Acute Pancreatitis

Evidence Based Approach

Dr Hicham Al Mawla

2016

Clinical Case
32-year-old

man
c/o acute onset abdominal pain
(presumed pancreatic origin)
h/o alcohol intake

What do you think?

Amylase

or lipase
Ultrasound or CT scan
If yes, When?

ICU

or medical ward
Enteral nutrition or TPN
Antibiotics
ERCP
Surgery

Evidence
A.

Proven
> 2 well designed trials, randomized
B. Possible/ Probable
1 well designed study, randomized
C. Consensus
agreed opinion with no supportive evidence

Guidelines
Atlanta
British

Society of Gastroenterology
International Association of Pancreas
Santorini Conference
World Congress of Gastroenterology

Background
Potentially

fatal
Mortality 0-25%
Necrosis

determines the prognosis

Panreas 1998 307-11

Background
Mild

AP (no necrosis) 0%

Sterile

necrosis 10%

Infected

necrosis 25%

Diagnosis
Laboratory
Amylase
Lipase

Radiological
US
CT scan

Blood tests
Amylase

and lipase
Plasma level peak within 24 hours
t1/2 of amylase << lipase

Amylase
Lipase

Sensitivity
67-100
82-100

Specificity
85-98
86-100

Gut 1997,41:431-35; Br J Surg 1998,84:1665-69.

Lipase has slightly higher sensitivity and

specificity and greater overall accuracy
than amylase
(Evidence category A)

Ultra Sound (US)

Little

part in the diagnosis of the acute

pancreatitis
Role in biliary pancreatitis
Stones in gallbladder
Common Bile Duct dilation

Br J Surg 1982;69:369-72

US findings should be examined in all

patients with possible acute pancreatitis
on admission
(Evidence category B)

CT scan
Not

necessary for the diagnosis

Diagnostic doubt
Atypical presentations
Asymptomatic hyperamylasaemia or

hyperlipasemia

Gastroenterol Clin N Am 1990;19:811-42

Routine use of CT scan within 24-48 hours

of admission
(Evidence category C)

Initial Management
Monitoring

temp., pulse, blood pressure,

and urine output
Treatment
Cardiopulmonary care
Sufficient fluid resuscitation
Pain control

Severity Stratification
Rationale
Differentiate mild from severe acute
pancreatitis

Desirable features of Markers

of Severity
Accuracy

- High sensitivity & PPV

Predictability within 24 hours of
admission
Easy to use

Clinical Features
Clinical

examination

Age > 70 years

Abdominal findings
increased tenderness
rebound
distension
hypoactive bowel sounds

In

first 24 hours of admission - unreliable

After 48 hours- as accurate as Ranson score

Multiple Factors Scoring

System
Ranson
Separate for alcohol and gallstone etiology
Score > 3 = severe acute pancreatitis

Glasgow
valid in all types of pancreatitis

Both of these systems require 48 hours from

the admission for full assessment
Can J Gastroent 2003 325-328

APACHE II
Acute

Physiology and Chronic Health Evaluation

as good as the Ranson or Glasgow at 24 and
48 hours of the admission
APACHE II score > 8 = Severe acute pancreatitis
Cumbersome to use if one does not use a pc or
palm - where the formula is easily downloaded

Br J Surg 1997,84:1665-69

 If

a multiple factor scoring system is to

be used, the best choice at present
appears to be APACHE II calculated at
24 hours Evidence category A

Tests
Trypsinogen

Trypsinogen activation peptide (TAP)

Trypsin
Inflammatory

Pancreatic
Amylase,

cascade (IL6, IL-8, TNF-)

II

C - reactive protein

III

injury

Lipase, Trypsinogen

IV

Markers for Leakage of

Pancreatic Enzymes
Amylase/

Lipase

Degree of elevation shows little correlation with

disease severity and prognosis

May have an inverse relationship with severity
Trypsinogen

Excreted into the urine

Used as a screening test for acute

pancreatitis

Trypsinogen activation peptide

(TAP)
Small peptide

Advantage
Appear very early during the disease

Disadvantage
Limited "diagnostic window".
decrease very quickly irrespective of the course of
the disease
Not suitable for rapid simple analysis

Markers of Inflammation
TNF-alpha
Major role in mediating inflammatory response
Conflicting reports as a predictor of severity

Interleukin-6

and 8.

Principal cytokine mediator

Measured in serum and urine
Discriminate severe from mild cases on day 1

C-reactive protein (CRP)

Acute

phase reactant
Synthesized by the hepatocytes
Synthesis is induced by the release of
interleukin 1 and 6
Peak in serum is three days after the onset
of pain
Most popular single test severity marker
used today
Isenmann et al Pancreas 1993;8:358-61

C-reactive protein (CRP)

Gold

standard for the prediction of the

necrotizing course of the disease
Accuracy of 86%
Readily available

C-reactive protein (CRP)

Advantage
Used to monitor the clinical course of the
disease
Disadvantage
Not always present on admission
Lack specificity

Recommendations
CRP

is currently the gold standard

Amylase and lipase of no value
High likelihood that IL-6/ TAP will
replace the CRP

