease observed in the placebo group. In
addition, patients in the PO group reported significantly
more improvements in individual GI symptoms, with few
adverse effects.
Safety and technical challenges. The major technical chal-
lenge with PO is the mechanism of delivery. Menthol must
be absorbed in the distal small bowel and colon to relieve
symptoms associated with IBS. Nonenteric-coated PO is
released and absorbed directly in the stomach, where it
may cause heartburn and gastric discomfort by relaxing the
115
lower esophageal sphincter100 ; PO administration directly
into a distal feeding tube (jejunal feeding tube) may fall
short of reaching the affected areas of the distal GI tract.
Enteric-coated PO has the potential to rupture in the
stomach, promoting similar gastroesophageal discomfort108
as nonenteric-coated PO. Despite this limitation, enteric-
coated PO is the common method of delivery, as it has
demonstrated effectiveness and good tolerability in multiple
clinical studies. Novel triple-coated microsphere technology
is designed for sustained release in the small intestine,
circumventing potential rupture in the stomach. This tech-
nology has potential to replace enteric-coated capsules as
the preferred mechanism of delivery in the near future.84,85
PO is generally recognized as safe by the Food and Drug
Administration, and according to the American College of
Gastroenterology Task Force, it has been determined to
pose no greater risk of adverse events when compared with
placebo.110
Side effects of oral PO are generally mild and most
commonly include heartburn and nausea.87,100 One study
reported a mild transient skin rash.107 To the best of
our knowledge, there is only 1 case report of oral allergy
to peppermint111 ; most reports cite topical or inhalation
exposure.112,113 The Academy of Pediatrics98 and a recent
clinical pediatric study84 support the safe use of PO in
most pediatric populations. In clinical studies, PO has
demonstrated greater efficacy for reducing IBS symptoms
than conventional interventions, such as antispasmodics,
antidepressants, and dietary fiber.100 It is likely safe and
effective for short-term treatment of IBS; however, long-
term effectiveness has yet to be determined.104 In the United
Kingdom, PO is approved as frontline IBS pharmacother-
apy, and it has been used for IBS therapy throughout Europe
for many decades.114 Studies are needed to determine what
format and dosage of PO can be safely and effectively
administered in the chronically TF patient with ETFI, with
consideration that some feeding tubes will be placed post-
pylorically. While evidence supports PO for IBS, there may
be broader applications for the tube-fed patient, given its
ability to relax GI smooth muscle and promote a soothing
effect.
Curcumin for Inflammation
Overview. Curcumin is a natural polyphenol constituent of
the spice turmeric, derived from the rhizomes of Curcuma
spp.115 It employs a wide spectrum of biological activities
and has been used for centuries in Chinese medicine to treat
a range of inflammatory diseases and symptoms affecting
the GI tract.116 Curcumin has been postulated to have
beneficial effects in people with various cancers,117,118 GI
diseases,116,119 cardiovascular disease,120 nephritis,121 liver
damage,122 and rheumatoid arthritis.123 Only data related
116
to benefits on inflammation and GI diseases are further
discussed.
Mechanisms. Although inflammatory processes do not di-
rectly cause ETFI, low-grade inflammation is implicated in
most individuals with inflammatory bowel disease (IBD)
and IBS, most of whom have at least 1 symptom of ETFI.
Curcumin’s ability to modulate inflammation is thought
to be in part related to its ability to suppress expression
of prostaglandin synthesis by way of cyclooxygenase 2
inhibition.124,125 Cyclooxygenase 2 is a major enzyme re-
sponsible for the conversion of arachidonic acid to proin-
flammatory prostaglandins and is upregulated in various
diseases.123,126,127 Furthermore, production of inflamma-
tory compounds within the epithelial mucosa is likely a
major mechanism of tissue injury in IBD; it is well accepted
that various inflammatory cytokines increase epithelial per-
meability, including interferon-γ , TNF-α, and interleukin
13.128,129 As inflammation and tissue injury persist, the GI
tract allows for an ingress of bacterial components into the
gut lining, triggering IBD symptomology.129 A mechanistic
nonintervention study in 2010 examined colonic mucosa
biopsies from adults and children with IBD, which were
cultured ex vivo with curcumin.130 The authors clarified that
curcumin’s protective effects are in part based on its ability
to inhibit key disease mediators, including p38 mitogen-
activated protein kinase and other proinflammatory cy-
tokines. There is an unmet need for nonpharmaceutic and
natural bioactive compounds that can reduce inflammation
and, thus, IBD symptomology.
Efficacy. Langhorst and colleagues131 performed a system-
atic review of potentially beneficial complementary and
alternative medicines for people affected with IBD. After
analyzing and including 26 randomized controlled trials and
3 nonrandomized controlled trials (20 in UC, 6 in Crohn’s
disease, 3 in both UC and CD), the reviewers found the
herbal therapy with the best evidence for UC maintenance
was curcumin and that it may have clinical benefits in other
forms of IBD.131
Recent literature consistently shows beneficial effects of
curcumin supplementation in IBD. A highly recognized ran-
domized, double-blind, placebo-controlled trial conducted
by Hanai and colleagues119 in 2006 examined the effec-
tiveness of curcumin supplementation in maintaining UC
remission. In a sample of 89 participants with quiescent
UC, 6-month supplementation with 2 g/d of curcumin,
in combination with standard therapy, showed significant
improvement in remission maintenance when compared
with placebo. Researchers concluded that curcumin is an
effective adjunctive therapy.
Taking work by Hanai et al a step further, Lang et
al116 were curious whether curcumin was able to induce
remission instead of maintain it. In a multicenter random-
Nutrition in Clinical Practice 33(1)
ized, double-blind, placebo-controlled trial, investigators
found that 1-month supplementation of 3 g/d of pure
curcumin, in combination with standard IBD medication,
was superior to placebo and medication at inducing clinical
remission in patients with mild to moderate UC (n =
50).116 Despite these findings, the results have been de-
bated in light of the curcumin formulation intervention
used; as opposed to natural curcumin found in nature,
the intervention in this case was a 95% pure curcumin
compound.132
Moving beyond IBD, IBS is a very common disorder
characterized by similar GI complications as with IBD,
including abdominal pain, bloating, and altered bowel
habits.24 A partially blinded randomized pilot study by
Bundy et al124 assessed the effects of varying doses of
curcumin extract tablets on healthy individuals with IBS
symptoms. Participants were randomized to receive either
72 mg (n = 102) or 144 mg (n = 105) of daily cur-
cumin extract for 8 weeks. Researchers observed a 53%
and 60% decrease in the prevalence of IBS in the 1-
and 2-tablet groups, respectively; IBS symptomology also
decreased with intervention. Other, less rigorous trials
seem to corroborate curcumin’s ability to ameliorate IBS
symptoms.133
Curcumin extract preparation (NCB-02; 72% curcumin)
has been evaluated for its safety and efficacy at inducing
remission when given as an enema in patients affected
with mild to moderate UC. In a randomized, double-
blind, placebo-controlled trial, Singla and colleagues134
randomized 45 patients to receive either standard treatment
and a curcumin enema (containing 140 mg of NCB-02)
or standard treatment and placebo for 8 weeks. The study
found no significant differences between curcumin inter-
vention and placebo regarding disease activity or remission
rates in an intention-to-treat group, but there was a trend
toward improved outcomes.134 Although not statistically
significant, clinical significance should be considered, as
clinical remission was observed in 43.4% of patients in the
curcumin group, as compared with 22.7% in the placebo
group.
Safety and technical challenges. Curcumin is well tolerated
in children at high doses (capsule format) up to 2 g/d.135
Furthermore, a database search of the safety of curcumin
from 1966 to 2002 by Chainani-Wu136 identified 6 clini-
cal trials where curcumin was tolerated from 1 to 8 g/d
in adults. Curcumin is a promising herb that should be
considered therapy for patients suffering from IBD and
potentially other IBS symptomology. However, because
tube-fed patients will require infusion of curcumin directly
into the GI tract, the tolerability and efficacy of curcumin
powder/extract infused enterally with water need to be
established.
Kuchnia et al
Summary and Practice Points
EN is paramount to populations that are mechanically or
anatomically unable to consume food orally, but symptoms
of ETFI can greatly hinder its ability to optimize health.
This review presents information about the clinical rele-
vancy of health-promoting natural bioactive food compo-
nents in preventing and managing ETFI. Although many
natural remedies are reviewed in the literature, currently,
rhubarb, ginger, banana flakes, PO, and curcumin appear to
be well-documented bioactive food components with poten-
tial to promote a healthy and functional GI tract during TF
administration.
There are a few main points to consider when eval-
uating research for the use of bioactives in conjunction
with TFs. First, dietary supplement manufacturers and
distributors are not required by law to obtain Food and
Drug Administration approval prior to marketing dietary
supplements.137 Bioactive ingredients obtained online or
from retail do not necessarily contain amounts of the active
ingredient listed. Thus, the formulation obtained needs to be
considered, and it is recommended that natural ingredients
are sought so that the level of active components can be
ensured. Second, in the evaluation of nutrition literature,
statistical significance (P value) is the determining factor
for whether an intervention is effective at producing the
desired outcome in patient populations. However, many
studies assessing bioactive efficacy have small sample sizes,
thus limiting power to detect a statistically significant ef-
fect. Moreover, statistical significance is not equivalent to
clinical significance; according to the American Statistical
Society, larger P values do not necessarily imply lack of
clinical importance or effect.138 Thus, clinical significance,
with cost-effectiveness, should be assessed accordingly when
evaluating literature on natural food bioactives. Third,
technological challenges need consideration in terms of
either getting a particular bioactive ingredient incorporated
into TF formula or getting the bioactive to the appropriate
portion of the GI tract where it can promote benefits. The
use of enteric-coated or microcapsule forms of PO in a
modular format may be an effective flush delivery option
that reduces the risk of feeding tube clogs139 ; bioactives
added to open feeding tube systems for drip infusion may
increase the rate of clogs. Finally, although meaningful
and safe dosages can be deduced from the literature, the
format given (extract, powder, decoction, etc) needs to
be considered to achieve target concentration of active
ingredients. These points are not easily overcome, but with
a concerted effort, appropriately designed studies in various
enterally fed patient populations can broaden perspective
on the benefits of natural food bioactives for the ulti-
mate goal of improving patient care and reducing adverse
outcomes.
117
Statement of Authorship
All authors equally contributed to the conception and design
of the work; A. J. Kuchnia and B. Conlon contributed to the
acquisition and analysis of the data; all authors contributed
to the interpretation of the data; and A. J. Kuchnia and B.
Conlon drafted the manuscript. All authors critically revised
the manuscript, agree to be fully accountable for ensuring the
integrity and accuracy of the work, and read and approved the
final manuscript.
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mentation with curcuminoids on dyslipidemia in obese patients: a
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121. Khajehdehi P, Zanjaninejad B, Aflaki E, et al. Oral supplementation
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122. Kim S-W, Ha K-C, Choi E-K, et al. The effectiveness of fermented
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123. Chandran B, Goel A. A randomized, pilot study to assess the efficacy
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128. Barbara G, De Giorgio R, Stanghellini V, et al. A role for inflamma-
tion in irritable bowel syndrome? Gut. 2002;51(1):i41-i44.
129. König J, Wells J, Cani PD, et al. Human intestinal barrier function in
health and disease. Clin Transl Gastroenterol. 2016;7(10):e196.
130. Epstein J, Docena G, MacDonald TT, et al. Curcumin suppresses
p38 mitogen-activated protein kinase activation, reduces IL-1beta
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Invited Commentary
Mid-Upper Arm Circumference Z-Score as Determinant
of Nutrition Status: Does Occam’s Razor Apply?
Cecelia Pompeii-Wolfe, RD, LDN, CNSC; and Timothy A. S. Sentongo, MD
Keywords
anthropometry; body composition; z-score; mid upper arm circumference; pediatrics; nutrition assessment; malnutrition
Malnutrition is an imbalance between nutrient requirement
and intake resulting in cumulative deficits of energy, pro-
tein, and micronutrients that may negatively affect growth,
development, and other relevant outcomes.1 In developed
countries, malnutrition is predominantly related to disease.2
Hospitalized undernourished children have increased co-
morbidities, longer hospital stays, higher hospital costs,
and greater likelihood of requiring continued medical care
after discharge.3 Despite this, malnutrition has not drawn
the appropriate attention or resources for intervention
because of underreporting and assumptions that it is an
inevitable consequence of underlying disease.4 Therefore,
the American Society of Parenteral and Enteral Nutrition
and Academy of Nutrition and Dietetics came up with a
consensus statement endorsed by the American Academy
of Pediatrics outlining basic indicators that can be used
to diagnose and document undernutrition in the pediatric
population aged 1 month to 18 years.1
Mid-upper arm circumference (MUAC) was among the
anthropometric indices recommended by the consensus
statement to assess nutrition status.1 MUAC is an appealing
tool for screening nutrition status because of the ease of use
when weight and height are difficult to obtain, measurement
involves simple inexpensive equipment, and with minimal
training users make fewer errors when compared with mea-
surements of weight and height.5 Multiple field studies have
shown that an age-independent and gender-independent
MUAC value of <115 mm outperforms all other anthropo-
metric indices in identifying severely malnourished children
at high risk of death.6-8 However, low MUAC also tends to
overidentify females and younger children.9 MUAC has a
stronger association with fat mass (FM) than fat free mass
(FFM),9,10 and FM is believed to play a key role in pro-
moting survival during undernutrition. Low MUAC’s high
predictive power may also be from overidentifying younger
children who in general have higher mortality rates. The use
of an age-independent and gender-independent absolute
cut-off value for low MUAC was based on the earlier work
of Dr. Derrick Jeliffe, who published the Wolanski’s tables
of normal growth of MUAC in the 1960s.11 These tables
Nutrition in Clinical Practice
Volume 33 Number 1
February 2018 121–123

