Acute PancreatitisAcute Pancreatitis Evidence Based ApproachEvidence Based Approach

Pankaj Singh MDDirector of Gastrointestinal Endoscopy

Central Texas VA Health System, TX

Assistant Professor

Texas A&M University

Clinical CaseClinical Case

32-year-old man c/o acute onset abdominal pain

(presumed pancreatic origin)h/o alcohol intake

What do you think?What do you think?Amylase or lipaseUltrasound or CT scan

– If yes, When?ICU or medical ward Enteral nutrition or TPNAntibioticsERCPSurgery

Evidence Evidence

A. Proven – > 2 well designed trials, randomized

B. Possible/ Probable – 1 well designed study, randomized

C. Consensus – agreed opinion with no supportive evidence

GuidelinesGuidelines

AtlantaBritish Society of GastroenterologyInternational Association of PancreasSantorini ConferenceWorld Congress of Gastroenterology

BackgroundBackground

Potentially fatalMortality – 0-25%

Necrosis determines the prognosis

Panreas 1998 307-11

BackgroundBackgroundMild AP (no necrosis) – 0%

Sterile necrosis – 10%

Infected necrosis – 25%

DiagnosisDiagnosis

Laboratory– Amylase– Lipase

Radiological– US– CT scan

Blood testsBlood testsAmylase and lipasePlasma level peak within 24 hourst1/2 of amylase << lipase

Sensitivity Specificity

Amylase 67-100 85-98

Lipase 82-100 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)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 scanCT scan

Not necessary for the diagnosisDiagnostic 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 ManagementInitial Management

Monitoring – temp., pulse, blood pressure, and urine output

Treatment – – Cardiopulmonary care– Sufficient fluid resuscitation– Pain control

Severity StratificationSeverity Stratification

RationaleDifferentiate mild from severe acute

pancreatitis

Desirable features of Markers Desirable features of Markers of Severityof Severity

Accuracy - High sensitivity & PPVPredictability within 24 hours of

admissionEasy to use

Clinical FeaturesClinical Features

Clinical examination– Age > 70 years– Abdominal findings

increased tenderness rebound distension hypoactive bowel sounds

In first 24 hours of admission - unreliableAfter 48 hours- as accurate as Ranson score

Multiple Factors Scoring Multiple Factors Scoring SystemSystem

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 IIAPACHE 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

TestsTests

Trypsinogen Trypsinogen activation peptide (TAP) I Trypsin

Inflammatory cascade (IL6, IL-8, TNF-) II

C - reactive protein III

Pancreatic injury

Amylase, Lipase, Trypsinogen IV

Markers for Leakage of Markers for Leakage of Pancreatic EnzymesPancreatic 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 Trypsinogen activation peptide (TAP)peptide (TAP)

– Small peptideAdvantage

– Appear very early during the diseaseDisadvantage

– Limited "diagnostic window". decrease very quickly irrespective of the course of

the disease

– Not suitable for rapid simple analysis

Markers of InflammationMarkers 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)C-reactive protein (CRP)

Acute phase reactant Synthesized by the hepatocytesSynthesis is induced by the release of

interleukin 1 and 6 Peak in serum is three days after the onset

of painMost popular single test severity marker

used today

Isenmann et al Pancreas 1993;8:358-61

C-reactive protein (CRP)C-reactive protein (CRP)

Gold standard for the prediction of the necrotizing course of the disease

Accuracy of 86%Readily available

Advantage Used to monitor the clinical course of the

disease

Disadvantage Not always present on admissionLack specificity

C-reactive protein (CRP)C-reactive protein (CRP)

CRP is currently the gold standardAmylase and lipase of no valueHigh likelihood that IL-6/ TAP will

replace the CRP

Recommendations

CT ScanCT ScanNormal

– Homogeneous enhancement of the whole pancreas

Abnormal – Non-visualization of a part of the pancreas

Sensitivity of 90-95%Specificity – 100%

RecommendationRecommendation

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 Is It Possible to Predict Severity

Early in Acute Pancreatitis?Early in Acute Pancreatitis?

