615002

research-article2015
PMJ0010.1177/0269216315615002Palliative MedicineHeneka et al.

Review Article

Palliative Medicine

Quantifying the burden of opioid 2016, Vol. 30(6) 520532

The Author(s) 2015
Reprints and permissions:
medication errors in adult oncology sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/0269216315615002

and palliative care settings: A systematic pmj.sagepub.com

review

Nicole Heneka1, Tim Shaw2, Debra Rowett3 and Jane L Phillips1,4

Abstract
Background: Opioids are the primary pharmacological treatment for cancer pain and, in the palliative care setting, are routinely used
to manage symptoms at the end of life. Opioids are one of the most frequently reported drug classes in medication errors causing
patient harm. Despite their widespread use, little is known about the incidence and impact of opioid medication errors in oncology
and palliative care settings.
Aim: To determine the incidence, types and impact of reported opioid medication errors in adult oncology and palliative care patient
settings.
Design: A systematic review.
Data sources: Five electronic databases and the grey literature were searched from 1980 to August 2014. Empirical studies published
in English, reporting data on opioid medication error incidence, types or patient impact, within adult oncology and/or palliative care
services, were included. Popays narrative synthesis approach was used to analyse data.
Results: Five empirical studies were included in this review. Opioid error incidence rate was difficult to ascertain as each study
focussed on a single narrow area of error. The predominant error type related to deviation from opioid prescribing guidelines, such
as incorrect dosing intervals. None of the included studies reported the degree of patient harm resulting from opioid errors.
Conclusion: This review has highlighted the paucity of the literature examining opioid error incidence, types and patient impact in
adult oncology and palliative care settings. Defining, identifying and quantifying error reporting practices for these populations should
be an essential component of future oncology and palliative care quality and safety initiatives.

Keywords
Analgesics, opioid, medication errors, patient safety, palliative care, oncology service, hospital

What is already known about the topic?

Medication errors are frequently under-reported across all inpatient settings.
Opioids are high-risk medicines due to the heightened risk of patient injury or catastrophic harm if they are incorrectly
prescribed and/or administered.
Opioids are the primary pharmacological treatment for cancer pain and are routinely used in the palliative care setting to
manage pain and other end-of-life symptoms.

1School of Nursing, University of Notre Dame Australia, Darlinghurst
Campus, Broadway, NSW, Australia
2Research in Implementation Science and eHealth (RISe), Faculty of
Health Sciences, University of Sydney, Sydney, NSW, Australia
3Drug and Therapeutics Information Service, Repatriation General
Hospital, Adelaide, SA, Australia
4Centrefor Cardiovascular and Chronic Care, Faculty of Health,
University of Technology Sydney, Sydney, NSW, Australia
Corresponding author:
Nicole Heneka, School of Nursing, University of Notre Dame Australia,
Darlinghurst Campus, PO Box 944, Broadway, NSW 2007, Australia.
Email: nicole.heneka1@my.nd.edu.au
Heneka et al. 521

Patients at the end of life are at greater risk of medication errors due to the seriousness of their illness and the complexity
of their treatment regimens, compounded by multiple routes of administration and dosing schedules of regular and as
needed (PRN) medicines.
Despite the widespread use of opioids in adult oncology and palliative care settings, there are little reported data on opioid
error incidence, types and patient impact from these settings.

What this paper adds?

This is the first systematic review to explore the scope and patient impact of opioid errors in adult oncology and palliative
care settings.
Deviations from opioid prescribing guidelines, for example, no as needed (PRN) analgesia ordered for patients on regular
opioids, no pre-emptive prescribing to treat opioid side effects and incorrect dosing intervals, were the most commonly
reported opioid error type.
Administration errors and errors of omission (forgetting to give a dose or giving the dose later than scheduled) were not
reported in the clinical setting.
Opioid error incidence, the scope of opioid error types for example, administration errors; errors of omission; calculation,
conversion or device errors and the patient impact of opioid errors in adult oncology and palliative care settings were
identified as under-explored areas of patient safety in this review.

Implications for practice, theory or policy

There is a need to further explore opioid error types, other than those resulting from deviations from opioid prescribing
guidelines, from both patient data and the perspectives of oncology and palliative care clinicians.
Further exploration of the degree of patient harm resulting from opioid errors in these care settings is also warranted.
Defining, identifying and quantifying error reporting practices in oncology and palliative care settings will benefit future qual-
ity and safety initiatives targeting the provision of quality care for patients with life-limiting illnesses.

