ACUTE PANCREATITISCHAIR OF FACULTY SURGERY # 2

FIRST MOSCOW STATE MEDICAL UNIVERSITY

NATROSHVILI A.G.

ANATOMY AND PHYSIOLOGY• DIGESTIVE

ENZYMES

• HORMONES

microscopic viewof pancreatic acini

pancreatic duct

duodenum

ANATOMY AND PHYSIOLOGY

trypsinogen trypsin

chymotrypsinelastasephospholipasecarboxypeptidase

enterokinase

chymotrypsinogenproelastaseprophospholipaseprocarboxypeptidase

duodenal lumen

Normal Enzyme Activation

ANATOMY AND PHYSIOLOGY

Exocrine Stimulation

• THE MORE PROXIMAL THE NUTRIENT INFUSION…THE GREATER THE PANCREATIC STIMULATION (DOG STUDIES)

• STOMACH – MAXIMAL STIMULATION

• DUODENUM – INTERMEDIATE STIMULATION

• JEJUNUM – MINIMAL / NEGLIGIBLE STIMULATION

• ELEMENTAL FORMULAS TEND TO CAUSE LESS STIMULATION THAN STANDARD INTACT FORMULAS

• INTACT PROTEIN > OLIGOPEPTIDES > FREE AMINO ACIDS

• INTRAVENOUS NUTRIENTS (EVEN LIPIDS) DO NOT APPEAR TO STIMULATE THE PANCREAS

ANATOMY AND PHYSIOLOGY

Protection• COMPARTMENTALIZATION - DIGESTIVE ENZYMES ARE

CONTAINED WITHIN ZYMOGEN GRANULES IN ACINAR CELLS

• REMOTE ACTIVATION - DIGESTIVE ENZYMES ARE SECRETED AS INACTIVE PROENZYMES WITHIN THE PANCREAS

• PROTEASE INHIBITORS – TRYPSIN INHIBITOR IS SECRETED ALONG WITH THE PROENZYMES TO SUPPRESS ANY PREMATURE ENZYME ACTIVATION

• AUTO “SHUT-OFF” – TRYPSIN DESTROYS TRYPSIN IN HIGH CONCENTRATIONS

ACUTE PANCREATITIS

Definition

• ACUTE INFLAMMATORY PROCESS INVOLVING THE PANCREAS

• USUALLY PAINFUL AND SELF-LIMITED

• ISOLATED EVENT OR A RECURRING ILLNESS

• PANCREATIC FUNCTION AND MORPHOLOGY RETURN TO NORMAL AFTER (OR BETWEEN) ATTACKS

ACUTE PANCREATITIS

Etiology

Gall-stones45%

Alcohol35%

Idiopathic10%

Other10%

ACUTE PANCREATITIS

Associated conditions

• CHOLELITHIASIS

• ETHANOL ABUSE

• IDIOPATHIC

• MEDICATIONS

• HYPERLIPIDEMIA

• ERCP

• TRAUMA

• END-STAGE RENAL FAILURE

• PENETRATING PEPTIC ULCER

ACUTE PANCREATITIS

Pathogenesis

Acinar cell injuryPremature enzyme

activationFailed protective

mechanisms

Audodigestion of pancreatic tissue

Local vascular insufficiency

Activation of white blood cells

Release of enzymes into the circulation

Local complicationsDistant organ

failure

ACUTE PANCREATITIS

Pathogenesis

• STAGE 1: PANCREATIC INJURY• EDEMA• INFLAMMATION

• STAGE 2: LOCAL EFFECTS• RETROPERITONEAL EDEMA• ILEUS

• STAGE 3: SYSTEMIC COMPLICATIONS

• HYPOTENSION/SHOCK• METABOLIC DISTURBANCES• SEPSIS/ORGAN FAILURE

SEVERITYMild

Severe

• MILD AP (NO NECROSIS) – 0%

Sterile necrosis – 10%

Infected necrosis – 25%

ACUTE PANCREATITIS

ACUTE PANCREATITIS

Clinical presentation• ABDOMINAL PAIN

• EPIGASTRIC

• RADIATES TO THE BACK (“BELT PAIN”

• WORSE IN SUPINE POSITION

• NAUSEA AND VOMITING

• FEVER

• LABORATORY

• ELEVATED AMYLASE OR LIPASE

• > 3X UPPER LIMITS OF NORMAL

• LIPASE HAS SLIGHTLY HIGHER SENSITIVITY AND SPECIFICITY AND GREATER OVERALL ACCURACY THAN AMYLASE (EVIDENCE CATEGORY A)

• RADIOLOGY

• ABNORMAL SONOGRAM OR CT

• DIFFERENTIAL DIAGNOSIS

• CHOLEDOCHOLITHIASIS

• PERFORATED ULCER

• MESENTERIC ISCHEMIA

• INTESTINAL OBSTRUCTION

• ECTOPIC PREGNANCY

ACUTE PANCREATITIS

Clinical presentation

Mild: edema, inflammation, fat necrosisSevere: phlegmon, necrosis, hemorrhage, infection, abscess, fluid collections

Retroperitoneum, perirenal spaces, mesocolon, omentum, and mediastinum

Adjacent viscera: ileus, obstruction, perforation

Cardiovascular: hypotensionPulmonary: pleural effusions, ARDSRenal: acute tubular necrosisHematologic: disseminated intravascular coag.Metabolic: hypocalcemia, hyperglycemia

PANCREATIC

PERIPANCREATIC

SYSTEMIC

ACUTE PANCREATITIS

Predictors of severity• WHY ARE THEY NEEDED?