C 2018 American Society for
Parenteral and Enteral Nutrition
DOI: 10.1002/ncp.10012
wileyonlinelibrary.com
demonstrated that for normal, well-fed Polish children,
MUAC in both genders increased by only about 10 mm
between the ages of 1–4 years. However, since then more
reference data became available showing that there were
small but consistent age and gender differences in MUAC
thus prompting the need to use an adjusted MUAC.12 Hall
et al13 used MUAC z-scores computed from Dutch reference
data to assess growth in Bangladeshi children and found
no gender differences in the prevalence of undernourished
children regardless of age. Subsequent observations by the
World Health Organization Expert Committee confirmed
that whereas the increments in MUAC between ages 1–
5 years are indeed small, gender differences existed in the
patterns of mid-upper arm growth that warranted separate
references.6 Therefore, in 1997 the World Health Organi-
zation published age-based and gender-based MUAC z-
score curves for children aged 6 years to 59 months. The
use of age-adjusted and gender-adjusted MUAC greatly
improved the detection of severe malnutrition in older
children; however, its superior performance as a predictor
of mortality declined.6
The authors have done a commendable job bring-
ing use of MUAC z-scores to the forefront. This is
the first report examining consistency between MUAC z-
scores,14 weight-for-length z-scores, and body mass index
(BMI) z-scores in predicting malnutrition in children aged
From the University of Chicago Comer Children’s Hospital, Chicago,
Illinois, USA.
Financial disclosure: None declared.
Conflict of interest: None declared.
Received for publication August 8, 2017; accepted for publication
August 31, 2017.
Corresponding Author:
Timothy A. S. Sentongo, MD, Associate Professor of Pediatrics,
Director Pediatric Nutrition Support, Director Pediatric
Gastrointestinal Endoscopy, The University of Chicago Comer
Children’s Hospital, 5841 S Maryland Avenue, Chicago, IL 60637,
USA.
Email: tsentong@peds.bsd.uchicago.edu
122
1–18 years. An absolute MUAC value <115 mm has been
identified as the strongest predictor of mortality in children
with malnutrition.8 Therefore, the attempt by the authors
to validate MUAC z-scores with weight-for-length and
BMI z-scores is commendable. The large sample size is
impressive, although it is notable that the patients were
seeking medical care in specialty clinics and thus more likely
to have been medically complex and with diverse growth
when compared with the general population. The findings
that the range of MUAC z-scores spanning malnutrition
was narrower than those for weight-for-length and BMI
z-scores may have arisen for a variety of reasons. First,
each anthropometric parameter reflects nutrition status
differently. For example, Chomtho et al10 compared MUAC
with FM and FFM measured by dual X-ray absorptiometry
in a group of children with cystic fibrosis and healthy
controls and found that MUAC correlated strongly with FM
but weakly with FFM. Likewise, Grijalva-Eternod et al9
examined the associations between MUAC and weight-for-
length in infants with FM and FFM obtained using air-
displacement plethysmography. They found that MUAC
was more strongly associated with variability in adiposity
relative to variability in FFM, whereas weight-for-length
was more strongly associated with length-adjusted relative
tissue mass.9 Therefore, whereas the weight-for-length z-
score was a better marker for tissue masses independent of
growth status, a low MUAC z-score was a composite index
of poor growth and wasting (including low adiposity).9
Second, another potential cause of variable ranges for
MUAC, weight-for-length, and BMI z-scores for similar
classifications of nutrition status may have arisen because
of the inclusion of too many extreme values in the data
analysis, that is, the authors’ only excluded values in excess
of ±8 standard deviations. On the contrary, when the
World Health Organization released new growth standards
in April 2006, they recommended that a narrower range
of ±5 standard deviations should be the cut-off for data
exclusion.15 Therefore, if the MUAC indicator indeed spans
a smaller range of z-score values, it may be most useful in
diagnosing severe malnutrition when z-scores fall beneath a
defined value.
Malnutrition is a complex process with often many fac-
tors involved (in the case of chronic disease related malnu-
trition) and requires clinical judgment using multiple factors
rather than single anthropometric data point z-scores. As
suggested in the consensus statement, serial MUAC mea-
surements can be very useful to monitor changes in body
composition using a patient as his or her own control.1 In
clinical practice, specifically pediatric critical care, having a
serial measurement on which to compare individual patients
with themselves during an in-patient admission can be very
helpful. Especially in an acute care setting where weights
can be difficult to obtain and/or affected by fluids and
volume status. Therefore, in the right context with defined
Nutrition in Clinical Practice 33(1)
parameters, MUAC may continue to be a very important
piece of nutrition assessment and pediatric malnutrition
diagnostics.
Occam’s razor simply stated is “Don’t complicate simple
things.” A good nutrition indicator is one that best reflects
the issue of concern or predicts a particular outcome.7
The λ, μ, and σ values that permit the calculation of
MUAC z-scores in children aged 2 months to 18 years
were recently made available through the work of Abdel-
Rahman et al.14 Therefore, we commend the authors for
trailblazing the use of MUAC z-scores across the pediatric
age spectrum.14 However, in contrast to absolute MUAC’s
ability to identify malnourished children at increased risk
for death, the predictive power of a MUAC z-score is yet
to be determined. In the process of transition to z-scores,
we may have lost the simplicity of age-independent and
gender-independent MUAC’s predictive power for clinical
outcome; thus Occam’s razor may now no longer apply.
More studies should be done to validate MUAC z-score with
other anthropometric parameters and clinical outcomes
across the pediatric age spectrum.
Statement of Authorship
T. Sentongo and C. Pompeii-Wolfe jointly drafted the commen-
tary and critically revised it. Both authors read, approved, and
are fully accountable for ensuring the integrity and accuracy of
the final manuscript.
References
1. Becker P, Carney LN, Corkins MR, et al. Consensus statement of the
Academy of Nutrition and Dietetics/American Society for Parenteral
and Enteral Nutrition: indicators recommended for the identification
and documentation of pediatric malnutrition (undernutrition). Nutr
Clin Pract. 2015;30:147-161.
2. Mehta NM, Corkins MR, Lyman B, et al. Defining pediatric malnu-
trition: a paradigm shift toward etiology-related definitions. JPEN J
Parenter Enteral Nutr. 2013;37:460-481.
3. Abdelhadi RA, Bouma S, Bairdain S, et al. Characteristics of hospi-
talized children with a diagnosis of malnutrition: United States, 2010.
JPEN J Parenter Enteral Nutr. 2016;40:623-635.
4. Corkins MR. Why is diagnosing pediatric malnutrition important?
Nutr Clin Pract. 2017;32:15-18.
5. Velzeboer MI, Selwyn BJ, Sargent F 2nd, Pollitt E, Delgado H. The
use of arm circumference in simplified screening for acute malnutri-
tion by minimally trained health workers. J Trop Pediatr. 1983;29:
159-166.
6. de Onis M, Yip R, Mei Z. The development of MUAC-for-age reference
data recommended by a WHO expert committee. Bull World Health
Organ. 1997;75:11-18.
7. World Health Organization Expert Committee. Physical Status: The
Use and Interpretation of Anthropometry. Geneva, Switzerland: World
Health Organization; 1995:1-452. World Health Organization technical
report series 854.
8. WHO Child Growth Standards and the Identification of Severe Acute
Malnutrition in Infants and Children: A Joint Statement by the World
Health Organization and the United Nations Children’s Fund. Geneva,
Switzerland: World Health Organization; 2009.
Pompeii-Wolfe and Sentongo
9. Grijalva-Eternod CS, Wells JC, Girma T, et al. Midupper arm circum-
ference and weight-for-length z scores have different associations with
body composition: evidence from a cohort of Ethiopian infants. Am J
Clin Nutr. 2015;102:593-599.
10. Chomtho S, Fewtrell MS, Jaffe A, Williams JE, Wells JC. Evaluation
of arm anthropometry for assessing pediatric body composition:
evidence from healthy and sick children. Pediatr Res. 2006;59:860-
865.
11. Jelliffe DB. The Assessment of the Nutritional Status of the Community
(With Special Reference to Field Surveys in Developing Regions of the
World). Geneva, Switzerland: World Health Organization; 1966:3-271.
World Health Organization monograph series 53.
123
12. Voorhoeve HW. A new reference for the mid-upper arm circumference?
J Trop Pediatr. 1990;36:256-262.
13. Hall G, Chowdhury S, Bloem M. Use of mid-upper-arm circumference
z scores in nutritional assessment. Lancet. 1993;341:1481.
14. Abdel-Rahman SM, Bi C, Thaete K. Construction of lambda, mu,
sigma values for determining mid-upper arm circumference z scores
in U.S. children aged 2 months through 18 years. Nutr Clin Pract.
2017;32:68-76.
15. Mei Z, Grummer-Strawn LM. Standard deviation of anthropometric
Z-scores as a data quality assessment tool using the 2006 WHO
growth standards: a cross country analysis. Bull World Health Organ.
2007;85:441-448.
Clinical Research

Nutrition in Clinical Practice

Volume 33 Number 1
Evaluating Mid-Upper Arm Circumference Z-Score February 2018 124–132

C 2018 American Society for

as a Determinant of Nutrition Status Parenteral and Enteral Nutrition

DOI: 10.1002/ncp.10018
wileyonlinelibrary.com

Karen Stephens, MS, RD, CSP, LD1 ; April Escobar, MS, RD1 ;
Erika Nicole Jennison, MS, RD1 ; Lindsey Vaughn, MS, RD1 ;
and Rhonda Sullivan, MS, RD1 ; Susan Abdel-Rahman, Pharm.D.2,3 ;
on behalf of the CMH Nutrition Services Z-Score Research Team

Abstract
Background: Mid-upper arm circumference (MUAC) z-score, has recently been listed as an independent indicator for pediatric
malnutrition. This investigation examined the relationship between MUAC z-score and the z-scores for conventional indicators
(ie, weight-for-length and body mass index) to expand the available evidence for nutrition classification z-score threshold ranges
in U.S. practice settings. Methods: This was a single-center study of children through 18 years of age seen between October 2015
and September 2016. Height and weight were obtained on intake. MUAC was measured at midpoint of the humerus, between the
acromion and olecranon. Age-specific and gender-specific z-score values were calculated using published λ, μ, and σ values derived
from Centers for Disease Control and Prevention reference data. Nutrition status was determined from biochemical data; prior
history; anthropometrics; weight gain velocity; weight loss, if present; and nutrient intake. Results: 5,004 children (7.5 ± 5.7 years,
53% boys) were evaluated. As expected, MUAC z-scores were significantly correlated with body mass index (r = 0.789, P < .01) and
weight-for-length (r = 0.638, P < .01) z-scores. There was a large degree of overlap in z-scores for all indicators between nutrition
status groups; however, MUAC z-scores spanned a narrower range of values such that mean MUAC z-scores are lower in children
classified as overweight/obese and higher in children who were severely malnourished than the corresponding body mass index or
weight-for-length z-scores. Conclusion: These data are the first to suggest that the z-score ranges used to define various stages of
malnutrition may not be the same for all indicators. (Nutr Clin Pract. 2018;33:124–132)

Keywords
mid-upper arm circumference; pediatrics; nutrition assessment; malnutrition; anthropometry; body composition; z-score

Background starving, and/or purging, leading to nutrient deficits. The

Although pediatric malnutrition has long been recognized
as a serious medical problem in developing countries, in-
creased focus is being made to address this issue in the
United States. For infants, children, and adolescents, lack
of adequate nutrition intake to meet individual needs affects
proper growth and development, increases vulnerability to
acute and chronic diseases, and contributes to increased
use of resources.1,2 The causes of malnutrition are mul-
tifactorial, including food insecurity, when families have
difficulty providing enough food for all family members;
acute illnesses leading to decreased intake; chronic illnesses
limiting ability to eat; increased metabolic needs from
acute and chronic illnesses or injuries; malabsorption or
maldigestion of nutrients; and psychosocial issues, such
as abuse or neglect.3,4 Children with special healthcare
needs are especially at risk for malnutrition as a result of
chronic diseases, congenital anomalies, severe injuries, and
acute illnesses to name a few.5 In addition, patients with
eating disorders are at risk as a result of self-restriction,
consequences of malnutrition on the pediatric population
are different than on adults, requiring early screening and
From the 1 Department of Nutrition Services, Children’s Mercy
Hospital, Kansas City, Missouri, USA; 2 Division of Clinical
Pharmacology, Medical Toxicology, and Therapeutic Innovation,
Children’s Mercy Hospital, Kansas City, Missouri, USA; and
3 Department of Pediatrics, University of Missouri-Kansas City,
School of Medicine, Kansas City, Missouri, USA.
Financial disclosure: This work was supported in part by a grant from
the New England Pediatric Device Consortium.
Conflicts of interest: None declared.
Received for publication March 3, 2017; accepted for publication June
30, 2017.
Corresponding Author:
Karen Stephens, MS, RD, CSP, LD, Nutrition Services, Children’s
Mercy Hospital, 3101 Broadway, 10th Floor, Kansas City, MO 64111,
USA.
Email: klstephens@cmh.edu
Stephens et al
intervention to avoid stunting and other serious outcomes
for a developing child.1
In the recent Academy of Nutrition and Dietet-
ics/American Society for Parenteral and Enteral Nutri-
tion (AND/ASPEN) Consensus Statement on Indicators
Recommended for the Identification and Documentation
of Pediatric Malnutrition, mid-upper arm circumference
(MUAC) was listed as an independent indicator for di-
agnosing pediatric malnutrition.5-7 The Consensus Panel
recommended that “MUAC measurements should be part
of the full anthropometric assessment in all patients,” and
acknowledged that “MUAC has been indicated as a more
sensitive prognostic indicator for mortality than weight-for-
height parameters in malnourished pediatric patients.”8-13
Explicit recommendations for the use of z-score, decline in
z-score, and negative z-score were included to classify and
document pediatric malnutrition.5
At the time of publication, MUAC z-score values were
available from the World Health Organization for the global
pediatric population through 5 years of age, but these values
reflected MUAC in optimally growing children.14 We sub-
sequently generated the necessary parameters to calculate
MUAC z-scores for U.S. children 2 months through 18 years
of age using data from the Centers for Disease Control and
Prevention (CDC) National Health and Nutrition Exami-
nation Survey (NHANES) and integrated into our nutrition
screening assessment.15 In this investigation, we examine the
primary indicators of nutrition status (ie, weight-for-length,
body mass index [BMI], and MUAC) in a large cohort
of children and explore the relationships within indicators
and between indicators and nutrition status to expand the
available empiric evidence for nutrition classification z-score
threshold ranges in U.S. practice settings.
Methods
Participants and Study Design
This was a single-center study of all children younger than
or equal to 18 years of age seen between October 2015 and
September 2016 by the Nutrition Services Department at
Children’s Mercy Hospital (CMH) and affiliated clinics. No
child was excluded for any reason irrespective of underly-
ing pathological conditions or anatomical deformities. All
children were enrolled under a protocol that was reviewed
and approved by the institutional review board at our CMH.
All nutrition staff were required to participate in pediatric
malnutrition competency training and assessment prior to
study involvement. This included a presentation for all staff
members with accompanying written resource materials
on nutrition classification. The completion of case studies
was required to practice identification of indicators for
diagnosing malnutrition and to write appropriate problem,
etiology, signs/symptoms statements. (problem, etiology,
125
signs/symptoms statements are nutrition diagnostic sen-
tences describing the nutrition problem being identified, the
cause or contributing factors of the problem, and evidence
supporting the diagnosis.)16 Practice sessions were held to
identify humeral landmarks, locate the mid-upper arm,
measure MUAC, and assist with proper documentation of
malnutrition diagnoses. A competency quiz was required
to be completed by all staff members. An additional com-
petency presentation and review was conducted 9 months
later.
Data Collection
Per hospital protocol, children who could stand unassisted
were positioned with their heels, buttocks, and head in
contact with a height rule and their height measured using
a wall-mounted stadiometer. Recumbent length was mea-
sured through 24 months of age in all infants and in children
25–36 months of age who were unable to stand using an in-
fantometer. In the fractionally small proportion of children
for whom standing height or recumbent length could not be
measured (eg, scoliosis, spasticity, contractures), segmental
length was obtained by summation of measurements from
the top of the head to the acromion, the acromion to the
iliac crest, the iliac crest to the patella, and the patella to
the bottom of the heel.17 All length/height measures were
obtained to the nearest 0.1 cm. Each child was weighed with
no shoes and as little outer clothing as possible using an
electronic scale. Weight was measured to the nearest gram
in infants and to the nearest 0.1 kg in older children and
adolescents. All length/height and weight measurements
were evaluated against reference growth charts constructed
by the CDC (eg, weight and length/height for age from birth
to 36 months, weight and length for age from 2–20 years).18
MUAC was measured to the nearest 0.1 cm at the midpoint
of the humerus, between the acromion and olecranon, with
the arm hanging down at the child’s side using a paper-based
circumferential measuring tape. MUAC measurements were
evaluated against reference curves constructed from CDC
NHANES data as described later.19
Nutrition status was determined by reviewing biochemi-
cal data; prior history; anthropometrics; weight gain veloc-
ity; weight loss, if present; and nutrient intake.16 In an effort
to systematically assign nutrition classification, indicators
from the AND/ASPEN consensus statement were employed
to diagnose and treat patients aged between 1 month and
18 years.5 This included single data points for weight-
for-length z-score, BMI z-score, and MUAC z-score. Two
or more data points were used to determine weight gain
velocity, weight loss, deceleration in weight-for-length z-
score, and estimation of adequacy of nutrient intake. In a
subset of children (no less than 20%), nutrition classification
was independently assigned by a blinded reviewer via retro-
spective review of patient data. Of 10 registered dietitians
126
serving as reviewers, 3 were randomly assigned to each
pediatric profile and asked to provide their assessments of
nutrition status. Database entry was performed by a single
individual, and 100% of the entries were quality assured by a
second individual. Incomplete datasets were permitted if at
least 1 anthropometric z-score (eg, BMI, weight-for-length,
MUAC) could be computed.
Data Analyses
Lambda, μ, and σ data from the CDC were used to
calculate gender-specific and age-specific z-scores for height,
weight, weight-for-length (in infants aged 24 months or
younger), and BMI (in children older than 24 months).19
Lambda, μ, and σ data for the calculation of MUAC
z-scores were generated and validated at our institution
based on anthropometric data (NHANES) from years
1999–2012.15 The z-scores were calculated according to the
following:
zi = (((xi /M)∧ L) − 1)/(LS)
where zi represents the individual z-score, xi the individual
MUAC value, and L, M, S the λ, μ, and σ values, respec-
tively. For cases where L = 0, the z-score was calculated
according to zi = ln(xi /M)/S. Extreme outliers that may
have been the result of measurement/data entry error were
identified numerically (ie, values in excess of ±8 standard
deviations from the mean) and examined against the other
anthropometric values for that child. Only those values that
met all of the following 3 criteria were rejected: biologically
implausible, highly discordant with the other measures, and
could not be reconciled by the registered dietitian.
Descriptive statistics (including means, medians,
standard deviations, and frequency charts) were compiled
for raw anthropometric data and anthropometric z-scores.
Correlations between BMI z-score or weight-for-length
z-score and MUAC z-score were examined by least squares
linear regression. Differences in mean z-scores by assigned
nutrition classification were determined using analysis
of variance. Bland-Altman plots were used to explore
the limits of agreement between z-scores. Reliability
between raters with respect to nutrition classification was
assessed with the intraclass correlation coefficient. All
statistical analyses were performed in SPSS version 23
(IBM, Armonk, NY).
Results
A total of 5,004 children were evaluated by 59 registered
dietitians. Patients averaged 7.5 ± 5.7 years of age,
with a slight preponderance of boys (2668, 53%) over
girls (2336, 47%). The majority of children (3774, 75%)
were evaluated in an outpatient setting (eg, general
pediatrics, gastroenterology, pulmonology, endocrinology,
Nutrition in Clinical Practice 33(1)
hematology/oncology, cardiology, weight management, and
feeding clinics). A nutrition classification was submitted
for 97.2% of children. Sufficient anthropometric data
were provided for the calculation of BMI z-score in 3,802
children (median 9.3 years, range 2–18 years), weight-for-
length z-score in 1,131 infants (median 10 months, range
2–23 months), and MUAC z-score in 4,972 infants and
children. The distributions of age, weight, and length/height
for the participants are depicted in Figure 1. Notably, the
children enrolled in this investigation were slightly lighter
and shorter than the average U.S. population as evidenced
by mean z-scores for weight (−0.55) and length/height
(−0.81) that fell below zero. However, this population of
children was also more varied than the U.S. population as
reflected by standard deviations for z-score that exceeded 1
for both weight (1.90) and length/height (1.66).
As illustrated in Figure 2, MUAC was significantly corre-
lated with BMI (slope, 0.63; intercept, −0.4; r = 0.789; P <
.01) and weight-for-length (slope, 0.56; intercept; −0.11; r =
0.638; P < .01). In both cases, the intercept of the regression
equation was negative, suggesting that, on average, MUAC
z-score values were slightly lower than corresponding BMI
or weight-for-length z-scores. A slope of <1 for both
relationships suggests that a 1-unit (ie, 1 standard deviation)
change in BMI or weight-for-length corresponds with less
than a full standard deviation difference in MUAC z-score.
In essence, MUAC z-scores span a narrower range of values
than either BMI or weight-for-length. As such, the mean
MUAC z-score is lower in overweight children and higher
in severely malnourished children than the corresponding
BMI or weight-for-length z-score (Figure 3).
Importantly, the range of MUAC, BMI, and weight-
for-length z-scores distributed among the registered dieti-
tian classifications was very broad (Figure 4a,b). When
compared with the z-score thresholds recommended by
AND/ASPEN, the majority of children classified as over-
weight or normal by the registered dietitian have corre-
sponding z-score rages of >1 and 1 to −1, respectively,
whether considering BMI, weight-for-length, or MUAC
(Table 1). There was a similar finding for children classified
with mild malnutrition and the MUAC z-score range of −1
to −2 (Table 1). However, for the other classifications, less
than a majority of z-score ranges were concordant with the
recommended classification (Table 1). As a result of this
large degree of overlap in z-scores, all 3 of the parameters
vary with respect to their predictive performance.
Tables 2 and 3 detail concordance between MUAC z-
scores and BMI or weight-for-length z-scores when exam-
ined quantitatively without regard for registered dietitian
classification. The data in these tables reflect the fact that
MUAC z-scores tend to be lower than reference z-scores
in overweight children and higher in those children with
more than moderate malnutrition. Consequently, different
nutrition status thresholds or z-score ranges may be required
Stephens et al 127