Introduction
Medication errors are one of the leading patient safety risks
and the most common type of healthcare error.1 While there
is great variation across services and facilities, medication
errors account for approximately 20% of hospital errors.24
This equates to, on average, at least one medication error,
per inpatient, per day.5 Although medication errors are more
likely to result in serious patient harm and death than other
incident types,6 they are often under-reported7 or undetected
by hospital staff, even in healthcare settings with established
incident reporting systems in place.8 In a recently published
study comparing medication errors identified by audit and
reported to an incident system in the acute care setting, only
1.2 incident reports per 1000 prescribing errors were identi-
fied, and there were nil incident reports by staff for over
2000 clinical administration errors identified during direct
observation,8 suggesting that the error rate above could be
even higher than currently reported.
Despite medication administration appearing to be a
relatively simple process, there is huge scope for error
at each of the more than 30 individual steps involved in
the delivery of a single dose of medication.9 While
there is no standardised definition of medication
error,10 the US National Coordinating Council for
Medication Error Reporting and Prevention defines a
medication error as any preventable event that may
cause or lead to inappropriate medication use or patient
harm while the medication is in the control of the health
care professional, patient, or consumer.11 Medication
error categories have been developed to standardise
reporting and define the relationship between error type
and harm.12,13 Error categories include errors of prescrib-
ing, omission, dosing, dosage form, administration tech-
nique and timing,13 while the relationship between error
and harm ranges from potential for error (no harm to
patient) to patient death as a result of an error.12
Numerous patient-related risk factors, such as
advanced age, impaired hepatic or renal function,
impaired cognition, chronic comorbidities and polyphar-
macy, are associated with an increased risk of medication
error.14,15 Medication errors disproportionally affect
patients at the end of life due to their frailty, seriousness
of their illnesses, the complexity of their treatment
regimen(s) and the adverse impact of errors on dying
patient populations.3,15
Medication errors in oncology and palliative
care settings
Adult oncology and palliative care patients are a specific
example of populations at increased risk of medication
errors due to the factors noted above. Although several
studies report medication errors in adult oncology, the
522 Palliative Medicine 30(6)
majority of these errors relate to chemotherapeutic agents,
with few studies reporting errors due to other commonly
used medications to manage symptoms in cancer care.1619
Similarly, there is very little empirical research on medica-
tion errors in adult palliative care settings.20
The data from 13 specialist palliative care units in the
United Kingdom reported approximately two medication
errors per occupied bed per annum across all services,21
while one UK hospice calculated error rates based on esti-
mated total drug administration, reporting an error rate of
0.03%.22 Medication error rates of 2.3 errors per month
and 1.3 errors/month were reported in two separate hos-
pice organisations in the United States over an 18-month
audit period,23 and a palliative care inpatient facility in
New Zealand reported an average of 6.6 medication inci-
dents (actual or perceived errors) per month over 2years of
voluntary reporting.24 These lower medication error rates
are thought to reflect under-reporting in the palliative care
setting.25,26 In contrast to the error rates reported in the lit-
erature, approximately two-thirds of surveyed palliative
care professionals perceived medication errors to occur
moderately often or frequently.27
Opioid medication errors and the potential for
harm
In addition to patient-related risk factors, several drug
classes are associated with an increased risk of medica-
tion error and are classified as high-risk and/or high-alert
medicines because of the heightened risk of causing
patient injury or catastrophic harm if used in error.28,29
Opioid medications (opioids) are one example of high-
risk medicines and are the most frequently reported drug
classes in medication errors causing patient harm,30,31
including fatal and serious non-fatal outcomes,6,32,33 and
preventable adverse events that lead to patient harm.34 A
retrospective analysis of opioid errors from an anony-
mous national medication error reporting database identi-
fied 644 harmful errors over a 7-year period on patient
care units.35 This analysis excluded opioid errors result-
ing from patient-controlled analgesia or opioid errors
identified in intensive care units and surgery/procedures.
Six of these opioid errors resulted in death with more
than half reported as administration errors resulting in
opioid overdose.35
Opioids are widely used in oncology and palliative care
and are the primary pharmacological treatment for cancer
pain.3638 In the palliative care setting, opioids are rou-
tinely used to manage a range of cancer and non-cancer
pain and other symptoms, including dyspnoea and
cough.39,40 In high-income countries, the majority of
patients utilising palliative care services have a primary
diagnosis of cancer;4143 consequently, both oncology and
palliative care patients are likely to receive opioids for
pain or symptom management at some point in the course
of their illness. Increasingly, the adult oncology and pallia-
tive care populations are composed of older people,41 with
more than one chronic co-morbid disease which may alter
medication pharmacodynamics and pharmacokinetics.15,44
This older population is also likely to be taking other med-
ications for symptom control, particularly at the end of
life.45,46 These factors all increase this vulnerable groups
risk of medication error and patient harm.15,32,47
The potential for opioid errors in cancer and palliative
care populations may also be higher due to varying routes
of administration, particularly intravenous administration,5
numerous dosage forms with differing potencies, similar
drug names (e.g. morphine/hydromorphone, oxycodone/
oxycontin) and routine dose calculation and conversion in
the clinical setting.28,35,48 Despite the enormous scope for
opioid errors in oncology, few studies report opioid medi-
cation errors per se.16 There is emerging evidence that the
leading cause of medical error in palliative care is associ-
ated with drug treatment for symptom control, including
opioid prescribing and administration.20,25,27 Despite these
findings, and the widespread use of opioids, little is known
about the degree of error reporting, or the incidence and
impact of opioid medication errors in the specialist cancer
and palliative care setting.20,25 Identifying, better under-
standing and addressing opioid errors are crucial elements
of improving patient safety in adult oncology and palliative
care settings.
Objectives
This systematic review aims to (1) determine the incidence
of reported opioid medication errors in adult oncology and
palliative care settings, (2) identify which types of opioid
medication errors are most frequently reported in these set-
tings and (3) determine the patient impact of opioid medi-
cation errors.
Method