• APPROPRIATE PATIENT THERAPY

• COMPARE RESULTS OF STUDIES OF THE IMPACT OF THERAPY

• WHEN ARE THEY NEEDED?• OPTIMALLY, WITHIN FIRST 24 HOURS (DAMAGE CONTROL

MUST BEGIN EARLY)

• WHICH IS BEST?

ACUTE PANCREATITIS

Scoring systems

• RANSON AND GLASGOW CRITERIA (1974)

• BASED ON CLINICAL & LABORATORY PARAMETERS

• SCORED IN FIRST 24-48 HOURS OF ADMISSION

• POOR POSITIVE PREDICTORS (BETTER NEGATIVE PREDICTORS)

• APACHE SCORING SYSTEM

• CAN YIELD A SCORE IN FIRST 24 HOURS

• APACHE II SUFFERS FROM POOR POSITIVE PREDICTIVE VALUE

• APACHE III IS BETTER AT MORTALITY PREDICTION AT > 24 HOURS

• COMPUTED TOMOGRAPHY SEVERITY INDEX

• MUCH BETTER DIAGNOSTIC AND PREDICTIVE TOOL

• OPTIMALLY USEFUL AT 48-96 HOURS AFTER SYMPTOM ONSET

ACUTE PANCREATITIS

Scoring systems: Ranson criteria for alcoholic pancreatitis

AT ADMISSION

1. AGE > 55 YEARS

2. WBC > 16,000

3. GLUCOSE > 200

4. LDH > 350 IU/L

5. AST > 250 IU/L

WITHIN 48 HOURS

1. HCT DROP > 10

2. BUN > 5

3. ARTERIAL PO2 < 60 MM HG

4. BASE DEFICIT > 4 MEQ/L

5. SERUM CA < 8

6. FLUID SEQUESTRATION > 6L

NumberMortality

<21%

3-416%

5-640%

7-8100%

ACUTE PANCREATITIS

Scoring systems: CT severity index

appearance normal enlarged inflamed 1 fluid collection

2 or more collections

grade A B C D E

score 0 1 2 3 4

necrosis none < 33% 33-50% > 50%

score 0 2 4 6

score morbidity mortality

1-2 4% 0%

7-10 92% 17%

Balthazar et al. Radiology 1990.

ACUTE PANCREATITIS

Severe pancreatitis

• SCORING SYSTEMS

• 3 RANSON CRITERIA

• 8 APACHE II POINTS

• 5 CT POINTS

• ORGAN FAILURE

• SHOCK (SBP < 90 MMHG)

• PULMONARY EDEMA / ARDS (PAO2 < 60 MMHG)

• RENAL FAILURE (CR > 2.0 MG/DL)

• LOCAL COMPLICATIONS

• FLUID COLLECTIONS PSEUDOCYSTS

• NECROSIS (MORTALITY 15% IF STERILE, 30-35% IF INFECTED)

• ABSCESS

ACUTE PANCREATITIS

Additional diagnostic tests: Ultrasonography

• LITTLE PART IN THE DIAGNOSIS OF THE ACUTE PANCREATITIS DUE TO BOWEL DILATATION

MAIN SIGNS: ENLARGED HYPOECHOGENIC PANCREAS, POSSIBLE FLUID COLLECTIONS

• ROLE IN BILIARY PANCREATITIS

• STONES IN GALLBLADDER

• COMMON BILE DUCT DILATION

US FINDINGS SHOULD BE EXAMINED IN ALL PATIENTS WITH POSSIBLE ACUTE PANCREATITIS ON ADMISSION (EVIDENCE CATEGORY B)

ACUTE PANCREATITIS

Additional diagnostic tests: CT-scan• HIGHLY INFORMATIVE

• NORMAL

• HOMOGENEOUS ENHANCEMENT OF THE WHOLE PANCREAS

• ABNORMAL

• NON-VISUALIZATION OF A PART OF THE PANCREAS

• SENSITIVITY OF 90-95%

• SPECIFICITY – 100%

• ROUTINE USE OF CT SCAN WITHIN 24-48 HOURS OF ADMISSION (EVIDENCE CATEGORY C)

• A DYNAMIC CT SCAN SHOULD BE PERFORMED IN ALL (PREDICTED) SEVERE CASES BETWEEN 3 AND 10 DAYS AFTER ADMISSION (EVIDENCE CATEGORY B)