Good clinical judgment– Specificity - 80%– Sensitivity - 40%

Scoring or biochemical methods – Specificity – 60%– Sensitivity – 95%

Etiological AssessmentEtiological Assessment

Needed in all patientsDifferentiate biliary from alcoholic

pancreatitisEarly abdominal US is recommended in

all patients (Evidence category A)

Initial Management of acute Initial Management of acute pancreatitispancreatitis

NutritionProphylactic AntibioticsAcid suppressionERCPSurgery

Nutrition - RationaleNutrition - Rationale

Hyper metabolic state– Total energy expenditure 1.5 x resting energy

requirementNutrition 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?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 nutritionParenteral nutrition

Rationale for - Pancreatic restInability to tolerate enteric feeding

Parenteral NutritionParenteral Nutrition

Rationale against Pancreatic rest

– Poorly definedIncreased risk of sepsis

– Gut atrophy - increased bacterial translocation

– HyperglycemiaGreater costs

Parenteral NutritionParenteral Nutrition

Nine uncontrolled retrospective studies Safe, well tolerated with few complicationsNo impact on the outcome

TPNTPN

Prospective randomized controlled trial

54

TPN IV F

Duration of hospital stay 16 10Line sepsis 10 1

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

Enteral NutritionEnteral Nutrition

Enteral NutritionEnteral Nutrition

Rationale for Minimal effect on pancreatic secretionsPrevention of gut mucosal atrophyAvoid TPN related complications

– Line sepsis– Hyperglycemia

Arch Surg 1999;134:287-292

Enteral NutritionEnteral Nutrition

Rationale againstSmall degree of pancreatic stimulationProximal displacement of the feeding

tube may worsen the disease outcome

Enteral nutritionEnteral 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 feedingEnteric 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 How about Nasogastric feeding ?feeding ?

AimAssess 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 NutritionEvolution in Nutrition

FastingTPN is betterEarly jejunal feeding is safeEarly jejunal feeding is superiorGastric feeding is as good as jejunal

feeding

Current RecommendationsCurrent 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 RecommendationsCurrent Recommendations

Jejunal feeding should be started within 48 hours

The optimal feeding formulae is unknownEnsure the jejunal placement of the tube Monitor for

– Hypertryglyceridemia/ hyperglycemiaTPN in patients who do not tolerate

enteral feeding

AntibioticsAntibiotics

Sepsis– Accounts for > 80% of deaths

Intestinal flora– Gram negative bacteria

Mechanism – translocation of the bacteria across the gut wall

Antibiotics - RationaleAntibiotics - Rationale

Early (1 week) Sterile necrosis – Massive inflammatory response – multi-system

organ failure (SIRS)

Late – – Infected necrosis

Why the controversy ?Why the controversy ?

Early trials in 1970’s did not show the benefit of antibiotics

Antibiotics that did not penetrated the pancreatic tissue

Evidence 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

RecommendationsRecommendations

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 Is there a downside with antibiotics ?antibiotics ?

Increased risk of fungal infections Associate with mortality as high as 85%

Fungal InfectionFungal Infection

CandidaTorulopsisCommensal organism found in

human gastrointestinal tractIncidence 10-40%

Fungal infectionFungal infection92 patients with infected pancreatic necrosis22 patients (24%) with Candida infectionPatients 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 InfectionFungal Infection

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

TherapyTherapy

Treatment– Antifungal therapy – definite role

Acid suppressionAcid suppression

Several RCT’s of H 2 receptor antagonists failed to show any clinical benefits

Management of the Biliary Management of the Biliary PancreatitisPancreatitis

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 What are the diagnostic criteria of biliary pancreatitis in patients with AP ?biliary pancreatitis in patients with AP ?

Abnormal liver function tests– ALT elevation of > 3 x normal

Ultrasound – Gallstone

What is the optimal method for What is the optimal method for biliary tract imaging ?biliary tract imaging ?

ERCPUltrasoundMRCPEUS

Endoscopic Retrograde Endoscopic Retrograde CholangiopancreatographyCholangiopancreatography

((ERCP)ERCP)

ERCP– Gold standard– Potential serious complications

Abdominal UltrasoundAbdominal Ultrasound

Sensitivity GB stone 60-80% CBD stone 30-60%

Magnetic Resonance Magnetic Resonance Cholangio-PancreatographyCholangio-Pancreatography

((MRCP)MRCP)

Sensitivity of > 90%

Endoscopy Ultrasound Endoscopy Ultrasound (EUS)(EUS)

EUS– Sensitivity of > 95% – Specificity of > 95-

100%

When is early ERCP When is early ERCP indicated ?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 When is early ERCP NOTNOT indicated ?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 necrosisPancreatic 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 necrosisSterile 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 necrosisInfected necrosis

CT guided FNA with gram stain and culture is a confirmatory test (Evidence A)

Infected NecrosisInfected Necrosis

Infected necrosisInfected 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 NecrosisInfected Necrosis

Necrosectomy is indicated in a confirmed infected pancreatic necrosis

(Evidence A)

Management of Acute PancreatitisManagement of Acute Pancreatitis

Management of Acute PancreatitisManagement of Acute Pancreatitis

June 10, 323 BC

Clinical CaseClinical 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 EndThe End

To take the post test for credit of attendanceDownload the post test, complete and Return to Dr. S.K. Oliver at

skoliver@swmail.sw.org

Post test question onePost 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 twoPost 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 threePost 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 fourPost 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 EndThe End