Reporting of this systematic review was guided by The
Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA Statement).49
Eligibility criteria
Studies were included if they were published in English in
a peer-reviewed journal, reporting empirical data on opi-
oid medication error incidence, types or impact on patients,
within adult oncology and/or palliative care services,
including inpatient, ambulatory or community care set-
tings. All non-empirical studies such as review articles and
case reports were excluded from the review. The search
was limited to studies published since 1980, reflecting the
start of significant investment in specialist cancer and pal-
liative care services.50
Heneka et al. 523
Table 1. Search strategy (MEDLINE): conducted in August
2014.
1. opioid*.mp. or exp Analgesics, Opioid/ Set 1
2. opiate*.mp. or exp Morphine/
3. medication*.mp.
4. 1 or 2 or 3
5. error*.mp. or exp Medication Errors/ Set 2
6. adverse event*.mp.
7. exp Patient Safety/ or safety.mp. or *Safety/
8. 5 or 6 or 7
9. exp Palliative Care/ or exp Hospice and Set 3
Palliative Care Nursing/ or palliative.mp.
10. palliative care.mp. from potentially relevant studies and accommodate the
11. exp Hospice Care/ or hospice*.mp.
12. exp Terminal Care/
13. exp Terminally Ill/
14. dying.mp.
15. death.mp. or *Death/
16. end of life.mp.
17. cancer.mp.
18. oncology.mp. or exp Oncology Nursing/
or exp Medical Oncology/ or exp
Radiation Oncology/ or exp Oncology
Service, Hospital/
19. 9 or 10 or 11 or 12 or 13 or 14 or 15 or
16 or 17 or 18
20. 4 and 8 and 19
21. limit 20 to yr=1980-Current
Information sources and search strategy
A systematic search of the literature was undertaken
between 1 August and 31 August 2014 using MEDLINE,
Embase, Cumulative Index of Nursing and Allied Health
Literature (CINAHL), the Cochrane Library and Scopus
databases. The search strategy comprised three sets of
terms. Set 1 was designed to capture literature relating to
opioid medications. As there is no single, standardised
definition of medication error,10 Set 2 aimed to capture
terms relevant to errors. A range of search terms relating
to medication error, patient safety and adverse medication
events were employed to capture relevant citations. Set 3
limited the papers retrieved to oncology and palliative care
populations without limiting care settings (i.e. inpatient,
ambulatory, community and home care).
Terms within each set were combined using the Boolean
OR operator, and the sets were then combined using the
AND operator. Potential search terms were trialled on
MEDLINE and mapped to indexed medical subject headings
(MeSH). MeSH terms and keywords (.mp) identified in
MEDLINE were adapted to each database. Consultation with
a specialist research librarian and subject matter experts from
palliative care, oncology, pharmacy and quality and safety,
was undertaken to ensure that the search strategy was appro-
priate for the proposed review. A full electronic search strat-
egy utilising the MEDLINE database is included in Table 1.
Grey literature was searched using Google Scholar,
Public Affairs Information Service (PAIS) International, The
Grey Literature Report (New York Academy of Medicine),
System for Information on Grey Literature in Europe, Health
Management Information Consortium (HMIC), National
Technical Information Service (NTIS) and PsycEXTRA.
Additional search strategies included hand searching key
journals and reference lists of identified articles for eligible
papers and searching conference abstracts.
Data collection process
A data extraction tool51 was developed to capture data
varying methodologies and reported outcomes. Fields
included study design; setting; data source/participants;
medication reported; error definition, measure, incidence
and type and patient outcomes. Data extraction enabled a
summary of both quantitative and qualitative data and
informed the data analysis.
Study selection
The titles and abstracts of all papers were examined by two
authors (N.H. and J.P.) to determine whether they met the
inclusion criteria. Data from potentially relevant papers
(n=158) was extracted by one author (N.H.).
Bias rating and synthesis of results
The methodological quality of included studies (Table 2)
was assessed by the first author (N.H.) using the
QualSyst systematic review tool.52 QualSyst incorpo-
rates two scoring systems to evaluate the quality of both
quantitative and qualitative research studies. This tool
was considered appropriate for critical appraisal of the
included studies due to the varying study designs. The
level of evidence for each study was determined using
the Australian National Health and Medical Research
Council (NHMRC) evidence hierarchy.53 Due to the
range of study designs, synthesis of the results was
guided by the methods of Popay et al.54 and employed a
narrative synthesis approach.
Results
Study selection
The initial search of databases yielded 11,351 papers:
MEDLINE (n=2970), Embase (n=7255), CINAHL
(n=644), the Cochrane Library (n=6) and Scopus (n=476).
No papers meeting the inclusion criteria were found in the
grey literature. Removal of duplicates resulted in 9521
papers remaining for screening (Figure 1). On the basis of
title or abstract, 9529 papers were excluded leaving 150
papers eligible for assessment. Eight additional papers
were identified from the eligible papers following a hand
524 Palliative Medicine 30(6)
Figure 1. Flowchart of studies through the review process.
search of reference lists. Upon further screening, 133 full-
text papers were identified for review, and 128 papers were
excluded as they did not meet the eligibility criteria, leav-
ing five papers5559 which reported opioid medication error
incidence, type and/or impact in adult palliative care and
oncology settings.
Study characteristics, design and quality
Five empirical studies reporting opioid medication errors
in oncology or palliative care settings were included in this
review. Methodological quality varied across the studies
and the heterogeneity of the reported data precluded a
meta-analysis from being undertaken (Table 2). All
included studies met level IV evidence criteria as per the
Australian NHMRC Evidence Hierarchy.53
The majority (n=4) of the studies were published after
2010. All the studies were undertaken in the Northern
Hemisphere, with two studies undertaken in the United
States and one study each from Belgium, Germany and the
United Kingdom. These studies reported data from two
prospective surveys,55,58 a prospective chart audit,59 a lon-
gitudinal study56 and a retrospective case series.57
Most studies reported patient data,5659 with one study
reporting palliative care clinicians perceptions and
descriptions of medication error.55 Three studies reported
chart audit data, respectively, assessing general opioid
prescribing errors in palliative care inpatients and outpa-
tients with cancer pain,58 morphine prescribing errors in
oncology inpatients59 and dosage errors with transdermal
fentanyl in newly admitted palliative care inpatients.57
Settings, participants and opioid medication
reported
Inpatient setting data were reported in the majority of stud-
ies (n=3),55,57,59 with one study reporting both inpatient and
outpatient data58 and another study reporting data from the
home care setting.56 The data from all but one study59 were
generated from the specialist palliative care setting (n=4).
The vast majority of patients admitted to the palliative
care setting had a diagnosis of cancer (97%), all of whom
Table 2. Summary of included studies.