CT Scan
Normal
Homogeneous enhancement of the whole

pancreas
Abnormal
Non-visualization of a part of the pancreas

Sensitivity

of 90-95%
Specificity 100%

Recommendation
A dynamic

CT scan should be performed

in all (predicted) severe cases between 3
and 10 days after admission
(Evidence grade B)

Is It Possible to Predict Severity

Early in Acute Pancreatitis?
Good

clinical judgment

Specificity - 80%
Sensitivity - 40%

Scoring

or biochemical methods

Specificity 60%
Sensitivity 95%

Etiological Assessment
Needed

in all patients
Differentiate biliary from alcoholic
pancreatitis
Early abdominal US is recommended in
all patients
(Evidence category A)

Initial Management of acute

pancreatitis
Nutrition
Prophylactic

Antibiotics
Acid suppression
ERCP
Surgery

Nutrition - Rationale
Hyper

metabolic state

Total energy expenditure 1.5 x resting energy

requirement
Nutrition

depletion

Starvation
Preexisting protein-calorie malnutrition &

micronutrient deficiency
Crit care Med 1991;19:484-90;
J
parenter Enter Nutr 1989;13:26-29.

Nutrition who needs it?

Mild

AP

70-80% recover within 4-7 days

Moderate

to severe AP

Ranson score > 3

APACHE II > 8
Necrotic pancreas
Organ failure
Windsor et al. Gut 1998,42:431-35;
Kalfatentzos et al. Br J Surg 1997,84:1665-69

Parenteral nutrition
Rationale for Pancreatic rest
Inability to tolerate enteric feeding

Parenteral Nutrition
Rationale against
Pancreatic rest
Poorly defined

Increased

risk of sepsis

Gut atrophy - increased

bacterial translocation
Hyperglycemia
Greater

costs

Parenteral Nutrition
Nine

uncontrolled retrospective studies

Safe, well tolerated with few complications
No impact on the outcome

TPN
Prospective randomized controlled trial
54
TPN
IV F
Duration

of hospital stay 16
Line sepsis
10

10
1

Sax et al. Am J Surg 1987,153:117-22

Enteral Nutrition

Enteral Nutrition
Rationale for
Minimal effect on pancreatic secretions
Prevention of gut mucosal atrophy
Avoid TPN related complications
Line sepsis
Hyperglycemia

Arch Surg 1999;134:287-292

Enteral Nutrition
Rationale against
Small degree of pancreatic stimulation
Proximal displacement of the feeding
tube may worsen the disease outcome

Enteral nutrition
4

prospective randomized controlled trials

Significantly lower
Line sepsis
Infections per patients
Hyperglycemic episodes
Cost was significantly higher in TPN
No difference in mortality, ICU admissions,
multi-organ failure
Gut 1998,42:431-35; Br J Surg 1997,84:1665-69 JPEN
1997,21:14-20; J Submicrosc Cytol Pathol 1996,28:61-74.

Enteric feeding
Enteral

nutrition is feasible, well

tolerated and improves nutritional status
Enteral nutrition is certainly no worse
than TPN and is less costly

How about Nasogastric

feeding ?
Aim
Assess the safety and practicability of NG
feeding in severe acute pancreatitis
Methods
Prospective study
26 patients with severe acute pancreatitis
NG feeding within 48 hours of admission
Eatock et al. International Journal of Pancreatology, 2000

 Result
Pancreatic necrosis 15 patients
Severe organ failure - 11 patients

Feeding
Well tolerated in 22 patients
No evidence of clinical or biochemical

deterioration on commencing NG feeding

 NG

feeding appears safe, is well

tolerated and is possible in severe
acute pancreatitis

Evolution in Nutrition
Fasting
TPN

is better
Early jejunal feeding is safe
Early jejunal feeding is superior
Gastric feeding is as good as jejunal
feeding

Current Recommendations
Mild

to moderate
Ranson < 3
APACHE II < 8
do not require nutritional support

Severe

Ranson >3
APACHE II >10
Organ failure
Pancreatic necrosis
support

nutritional

Current Recommendations
Jejunal

feeding should be started within 48

hours
The optimal feeding formulae is unknown
Ensure the jejunal placement of the tube
Monitor for
Hypertryglyceridemia/ hyperglycemia

TPN

in patients who do not tolerate

enteral feeding

Antibiotics
Sepsis
Accounts for > 80% of deaths

Intestinal

flora

Gram negative bacteria

Mechanism

translocation of the
bacteria across the gut wall

Antibiotics - Rationale
Early

(1 week) Sterile necrosis

Massive inflammatory response multi-system

organ failure (SIRS)

Late

Infected necrosis

Why the controversy ?

