Acute Pancreatitis

See Also

Chronic Pancreatitis

Causes

See Pancreatitis Causes
See Medication Causes of Pancreatitis
Adult common causes
1. Alcohol Abuse (35% of cases)
2. Cholelithiasis (40% of cases)
Children common causes
1. Infection (e.g. Mumps, Viral Hepatitis, Coxsackievirus, Ascariasis, Mycoplasma)
2. Abdominal Trauma (e.g. handlebar injury)

Symptoms

Abdominal Pain
1. Mid-Epigastric Pain, Left Upper Quadrant Abdominal Pain or Periumbilical Abdominal Pain
2. Radiation into the chest or mid-back
3. Worse with eating and drinking (especially fatty foods) and in supine position
4. Boring pain that starts episodically and advances to become constant
5. Pancreatitis may be painless in some cases (e.g. toxin-induced)
Associated gastrointestinal symptoms
1. Nausea or Vomiting
2. Indigestion
3. Abdominal Bloating, distention or fullness
4. Clay-colored stool
Other associated symptoms
1. Decreased Urine Output
2. Hiccups
3. Tactile warmth

Signs

General
1. Low grade fever
2. Altered Mental Status (severe cases)
Cardiopulmonary Exam
1. Tachycardia
2. Hypotension
3. Hypoxemia (25%)
4. Left basilar rales (Pleural Effusion)
Abdominal Exam
1. Abdominal tenderness and guarding in the upper quadrants
2. Peritoneal signs may be present (e.g. abdominal rigidity or Rebound Tenderness
3. Bowel sounds decreased
4. Palpable upper abdominal mass
5. Cullen's Sign (periumbilical discoloration with subcutaneous Ecchymosis and edema)
6. Grey Turner's Sign (flank discoloration with Ecchymosis)
Skin Exam
1. Erythematous skin Nodules (Subcutaneous Fat Necrosis)
2. Jaundice (severe cases)

Labs

Serum Lipase elevated (preferred first-line study)
1. Serum Lipase >540-1000 U/L, depending on specific lab (>3 times normal)
  1. Test Sensitivity for Pancreatitis: 96% (and LR+ 30)
  2. Test Specificity for Pancreatitis: 96% (and LR- 0.03)
  3. Other conditions (e.g. Gastroenteritis, Diverticulitis) result in more mild Lipase elevations
2. Returns to normal in 7-14 days
Serum Amylase elevated
1. Replaced by Serum Lipase, which has higher Test Sensitivity and Test Specificity
2. Serum Amylase>360 U/L, depending on specific lab (>3 times normal)
  1. Test Sensitivity for Pancreatitis: 95% (and LR+ 21)
  2. Test Specificity for Pancreatitis: 95% (and LR- 0.05)
3. Returns to normal in 48-72 hours
4. Precautions
  1. Normal amylase does not exclude Pancreatitis
  2. Level of elevation does not predict disease severity
5. Some clinicians obtain Serum Amylase and serum Lipase simultaneously on initial evaluation
  1. Expect both increased in Pancreatitis (question diagnosis if only 1 increased)
  2. Serum Lipase to amylase ratio >4 (and especially >5) strongly suggests Alcoholic Pancreatitis
Serum Electrolytes
1. Hypocalcemia (25%)
2. Hyperglycemia
3. Hypomagnesemia (Alcoholism)
4. Hypophosphatemia (Alcoholism)
Complete Blood Count (CBC)
1. White Blood Cells increased to 15k-20k
2. Hematocrit repeated within 2 hours of initial 2 L bolus is a marker of adequate initial fluids if <44%
Fasting Triglycerides
1. Hypertriglyceridemia (15%)
  1. Very severe Hypertriglyceridemia (>1000 mg/dl) is responsible for 2-4% of Pancreatitis cases
  2. Consider acute Serum Triglyceride lowering with Insulin Infusion, plasmapheresis
Urinary trypsinogen-2 Level
1. May help predict Pancreatitis severity
2. Urinary trypsinogen-2 >50 ng/ml
  1. Test Sensitivity for Pancreatitis: 92% (and LR+ 13.1)
  2. Test Specificity for Pancreatitis: 93% (and LR- 0.09)
Liver Function Tests
1. Gallstone Pancreatitis
  1. Serum Bilirubin elevated
  2. Alkaline Phosphatase elevated
2. Alcoholic Pancreatitis
  1. Aspartate Aminotransferase elevated (AST) increased more than Alanine Aminotransferase (ALT)
Prognostic indicators
1. Hypoalbuminemia
2. Lactate Dehydrogenase (LDH) elevated
3. Venous Blood Gas (or Arterial Blood Gas)
4. Serum Calcium level
5. C-Reactive Protein
6. Interleukin-6 (IL-6) and Interleukin-8 (IL-8) if available
7. Urinalysis