Study, year, Design Setting Data source/ Focus Opioid (s) Error definition Error identification Error Error incidence Quality of
country NHMRC level participants reported measure (% of patients methods
of evidence53 with at least one (QualSyst)52
Heneka et al.

opioid error)
Dietz et Exploratory, Specialist Palliative care Incidents palliative Opioids Described by Example of error n/a n/a qualitative 20/20a
al., 2014,55 cross- palliative professionals care professionals participants described by qualitative data only reported
Germany sectional care (n=46) perceive as typical participants data only
survey institutions errors in their practice reported
IV and descriptions of
events
Mayahara 3-Day, mixed Palliative Patient As-needed (PRN) Deviations from
Opioids (strong Comparison of % of 49 18/18b
et al., methods care pain and analgesic errors by prescribed
and mild)36 patient medication patients
2014,56 longitudinal home medication non-professional analgesic diary with analgesic where
USA study: setting diary home-hospice medication, made medication regimen error
prospective Patient/ caregivers by the patients prescribed by the identified
survey and caregiver healthcare patients healthcare
audit dyads (n=46) provider, when provider
IV the analgesic was
administered
Botterman Retrospective Specialist Patient charts Patterns of strong Fentanyl Deviations from Patient chart audit % of 63 15/18b
and Criel, chart audit palliative (n=1154) opioid use, particularly international patients (patients
2011,57 IV care transdermal fentanyl, guidelines; where prescribed
Belgium inpatient in patients admitted frank signs and error transdermal
to a palliative care symptoms of identified fentanyl only)
inpatient unit opioid toxicity
Shaheen Prospective Palliative Patient charts Identification of Morphine, Deviations Patient chart audit % of 70 18/18b
et al., survey care patients with common errors in hydromorphone, from local and patients
2010,58 IV inpatient cancer pain opioid use through methadone, international where
USA and (n=117) assessment of fentanyl, opioid dosing error
outpatient clinicians opioid oxycodone and strategies identified
prescribing practices other opioids
Turner Prospective Specialist Patient charts Assessment of the Morphine Deviations from Patient chart audit % of Not defined 7/18b
et al., snapshot cancer containing quality and quantity of local palliative patients
1994,59 UK audit hospital morphine clinicians morphine careprescribing where
IV order prescribing in guidelines error
(N=144) accordance with local identified
Pre audit palliative care unit
(n=73); post guidelines, pre- and
audit (n=71) post guideline review