Figure 1. Histograms of age, weight, and length/height for infants (left) and children (right) enrolled in this investigation.
128
Figure 2. Scatterplot detailing the relationship between body
mass index z-score or weight-for-length z-score and mid-upper
arm circumference z-score.
for the different anthropometric parameters if similar con-
clusions expect to be drawn.
In an attempt to examine concordance between raters
with respect to nutrition classification, the raters partici-
pated in a blinded, retrospective review of data from 1,379
(27.6%) patients. The interclass correlation coefficient was
0.918 (95% confidence interval, 0.910-0.925), suggesting a
Figure 3. Mean (99% confidence limits) of body mass index and mid-upper arm circumference z-scores in children (left) and
weight-for-length and mid-upper arm circumference z-scores in infants (right) stratified by nutrition classification.
Nutrition in Clinical Practice 33(1)
high degree of concordance between raters at our institution
when classifying the nutrition status of children.
Discussion
Assessing and monitoring pediatric malnutrition has been
reemphasized with the recent publication of consensus
indicators.5 The use of standard anthropometrics is not
new, but the use of MUAC was something that had not
previously been incorporated into diagnostic criteria. Given
the acknowledgment by AND/ASPEN that recommended
indicators are a "work in progress,” we anticipated that
the integration of MUAC into practice standards at our
institution would raise the question of accuracy with our
dietitians when discordance between this new indicator
and established indicators (ie, BMI and weight-for-length)
arose.20 We could also foresee concerns surrounding reliance
on MUAC for special populations wherein height and/or
weight were unavailable. Consequently, this study was un-
dertaken concurrently with practice changes to examine
the performance of this newest indicator in the context of
established indicators.
Where possible, a comprehensive set of anthropometrics
were collected on the inpatients and outpatients seen by
nutrition services. However, there was a subset of patients in
whom selected measurements were unavailable. These mea-
sures were represented most often by height/length, followed
by weight, and then MUAC. Accordingly, the proportion
of cases for which the established indicators of BMI and
Stephens et al 129

Figure 4. (a) Histograms depicting the range of body mass index and mid-upper arm circumference z-scores in children, stratified
by nutrition classification. Median z-score values for each primary indicator are embedded in the panels. (b) Histograms depicting
the range of weight-for-length and mid-upper arm circumference z-scores in infants, stratified by nutrition classification. Median
z-score values for each primary indicator are embedded in the panels. BMI, body mass index; cm, centimeter; kg, kilogram; mos,
months; MUAC, mid-upper arm circumference; Wt-for-Lt, weight-for-length.
130 Nutrition in Clinical Practice 33(1)

Table 1. Percentage of Participants Where Predefined Z-Score Range Matches the Registered Dietitian Classification.

Registered Dietitian Over None Mild Moderate Severe

z-score range >1 1 to −1 −1 to −2 −2 to −3 <−3

25.4 48.3 47.6 59.2
BMI 97.5 2.5 68.7 6.0 45.1 6.6 47.3 5.1 40.8
21.9 26.0 31.9 77.3
Weight-for-length 94.4 5.6 59.8 18.3 48.8 25.1 48.6 19.4 22.7
15.4 25.3 44.4 71.6
MUAC 76.4 23.6 75.5 9.0 66.7 8.0 48.7 6.8 28.4

Superscripted values reflect the percentage of participants in each grouping with a z-score higher than the predefined range, whereas subscripted
values represent the percentage of participants in each grouping with a z-score lower than the predefined range. BMI, body mass index; MUAC,
mid-upper arm circumference.

Table 2. Concordance Between MUAC and BMI Z-Score Ranges Clustered in 1 Standard Deviation Intervals.

MUAC z-score

BMI z-score >3 3 to 2.1 2 to 1.1 1 to −0.9 −1 to −1.9 −2 to −2.9 ࣘ−3

>3 10 11 8 5 3 1 1
3 to 2.1 2 105 268 46 5 2 0
2 to 1.1 0 10 156 404 6 1 1
1 to −0.9 1 3 61 1167 404 47 10
−1 to −1.9 0 0 2 130 295 98 18
−2 to −2.9 0 1 1 29 103 132 33
ࣘ−3 0 1 2 11 31 53 60

BMI, body mass index; MUAC, mid-upper arm circumference.

Table 3. Concordance Between MUAC and Weight-for-Length Z-Score Ranges Clustered in 1 Standard Deviation Intervals.

MUAC z-score

Wt-for-Lt z-score >3 3 to 2.1 2 to 1.1 1 to −0.9 −1 to −1.9 −2 to −2.9 ࣘ−3

>3 6 0 1 2 1 0 1
3 to 2.1 1 8 9 3 2 1 0
2 to 1.1 3 13 58 41 2 1 0
1 to −0.9 2 16 60 304 65 14 5
−1 to −1.9 1 2 9 104 95 33 9
−2 to −2.9 0 1 0 30 68 57 17
ࣘ−3 0 0 0 10 25 25 19

MUAC, mid-upper arm circumference; Wt-for-Lt, weight-for-length.

weight-for-length z-score could not be calculated (1.4%)
exceeded, by slightly more than 2-fold, the proportion of
cases for which MUAC z-score could not be assessed (0.6%).
Importantly, when both measures were available, we could
demonstrate a strong correlation between MUAC and BMI
(r = 0.79) or weight-for-length (0.64) z-scores. However, the
indicators were not wholly concordant when stratified by the
z-score ranges recommended in the consensus guidelines.
MUAC z-scores appear to span a narrower range than z-
scores for BMI or weight-for-length, resulting in values
that are slightly smaller in the overweight/obese population
and slightly larger in the severely malnourished. These data
demonstrate that the z-score ranges used to define various
stages of malnutrition may not be the same for all indicators
of malnutrition and corroborate the impressions of earlier
colleagues who report that the different anthropometric
indices require index-specific interpretation.21,22
The nature of the population examined in this study
could be viewed as a limitation of this investigation. At
our institution, dietitians are engaged to evaluate patients
triggered to be “at risk” for nutrition concerns. These
include children in units caring for the critically ill (ie,
pediatric intensive care unit, neonatal intensive care unit,
burn unit); children with chronic underlying diseases (eg,
cystic fibrosis, cancer, diabetes, kidney disease, failure to
thrive); children with food allergies or special diet orders, in-
cluding specialty formulas; children on selected medications
including those with food–drug interactions; and children
Stephens et al
with poor appetite, excessive weight gain, significant weight
loss, inadequate growth, feeding tubes, or eating disorders.
Although broadly representative of the pediatric patients
cared for at our institution, they may not reflect the pop-
ulation at large. However, the broad distributions of age,
weight, and stature demonstrated across our population
provide some reassurance that trends in the relationship
between MUAC and BMI or weight-for-length were not
missed in a subset of children.
Consideration should also be given to the extreme vari-
ability in z-scores observed across children of every nutri-
tion classifications. Some examples may undoubtedly be a
result of measurement or transcription error. However, for
the majority of cases, this is a reflection of the pediatric pop-
ulation for whom we care. We observed BMI and weight-for-
length estimates to be uncharacteristically low in children
that were otherwise nutritionally replete such as those with
scoliosis or genetic conditions that affect a patient’s overall
growth. An extreme example in our population is the case
of a 17-year-old the size of a 2.5-year-old. Conversely,
we noted that BMI was atypically large in moderately or
severely malnourished patients where extreme and rapid
weight loss overlay the primary medical concern of obesity.
These scenarios underscore the importance of having sev-
eral independent indicators on which to rely when a single
indicator may be impractical or inaccessible. In this paper,
we evaluate MUAC, which has demonstrated longstanding
utility in the global healthcare arena, but other indicators
may also have a role.
As dietitians, our goal is to accurately diagnose malnu-
trition with the best standards available. The recent publica-
tion of parameters that enable MUAC z-score estimation in
children through 18 years of age permitted a careful exam-
ination of the recommended indicators across the whole of
our pediatric population using the same growth references
that are used for BMI and weight-for-length. In going
beyond the process of simply integrating these assessments
into practice to recording and evaluating these measures,
our staff began to accumulate empiric evidence for the
strength, limitations, and added value that each indicator
affords. As other groups reveal their findings we should be
able to not only standardize the diagnostic indicators we
apply but also refine the thresholds for malnutrition so as
to maximize our ability to predict and prevent malnutrition
in children of all ages.
Acknowledgments
Members of the CMH Nutrition Services Z-Score Research
Team in alphabetical order are the following: Linda Maria
Ahmu, Linette Ayers, Stella Bagby, Kate Barkman, Shannon
Beattie, Deborah Biondo, Linda Bird, Kimberly Brayer, Sarah
Camey, Christina Cash, Tina Coleman, Shelby Courtright,
Debbie Davis, Tracy Delaney, Lora Edwards, Ann Franklin,
Rachel Finn, Stephanie Garver, Nancy Green, Whitney Haas,
131
Lauren Hand, Beth Harrell, Cindy Hensley, Lori Hillsman,
Karen Josiah, Nicole Knecht, Margaret Kriley, Lauren Leible,
Erin Lindhorst, Sarah Marcy, Melissa Mereghetti, Bridget
Meyers, Jennifer Morton, Kim Munsterman, Melissa Newmas-
ter, Carrie Novak, Leah Oladitan, Meike Orlick, Sarah Owens,
Lucy Pappas, Sarah Peters, Lindsey Quint, Elena Riggs, Kasey
Rowzer, Olivia Scheuerman, Audrey Snell, Mindy Storm,
Kristi Thaete, Sara Thomas, Lindsey Thompson, Jessica Tower,
Kelly Tracy, Connie Urich, Barbara Warady, Tarine Weihe,
Jamie Wilkins.
Statement of Authorship
K. Stephens, A. Escobar, E. Jennison, and S. Abdel-Rahman
contributed to the conception and design of the research; all
authors contributed to the acquisition, analysis, and interpre-
tation of the data; K. Stephens and S. Abdel-Rahman drafted
the manuscript; all authors reviewed and critically revised the
manuscript, agree to be fully accountable for ensuring the
integrity and accuracy of the work, and read and approved the
final manuscript.
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circumference, body mass index and weight loss as indices of
undernutrition in acutely hospitalized patients. Clin Nutr. 2003;22:307-
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sigma values for determining mid-upper arm circumference Z-scores
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Clinical Research

Nutrition in Clinical Practice

Volume 33 Number 1
Monitoring Nutrition in Critical Illness: What Can We Use? February 2018 133–146

C 2017 American Society for

Parenteral and Enteral Nutrition

DOI: 10.1177/0884533617706312
wileyonlinelibrary.com
Suzie Ferrie, AdvAPD, MNutrDiet, PhD1,2 ; and Erica Tsang, APD, MNutrDiet1

Abstract
Background: Nutrition monitoring in the context of critical care presents unique challenges. Traditionally used anthropometric
and biochemical markers may be difficult to obtain or confounded by factors such as fluid status and the inflammatory response. A
previous survey identified 15 parameters in common use, all of which have confounding influences during critical illness. Materials
and Methods: A literature search was conducted to assess current use of commonly used nutrition-monitoring parameters and to
explore other possible methods that might be more useful. More than 1000 journal articles were reviewed to identify indicators of
nutrition status or nutrition progress that have been used in ICU studies. The most recent 200 articles were examined to quantify
the number of occurrences for each indicator. Each parameter was rated for availability and feasibility in the ICU. Results: There
were 53 parameters found, including the 15 already identified as commonly used; 27 were used in ࣙ3 recent studies. Less-well-
established nutrition indicators with potential for use in the ICU (moderate or high feasibility and availability) included ultrasound
measurement of arm or leg muscle thickness, fatigue scoring with the Chalder scale, urinary creatinine assay, and serum insulin-like
growth factor 1 level. None of these was among the commonly used indicators in recent studies. Conclusion: This study identifies
commonly used nutrition-monitoring parameters and discusses their feasibility and availability in the critical care setting. Further
investigation of nutrition indicators in ICU is needed, ideally as part of a randomized trial to reduce the effect of the many possible
confounding factors. (Nutr Clin Pract. 2018;33:133–146)

Keywords
nutrition assessment; critical illness; intensive care units; nutritional status