Early

trials in 1970s did not show the

benefit of antibiotics
Antibiotics that did not penetrated the
pancreatic tissue

Evidence
8

clinical trials
Five of these trials showed a significant reduction
in the incidence of pancreatic infections
1 trial showed a significant reduction in mortality
Limitations
Small sample size
None were double blinded randomized placebo

controlled trials

Recommendations
Prophylactic

antibacterial treatment is strongly

recommended in severe pancreatitis (Evidence B)
No evidence when to start prophylactic treatment or
how long to continue therapy
Appropriate antibiotics are those that are active
against in particular gram-negative organisms
Commence as early as possible after the
identification of a severe attack

Is there a downside with

antibiotics ?
Increased

risk of fungal infections

Associate with mortality as high as 85%

Fungal Infection
Candida
Torulopsis
Commensal

organism found in
human gastrointestinal tract
Incidence 10-40%

Fungal infection
92

patients with infected pancreatic necrosis

22 patients (24%) with Candida infection
Patients with Candida infections
Suffered higher mortality (64% vs. 19%, p=.0001)
More systemic complications
Were given preoperative antibiotics for a longer

period (19 vs 6 days; p=.0001)

World J. Surg. 25,372-76

Fungal Infection
Antibiotics

predispose to candida
infection of the pancreatic tissue which
increases the mortality substantially

Therapy
Treatment
Antifungal therapy definite role

Acid suppression

Several

RCTs of H 2 receptor
antagonists failed to show any clinical
benefits

Management of the Biliary

Pancreatitis
Passage

or impaction of a

stone
Women (age of 50-70)
Mortality 6%

?
What

are the diagnostic criteria of biliary

pancreatitis ?
What is the optimal method for biliary tract
imaging ?
When is early ERCP indicated ?

What are the diagnostic criteria of

biliary pancreatitis in patients with AP ?
Abnormal

liver function tests

ALT elevation of > 3 x normal

Ultrasound
Gallstone

What is the optimal method for

biliary tract imaging ?
ERCP
Ultrasound
MRCP
EUS

Endoscopic Retrograde
Cholangiopancreatography
(ERCP)
ERCP
Gold standard
Potential serious complications

Abdominal Ultrasound

GB

stone
CBD stone

Sensitivity
60-80%
30-60%

Magnetic Resonance
Cholangio-Pancreatography
(MRCP)
Sensitivity

of > 90%

Endoscopy Ultrasound
(EUS)

EUS
Sensitivity of > 95%
Specificity of > 95-

100%

When is early ERCP

indicated ?
Concomitant

cholangitis (Evidence A)
Significant persistent biliary obstruction
(bilirubin > 5 mg/ dl) (Evidence A)
ERCP in severe biliary pancreatitis
without biliary sepsis or obstruction (Evidence B)

Neoptolemos et al 1988; Fan NEJM 1993; Folsch NEJM 1997

When is early ERCP NOT

indicated ?
Mild

pancreatitis of suspected or proven

biliary etiology in the absence of the biliary
obstruction
(Evidence A)

Neoptolemos et al 1988; Fan NEJM 1993; Folsch NEJM 1997

Pancreatic necrosis
Sterile

necrosis Systemic Inflammatory

Response Syndrome (SIRS) (First week)
Mortality rate of 10-40%

Infected

necrosis Sepsis (After 3 weeks)

Mortality 20-70%

Sterile necrosis
Sterile

pancreatic necrosis surgery in

selected cases
Selected cases
Massive pancreatic necrosis (>50%) with a
deteriorating clinical course (Evidence C)
Patients with progression of organ dysfunction
No signs of the improvement
(grade B)

Infected necrosis
CT

guided FNA with gram stain and culture

is a confirmatory test
(Evidence A)

Infected Necrosis

Infected necrosis
Suspect if:
Exacerbation of clinical signs
Laboratory blood test changes

Shift to immature cells

Elevation of CRP

Increased APACHE II
Positive blood culture

Indication for Fine Needle Asperation (FNA)

Infected Necrosis
Necrosectomy

is indicated in a confirmed
infected pancreatic necrosis
(Evidence A)

Management of Acute Pancreatitis

Management of Acute Pancreatitis

June 10, 323 BC

Clinical Case

32-year-old man
c/o acute onset abdominal pain (presumed
pancreatic origin)
h/o alcohol intake
ALEXANDER THE GREAT
DIAGNOSIS:
ALCOHOLIC PANCREATITIS

The End
To take

the post test for credit of attendance

Download the post test, complete and
Return to Dr. S.K. Oliver at
skoliver@swmail.sw.org

Post test question one

Which of the following has an Evidence category A:
1. Lipase has slightly higher sensitivity and
specificity and greater overall accuracy than
amylase
2. Amylase has higher sensitivity and specificity
and greater overall accuracy than lipase
3. US findings should be examined in all patients
with possible acute pancreatitis on admission
4. Routine use of CT scan within 24-48 hours of
admission

Post test question two

Which of the following is the most popular
single test severity marker used today?
1. Trypsinogen activation peptide
2. TNF- alpha
3. C Reactive Protein
4. Interleukin 6&8

Post test question three

Which of the following is associated with gut
atrophy?
1. NG feedings
2. Jejunal feedings
3. Parenteral feedings
4. Enteric feedings

Post test question four

When is early ERCP not indicated?
1. Concomitant cholangitis
2. Mild pancreatitis of suspected or proven biliary
etiology in the absence of the biliary obstruction
3. Significant persistent biliary obstruction
(bilirubin > 5 mg/ dl)
4. ERCP in severe biliary pancreatitis without
biliary sepsis or obstruction

The End