NHMRC: National Health and Medical Research Council; n/a: not available.
aQuantitative data scoring system/18.
bQualitative data scoring system/20.
525
526 Palliative Medicine 30(6)
had been ordered at least one opioid on or during their
admission. The home care study56 reported data from
patient/caregiver dyads (n =
46) with the majority of
patients (63%) having a cancer diagnosis.
Opioid medications were variously described as opi-
oids (n=1), which encompassed morphine, hydromor-
phone, methadone, fentanyl and other,58 or analgesic
mild/strong opioid (n=1).56 One study explicitly to a specialist palliative care inpatient unit over a 7-year
assessed morphine use,59 while another study identified
morphine, diamorphine and fentanyl as opioids of interest,
but primarily reported data on transdermal fentanyl.57
Definitions, identification and measure of error
There were various definitions of error employed across
the studies, including deviations from opioid dosing strate-
gies from local practice,57 local palliative careprescribing
guidelines,59 US Agency for Health Care Policy and Research
recommendations,57,58 European Association of Palliative
Care recommendations,57,58 World Health Organisation
guidelines57,58 and American Pain Society recommenda-
tions.58 In the home care setting, an error was defined as
any deviation by the caregivers from the prescribed analge-
sic medication, made by the patients healthcare provider,
when the analgesic was administered.56 One study examined
perceptions of error types by palliative clinicians and, as
such, did not explicitly define error.55
Three studies identified errors through patient chart
audit, either retrospectively57 or prospectively.58,59
Comparisons of patients medication diaries with the anal-
gesic medication regimen prescribed by the patients health-
care provider were used to identify errors in the home care
setting.56 An anonymous survey asking palliative care clini-
cians to describe a typical case in which an error occurred
was used to identify error types and causes across palliative
care institutions (n=168) in one state in Germany.55 None of
the studies included in this review utilised incident reports
as a method for opioid error identification or employed
observations to detect opioid errors in the clinical setting.
The four studies reporting patient data reported errors
as a percentage of patients in which an error was deemed
to have occurred, based on comparison to pre-established
prescribing and dosing criteria. Each study examined
differing aspects of opioid use, including general opioid
prescribing practices,58 morphine prescribing and admin-
istration practices,59 fentanyl dose on and during
admission to the service,57 and opioid administration
by non-professional caregivers.56
Error incidence
There was great variation in the reporting of opioid errors
across the included studies. One study examined prescribing
patterns for patients with cancer pain (n=117), incorporat-
ing a range of opioids, (i.e. morphine, hydromorphone,
methadone, fentanyl, oxycodone and other opioids), to
identify errors in opioid prescribing and dosing strategies.58
This study identified at least one incorrect opioid order in
70% of patients with cancer pain over an 80-day audit
period.58 Dosage errors were identified in 63% of patients
(n=199) prescribed transdermal fentanyl in a study examin-
ing patterns of strong opioid use in patients newly admitted
period (n=1154).57 Two audits of morphine prescribing
practices in a specialist cancer hospital were conducted over
1day each, 13months apart. The audits were undertaken at
baseline (n=73) and following changes to the hospital based
palliative care departments prescribing guidelines (n=71).
While the overall incidence of opioid errors was not directly
reported in this study, error incidence by error type ranged
from 5% to 81% across both audit days (Table 3).59 For non-
professional family caregivers in the home care setting,
administering both strong and mild opioids, an administra-
tion error incidence of 49% was reported in a longitudinal
study conducted over three consecutive days.56
Error type
The predominant error types in the clinical setting related
to deviations from opioid prescribing guidelines (Table 3).
Despite different local and national guidelines being uti-
lised across the two studies which audited opioid prescrib-
ing strategies for patients with cancer,58,59 several common
deviations from opioid prescribing guidelines were identi-
fied. These included no as needed (PRN) analgesia
ordered for patients with regular opioid orders (17%29%
of patients), no pre-emptive prescribing of anti-emetics
and/or laxatives to treat opioid side effects (15%24% of
patients) and incorrect opioid dosing intervals (11%81%
of patients). One of these studies also reported changes in
the frequency of deviations from opioid prescribing guide-
lines following a review of local guidelines (Table 3),
including errors relating to regular analgesia orders (PRN
oral morphine only ordered/nil regular analgesia ordered),
ordering multiple PRN analgesics and ordering multiple
opioids from the same class.59
A study examining transdermal fentanyl orders prior to
admission to a specialist inpatient palliative care unit
found that patients transferred from hospital or the home
care setting had been ordered a threefold higher median
oral morphine equivalent dose than patients treated with
oral, intravenous and subcutaneous morphine.57 Nearly
two-thirds (63%) of these patients had signs and symptoms
of opioid overdose or toxicity noted on or during their
admission to the palliative care unit.57 The majority (70%)
of these patients had been transferred from hospital to the
palliative care unit and, prior to admission, were capable
of taking oral analgesia as per opioid administration guide-
lines, yet had been inappropriately prescribed transdermal
rather than oral opioids.57
Heneka et al. 527

Table 3. Error type and incidence (% of patients).