What parameters are used to monitor nutrition progress in Methods

the critically ill? A previous survey described the practices
of intensive care unit (ICU) dietitians in Australia and
New Zealand in their nutrition assessment and monitoring
of critically ill patients.1 The survey interviewed at least
1 dietitian in each of the 182 ICUs in Australia and
New Zealand and found that the group reported using a
variety of indicators when identifying patients most in need
of nutrition support and when measuring their nutrition
progress. The most commonly used nutrition indicator used
by this group was body weight (reported by 53% of the
dietitians), followed by biochemical parameters (reported
by 50%), including prealbumin, albumin, hemoglobin, and
nitrogen balance. Anthropometric measures were used by
<10% of the respondent dietitians. The literature, however,
yields a variety of other measures that may be considered
for everyday use in the ICU setting. Ideally, such measures
would indicate how patients respond to nutrition in the
short term and would correlate with patients’ long-term
outcomes. The aim of this review was to assess current
use of such nutrition parameters, to identify any additional
measures of nutrition status or nutrition risk that studies
in the literature used (focusing on parameters that may
be associated with objective meaningful patient outcomes),
and to evaluate their potential for use.
A search was conducted for all publications in MEDLINE,
Embase, and CINAHL from the earliest date available in
each database and without any limitation on language of
publication. The search was conducted as follows: terms ex-
pressing the target population—“critical illness,” “critically
ill,” “critical care,” “intensive care,” “ICU,” “ITU,” “sepsis,”
“bacteremia”; combined with terms expressing outcomes—
“outcome$,” “predict$,” “indicat$,” “infectio$,” “wound,”
“complicat$,” “mortality,” “morbidity,” “LOS” and “stay”;
as well as “nutrition$” in combination with “assessment,”
“risk,” “screening,” “status.” The search was confined
through standard restrictions to clinical studies of adult
patients.
From the 1 Royal Prince Alfred Hospital, Sydney, Australia; and the
2 Universityof Sydney, Sydney, Australia.
Financial disclosure: None declared.
Conflicts of interest: None declared.
This article originally appeared online on December 14, 2018.
Corresponding Author:
Suzie Ferrie, AdvAPD, MNutrDiet, PhD, Critical Care Dietitian,
Royal Prince Alfred Hospital, Missenden Road, Camperdown NSW
2050, Australia.
Email: suzie.ferrie@sswahs.nsw.gov.au
134
Each article obtained in the search was independently
examined by 2 researchers to identify any parameters dis-
cussed/used as general indicators of nutrition status or
nutrition progress (serum levels of individual micronutrients
were excluded) and, in particular, indicators of protein
status, muscle mass, or catabolism. All such parameters
found were listed, and then both researchers independently
rated each for their availability and feasibility as a nutrition
assessment or monitoring parameter for use in the ICU
setting. Differences were resolved by discussion and, where
needed, further enquiry from colleagues both locally and
internationally.
Availability was assessed as follows:
High: the equipment or test can be obtained easily or
routinely in nearly all hospitals.
Moderate: the equipment or test can be obtained in many
hospitals but may not be routinely available.
Low: the equipment or test is available only at selected
facilities or for research purposes.
Feasibility was defined as follows:
High: the test is easy to order or administer, without
significant training requirements, expense, or organi-
zational effort, and critical illness is not a barrier to
implementing the test.
Moderate: the test may require additional effort, training,
or equipment at a moderate cost, or some aspect of
critical illness or the ICU setting will occasionally be a
barrier to implementing the test.
Low: there is a high expense or technical difficulty asso-
ciated with the test; it is invasive or onerous to arrange;
or some aspect of critical illness or the ICU setting will
frequently be a barrier to implementing the test.
To assess how commonly used these parameters are,
the most recent 200 articles (from January 2013 onwards)
were closely examined to quantify all parameters used in
each study. Less commonly used parameters that were rated
at least moderate for feasibility and availability were then
identified, and all articles from the full set were retrieved to
explore their potential use and association with outcome in
the ICU setting.
Results
A total of 1027 journal articles obtained in the search
mentioned 53 general nutrition-related parameters. Of the
200 most recent articles, 16 articles were excluded, as they
were not studies of adult critically ill patients; a further 72
articles were excluded because they did not measure any
nutrition parameter after baseline. In the remaining 112
recent articles, the number of occurrences was counted for
Nutrition in Clinical Practice 33(1)
each indicator; see Figure 1 for all indicators that were
measured after baseline in ࣙ3 studies.
The most commonly used parameters in these studies
were simple anthropometric and biochemical indicators,
such as serum albumin level and body weight. Other
than weight—which is significantly confounded by fluid
in critical illness (and therefore rated only moderate for
feasibility—the most commonly used measures were rated
high for availability and high for feasibility. See Table 1 for
the rating of all indicators found.
High-feasibility measures that were rated moderate for
availability included some of the biochemical tests that may
be conducted only in major laboratories (eg, cytokines, α-1-
acid glycoprotein) and the composite scores or indices that
incorporate such tests (eg, the original NUTRIC score [Nu-
trition Risk in the Critically Ill],2 Prognostic Inflammatory
and Nutrition Index [PINI]3 ). Anthropometric measures
relying on skinfold calipers also fell into this category (eg,
triceps skinfold thickness and the calculated mid upper arm
muscle circumference based on it).
High-availability measures that were rated as moderate
for feasibility included body weight and height (and calcu-
lations based on them) and fatigue score, which requires the
patient to be sufficiently alert to answer questions to rate
various subjective aspects of fatigue.
Moderate-feasibility measures that were rated as moder-
ate for availability included handgrip strength (which relies
on a handgrip dynamometer and can be performed only
if the patient is alert and able to follow commands) and
ultrasound measurements of the muscles in the upper arm
and forearm and the upper leg at the two-thirds point
(near the knee), which require some training and a small 2-
dimensional ultrasonograph of the sort commonly used in
ICUs to assist in venous catheter placement. The mid thigh
measurement of the rectus femoris muscle was rated lower
for feasibility as it is technically more difficult, particularly
if the patient has large limbs, edema or excess adipose
tissue. See Table 2 for details of the less common indicators
that were rated at least moderate for both availability and
feasibility.
Parameters mentioned in the literature that were rated
low for either feasibility or availability included (1) unusual
laboratory tests (eg, plasma fibronectin level, individual
amino acids measured in blood or urine, or mononuclear
cell mitochondrial complex 1) and any scores or indices
relying on these (eg, Prognostic Nutritional Index [PNI]4
or nitrogen balance calculated by assaying urinary total
nitrogen rather than extrapolating from urea nitrogen),
(2) any tests requiring radiolabeled substances, (3) delayed
hypersensitivity skin testing, (4) any tests requiring body
composition equipment (eg, dual-energy x-ray absorptiom-
etry scan or bioelectrical impedance), (5) tissue biopsy, or
(6) involuntary muscle contraction measurements. Lung
function tests requiring voluntary respiratory effort were
Ferrie and Tsang
Figure 1. Number of occurrences of nutrition indicators in 112 recent nutrition studies based in the intensive care unit.
rated low for feasibility given that many patients in the ICU
will require some form of ventilation for much of their
ICU stay. Parameters requiring the patient to mobilize (eg,
standing height) may have low feasibility in the critically ill.
Discussion
The most commonly used parameters in this audit of recent
ICU nutrition articles were simple anthropometric measure-
ments and routine laboratory tests that have the highest
availability and feasibility, and many of these were the same
indicators reported in common use by ICU dietitians in
Australia and New Zealand.1 These continue to be widely
used despite the fact that they do not have consistent
association with outcome.5
Practical constraints are one reason for this. Limb cir-
cumferences require only a nonstretchable tape measure
135
and a marker pen, and it can be easily performed on an
unconscious patient, with good reproducibility6 ; skinfold
measurements (which can then be used to estimate mus-
cle area7,8 ) require special skinfold calipers and a small
amount of training to achieve accuracy and consistency
of technique. Limb circumferences and skinfolds at upper
body sites tend not to be affected by the body’s fluid status
unless the patient is positioned in an unusual way (eg,
lying completely flat or prone). Such measures have been
established as being useful outside the ICU, particularly
when serial measures are used to identify trends. For the
critically ill, however, simple anthropometry may be less
useful. While mid arm circumference correlated closely
with weight change6 and low mid arm circumference pre-
dicted ICU mortality in 1 study9 and 6-month mortality
in another,10 elsewhere there was no such association for
either arm circumference or skinfolds,11,12 and mid arm
136 Nutrition in Clinical Practice 33(1)

Table 1. Nutrition-Related Assessment and Monitoring Parameters Used in Studies of the Critically Ill.

Availability

Feasibility High Moderate Low

High Mid upper arm circumference Triceps skinfold thickness Serum amino acids
Recumbent body lengtha Mid upper arm muscle Plasma fibronectin
Recumbent arm wingspana circumference Serum leptin
Height estimated from ulnar Serum prealbumina Mononuclear cell mitochondrial
lengtha Serum retinol-binding protein complex 1
Serum albumina Serum cytokine level (interleukin Serum α-1 acid glycoprotein
Serum transferrina 6) PINI score
Serum ureaa Original NUTRIC score Serum α-1-antitrypsin
Serum creatininea Maastricht Index
Hemoglobina Insulin-like growth factor 1
Total lymphocyte counta
Subjective Global Assessmenta
NRS-2002 score
Updated NUTRIC score
Estimated body cell mass (from
limb circumferences)
Moderate Weighta Ultrasound upper arm Nitrogen balance (urinary total
Percentage weight changea measurement nitrogen)
Body mass indexa Ultrasound forearm measurement Urinary 3-methyl histidine
Nitrogen balance (urinary urea Ultrasound thigh two-thirds Body composition (DEXA scan)
nitrogen)a measurement Body composition (bioelectrical
Urinary creatinine Handgrip strength impedance)
Fatigue score Modified PNI score (with grip Body composition (in vivo
strength) neutron activation)
Whole-body amino acid kinetics
(radiolabeled Leu or Tyr)
Delayed hypersensitivity skin
testing
PNI score (with skin testing)
Low Standing height Ultrasound rectus femoris Adductor pollicis involuntary
thickness muscle function
Muscle thickness measurement on MRI measurement of muscle
CT scan bioenergetics
Lung function testsa Limb arteriovenous amino acid
level comparisons
Lymphocyte activity measured
with radiolabeled thymidine
Muscle biopsy measure of protein
synthesis
Metabolomic analysis

CT, computed tomography; DEXA, dual-energy x-ray absorptiometry; MRI, magnetic resonance imaging; NRS, nutrition risk screening;
NUTRIC, Nutrition Risk in the Critically Ill; PINI, prognostic inflammatory and nutrition index; PNI, prognostic nutrition index.
a Reported as used by dietitians in a recent survey.1

