Transcript Management of Acute Pancreatitis Evidence Based Approach

Acute Pancreatitis
Evidence Based Approach
Pankaj Singh MD
Director of Gastrointestinal Endoscopy
Central Texas VA Health System, TX
Assistant Professor
Texas A&M University
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 cascade (IL6, IL-8, TNF-)
I
II
C - reactive protein
 Pancreatic injury
III

IV
Amylase, Lipase, Trypsinogen
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 2
– 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
nutritional support
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 1970’s 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 RCT’s 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
I.
Confirm
Acute
Pancreatitis
I.
Confirm Acute
Acute Pancreatitis
Pancreatitis
I. Confirm
Amylase/
Lipase
Amylase/
Lipase
Amylase/ Lipase
Lipase
>
Amylase
Lipase
> Amylase
Amylase
Lipase >
Trypsinogen
2
Trypsinogen
2
Trypsinogen 2
CT
scan -- Atypical
cases
CT
CT scan
scan - Atypical
Atypical cases
cases
II.
Initial Management
II.
II. Initial
Initial Management
Management
Pain
control/ Fluid
Pain
Pain control/
control/ Fluid
Fluid
NPO
NPO
NPO
NG
NG Tube
Tube NOT
NOT recommended
recommended
III. Severity Stratification
III.
III. Severity
Severity Stratification
Stratification
APACHE II
APACHE
II
APACHE
II
C-Reactive
Protein
C-Reactive
C-Reactive Protein
Protein
Mild AP
Mild
Mild AP
AP
Severe AP
Severe
Severe AP
AP
Management of Acute Pancreatitis
Mild
MildAP
AP
80%
80%of
ofcases
cases
<<5%
5%of
ofmortality
mortality
Severe
SevereAP
AP
20%
20%of
ofcases
cases
>>95%
95%of
ofmortality
mortality
Recommended
Recommended(All
(Allpts.)
pts.)
Admit
Admitto
togeneral
generalward
ward
Refeed
Refeedwhen
whenpain
painsubsides
subsides
Recommended
Recommended
Admit
Admitto
toICU
ICU
Antibiotics
Antibiotics
CT
CTscan
scan--day
day33
Not
NotRecommended
Recommended
Antibiotics
Antibiotics
CT
CTscan
scan
PPI
PPI
Necrosis
Necrosis
SterileSterile-observe
observe
IfIfinfection
infectionsuspected
suspected--FNA
FNA
Necrosectomy
Necrosectomyin
ininfected
infectednecrosis
necrosis
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
[email protected]
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