Dietz et al.55 Mayahara et al.56 Botterman and Shaheen et al.58 Turner et al.59
Criel57

% % % % % Pre guideline
change/% post
guideline change
Deviations from opioid prescribing guidelines
1. No PRN analgesia ordered * * * 17 26/29
2. PRN oral morphine only ordered/nil * * * * 43/5
regular analgesia
3. Multiple PRN analgesics ordered * * * * 32/*
4. Opioid side effects not prescribed for * * * 15 24/22
5. Incorrect dosing intervals * * * 11 81/81
6. Multiple opioids from same class ordered * * * 10 *
7. Incident pain not treated * * * 8 *
8. Incorrect route/formulation for pain type a * b 8 *
9. Inadequate trial of initial opioid * * * 5 *
10. More than one opioid changed at a time * * * 2 *
11. Inappropriate dose a * 63c * *
Titration errors
1. Failure to titrate * * * 9 *
2. Incorrect titration a * * * *
Calculation errors
1. Incorrect dose conversion for new route a * * 3 *
2. Incorrect dose calculation for opioid * * * 2 *
rotation
Administration errors
1. No analgesic given * 21 * * *
2. Too low a dose of prescribed analgesic * 9 * * *
3. Over-the-counter medication instead of * 6 * * *
prescribed analgesic
4. Discontinued prescribed mild opioid given * 6 * * *
5. Sedative given, not prescribed analgesic * 6 * * *
6. Too high a dose of prescribed analgesic * 3 * * *
7. Discontinued prescribed strong opioid * 1 * * *
given
Perceptions of opioid errors
1. Incorrect titration and conversion of a * * * *
opioids
2. Over dosage of opioids caused by fear of a * * * *
the patients pain
3. Inappropriate switch from oral to a * * * *
subcutaneous morphine
Adverse effects
1. Appearance of adverse drug effects (from a * * * *
opioid over dosage)
2. Patient suffers from severe withdrawal a * * * *
symptoms (opioid switching)
3. Higher pain intensity when analgesic * d * * *
regimen not adhered to
4. S igns and symptoms of opioid overdose or * * b * *
toxicity due to transdermal fentanyl

Entries with the symbol * indicate not reported.