circumference had no consistent association with energy
intake and expenditure or with muscle biopsy in 1 study.13
Despite correlating with outcome when spot-tested, arm
and leg anthropometry is slow to respond to nutrition
therapies.14,15 Similar criticisms can be made of assess-
ment tools such as Subjective Global Assessment16 and
Nutritional Risk Screening,17 which are useful in an ini-
tial assessment of nutrition status/risk and predictive of
outcome14,18-21 but cannot be used for short-term monitor-
ing, as they are slow to change over time.
Simple measurement of body weight is a common and
available parameter that can present some feasibility dif-
ficulties in the ICU setting. It can be difficult to weigh
a patient connected to ventilation and monitoring lines.
Weighing beds and lifters may have limited accuracy, and
even when weight can be obtained, it is (early in the ICU
 Table 2. Novel Parameters for Assessing and Monitoring Nutrition in the Critically Ill.
Parameter How to Measure It
Ultrasound measure of Two-dimensional ultrasonograph
muscle thickness transducer applied
perpendicularly to surface of
mid upper arm, mid forearm, or
mid upper leg. Muscle thickness
or muscle area is measured on
the image.
CT scan measure of Scroll through CT images to locate
muscle area the correct body cross section
(eg, middle of third lumbar
vertebra). Measure the muscle
area with digital analysis or
manually.
Fatigue score Verbal administration of
qualitative questionnaire such as
Chalder scale (see Figure 2) or
POMS or simple visual analog
scale.
137
Interpretation Comments on Use Studies Found Association With Outcome
Assess muscle size Can be measured Gruther (2008)105 Rectus femoris thickness negatively correlated
independent of fat frequently; measures with ICU length of stay (observational
and fluid. change within days. study, n = 118).
Puthucheary (2013)102 Rectus femoris muscle area change over 7 d
correlated with muscle breakdown and
SOFA score (observational study, n = 28).
Parry (2015)103 Rectus femoris muscle area and muscle
thickness over 10 d correlated with muscle
strength (observational study, n = 22).
Compare with normal Requires an existing CT Moisey (2013)40 Total muscle area at third lumbar vertebra
values (eg, for psoas scan of head (for predicted mortality and LOS in elderly
area adjusted for masseter muscle) or patients with trauma (observational study,
height).38 abdomen/pelvis/spine (for n = 149).
lumbar psoas muscle). Masuda (2014)108 Preoperative psoas area predicted sepsis and
Sequential measures (if mortality as well as response to nutrition
scan images are available) support after liver transplant
must be at same body (observational study, n = 204).
cross section each time. Weijs (2014)109 Total muscle area at third lumbar vertebra
predicted mortality (observational study, n
= 240).
Fairchild (2015)41 Pretrauma psoas area predicted discharge
destination in elderly patients with trauma
(observational study, n = 252).
Kalafateli (2016)110 Perioperative psoas area predicted mortality
and LOS after liver transplant
(observational study, n = 232).
Paknikar (2016)42 Preoperative psoas area predicted mortality
and complication risk in cardiovascular
surgery (observational study, n = 295).
Wallace (2017)37 Both psoas and masseter predicted 2-y
mortality in elderly patients with trauma
(observational study, n = 487).
Any improvement Requires patient to be Watters (1997)29 No difference in fatigue or handgrip scores
relates to overall conscious and able to between groups; no difference in ICU or
functional and communicate yes/no. Can hospital LOS (RCT, n = 28).
well-being status. be measured frequently; Gupta (2001)111 Correlated with respiratory function over 7 d
score changes (observational study, n = 15).
significantly within days. Ferrie (2016)112 Correlated with handgrip and muscle
thickness at ICU day 7; correlated with
protein intake; Chalder score >8 predictive
of hospital mortality (RCT, n = 119).
(continued)
138
Table 2. (continued)
Parameter How to Measure It
NUTRIC score Updated version of score (without Score ࣙ5 represents
IL-6) consists of points allocated patients likely to
for variables collected at ICU
admission (age, APACHE II
score, SOFA score, number of
comorbidities, and days in
hospital prior to ICU).
Serum IGF-1 level also 5-mL specimen of clotted blood.
known as Some laboratories require blood
somatomedin C to be spun immediately and
frozen serum sent for the
analysis; check local
requirements.
APACHE, Acute Physiology and Chronic Health Evaluation; CT, computed tomography; ICU, intensive care unit; IGF-1, insulin-like growth factor 1; IL-6, interleukin 6; LOS, length of
stay; NUTRIC, Nutrition Risk in the Critically Ill; POMS, Profile of Mood States; RCT, randomized controlled trial; SOFA, Sepsis-Related Organ Function Assessment.
Interpretation Comments on Use Studies Found Association With Outcome
Scored from variables at Heyland (2011)2 Predicts effect of nutrition support in
ICU admission only. reducing the risk-mortality relationship
benefit from optimal (observational study, n = 211).
nutrition support in Coltman (2015)113 Higher score associated with muscle wasting,
ICU. reduced handgrip strength, and increased
LOS (observational study, n = 294).
Ferrie (2016)112 Higher score associated with reduced
handgrip strength and muscle thickness but
no effect of nutrition support on outcome
(RCT, n = 119).
Reference range is Weekly measure may track Hawker (1987)76 Correlated with 5-d nitrogen balance and
based on age and protein status. intake (observational study, n = 20).
sex; below-normal Mattox (1988)36 Correlated with 21-d nitrogen balance
levels associated (observational study, n = 12).
with poor nutrition Cavaliere (1992)114 Postoperative level correlated with
status. preoperative nutrition (observational study,
n = 24).
Clark (1996)71 No correlation with total body protein
measured by in vivo neutron activation over
21 d of ICU (observational study, n = 24).
Mertes (1996)115 Correlated with 6-d nitrogen balance
(observational study, n = 24).
Tormo (1999)116 No correlation with mortality (observational
study, n = 119).
Saadeh (2001)117 Correlated with 12-d nitrogen balance
(observational study, n = 5).
Gianotti (2002)118 Correlated with 28-d nitrogen balance after
burn (observational study, n = 22).
Sevette (2005)119 Correlated with 14-d nitrogen balance (RCT,
n = 35).
Kyle (2006)120 Correlated with 5-d nutrition intake
(observational study, n = 123).
Tejera (2007)121 Admission level correlated with hospital
mortality (observational study, n = 226).
Khan (2015)122 No correlation with short-term catabolism in
sepsis model (observational study, n = 6).
Ferrie and Tsang
Figure 2. Chalder Fatigue Scale. Adapted from Chalder T,
Berelowitz G, Pawlikowska T, et al. Development of a fatigue
scale. J Psychosom Res. 1993;37(2):147-153. Copyright 1993
by Elsevier.
admission) more a reflector of fluid status than nutrition
status.22 Loss of weight due to muscle mass loss may be
masked by fluid weight gain so that the worse outcomes
in the ICU are among those who maintain or gain weight
rather than lose it.23
Critical illness and the ICU setting can present barriers
for other valued tests. For example, handgrip strength has
been shown to predict outcome in a range of settings and
conditions,24 is decreased in proportion to body protein
loss25 and surgical stress,26 and appears to respond early
to nutrition intervention27,28 ; however, it is not possible
to measure it with an unconscious patient and may be
confounded by sedation even when patients are awake. Al-
though they may correlate well with nutrition status,29 tests
of respiratory function, such as FEV1 (forced expiratory
volume in 1 second) or a simple “blow this paper” test,
require patients to be alert and free of ventilatory support.
Fatigue Score
Fatigue scoring systems require the patient to respond
and evaluate subjective impressions of fatigue, so they
have limited applicability early in the ICU admission for
most patients. However, they are attractive because a short
and simple set of questions (eg, the 11-question Chalder
Fatigue Scale30 ; see Figure 2) requires minimal resources to
administer. Fatigue affects the patient’s ability to participate
in treatments and rehabilitation, as well as one’s mental
health,31 and may be affected by nutrition32 and reflect
nutrition status.33 Unlike many of the other indicators that
139
are at best surrogate measures of the patient’s condition,
fatigue scoring is a direct and meaningful measure that is
truly patient focused.
Indicators With Low Feasibility and/or Low
Availability
Parameters with low availability are not usually possible in
an ordinary hospital environment—for example, radiola-
beled amino acid studies, muscle biopsy, or specialized labo-
ratory tests such as fibronectin (which has been suggested as
a sensitive indicator of response to nutrition34-36 ). Others—
such as dual-energy x-ray absorptiometry scanning, mag-
netic resonance imaging, or computed tomography (CT)
scans—require the patient to be transferred out of the ICU,
and they may involve high doses of radiation, making them
unfeasible for everyday nutrition monitoring of unstable
critically ill patients. Nevertheless, CT scan has been used
in some recent studies to visualize the cross section or
area of particular muscles. Studies have used the masseter
muscle37 (in the cheek) on head CT scans, the psoas muscle38
(adjacent to the lumbar spine) on abdominal CT scans, or
automated scan analysis of total muscle area at a particular
cross section. Measurement is generally limited to patients
who are already undergoing a clinically indicated CT scan,
so it is not useful for ongoing monitoring during the ICU
stay; however, its advantages include the fact that it can be
conducted retrospectively, requires little training, and does
not require the patient to be conscious. The psoas muscle,
in particular, is minimally affected by day-to-day changes
in functional status as, compared with limb muscles, it is
less subject to wasting from disuse. Few studies have used
this measure of patients in the ICU, but it appears to
correlate with total lean body mass37,39 and is associated
with outcome.40-42
Some parameters have low feasibility due to technical
problems that render them impractical in the ICU setting.
One such example is adductor pollicis muscle function,
which can be measured in an unconscious patient by elec-
trically stimulating the nerve and measuring the strength
of thumb contraction.43 Muscle function measured in this
way has been shown to reflect early changes in nutrition,43,44
but it requires specialized equipment and is uncomfortable
and technically difficult45 with low specificity.46 In addition,
it has several confounders among the critically ill, such
as tissue electrical conductivity (affected by skin moisture
that changes constantly and by subcutaneous fat that may
be decreasing over time), tendon contractility (which may
increase in a bedbound person), and muscle mass (which
will usually be catabolized over time in critical illness).
Another example is bioelectrical impedance, which has
been suggested to indicate early changes in nutrition by
measuring body cell mass.47 However, it relies on stable fluid
and electrolyte status, which is uncommon in critical illness.
140
Consequently, the measurements obtained in the ICU tend
to reflect fluid changes rather than body composition.48
Delayed hypersensitivity skin testing (with a mixture of
antigens such as tuberculosis, candida, and mumps), in
addition to being invasive and uncomfortable, appears to
be affected more by severity of illness than by nutrition,
making it more useful as a prognostic indicator49 than a
parameter for nutrition assessment or monitoring.50-52 This
method has fallen out of use, leading to its low rating for
availability. The composite score PNI,4 which includes skin
testing, is rated low as a result. PNI combines serum albumin
in g/dL, serum transferrin in mg/dL, triceps skinfold in
mm, and skin test reactivity rated 0–2. It is expressed as a
percentage risk of complications, as follows:
PNI = 158 − [16.6 × albumin] − [0.78 × tricepsskinfold]
−[0.20 × serumtransferrin] − [5.8 × skintestreactivity].
Its authors suggest that the PNI indicates which patients
would most benefit from nutrition support,4 rather than
measuring nutrition status per se.53 Other researchers have
attempted to modify the PNI to incorporate a more widely
available measure, handgrip strength, as a substitute for the
skin testing54 ; however, the method for this version is poorly
reported (eg, component units are not specified), and the
heavy weighting of the anthropometry component means
that it does not easily identify risk among overweight and
obese patients. In normal-weight patients, it may be more
reflective of the acute phase response than nutrition.55
Similarly, the NUTRIC score2 identifies nutrition risk
rather than nutrition status. It is designed to identify pa-
tients who will benefit most from optimal nutrition support
in the ICU, and it combines several variables collected at
ICU admission. Again, this score is designed as a prognostic
tool rather than for ongoing monitoring. The original
version of NUTRIC incorporated interleukin 6, but this
was subsequently dropped from the scoring56 so that it can
be used in settings where interleukin 6 is not available.
Laboratory Tests
Biochemical measures are convenient to obtain in the ICU
setting; however, improvements in such parameters are not
consistently associated with improvement in outcome when
controlled for severity of illness.5 There may be several
reasons for these limitations. The significant fluid shifts in
critical illness can affect the serum concentrations of several
of the most commonly used biochemical indicators. Visceral
or “hepatic” proteins, such as albumin and prealbumin,
are affected by the acute phase response independent of
nutrition status or nutrition input.57 For example, preal-
bumin level tends to fall at the beginning of the ICU
admission even when nutrition support has been success-
fully initiated,58,59 and the level may recover as the acute
Nutrition in Clinical Practice 33(1)
phase response declines, even if the patient is not receiving
adequate nutrition60 or is continuing to lose weight.61 Yet,
some studies suggest that if the acute phase response is
reasonably stable, the prealbumin levels then correlate with
nutrition intake62,63 but perhaps not outcome.64 Prealbumin
is not available at all hospital laboratories. Serum albumin
level is routinely measured in most hospitals and is a
strong prognostic indicator65 even in critical illness,66,67 but
it has a long half-life and does not respond promptly to
significant alteration in nutrition input,68 making it less
useful as a parameter for sequential monitoring of nutrition
progress—a use not supported in the literature. Similarly,
total lymphocyte count is widely available and valuable as
a prognostic indicator,69,70 leading to its use in screening
tools, but again there is no evidence to support the use
of sequential lymphocyte counts in monitoring a patient’s
response to nutrition support.
Some less common laboratory tests used in the litera-
ture may be better indicators of nutrition than the afore-
mentioned routine tests. However, before less-well-known
indicators are used, it is important to obtain information
about the assay methods and their coefficients of variation,
whether there are particular blood processing and storage
conditions required, whether any losses occur over time
or with altered conditions, how quickly the indicator re-
sponds to change in treatment, whether there are age or
sex differences in results, and whether there is available
reference material to check accuracy and reproducibility.
For nonstandard tests, it may not be easy to answer these
questions satisfactorily.
Insulin-like growth factor 1, also known as
somatomedin-C, is a less common test but appears
potentially viable as an indicator of nitrogen balance.
It mediates the anabolic effects of growth hormone and
therefore should reflect nitrogen utilization; however, in 1
study, it had no correlation with nitrogen balance,34 and
in another there was no association with measurements of
body protein status,71 perhaps because sepsis affects protein
metabolism independent of the insulin-like growth factor 1 /
growth hormone axis. In other studies, though, it correlated
with nitrogen balance72 without being confounded by renal
function73 or the acute phase response.74-76
Composite Indicators
Adjusting mathematically for the effects of the acute phase
response is the approach taken in several composite indices.
One prominent example is the PINI,3 which combines
C-reactive protein, α-1 acid glycoprotein, albumin, and
prealbumin—with all units as mg/L, except for albumin in
g/L. These are combined as follows:
[C − reactive protein × α − 1 acid glycoprotein] /
[albumin × prealbumin].
Ferrie and Tsang
This index has been suggested as a way to relate “nutri-
tion” indicators to the acute phase response. Its authors sug-
gest that scores <10 reflect low or no risk of a poor outcome;
10–20, moderate risk; and >20, high or extreme risk.3 The
PINI appears to predict clinical progress,77 but the strong
influence of C-reactive protein on the score means that the
PINI may simply be reflecting the course of the acute phase
response and its association with clinical progress, rather
than any effect of nutrition.78 The PINI is rated low for avail-
ability, as most hospitals do not perform assays for α-1 acid
glycoprotein (also known as orosomucoid), an acute phase
protein that may be independently predictive of outcome.79
Note that C-reactive protein may be an unreliable indicator
of the acute phase response in patients who are underweight
or malnourished or have impaired immunity,80 which could
further confound the result. Another combined score is the
Maastricht Index,81 which consists only of high-availability
or moderate-availability parameters: serum albumin level,
prealbumin, lymphocyte count, and weight (expressed as a
percentage of ideal body weight). How to calculate ideal
weight is not specified. Units are presented as g/L for
albumin and prealbumin and 109 /L for lymphocytes. The
Maastricht Index is expressed as follows:
2.68 − [0.24 × albumin] − [19.21 × prealbumin]
− [1.86 × lymphocyte count]
− [0.04 × percentage of ideal body wieght].
Scores >0 were associated with diagnosed malnutrition
in the original Maastricht study, in which patients with a
significant acute phase response were excluded and mal-
nutrition was assessed by a physical examination of tissue
stores, hair/nail condition, nutrition history, and nutrition-
impact symptoms (like the Subjective Global Assessment).
However, since most of the variables are affected by the
acute phase response, this index is likely to express nutri-
tion risk rather than nutrition status when applied to the
critically ill; indeed, in 1 randomized controlled trial, the
preoperative score predicted hospital length of stay but not
response to nutrition support.82 The score has been reported
to change significantly within the ICU admission83 to reflect
the patient’s progress, but given that serum albumin level,
body weight, and lymphocytes all alter very slowly, this is
likely to be reflective of only prealbumin changing.
Amino Acid Metabolites and Metabolomics
To assess body protein status, the blood or urine levels of
particular amino acids or their metabolites might be of
value. Several can help to assess the extent of catabolism.
For example, the blood level of arginine is usually low,
as any dietary arginine left over after protein synthesis is
quickly converted to urea in the liver, but in a catabolic state
141
the level rises as endogenous protein breakdown releases
arginine into the systemic circulation without a correspond-
ing increase in urea conversion.84 Similarly, lysine levels
increase during catabolism. Tyrosine is not synthesized
or degraded by muscle; thus, net production of tyrosine
must represent net protein breakdown.85 Blood levels of
essential amino acids, conditionally essential amino acids
(eg, glutamine), and urinary 3-methyl histidine (a measure
of protein breakdown, as there is no oxidation or muscle
reuptake of histidine86-88 ) could help to assess the patient’s
protein status. However, performing a full amino acid profile
regularly for each patient in the ICU may not be a feasible
method of nutrition monitoring. Changes in amino acid
production may occur in muscle but not be reflected in the
plasma levels,89 and amino acid profiles are altered when
parenteral nutrition is used (as it bypasses gut metabolism),
making it difficult to interpret the results of many patients
in the ICU.
While the potential of metabolomics in pharmacology
and toxicology has been well established, its use is
relatively novel in the ICU setting. Metabolomics refers
to the broad quantification of each patient’s set of
body metabolites, the host of small-molecule substances
that arise from the metabolism of macronutrients and
micronutrients and that can be measured in different
body fluids. Apart from the genetic influences on each
individual’s metabolomic profile (or “metabotype”) and
the effects of gut flora and nutrition intake, unique
patterns can be identified that are characteristic of
particular processes, such as sepsis or inflammation, and
some specific patterns may be predictive of outcome.
In one study, 10 metabolites (5-methylthioadenosine,
1-palmitoylglycerophosphoethanolamine, N-6-trimethyll-
ysine, nicotinamide, N-acetylmethionine, pyroglutamine,
valerate, hypoxanthine, kynurenine, and phenyllactate)
were associated with nutrition status, and 7 were predictive
of 28-day mortality.90 Recent technological advances now
allow high-resolution screening of the human metabolome.
A combination of gas and/or liquid chromatography is used
to separate metabolites in the sample, and spectroscopy is
used to quantify them. At this stage, there is no identified
subset of useful metabolites for targeted profiling of
patients in the ICU, and this field is still developing (eg,
identification of all the relevant compounds is not yet
complete, and there is no publicly available comprehensive
library of small molecules). Nevertheless, the potential
for metabolomics to identify derangements in a range of
metabolic pathways in critical illness renders it promising
for nutrition monitoring in the future.
Other Measures of Protein Metabolism
Nitrogen balance, as estimated from urinary urea nitrogen
in a 24-hour urine collection, is widely used for measuring
142
patients’ protein losses, which can be helpful in estimating
protein requirements. However, there are practical difficul-
ties in ensuring a complete 24-hour collection, it cannot be
used if the patient is anuric, and it is difficult to interpret in
renal impairment, which may limit its applicability for the
critically ill. There is a time delay before a change in intake is
seen as a significant change in urinary nitrogen appearance,
perhaps 60 hours for a stable patient and longer (up to
a week) where changes in the patient’s clinical condition
make it difficult to detect trends in output; also unquantified
losses of nitrogen (eg, from wound drains) can confound
the result for many patients in the ICU.91 Changes in body
water and serum urea level can alter the results if urea
nitrogen is used as the measure, and calculation methods
differ.92,93 One recommendation is to use a direct measure
of total urinary nitrogen, rather than estimating from urea
nitrogen,94 since the proportion of urinary nitrogen found
in the urea (usually about 80%; the remainder is in creatinine
and ammonia) decreases in fasting and can vary even within
the same patient.95 Unfortunately, total urinary nitrogen is
a test performed in few laboratories, making it less useful
for routine monitoring. Even with an accurate measure of
nitrogen balance, however, in critical illness there may not
be a consistent correlation between function and muscle
mass or protein loss,45,96 and nitrogen balance might not be
clearly associated with outcome,97 making nitrogen balance
less useful as a nutrition indicator, especially early in the
ICU stay.
Serum creatinine has been suggested as a useful and
readily available marker of muscle mass in patients with
normal renal function.93,98 However, decreases seen during
the acute phase response may simply be due to coreactivity
with albumin in assays based on the Jaff é reaction, so an
enzymatic creatinine assay would need to be performed to
establish this. Level of creatine kinase (also known as creati-
nine phosphokinase) could help to elucidate whether a lower
serum creatinine level is due to a reduction in muscle mass.
Urinary creatinine measurements may be useful. Creatinine
height index99 assumes a fixed ratio between muscle mass
and creatinine excreted in the urine, about 20 kg of muscle
per daily gram of urinary creatinine, to give an estimate of
lean body mass. Low creatinine height index may be more
specific than low weight in predicting outcome.100
Ultrasound Muscle Measurement
One relatively novel and promising indicator is bedside
ultrasound measurement of muscle thickness or cross-
sectional area.101 This is an instantaneous and noninva-
sive measure, and although a small 2-dimensional ultra-
sonograph is required for measurement, such equipment
is already in wide use in ICUs to assist venous catheter
insertion. Training is needed for operating the equipment
and interpreting the images, but such training need not
Nutrition in Clinical Practice 33(1)
Figure 3. Ultrasound image of mid upper arm muscle
thickness.
be lengthy if it is specific to the arm and leg sites to be
used for nutrition monitoring. Generally existing studies
have focused on muscle cross-section area (eg, of the rectus
femoris at mid thigh102 or two-thirds of the way down103 )
or muscle thickness at mid thigh,104,105 mid upper arm,
and mid inner forearm,106 which can be measured, from
bone to membrane, with the on-screen calipers included
in most ultrasonograph models (see Figure 3 for a sample
image). An additional measurement point, two-thirds down
the thigh, is technically easier to measure in patients with
edema or large limbs.104 Ultrasound enables a distinction
to be made between lean tissue and fat tissue or edema106
to identify muscle wasting even where body weight or
limb circumferences are stable or increased,107 and the
measurements correlate with muscle strength103 and change
significantly within days, enabling serial measurements.102
It seems that there are many parameters available for
monitoring nutrition in the critical care setting, with varying
accessibility and feasibility. But in the choice of which
measures to use in everyday practice, it is important to take
into account whether they are meaningful at the level of the
individual patient—that is, they reflect how the patient feels
and/or functions, and they are associated with the patient’s
outcome. For conscious patients, such meaningful measures
include fatigue scoring and functional tests (eg, handgrip
strength and FEV1 ). Most blood tests do not fulfil this re-
quirement and should not be used for nutrition monitoring;
however, they may still be useful for evaluating the severity
of the patient’s acute phase response (ie, indicating nutrition
risk). For patients who are not awake to follow instructions,
it is worth exploring the use of bedside ultrasound, which
has begun to demonstrate utility in this population. It
is important to note that even the most meaningful of
the aforementioned parameters have been tested only in
Ferrie and Tsang 143