Diagnostics

Electrocardiogram
1. May demonstrate non-specific ST segment abnormality or T Wave abnormality
2. Evaluates differential diagnosis in undifferentiated Epigastric Pain (referred Chest Pain)

Imaging
First-Line Studies

Right Upper Quadrant Transabdominal Ultrasound (preferred imaging in early Pancreatitis to evaluate biliary tract)
1. First-line study in Acute Pancreatitis evaluation (but limited by body habitus and overlying bowel gas)
2. May demonstrate Pancreas enlargement or edema
3. Evaluate for Cholelithiasis! (gallstone Pancreatitis is most common cause, and requires surgical management)
  1. Gallstone Test Sensitivity 87-98%
CT Abdomen with contrast (preferred imaging later in Acute Pancreatitis to evaluate for complications)
1. Consider in severe Abdominal Pain, pancreatic necrosis or when other complications are suspected
2. Acute Pancreatitis typically shows peripancreatic inflammation and fat stranding (but may be absent early in course)
3. Identifies pancreatic edema and necrosis as well as extrapancreatitc changes including fluid accumulation
4. Test Sensitivity for severe Pancreatitis: 78% (and LR+ 5.57)
5. Test Specificity for severe Pancreatitis: 86% (and LR- 0.26)
6. Predicts and evaluates Pancreatitis complications, length of hospital stay and prognosis
  1. See CT Severity Index in Pancreatitis (Balthazar Computed Tomography Severity Index)

Imaging
Cholangiography

Magnetic Resonance Cholangiopancreatography (MRCP)
1. Consider in cases where ERCP not possible
2. Similar efficacy to CT in identifying Pancreatitis
3. Detects Common Bile Duct Stones in 81-100% of cases
  1. Negative Predictive Value: 98%
  2. Positive Predictive Value: 94%
  3. May miss Gallstones <4mm
Endoscopic Ultrasonography
1. Gallstone Test Sensitivity 100%, Specificity 91%
ERCP Indications
1. Evaluate atypical causes of Pancreatitis
  1. Microlithiasis
  2. Sphincter of Oddi Dysfunction
  3. Pancreas divisium
  4. Pancreatic duct strictures
2. Urgent intervention
  1. Biliary Sepsis
  2. Biliary obstruction and severe Pancreatitis
  3. Ascending Cholangitis
  4. Progressive Jaundice or Hyperbilirubinemia

Imaging
Other studies

Abdominal XRay (non-specific abnormalities in 50%)
1. Total or partial ileus (Sentinel loop)
2. Spasm of transverse colon
MRI Abdomen
1. Indications
  1. IV contrast contraindicated
  2. Unclear diagnosis
  3. Refractory Acute Pancreatitis course after 2-3 days of conservative management
2. May better defining peripancreatic changes
3. Pancreatitis Test Sensitivity 83%, Specificity 91%
4. Test Sensitivity for Pancreatitis: 79%, and for severe Pancreatitis, 83%
5. Test Specificity for Pancreatitis: 92%, and for severe Pancreatitis 91%

Diagnosis
Atlanta Criteria (requires 2 of 3 findings)