ACUTE PANCREATITIS

Additional diagnostic lab tests

• AMYLASE AND LIPASE

• PLASMA LEVEL PEAK WITHIN 24 HOURS

• T1/2 OF AMYLASE << LIPASE

Sensitivity Specificity

Amylase 67-100 85-98

Lipase 82-100 86-100

• 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

ACUTE PANCREATITIS

Additional diagnostic lab tests

• 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

• GOLD STANDARD FOR THE PREDICTION OF THE NECROTIZING COURSE OF THE DISEASE

• ACCURACY OF 86%

• READILY AVAILABLE

C-REACTIVE PROTEIN (CRP)

Isenmann et al Pancreas 1993;8:358-61

ACUTE PANCREATITIS

Initial management of acute pancreatitis• PANCREATIC REST & SUPPORTIVE CARE

• FLUID RESUSCITATION* – MAY REQUIRE 5-10 LITERS/DAY

• CAREFUL PULMONARY & RENAL MONITORING – ICU

• MAINTAIN HEMATOCRIT OF 26-30%

• PAIN CONTROL – PCA PUMP

• CORRECT ELECTROLYTE DERANGEMENTS (K+, CA++, MG++)

• PROTON PUMP INHIBITORS

• SANDOSTATINE

• RULE-OUT NECROSIS

• CONTRASTED CT SCAN AT 48-72 HOURS

• PROPHYLACTIC ANTIBIOTICS IF PRESENT

• SURGICAL DEBRIDEMENT IF INFECTED

• NUTRITIONAL SUPPORT

ACUTE PANCREATITIS

Initial management of acute pancreatitis: ERCP• GALLSTONE PANCREATITIS

• CHOLANGITIS

• OBSTRUCTIVE JAUNDICE

• RECURRENT ACUTE PANCREATITIS

• STRUCTURAL ABNORMALITIES

• NEOPLASM

• BILE SAMPLING FOR MICROLITHIASIS

• SPHINCTEROTOMY IN PATIENTS NOT SUITABLE FOR CHOLECYSTECTOMY

• NOT INDICATED IN CASE OF 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

ACUTE PANCREATITIS

Antibiotics• SEPSIS

• ACCOUNTS FOR > 80% OF DEATHS

• INTESTINAL FLORA

• GRAM NEGATIVE BACTERIA

• MECHANISM – TRANSLOCATION OF THE BACTERIA ACROSS THE GUT WALL

• 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

ACUTE PANCREATITIS

Pancreatic necrosis

• STERILE NECROSIS – SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS) (FIRST WEEK)

• MORTALITY RATE OF 10-40%

• 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)

ACUTE PANCREATITIS

Pancreatic necrosisInfected necrosis – Sepsis (After 3 weeks)

Mortality – 20-70%• US OR CT GUIDED FNA WITH GRAM STAIN AND CULTURE IS A CONFIRMATORY TEST (EVIDENCE A)

SUSPECT IF:

• EXACERBATION OF CLINICAL SIGNS

• LABORATORY BLOOD TEST CHANGES• SHIFT TO IMMATURE CELLS

• ELEVATION OF CRP

• INCREASED APACHE II

• POSITIVE BLOOD CULTURE

• NECROSECTOMY IS INDICATED IN A CONFIRMED INFECTED PANCREATIC NECROSIS (EVIDENCE A)

ACUTE PANCREATITIS

Pancreatic necrosisInfected necrosis – Sepsis (After 3 weeks)

Mortality – 20-70%• US OR CT GUIDED FNA WITH GRAM STAIN AND CULTURE IS A CONFIRMATORY TEST (EVIDENCE A)

SUSPECT IF:

• EXACERBATION OF CLINICAL SIGNS

• LABORATORY BLOOD TEST CHANGES• SHIFT TO IMMATURE CELLS

• ELEVATION OF CRP

• INCREASED APACHE II

• POSITIVE BLOOD CULTURE

• NECROSECTOMY IS INDICATED IN A CONFIRMED INFECTED PANCREATIC NECROSIS (EVIDENCE A)

ACUTE PANCREATITIS

Algorithm

Confirm acute pancreatitis

Amylase/LipaseTrypsinogetn2

CT scan in atypical cases

Initial management

Severity stratification

IV fluid/pain conrol

Scoring systemsC-reactive protein

Mild acute pancreatitis

Severe acute pancreatitis

ACUTE PANCREATITIS

Algorithm

Mild acute pancreatitis

Severe acute pancreatitis

RECOMMENDEDAdmit to general ward

Refeed when pain subsides

NOT RECOMMENDEDAntibiotics

CT scan

RECOMMENDEDAdmit to ICUAntibiotics

CT-scan – day 3

NECROSISSterile – observe (CT, US)

Infection suspected – fine needle aspiration/drainage under US or CT control

Infected necrosis – necrosectomyOpen drainage of abscesses, retroperitoneal space