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Clinical Research

Nutrition in Clinical Practice

Volume 33 Number 1
Enteral Feeding Tube Clogging: What Are the Causes February 2018 147–150

C 2018 American Society for

and What Are the Answers? A Bench Top Analysis Parenteral and Enteral Nutrition
DOI: 10.1002/ncp.10009
wileyonlinelibrary.com

Christopher M. Garrison, PhD, RN CNE

Abstract
Background: Clogged enteral feeding tubes remain a significant barrier to the delivery of nutrition, hydration, and medications to
patients who cannot tolerate oral intake. There is limited research that compares the relative efficacy of different methods used to
clear a clogged feeding tube. The objectives of this study were to better understand the factors that contribute to enteral feeding
tube clogging and to test the efficacy of 3 methods for clearing clogged feeding tubes. Methods: Three formulations of clogs were
artificially created and tested in vitro and composed of various quantities of crushed medication (ie, aspirin) and 0.15 g coagulated
protein (ie, tofu). The following 3 clog clearing strategies were tested on all clog types (n = 5 clogs/formulation/treatment): warm
water flushes, an enzyme treatment, and an actuated mechanical occlusion clearing device. Results: The variable among the clog
types that appears most responsible for decreased clearing success is the state of the coagulated protein. Dried-out protein appears
to makes a greater difference than increasing the medication quantity. The actuated mechanical occlusion clearing device was
significantly more successful (93%) when compared with warm water flushes (20%) and the commercially available enzyme treatment
(33%; P < .005) at clearing the clogs. The actuated device required significantly less total procedure time (P < .005) and total nursing
time (P < .005) when compared with the other 2 clearing methods. Conclusions: When clogs occur, they can be quickly and effectively
resolved by the actuated device, but other methodologies such as water and enzyme treatments may be of assistance. (Nutr Clin
Pract. 2018;33:147–150)

Keywords
enteral access; drug-nutrient interactions; enteral nutrition; enteral tube clogs

Introduction multiple methods for clearing a clogged enteral feeding tube

Clogged enteral feeding tubes remain a significant barrier to
effective delivery of nutrition, hydration, and medications
to patients who cannot tolerate oral intake.1,2 It is estimated
that up to 35% of enteral tubes will become clogged.1,3 A
clogged tube not only interrupts nutrition but also creates
discomfort for the patient if he or she needs to undergo
an additional invasive procedure to replace the tube. In
addition, the use of fluoroscopy to replace a clogged tube
can cost as much as $1000 and exposes the patient to
additional radiation.4 If the patient is in the home or long-
term care setting, the clogged tube may necessitate a visit
to the emergency department, further increasing patient
burden and replacement cost.5 In addition to the impact
on patients, clogged tubes require significant nursing time
to resolve.4
The prevention of feeding tube clogs is preferable to
having to manage a clogged tube. Recommendations for
the prevention of tube clogs include adequate flushing,
thoroughly pulverizing tablets prior to administration, not
mixing medications together prior to administration, lim-
iting residual checks, and avoiding instilling acidic liquids
through the tube.1,3,5 When a feeding tube is clogged,
are used in clinical practice. Some of these practices, such
as the use of colas, meat tenderizers, and acidic juices, lack
any empirical evidence for safety or efficacy.1,2,4,6 The use of
acidic liquids may actually worsen the clog because enteral
feeding proteins coagulate in an acidic environment.1,6
The recommended methods for clearing a clog include
warm water flushes, enzymatic agents, and mechanical
devices.1,2,4,7,8 These methods have found some degree of
empirical support for effectiveness, but limited research
From the The Pennsylvania State University, College of Nursing,
University Park, Pennsylvania, USA.
Financial disclosure: None declared.
Conflicts of interest: Funding of $2750 to attend 2017 American
Society for Parenteral and Enteral Nutrition conference by Actuated
Medical.
Received for publication July 26, 2017; accepted for publication
September 23, 2017.
Corresponding Author:
Christopher M. Garrison, PhD, RN CNE, The Pennsylvania State
University, College of Nursing, 201 Nursing Sciences Building,
University Park, PA 16802, USA
Email: cmg35@psu.edu
148 Nutrition in Clinical Practice 33(1)

Table 1. Three Formulations of Clogs Artificially Created and

Tested In Vitro.

Coagulated Protein Crushed Medication

Clog Type (ie, Tofu) (ie, Aspirin)

I 0.15 grams wet 0.053 grams

II 0.15 grams dried 0.053 grams
III 0.15 grams dried 0.080 grams

that compares the relative efficacy of each method has

been published. The objectives of this study were to better
understand the factors that contribute to enteral feeding
tube clogging and to test the efficacy of 3 methods for
clearing clogged feeding tubes.

Methods
Three different clog clearing strategies were compared on in
vitro clogged tubes (8 Fr, 107 cm) small-bore nasoenteral
feeding tubes. The 8 Fr tube was used because smaller
diameter tubes are more likely to clog.1,4 Three formulations
of clogs were artificially created and tested in vitro (Table
1). They were composed of various quantities of crushed
medication (ie, aspirin) and 0.15 g coagulated protein
(ie, tofu). Aspirin was chosen as the crushed medication
because the acidic pH contributes to clog formation. All
clogs were produced by the same engineer. Attempts to
clear the clogs were completed in an anatomical model Figure 1. Anatomical model. This anatomical model was used
to test clog clearing methods. It was designed to mimic the
(Figure 1). This model was constructed to mimic the normal
normal anatomy of the upper digestive tract.
anatomy of the upper digestive tract, which added to the
external validity of the study results. A single investigator
performed each test and was blinded to clog type during beginning of the attempt exceeded 2.5 hours or if active
the procedure. The following 3 clog clearing strategies were nursing time (excluding dwell times) exceeded 30 minutes.
tested on all clog types (n = 5 clogs/formulation/treatment):
warm water flushes, a commercially available enzyme treat- Statistical Analysis
ment (Clog Zapper, Corpak Medsystems, Inc., Buffalo
Grove, IL), and an actuated mechanical occlusion clear- Success rates for clog clearing strategies were compared
ing device (TubeClear System, Actuated Medical, Inc., using the χ 2 statistic, where expected cell counts were all
Bellefonte, PA). >5 or Fisher’s exact test if expected cell counts were <5.
The protocol for warm water flushes involved using a 60 Active nursing time and total time spent per clog were
mL syringe with water at a temperature of between 27°C compared using the Kruskal-Wallis statistic. A 2-tailed P
and 43°C. Flushing was carried out using a back-and-forth < .05 was considered significant for all statistical tests. IBM
motion for a total of 5 minutes. 4 If the clog failed to SPSS Statistics 24 (IBM Corp., Armonk, NY) was used for
clear, the water was allowed to dwell for 20 minutes until statistical analysis.
another 5 minutes of flushing was attempted. The enzyme
treatment was used in accordance with the manufacturer’s Results
instructions, which included allowing the enzyme solution
to dwell for an hour and repeat the treatment if the clog was
Comparison of Clearing Rates
not successfully cleared on the first attempt. The actuated Success rates for clog clearing were compared by clearing
device was used in accordance with the manufacturer’s method and type of clog. The actuated device (93%) was
instructions until the clog was cleared or the clog clearing more successful than either the enzyme treatment (33%) or
attempt was deemed a failure. Clog clearing attempts for warm water (20%) regardless of clog type (χ 2 = 18.32, P <
all methods were deemed failures if total time from the .005; Figure 2). Type I clogs proved easier to clear than other
Garrison 149

Figure 2. Percentage of clogs cleared by treatment method.

clog types, and no significant difference in clog clearing

success rates was found between clog clearing strategies
for these clogs. Type I clogs, composed of wet protein
and aspirin, were significantly easier to clear (73%) when
compared with type II (dry protein and aspirin) and type
III (dried protein and a higher dose of aspirin; 33%) clogs,
regardless of clearing method (χ 2 = 5.380, P = .02). For
type II clogs, the actuated device (80%) was superior to the
enzyme treatment (0%; likelihood = 8.456, Fisher’s exact,
P = .048). For type III clogs, the actuated device (100%)
was superior to both the enzyme treatment (20%; likelihood
= 8.456, Fisher’s exact P = .048) and warm water (0%;
likelihood = 13.863, Fisher’s exact P = .008).
Figure 3. Total time spent in clog clearing attempt by
treatment method.
Comparison of Time
Total procedure time spent and total nursing time were
compared by clearing method and type of clog. The actu-
ated device required significantly less total procedure time
(Kruskal-Wallis P < .005) and total nursing time (Kruskal-
Wallis P < .005) when compared with the other 2 clearing
methods (Figures 3 and 4).

Discussion
Clogged feeding tubes continue to be a challenge, and
limited evidence is available for the best method to clear
a clogged tube. The results of this study indicate that an
actuated device, enzyme treatment, and warm water flushes Figure 4. Total active nursing time spent in clog clearing
attempt by treatment method.
were all efficacious in clearing the least-challenging clogs.
150
The actuated device was significantly better than the other
methods at clearing the most difficult clogs both in terms
of success rates and time spent. Therefore, because the clog
type is unknown in vivo, the actuated device may restore
tube patency more quickly. Quickly clearing a clogged
enteral tube will preclude the need to insert a new tube
and minimize interruptions in nutrition, hydration, and
medication administration.
Factors that contribute to making a clog more diffi-
cult to clear were evaluated. The hydration state of the
coagulated protein appears to be more critical than the
amount of medication included in the clog in determining
how difficult a clog was to clear. Clogs composed of dried-
out coagulated protein were more difficult to clear than
those that contained wet coagulated protein. This finding
implies that allowing precipitated material to dry out in a
feeding tube makes it more difficult to clear the clogged
tube. This reinforces the importance of flushing tubes
frequently with an adequate amount of water, particularly
before and after administration of crushed medications,
as the prevention of clogs is preferred to having to re-
solve them regardless of the method chosen to clear the
clog.
This study compared 3 strategies for clearing clogged
tubes in a controlled setting. A good laboratory practices
compliant protocol was followed. The study found that
warm water flushes, enzyme treatment, and the actuated de-
vice all had some degree of efficacy in clearing clogged tubes,
which is consistent with the limited research in the literature.
The comparison of strategies using different clog severities
is a unique contribution of this study. Limitations of the
study include a small sample size, the use of in vitro testing,
and the use of a single protein (tofu) in clog formulation.
It would be useful to replicate these findings with a larger
sample size, with different feeding formulations, or in vivo;
however, despite the limited sample, significant differences
were found between clearing strategies and types of clogs.
Nutrition in Clinical Practice 33(1)
Conclusions
Clogged feeding tubes present a significant burden to both
patients and clinicians. Findings from this study indicate an
actuated device had better success rates at clearing clogs,
especially more difficult clogs, and required less nursing and
total time. It suggests that the other methods (ie, warm
water or enzyme treatment) may be effective on easier clogs.
However, because the clog type is unknown in vivo, the
actuated device may lead to quicker restoration of tube
patency, minimizing interruptions in nutrition, hydration,
and medication administration. It was also found that
allowing precipitated protein to become dry increased the
difficulty of clearing the clogged enteral feeding tube.
Statement of Authorship
The primary author of this manuscript was responsible for the
study design, data collection, data analysis, composition of the
manuscript and agrees to be accountable for all aspects of this
research.
References
1. Dandeles LM, Lodolce AE. Efficacy of agents to prevent and treat
enteral feeding tube clogs. Ann Pharmacother. 2011;45:676-680.
2. Malhi H, Thompson R. PEG tubes: dealing with complications. Nurs
Times. 2014;110:18-21.
3. Blumenstein I, Shastri YM, Stein J. Gastroenteric tube feeding: tech-
niques, problems and solutions. World J Gastroenterol. 2014;20:8505-
8524.
4. Fisher C, Blalock B. Clogged feeding tubes: a clinician’s thorn. Pract
Gastroenterol. 2014;38:16-22.
5. Shipley K, Gallo AM, Fields WL. Is your feeding tube clogged?
Maintenance of gastrostomy and gastrojejunostomy tubes. Medsurg
Nurs. 2016;25:224-228.
6. Williams NT. Medication administration through enteral feeding tubes.
Am J Health-Syst Pharm. 2008;65:2347-2357.
7. Arriola TAD, Hatashima A, Klang MG. Evaluation of extended-release
pancreatic enzyme to dissolve a clog. Nutr Clin Pract. 2010;25:563-564.
8. Klang MG, Ghandi UD, Mironova. Dissolving a nutritional clog with a
new pancreatic enzyme formulation. Nutr Clin Pract. 2013;28:410-412.
Clinical Research

Nutrition in Clinical Practice

Volume 33 Number 1
Hang Height of Enteral Nutrition Influences the Delivery of February 2018 151–157

C 2017 American Society for

Enteral Nutrition Parenteral and Enteral Nutrition

DOI: 10.1177/0884533617700132
wileyonlinelibrary.com

Renee Walker, MS, RD, LD, CNSC, FAND1 ; Lauren Probstfeld, MS, RD, CNSC1 ;
and Anne Tucker, PharmD, BCNSP2

Abstract
Purpose: Adequate enteral nutrition (EN) delivery to critically ill patients is difficult to achieve. Given the large number
of unpreventable influences affecting adequate caloric intake, further research on preventable influences of adequate EN
administration is warranted. The purpose of this study was to evaluate whether hang height of EN formula, formula viscosity,
or flow rate influences pump accuracy and formula delivery. Methods: Formulas of varying viscosities (1.0, 1.5, and 2.0 kcal/mL)
were infused at different hang heights (0, 6, 12, and 18 inches) and rates (20, 40, and 80 mL/h). The mean percent difference and
the bias between the programmed volume, volume reported, and volume delivered were calculated for the different hang heights,
formula compositions, and infusion rates studied. Results: For all prespecified hang heights and infusion rates, the volume delivered
was less than the programmed volume and volume reported; the mean percent difference increased as the hang height decreased. The
volume was overestimated for both the programmed volume (14.4% ± 5.5%) and volume reported (12.9% ± 6.7%) compared with
volume delivered. The overestimation bias was significantly influenced by differences in hang height as well as type of formula (P <
.0001, each) but not by rate of delivery (P = .4633 for programmed volume and .8411 for volume reported). Conclusions: Measures
should be taken in clinical practice to ensure adequate hang height of EN. Appropriate hang height of EN may result in more
accurate delivery of nutrition provisions to the critically ill patient and subsequently reduce complications related to underfeeding.
(Nutr Clin Pract. 2018;33:151–157)

Keywords
enteral pump accuracy; enteral nutrition; nutritional support; critical illness; infusion pumps; quality improvement