aQualitative example reported.
bLarge majority actual numbers not reported.
cTransdermal fentanyl only.
dNon-professional caregivers adherence to analgesic regimen correlated significantly with mean worst pain score: 0.37 (p0.001).
528 Palliative Medicine 30(6)
Clinicians involved in a study exploring palliative care
professionals perceptions and experience of error types
acknowledged the route of administration errors and inap-
propriate dosages as being prevalent in the palliative care
setting; however, these perceived error types were not
quantified in this study.55 Titration and calculation errors
were reported in two studies55,58 accounting for 9% and 5%
of errors, respectively. In the home care setting, adminis-
tration errors by non-professional caregivers were primar-
ily due to caregivers withholding opioid analgesia even
though it was indicated (21% of caregivers) or giving too
low a dose of opioid analgesia (9%).56 None of the included
studies reported administration errors made by healthcare
professionals.
Patient impact
While patient impact was described in terms of opioid
effects and pain intensity, none of the studies explicitly
rated the degree of patient harm resulting from opioid
errors. In one study, patients receiving inappropriately
high doses of fentanyl on admission to a palliative care
unit were observed to have frank signs and symptoms of
opioid overdose or toxicity; however, no deaths were
reported as a result of overdose.57 In the home care setting,
errors with opioid analgesia, administered by non-profes-
sional caregivers, occurred in almost half (49%) of all
administrations (n=422) over the 3-day study period, with
21% of patients receiving no analgesia when they reported
pain.56 This study identified a significant correlation
between non-professional caregiver administration error
and mean worst pain score (0.37, p0.001).56 Two other
studies also noted the importance of timely and adequate
pain management in patients with cancer pain and how
effective pain management may be compromised if pre-
scribing guidelines are not adhered to.58,59 A qualitative
study described palliative care professionals observations
of adverse effects from opioid over dosage and the severe
withdrawal symptoms caused by inappropriate opioid
switching.55
Discussion
Despite the prevalence of opioid prescribing and adminis-
tration in cancer and specialist palliative care, and the
scope for prescribing and administration errors that can
have potentially adverse consequences, this review has
identified that this is an under-explored area of patient
safety. In this review, the most commonly reported opioid
error type related to deviation from opioid prescribing
guidelines in the clinical setting.5759 Opioid administra-
tion errors were only reported in the context of non-profes-
sional caregivers in the home care setting.56 Opioid
administration errors in the clinical setting were not
reported in any of the included studies, nor were errors of
omission (forgetting to give a dose or giving the dose later
than scheduled), with no recognition of the dosing cas-
cades that might follow from inadequate pain relief from
such errors. It is difficult to draw a direct comparison of
error incidence, as audit periods in these studies varied and
each study focussed on a single aspect of opioid error.
Similarly, neither patient nor clinical outcomes resulting
from opioid errors could be clearly identified from the
literature.
Outside of chemotherapy errors, the opioid error rates
in oncology and palliative care settings reported in the lit-
erature are considerably higher than for all other reported
medication error rates, where the highest reported medica-
tion error incidence was 6.6 medication incidents per
month.24 A literature review of published case reports and
case series, describing opioid-related problems across all
care settings that resulted in patient harm (n=105), found
only 18% of the included papers reported errors or adverse
events in patients with cancer, despite the frequency of
opioid prescription in this setting.16
While there is also wide variation in reported opioid
error incidence in the acute care setting,6062 these opioid
error rates provide the best baseline for comparison with
the error incidence rates reported in adult oncology and
palliative care. A retrospective audit in an acute general
hospital in Ireland found that opioid errors accounted for
12% of all medication errors (n=448) over a 5-year
period.60 In a 24-h snapshot audit of medical and surgical
patients in teaching hospital in the United Kingdom, 27%
of patient charts with an opioid order (n=330) were found
to have an opioid error.62 In a large district general hospi-
tal, also in the United Kingdom, a prescribing audit of
intramuscular opioid analgesics over a 2-week period
identified errors in 60% of opioid prescriptions (n=120).61
These higher acute care opioid error rates may reflect bet-
ter reporting and/or sub-optimal opioid prescribing and
administration clinical capabilities in the acute care
setting.
Similar to what was identified in this review, prescrib-
ing strategy35,6063 and administration errors33,35,60 are the
primary opioid error types occurring in the adult acute care
settings. These errors are predominantly associated with
the use of morphine, hydromorphone, fentanyl and oxyco-
done.33,35,62 Various case reports have also described opi-
oid errors in cancer and palliative care populations related
to wrong route errors,64 conversion errors from hydromor-
phone to methadone65 and over dosage with both morphine
and hydromorphone following terminal extubation.66
Similarly, in a recent literature review, the predominant
opioid error types in patients with cancer, across a range of
settings, related to drug interactions (17% of patients with
cancer) and excessive opioid administration (20% of
patients with cancer).16 Outside of acute care, 79% of anal-
gesic medication errors (n=3949) over a 2-year period in
US nursing homes were related to opioid errors.67
Heneka et al. 529
Summary
Overall opioid error incidence in cancer/palliative care
populations was difficult to ascertain as each study
focussed on a single narrow area of error, such as deviation
from local and national opioid prescribing guidelines,58,59
transdermal fentanyl dosage57 and non-professional car-
egiver opioid administration errors.56 The most common
opioid errors identified related to under-prescribing of opi-
oids for cancer pain,58,59 failure to order PRN analgesia for
patients with regular opioid orders,58,59 incorrect dosing
intervals,58,59 incorrect route or formulation for pain
type57,58 and failure to pre-emptively prescribe for opioid
side effects.58,59 A recent review article68 also identified
strategic, titration and conversion errors as the key opioid
error categories in patients with cancer pain.
Interestingly, the predominant general medication error
types reported in the palliative care literature are adminis-
tration errors,23,24 documentation or transcribing errors23,24
and errors related to syringe driver use.24,69 Errors of omis-
sion70 and errors as a consequence of medication reconcili-
ation practices44 have also been reported in palliative care
inpatient settings. However, none of these error types was