A difference exists between the quantity of enteral nutrition
(EN) ordered by a clinician and the amount of EN actually
delivered to the patient. Researchers have found that most
patients requiring EN do not reach 80%–90% of their
estimated energy requirements, which predisposes them
to caloric deficits during hospitalization and subsequent
adverse effects related to underfeeding.1-4 Published studies
have concluded that EN intake is inadequate primarily
due to unnecessary EN interruptions. High gastric residual
volume measurements have been identified as the most
common reason EN infusion is interrupted; however, other
factors such as intestinal dysfunction, surgical/medical pro-
cedures, ventilator weaning, hemodynamic instability, and
mechanical problems related to EN feeding tube devices and
infusion pumps also factor into this problem.1,2,4 Given the
large number of unpreventable influences on adequate EN
administration, an examination of preventable influences
related to EN administration was warranted. In 2013,
the Michael E. DeBakey Veteran Affairs Medical Center
(MEDVAMC) began using the Covidien (Mansfield, MA)
Kangaroo Epump Enteral Feed and Flush Pump System.
Clinicians noticed discrepancies between the 24-hour EN
delivery histories provided by the EN pump and the hourly
EN infusion record written by the nurses on the intensive
care unit (ICU) flow sheets. Upon contacting the pump
manufacturer regarding this discrepancy, information was
shared that a hang height of 18 inches is recommended
between the infusion pump and the EN formula container
for optimal EN delivery results.5 Further observation noted
that this recommended hang height was inconsistently
adhered to in daily practice. In general, research on the
accuracy of enteral feeding pumps is lacking. Only a few
researchers have evaluated pump accuracy and have taken
into account pump manufacturer, tubing age, formula vis-
cosity, and/or differing rates6-8 ; but none, to our knowledge,
From 1 Michael E. DeBakey Veteran Affairs Medical Center,
Houston, Texas, USA; and the 2 University of Houston College of
Pharmacy, Houston, Texas, USA. Anne Tucker’s current affiliation is
University of Texas MD Anderson Cancer Center, Houston, Texas,
USA.
Financial disclosure: None declared.
Conflicts of interest: None declared.
This article originally appeared online on December 14, 2017.
Corresponding Author:
Renee Walker, MS, RD, LD, CNSC, FAND, Michael E. DeBakey
Veteran Affairs Medical Center, 2002 Holcombe Blvd, Rm 4a-340,
Houston, TX 77030, USA. Email: rnew00@aol.com
152
Figure 1. Enteral nutrition hang height was measured from the bottom of the 1-L bag to the top of the Kangaroo Epump at 18
inches, 12 inches, 6 inches, and 0 inches.
have evaluated the impact of hang height on EN delivery.
The purpose of this study was to determine whether the
hang height of EN formula, formula viscosity, or flow rate
influences EN pump accuracy and formula delivery.
Materials and Methods
The presentation of results from this project was approved
by the MEDVAMC Research and Development Committee.
This project was also determined by the Baylor College
of Medicine Institutional Review Board to not constitute
human subjects research as the data collected and used were
not about living subjects and there was no interaction with
human subjects. This in vitro study used a simulated patient
care environment and was conducted at the MEDVAMC.
Three calibrated Covidien Kangaroo Epump Enteral Feed
and Flush Pump Systems were obtained for use in this
study to minimize discrepancy and ensure reproducibility.
The experiment was conducted in triplicate. EN formulas
of differing viscosities (1, 1.5, and 2.0 kcal/mL) were infused
over 24 hours at varying hang heights (0, 6, 12, and 18 in.)
and rates (20, 40, and 80 mL/h). See Figure 1 for experiment
diagram. The 2.0-kcal/mL formula was excluded from the
80-mL/h run rate since this formula rarely exceeds 60 mL/h
in clinical practice. EN formula was collected in clean, dry
containers. The volume of EN formula was captured by
3 different methods: programmed volume (calculated as
infusion rate multiplied by 24 hours), the volume reported
Nutrition in Clinical Practice 33(1)
(24-hour intake history recorded by enteral pump), and
the volume delivered (the volume of EN infused into the
canister over 24 hours measured by a 60-mL syringe).
We chose to use the 60-mL catheter tip syringe rather
than the graduated cylinder as syringe measurements have
been suggested to be more accurate.9 Since the EN pump
automatically primes with water, this volume of prime water
was taken into account during analysis. All volumes were
recorded in milliliters per 24 hours. The infused formula
was drawn up by the 60-mL syringe multiple times until
all formula was obtained from the canister. The percent
difference of the volumes of EN delivered based upon the
programmed volume and the volume reported compared
with the volume delivered were calculated. Finally, all
variables were included in a multivariate linear regression
to assess the independent influence of each variable on
overestimation bias. All P values were 2-sided, and a P value
less than .05 was considered statistically significant. All data
were analyzed using SAS statistical software version 9.3
(SAS Institute, Cary, NC).
Data Analysis and Results
For all prespecified hang heights and infusion rates, the
volume delivered was less than the programmed volume and
volume reported; the mean percent difference increased as
the hang height decreased (Tables 1 and 2; Figures 2 and
3). The volume was overestimated for both the programmed
 Table 1. Mean Percent Differences Between Volume Delivered and Volume Reported of Enteral Formulas at Varying Hang Heights and Ratesa .
Enteral Formulas

1.0 kcal/mL 1.5 kcal/mL 2.0 kcal/mL

Hang
Height, in. 20 mL/h 40mL/h 80 mL/h Mean 20 mL/h 40 mL/h 80 mL/h Mean 20 mL/h 40 mL/h Mean

0 −9.5 ± 1.2 −8.2 ± 3.2 −11.9 ± 3.1 −9.8 ± 2.8 −17.6 ± 1.8 −13.4 ± 2.0 −20.4 ± 8.3 −17.13 ± 4.0 −11.7 ± 1.4 −6.1 ± 3.7 −8.9 ± 3.9
(–10.9, –8.8) (–11.8, –5.8) (–14.6, –8.5) (–14.6, –5.8) (–19.7, –16.5) (–15.5, –11.5) (–29.4, –13.2) (–29.4, –11.5) (–13.1, –10.4) (–10.2, –3.1) (–13.1, –3.1)
6 −6.9 ± 1.6 −8.3 ± 0.3 −12.8 ± 5.4 −9.3 ± 3.9 −16.2 ± 2.17 −16.6 ± 3.9 −12.2 ± 2.6 −15.0 ± 2.9 −16.5 ± 2.2 −11.0 ± 0.6 −13.7 ± 3.3
(–8.8, –5.8) (–8.5, –7.9) (–19.0, –9.1) (–19.0, –5.8) (–18.7, –14.8) (–20.8, –13.0) (–14.7, –9.6) (–20.8, –9.6) (–17.9, –14.0) (–11.7, –10.5) (–17.9, –10.5)
12 −10.2 ± 1.7 −4.6 ± 3.0 −9.2 ± 1.1 −7.7 ± 3.2 −14.2 ± 7.6 −16.5 ± 3.4 −12.7 ± 4.8 −14.5 ± 5.1 −8.2 ± 2.0 −6.8 ± 3.6 −7.5 ± 2.7
(–11.3, –9.0) (–8.1, –2.7) (–10.0, –7.9) (–11.30, –2.7) (–22.7, –8.3) (–19.4, –12.7) (–16.9, –7.5) (–22.7, –7.5) (–10.5, –6.9) (–10.9, –4.2) (–10.9, –4.2)
18 −4.8 ± 2.2 −6.3 ± 4.3 −4.2 ± 6.8 −5.2 ± 3.7 −13.2 ± 4.0 −9.7 ± 3.1 −9.3 ± 4.1 −10.7 ± 3.8 −13.4 ± 0.8 −11.4 ± 3.8 −12.4 ± 2.7
(–6.6, –2.4) (–11.2, –3.6) (–9.0, 0.6) (–11.2, 0.6) (–17.2, –9.3) (–13.3, –7.6) (–14.0, –6.2) (–17.2, –6.2) (–14.3, –12.7) (–15.6, –8.2) (–15.6, –8.2)
Meanb −7.6 ± 2.6 −6.8 ± 3.1 −10.0 ± 4.8 −8.1 ± 3.7 −15.3 ± 4.3 −14.1 ± 4.0 −13.7 ± 6.3 −14.3 ± 4.9 −12.5 ± 3.4 −8.8 ± 3.7 −10.6 ± 4.0
(–11.3, –2.4) (–11.8, –2.7) (–19.0, 0.6) (–19.0, 0.6) (–22.7, –8.3) (–20.8, –7.6) (–29.4, –6.2) (–29.4, –6.2) (–17.9, –6.9) (–15.6, –3.1) (–17.9, –3.1)
a Values represent mean ± standard deviation (minimum, maximum).
b Mean ± standard deviation (minimum, maximum) of all formulas and rates: –11.1 ± 5.0 (–29.4, 0.6).

Table 2. Mean Percent Differences Between Volume Delivered and Programmed Volume of Enteral Formulas at Varying Hang Heights and Ratesa .
Enteral Formulas

1.0 kcal/mL 1.5 kcal/mL 2.0 kcal/mL

Hang
Height, in. 20 mL/h 40 mL/h 80 mL/h Mean 20 mL/h 40 mL/h 80 mL/h Mean 20 mL/h 40 mL/h Mean

0 −10.2 ± 1.3 −11.1 ± 2.6 −12.8 ± 2.6 −11.4 ± 2.2 −20.2 ± 2.5 −15.0 ± 1.9 −18.4 ± 3.0 −17.8 ± 3.0 −14.8 ± 1.3 −10.3 ± 3.5 −12.5 ± 3.4
(–11.7, –9.4) (–14.0, –9.2) (–14.3, –9.9) (–14.3, –9.2) (–22.9, –17.9) (–17.1, –13.5) (–20.7, –15.0) (–22.9, –13.5) (–16.2, –13.5) (–14.1, –7.4) (–16.2, –7.4)
6 −8.8 ± 2.0 −9.8 ± 0.3 −11.2 ± 1.0 −10 ± 1.6 −16.1 ± 1.9 −18.3 ± 4.2 −15.4 ± 2.4 −16.6 ± 2.9 −17.6 ± 2.1 −14.8 ± 0.8 −16.2 ± 2.1
(–11.0, –7.1) (–10.1, –9.5) (–12.3, (–12.3, –7.1) (–18.3, –15.0) (–22.7, –14.5) (–17.6, –12.8) (–22.7, –12.8) (–19.0, –15.3) (–15.7, –14.2) (–19.0, –14.2)
–10.3)
12 −10.4 ± 1.4 −8 ± 2.3 −10.8 ± 1.3 −9.7 ± 2.0 −14.6 ± 4.3 −17.0 ± 3.1 −12.8 ± 2.9 −14.8 ± 3.5 −11.1 ± 2.1 −9.0 ± 3.6 −10.1 ± 2.9
(–11.8, –9.1) (–10.6, –6.3) (–11.7, –9.4) (–11.8, –6.3) (–19.2, –10.6) (–19.5, –13.5) (–15.0, –9.5) (–19.5, –9.5) (–13.4, –9.4) (–13.1, –6.6) (–13.4, –6.6)
18 −6.6 ± 1.4 −7.7 ± 3.5 −4.3 ± 2.6 −6.2 ± 2.8 −12.6 ± 2.1 −11.1 ± 2.9 −12.3 ± 3.2 −12.0 ± 2.5 −11.8 ± 0.7 −10.6 ± 2.0 −11.2 ± 1.5
(–8.0, –5.3) (–11.8, –5.2) (–6.7, –1.5) (–11.8, –1.5) (–14.0, –10.2) (–14.4, –8.9) (–15.9, –9.9) (–15.9, –8.9) (–12.5, –11.0) (–12.7, –8.6) (–12.7, –8.6)
Meanb −9.0 ± 2.1 −9.2 ± 2.6 −9.8 ± 3.8 −9.3 ± 2.8 −15.9 ± 3.8 −15.3 ± 3.9 −14.7 ± 3.5 −15.3 ± 3.7 −13.8 ± 3.0 −11.2 ± 3.3 −12.5 ± 3.4
(–11.8, –5.3) (–14.0, –5.2) (–14.3, –1.5) (–14.3, –1.5) (–22.9, –10.2) (–22.7, –8.9) (–20.7, –9.5) (–22.9, –8.9) (–19.0, –9.4) (–15.7, –6.6) (–19.0, –6.6)
a Values represent mean ± standard deviation (minimum, maximum).
b Mean ± standard deviation (minimum, maximum) of all formulas and rates: –12.4 ± 4.2 (–22.9, –1.5).

153
154 Nutrition in Clinical Practice 33(1)

Figure 2. Mean percent differences between volume delivered and programmed volume of enteral formulas at varying hang
heights and rates.

Figure 3. Mean percent differences between volume delivered and volume reported of enteral formulas at varying hang heights
and rates.

volume (14.4% ± 5.5%) and volume reported (12.9%
± 6.7%) compared with volume delivered (Table 3). To
determine the primary reason for the overestimation of
programmed volume and volume reported, hang height,
infusion rate, and product were included in 2 separate
multivariate linear regression models (Table 4) to assess the
amount overestimated by programmed volume (model 1)
and volume reported (model 2). In both models, the over-
estimation bias was significantly influenced by differences
in hang height (P < .0001 for both models) and type of
formula (P < .0001 for both models) but not by rate of
delivery (P = .4633 for programmed volume and .8411 for
volume reported). The 1-kcal/mL enteral formula had the
lowest mean bias of formula delivery (programmed volume:
10.4% ± 3.4%; volume reported: 9.0% ± 4.5%). However,
bias did not differ in the other 2 formulas despite an increase
in caloric density.
Discussion
We believe our study is the first to evaluate the impact
of hang height on the accuracy of enteral delivery. The
concept that pump error affects delivery of EN is not
new; however, incorporating the hang height variable is a
 Table 3. Overestimation of Formula Delivery Using Programmed Volume or Volume Reported Compared With Volume Delivered.
Bias Compared With
Programmed Volume, Mean ± SD Volume Reported, Mean ± SD Volume Delivered, Mean ± SD Volume Delivereda

Hang Programmed Volume

Height, in. 20 mL/h 40 mL/h 80 mL/h Mean 20 mL/h 40 mL/h 80 mL/h Mean 20 mL/h 40 mL/h 80 mL/h Mean Volume Reported

0 486 ± 9 961 ± 1 1921 ± 1 1023 ± 570 474 ± 8 930 ± 11 1941 ± 1071012 ± 586 413 ± 24 841 ± 31 1621 ± 76877 ± 481 16.6 ± 5.7 14.6 ± 7.9
(8.0, 29.7) (3.2, 41.7)
6 486 ± 0 961 ± 1 1920 ± 0 1020 ± 571 475 ± 5 935 ± 13 1905 ± 1011005 ± 571 412 ± 21 823 ± 41 1665 ± 54879 ± 499 16.5 ± 5.3 14.6 ± 5.7
(7.6, 29.4) (6.1, 26.3)
12 484 ± 6 960 ± 0 1918 ± 5 1021 ± 569 478 ± 16 939 ± 13 1901 ± 45 1030 ± 567 426 ± 13 851 ± 48 1692 ± 46902 ± 504 13.4 ± 4.8 11.8 ± 6.7
(6.7, 24.2) (2.8, 29.4)
18 480 ± 0 960 ± 1 1918 ± 5 1020 ± 571 481 ± 11 954 ± 32 1883 ± 50 971 ± 536 431 ± 15 866 ± 28 1758 ± 96926 ± 530 10.8 ± 4.3 10.4 ± 5.5
(1.5, 18.9) (5.8, 20.8)
Mean 484 ± 3.8 961 ± 0.8 1919 ± 2.8 1021 ± 561 477 ± 10 940 ± 17 1886 ± 1181005 ± 557 421 ± 18 845 ± 37 1684 ± 68896 ± 496 14.4 ± 5.5 12.9 ± 6.7
(1.5, 29.7) (0.6, 41.7)
a Values represent mean ± standard deviation (minimum, maximum).

155
156
Table 4. Results of the Multivariate Linear Regression Used to Assess the Independent Influence of Each Variable on
Measurement Bias of the Programmed Volume and the Volume Reported.
Source of Variation df Parameter Estimate
Programmed volume
Intercept 1 0.10056
Hang height 1 −0.00343
Infusion rate 1 −0.00011999
Enteral product 1 0.03947
Volume reported
Intercept 1 0.06729
Hang height 1 −0.00264
Infusion rate 1 0.00004891
Enteral product 1 0.04109
new concept. Our study found that as the hang height of
enteral formula increases to the manufacturer’s suggested
height of 18 inches from the top of the pump, formula
delivery becomes more accurate. Tepaske et al6 investigated
13 commercially available EN pump systems and found that
deficits in EN delivery ranged from a minimal deficit of
0.5% through 13.5%. In 1994, Dietscher et al7 questioned
pump accuracy and found that inaccuracy of >10% exists
depending on the pump manufacturer. Ray et al8 evaluated
the flow accuracy of the Baxter (Deerfield, IL) Flo-Gard
6201 pump into pressurized monoplace hyperbaric cham-
bers and found that an EN infusion at 100 mL/h showed
approximately a 3% increase in the measured vs set flow
rate. In addition to percent pump error, formula viscosity
also affected volume of enteral delivery. One manufacturer
reported that thinner formulas often infuse like water and
deliver more accurately.10 Our study had similar findings in
that the lowest kcal/mL formula had the least overestima-
tion bias or best delivery accuracy. This is in comparison
to Dietscher et al,7 who concluded that a highly viscous
formula (2.0 kcal/mL) containing a protein modular had the
slowest flow rate, with one pump infusing only 53% of the
expected formula volume. Our findings suggested that our
most viscous formula (2.0 kcal/mL) had better accuracy at
a hang height of 12 inches, whereas the 1.0- and 1.5-kcal/mL
formulas were most accurate at an 18-inch hang height. The
final variable that we studied was flow rate. Overestimation
bias was not significantly influenced by flow rate at 20, 40,
or 80 mL/h. A lack of correlation between overestimation
bias and flow rate suggests that the reduced accuracy of
formula delivery can be attributable to hang height of
enteral formula or viscosity of enteral formula and not to
the flow rate of varying formulas. The literature comparing
formula delivery accuracy and flow rate is limited. More
research is needed in this area to adequately understand the
correlation between formula delivery accuracy and formula
flow rate.
The results of this study determined that EN formula
hang height influences the amount of EN delivered to
Nutrition in Clinical Practice 33(1)
Standard Error t Value Pr > |t|
0.01286 7.82 <.0001
0.00056634 −6.05 <.0001
0.00016292 −0.74 0.4633
0.00439 9.00 <.0001
0.01905 3.53 0.0007
0.00083888 −3.14 0.0023
0.00024321 0.20 0.8411
0.00652 6.30 <.0001
patients. We have noticed that in daily practice, EN formulas
are rarely hung at a height of 18 inches from the pump.
Typically, the hang height is significantly lower than this,
which subsequently results in underfeeding, as suggested by
the results of this study. Because the effects of underfeeding
negatively affect patient outcomes, we have informed the
Biomedical Department at our facility of the need to label
each pump with a reminder for nursing to hang EN formula
at the manufacturer’s suggested 18-inch hang height. This
information will also be incorporated into our hospital’s
EN protocol and should be considered for other institutions
using the Covidien Kangaroo Epump Enteral Feed and
Flush Pump System.
Limitations and Strengths
One study limitation is that the formula was not collected
in a closed system. Our open collection system allowed
for some evaporation of formula prior to collecting it via
syringe, although we believe this amount was negligible.
Another limitation is the possibility of not collecting all
of the formula in the syringe. The nectar-like formula was
more difficult to collect as it thickened and hardened around
the inside of the collection container. We estimated 5 addi-
tional milliliters of formula for the nectar-thick (2 kcal/mL)
formula, which was added to the collection volumes. A
third limitation was that our study did not fully simulate
an actual patient feeding scenario; we only used the spike
set to infuse formula directly into the container and did
not attach the spike set to an enteral feeding device (ie,
percutaneous endoscopic gastrostomy, nasogastric tube).
Gravity infusion in vitro studies show that the internal
diameter of feeding tubes affects the volume of formula
delivered.11 Finally, we recognize that the dead space, which
is the volume remaining in the syringe after the plunger has
been completely pushed down, may not have been captured.
Several strengths were present in our study. First, 3
enteral pumps were used simultaneously to run the exact
same regimens. This allowed for identification of variability
Walker et al
among feeding pumps and assisted us in strengthening the
reproducibility of study results. Second, each regimen ran
for 24 hours in an attempt to mimic actual delivery of EN
feeding to a patient. Finally, syringe measurements were
conducted by the same 2 researchers throughout the study,
minimizing measurement bias.
Conclusion
Enteral hang height can alter EN formula delivery. Mea-
sures should be taken in clinical practice to ensure adequate
hang height of EN as suggested by the enteral pump
manufacturer. Appropriate hang height of EN may result
in more accurate delivery of nutrition provisions to the
critically ill patient and subsequently reduce complications
related to underfeeding.
Acknowledgments
The team would like to thank Stephanie Bird, PharmD, for
her assistance with processing necessary paperwork to obtain
approval from our Research Department. In addition, the team
would like to thank Kevin Garey, PharmD, MS, from the
University of Houston College of Pharmacy for his assistance
with the statistical analysis and interpretation of our results.
Statement of Authorship
R. Walker, L. Probstfeld, and A. Tucker contributed to the
conception/design of the research; contributed to the acquisi-
tion, analysis, or interpretation of the data; critically revised the
manuscript; and agree to be fully accountable for ensuring the
integrity and accuracy of the work. R. Walker and L. Probstfeld
drafted the manuscript. All authors read and approved the final
manuscript.
157
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MK. Nutritional adequacy in patients receiving mechanical
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3. De Jonghe B, Appere-De-Vechi C, Fournier M et al. A prospective
survey of nutritional support practices in intensive care unit patients:
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G. Enteral nutrition practice in a surgical intensive care unit: what
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Pump With Pole Clamp, Programmable. Mansfield, MA: Covidien;
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Mathus-Vliegen EMH. Clinically relevant differences in accuracy of
enteral nutrition feeding pump systems. JPEN J Parenter Enteral Nutr.
2006;30(4):339-343.
7. Dietscher JE, Foulks CJ, Waits M. Accuracy of enteral pumps: in
vitro performance. JPEN J Parenter Enteral Nutr. 1994;18(4):359-
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Letter to the Editor
Determining Efficacy, Safety, and Preparation
of Standardized Parenteral Nutrition
We read with interest the suggestion from Yu and
colleagues1 that commercially available 3-chamber par-
enteral nutrition (PN) bags provide noninferior nutrition
efficacy and safety when compared with compounded
monobags. The actual number of patients screened to
randomize the 240 patients included would allow for a
better understanding of the patient population studied and
how patients with nutrition requirements exceeding 2100
kcal/day were determined. The authors provided the PN
composition of the 3-chamber and compounded monobags;
however, there was a notable difference in the amount
of phosphate provided (11.25 vs 0.75 mmol/bag) with
laboratory assessments only reported from days 1 and 7,
questioning the safety of such a comparison because more
patients in both groups (16% and 19%) had phosphorus
imbalances (ie, unclear if hypophosphatemic or hyperphos-
phatemic) while receiving a minimum of 1435 kcal/day (only
postoperative day 1 reported). Other efficacy and safety
considerations missing include the average PN duration
and nutrient amounts received per day (eg, kcal/kg/day and
grams protein/kg/day), cancer diagnosis, serum albumin
level, intensive care unit days, and weight changes postop-
eratively. Although a cost analysis was not performed, the
investigators recorded PN preparation times at 5 Chinese
hospitals for 1 year as a measure of efficiency. However, the
average number of PN monobags compounded daily at each
of these 5 hospitals was not provided to compare the times
reported or pharmacy staffing.
Whether 3-chamber PN bags reduce manpower and
confer cost savings when compared with compounded
monobags is a well-studied concept. A recent systematic
review identified 6 studies comparing PN preparation times
for 3-chamber bags, multibottle systems, and compounded
monobags.2 Unfortunately, Yu and colleagues failed to spec-
ify the activities timed as PN preparation (eg, prescribing
PN, including entering the PN order; review and compound-
ing each PN formulation; final PN product verification by a
pharmacist; PN administration by a nurse) and the method-
ology used for timing this endpoint, which obscures the true
time-savings provided. It is also unclear if an automated
compounding device was used for PN preparation and if
the time to set this up daily was included as well as the time
for a pharmacy technician because this has been reported to
take up to 80 minutes per compounded PN monobag.3 The
investigators report that the preparation of 3-chamber PN
Nutrition in Clinical Practice
Volume 33 Number 1
February 2018 158–159

C 2018 American Society for
Parenteral and Enteral Nutrition
DOI: 10.1002/ncp.10025
wileyonlinelibrary.com
bags was approximately 7 minutes shorter than preparation
of conventional PN monobags (4.90 ± 4.41 vs 12.13 ±
5.62 minutes; P < .001). Considering the complexity of a
PN monobag formulation and the number of components
required, a mean preparation time of 12 minutes speaks
either to the efficiency of the institution or the flawed
timing methodology used. PN monobag preparation times
reported in the literature range widely from 20 minutes
to 12 hours depending on the time from prescription to
start of PN.2-7 Time savings for each multichamber PN bag
prepared in these studies range from 12 to 60 minutes and
represents a cumulative benefit for institutions compound-
ing more PN prescriptions (assuming equivalent patient
outcomes). Discounting the possibility that the investigators
were overly conservative in their reporting of PN regimen
preparation time, their affirmation that multichamber bags
simplifies preparation is reasonable. It is more than likely
that the time savings realized at other institutions using
multichamber PN bags may be even greater under real-
world conditions.
Chelsea K. Krueger, PharmD
Division of Pharmacy, University of Texas MD Anderson
Cancer Center, Houston, Texas, USA
Todd W. Canada, PharmD, BCNSP, BCCCP, FASHP,
FTSHP
Division of Pharmacy, University of Texas MD Anderson
Cancer Center, Houston, Texas, USA
References
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of standardized parenteral nutrition regimens: three-chamber bags vs
compounded monobags-a prospective, multicenter, randomized, single-
blind clinical trial. Nutr Clin Pract. 2017;32:545-551.
2. Alfonso JE, Berlana D, Ukleja A, Boullata J. Clinical, ergonomic, and
economic outcomes with multichamber bags compared with (hospi-
tal) pharmacy compounded bags and multibottle systems: a system-
atic literature review. JPEN J Parenter Enteral Nutr. 2017;41:1162-
1177.
3. Blanchette LM, Huiras P, Papadopoulos S. Standardized versus custom
parenteral nutrition: impact on clinical and cost-related outcomes. Am
J Health-Syst Pharm. 2014;71:114-121.
4. Pichard C, Schwarz G, Frei A, et al. Economic investigation of the
use of three-compartment total parenteral nutrition bag: prospective
randomized unblinded controlled study. Clin Nutr. 2000;19:245-251.

5. Berlana D, Sabin P, Gimeno-Ballester V, et al. Cost analysis of adult
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 Nutrition in Clinical Practice
Volume 33 Number 1
Reviewer Acknowledgments February 2018 160–161

C 2018 American Society for

Parenteral and Enteral Nutrition

DOI: 10.1002/ncp.10061
wileyonlinelibrary.com

The editorial team of Nutrition in Clinical Practice wishes to thank the below-named individuals for the peer reviews they
submitted in 2017, ensuring that the Journal publishes only the highest quality articles.

Acosta, Laura Chen, Kong Fryer, Jonathan Mallett, Renee

Adams, Stephen Chen, Yimin Giaginis, Constantinos Malone, Ainsley
Akers, Mary Chhapola, Viswas Gillis, Chelsia Mandrell, Belinda
Alberda, Cathy Citty, Sandra Goday, Praveen Marian, Mary
Amagai, Teruyoshi Clemens, Roger Gomez-Perez, Sandra Marini, Elisabetta
Anderson, Diane Cober, Mary Gonzalez, Maria Martindale, Robert
Anthony, Patricia Cohen, Deborah Green Corkins, Kelly Martinez, Enid
Arai, Katsuhiro Cole, Conrad Griffin, Oonagh Martucci, Renata
August, David Compher, Charlene Gura, Kathleen Matarese, Laura
Ayers, Phil Cook, Robin Hair, Amy Mayes, Theresa
Bahirwani, Ranjeeta Corkins, Mark Hall, Beth McCarthy, Mary
Bailey, Emily Correia, Maria Isabel Hamilton-Reeves, Jill McGinnis, Carol
Barao, Katia Corrigan, Mandy Han-Markey, Theresa McNelis, Kera
Barone, Michele Coulter, Sarah Harris, Mary Beth Mercer, David
Barrocas, Albert Crenn, Pascal Hicks, Faith Merriman, Louise
Bear, Alexandria Cresci, Gail Hofmann, Cecilia Merritt, Russell
Bechard, Lori Crowley, Nina Hortencio, Taı́s Daiene Miller, Keith
Beggs, Megan Curtis, Caitlin Huang, Eunice Miller, Sarah
Beindorff, Mary Dahl, Wendy Ireton-Jones, Carol Mirtallo, Jay
Bellini, Sarah Daley, Brian Jeejeebhoy, Kursheed Mogensen, Kris
Berry, Amy DeChicco, Robert Jeffery, Emily Moisey, Lesley
Bianchi, Iara Derenski, Karrie Johnson, Abigail Moreno, Yara
Biller, Julie DiBaise, John K. Johnson, Deborah Mozer, Marisa
Bistrian, Bruce DiMaria-Ghalili, Jones, Christian Mueller, Charles
Bliss, Donna Rose Ann Jurewitsch, Brian Muir, Jane
Bonnes, Sara DiTucci, Angela Keeler, David Mullin, Gerard
Booi, Amy Duesing, Lori Klein, Michael Mundi, Manpreet
Boullata, Joseph Ead, Neil Kones, Richard Murad, Leonardo
Bourgault, Annette Earthman, Carrie Kovacevich, Debbie Nasser, Roseann
Bratton, Michelle El-Matary, Wael Kozeniecki, Michelle Nelinson, Janna
Brown, Ann-Marie Elke, Gunnar Krenitsky, Joe Nguo, Kay
Brown, Trish Epp, Lisa Kumpf, Vanessa Niakan Lahiji,
Brunet-Wood, M. Kim Escuro, Arlene Lacaille, Florence Mohammad
Buchholz, Bettina Esper, Dema Larsen, Bodil Nishioka, Shinta
Burns, David Evans, David Larson-Nath, Catherine Nucci, Anita
Bury, Christan Ferrie, Suzie Laviano, Alessandro Nystrom, Erin
Cade, John Fiaccadori, Enrico Lee, Dale Paddon-Jones, Douglas
Canada, Todd Finch, Carolyn Lee, Jenny Parian, Alyssa
Carney, Liesje Fletcher, Jane Lewis, Sherri Parrish, Carol
Carpenter, Debbie Flores, Ana Lipman, Timothy Patel, Jayshil
Casey, Linda Frankenfield, David Lyman, Elizabeth Patole, Sanjay
Chan, Lingtak-Neander Freitas, Ellen Mager, Diana Perry, Virginia
 161

Peterson, Sarah Rollins, Carol Skipper, Annalynn Wakabayashi, Hidetaka

Petzel, Maria Rosenthal, Martin Skouroliakou, Maria Walker, Valencia
Phillips, Stuart Rugeles, Saúl Smith, Carol Ward, Leigh
Plant, Maria Russell, Mary Smith, Diarmuid Weimann, Arved
Pleva, Melissa Sabino, Kim Spilman, Sarah Wessel, Jackie
Plogsted, Steve Sacks, Gordon Sriram, Krishnan Winkler, Marion
Porter, Judi Savoie, Kate Stansfield, Brian Wooley, Jennifer
Posthauer, Mary Ellen Sax, Harry Stubbins, Renee Worthington, Patricia
Premaor, Melissa Schwartz, Denise Thompson Motta, Yamada, Yosuke
Rabito, Estela Schwenk, W. Frederick Rachel Ybarra, Joseph
Rahhal, Riad Seidner, Douglas Valentine, Christina Yost, Gardner
Rahimi, Robert Sentongo, Timothy van der Sande, Frank Young, Lorraine
Raphael, Bram Seres, David Vanek, Vincent Zelig, Rena
Rath, Mary Shanbag, Preeti Vargas, Ashley Zhang, Bin
Ringwald-Smith, Karen Shen, Emily Vermilyea, Sarah
Roberts, Susan Singer, Pierre Votruba, Susanne