reported in the studies included in this review.
It is worth noting that the studies reporting opioid pre-
scribing strategy errors57,58 utilised different guidelines as
the basis against which opioid errors could be defined,
which may account for the wide variation in reported error
incidence. In these studies, non-adherence to guideline rec-
ommendations, for example, failure to order PRN analgesia
for patients with regular analgesia orders, was also identi-
fied as an error even if it did not directly result in patient
harm. Importantly, clinical guidelines provide a framework
for best practice allowing for flexible implementation at the
patient level, subject to expert clinical judgement in each
case.37,71 As such, there may be sound reasons why clini-
cians choose to deviate from these guidelines,72 and, pro-
viding these reasons have been documented, these
deviations should not constitute an opioid error.73
Of note, no studies examined opioid administration
errors in the clinical setting; however, administration
errors by non-professional caregivers in the home hospice
setting were explored in one study.56 In the acute care set-
ting, prescribing and administration errors with the poten-
tial to cause patient harm are often undetected by hospital
staff and, hence, are not reported.8 While it cannot be con-
firmed, it is highly probable that these errors may also be
occurring in the specialist oncology and palliative care set-
tings and are not being reported. The harm experienced by
patients as a result of opioid errors was not specifically
reported in any of the included studies, rather patient
impact was observed relative to pain intensity56 and the
immediate adverse effects from an opioid over dosage.55,57
The lack of detailed patient harm data resulting from opi-
oid errors prevented an assessment of the relationship
between error type and patient harm being undertaken.
Implications for clinical practice
Quality and safety standards in palliative care provide a
framework to meet the unique needs of people at the end of
life,74 with a small but growing body of research address-
ing patient safety issues in palliative care specifi-
cally.2527,7577 As identified in this review, medication
error reporting in adult oncology is predominantly related
to chemotherapeutic agents, with little data on errors with
other high-risk medications used in symptom control.
Similarly, reported medication error rates in the palliative
care setting appear lower than in acute care settings,
despite this patient population being at increased risk of
medication errors and related adverse events due to
increasing age, polypharmacy and exposure to medica-
tions with a narrow therapeutic index, such as opioids.
Defining, identifying and quantifying error reporting prac-
tices in these settings, and promoting comparative data
collection, are essential components of any ongoing qual-
ity and safety initiatives to ensure the provision of quality
care for patients with life-limiting illnesses.
Implications for future research
This review has highlighted the paucity of the literature
examining and reporting opioid error incidence, types and
patient impact in adult oncology and palliative care set-
tings. There is scope for future research in these clinical
settings which quantifies and identifies opioid error types
in addition to those related to deviations from prescribing
guidelines, that is, errors of administration, omission, tran-
scription and documentation, calculation/conversion and
device errors, and identifies the degree of patient harm
from opioid errors.
Exploring oncology and palliative care clinicians per-
ceptions of opioid error type and frequency in their clinical
practice, knowledge and attitudes towards opioid error
reporting specifically and the impact of opioid errors on
the clinician, will provide valuable insight into the com-
plexity of opioid errors from the clinicians perspective.
Additionally, a comparison of opioid error incidence, types
and patient impact in oncology and palliative care relative to
other acute care and inpatient settings, via comprehensive
audit, will be beneficial as a benchmark for future quality
improvement initiatives across health services. Reviews of
local, state-wide and national data on reported opioid errors,
categorised by setting, may also be indicated.
Limitations
This review excluded papers not published in English,
which may contribute to the risk of selection bias. Data
extraction was undertaken by a single reviewer to assess
eligibility of included studies; however, multiple inde-
pendent reviewers rated study quality (J.L.P. and T.S.).
As there is no standardised definition of medication
530 Palliative Medicine 30(6)
error,10 despite employing a broad search strategy for
MeSH terms and key words relating to error, it is possible
that some papers may not have been identified through
database searching due to the multiplicity of terms used
to describe medication errors. Drug interactions with opi-
oids and prescribing errors relating to adjuvant medica-
tions recommended for use with opioids, for example,
non-opioid analgesia, aperients and anti-emetics, were
not explicitly identified as part of this review. The hetero-
geneity of the data reported in the included studies limits
generalisability of this review in oncology and palliative
care settings.
Conclusion
This review examined the reported incidence, types and
impact of opioid medication errors in adult oncology and
palliative care settings. Despite routine use of opioids for
the management of cancer pain and end-of-life symp-
toms, in a population already vulnerable to harm from
medication errors, little remains known about the inci-
dence, error types and patient impact of opioid errors in
these settings. Reported medication error rates, particu-
larly in adult palliative care settings, appear to be low, in
contrast to perceptions and experiences of palliative care
professionals and the incidence of strategic prescribing
errors reported in the literature. There is a need to further
explore opioid error types, other than those resulting
from deviations from opioid prescribing guidelines, and
the degree of patient harm resulting from these errors,
from both patient data and the perspectives of oncology
and palliative care clinicians, in order to better under-
stand and address the patient safety issues in these vul-
nerable patient populations.
Acknowledgements
The authors gratefully acknowledge the contribution of Ms
Caroline Yeh, Librarian, St Vincents Hospital, Sydney, in the
development of the literature search strategy. Planning for this
paper was undertaken by N.H., J.L.P. and T.S. Data collection
and management was undertaken by N.H. and reviewed by J.L.P.
and T.S. J.L.P., T.S. and D.R. provided significant critical review
of the article. All authors reviewed and gave final approval of the
version to be published.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship and/or publication of this
article.
Funding
This work was supported by an Australian Government,
Collaborative Research Networks (CRN) program scholarship
(NH) for the research project: Healthy People, Healthy Country:
Translating evidence into action to improve health and wellbeing
in vulnerable populations.
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