Symptoms suggestive of Pancreatitis (Epigastric Abdominal Pain, Vomiting, epigastric tenderness)
Increase >3 fold over normal, the serum Lipase (>540-1000 U/L, depending on lab) or the Serum Amylase
Characteristic imaging findings

Differential Diagnosis

Bowel perforation (peptic ulcer perforation)
Acute Cholecystitis or Ascending Cholangitis
Chronic Pancreatitis
Acute Intestinal Obstruction
Mesenteric Ischemia
Renal Colic
Myocardial Ischemia (Angina)
Aortic Dissection
Connective Tissue Disorders
Pneumonia
Gastric outlet obstruction
Acute Hepatitis
Diabetic Ketoacidosis
Pancreatic Cancer
Tubo-Ovarian Abscess

Evaluation
Severity scoring systems

Ranson Criteria
BISAP Score
Revised Atlanta Criteria for Acute Pancreatitis Severity
Acute Physiology and Chronic Health Evaluation II (APACHE II Score)
Modified Glasgow Severity Criteria for Pancreatitis (Imrie Scoring System for Pancreatitis, PANCREAS Score)
BALI Score
1. Simple scoring system (4 criteria), but requires Interleukin-6 (IL-6) level
CT Severity Index in Pancreatitis (Balthazar Computed Tomography Severity Index)
1. Superior to Ranson Criteria and APACHE II Score in its predictive value
2. Bollen (2012) Am J Gastroenterol 107(4): 612-9 [PubMed]

Management
Emergency Department Approach

Protocol Indications
1. Suspected Acute Pancreatitis (e.g. Epigastric Abdominal Pain, Vomiting, abdominal tenderness to palpation)
Initial evaluation confirms Pancreatitis diagnosis and identifies gallstone Pancreatitis (or Common Bile Duct Stone)
1. Serum Lipase >3 times upper limit normal (threshold approaches 1000, depending on lab used)
2. RUQ Ultrasound (preferred) or CT Abdomen (if severe Pancreatitis and delayed diagnosis)
Initial Management
1. Lactated Ringers (LR) 2 Liter bolus at 10 ml/kg/h, followed by LR at 250 ml/hour
  1. Most important initial single measure
  2. See fluid Resuscitation below regarding indications for additional fluid boluses
2. Other measures
  1. Antiemetics (e.g. Ondansetron)
  2. Opioid Analgesics (e.g. Hydromorphone)
Determine underlying cause
1. Gallstone Pancreatitis
  1. Surgical consult for Cholecystectomy
  2. Suspected Common Bile Duct Stone (bile duct dilitation, increased Liver Function Tests)
    1. Obtain ERCP (preferred) or MRCP
2. Alcoholic Pancreatitis
  1. Alcohol cessation
  2. Alcohol Withdrawal protocol
  3. Give Thiamine, Multivitamin, Folic Acid, Magnesium
3. Hypertriglyceridemia (Serum Triglycerides >500)
  1. Evaluate for Diabetes Mellitus (e.g. Hemoglobin A1C)
  2. Very high Serum Triglycerides (>1000 mg/dl)
    1. Admit to ICU and aggressive Triglyceride lowering
    2. Early and aggressive Serum Triglyceride lowering is associated with better outcomes
    3. Insulin Infusion 0.25 units/kg/h with dextrose infusion unless hyperglycemic
    4. Plasmapheresis (consult nephrology) if Insulin Infusion is not effective or Pancreatitis is refractory
4. Idiopathic Pancreatitis
  1. See Medication Causes of Pancreatitis
  2. Consult gastroenterology
  3. Consult pharmacy for medication causes
  4. Review patient history for toxin exposures
Later evaluation and management
1. Early initiation of oral clear fluids, low-fat full liquids and low residue soft-solids prevents bowel atrophy
Disposition: Indications for discharge and outpatient management
1. Non-toxic appearance
2. Normal Vital Signs
3. Tolerating oral intake
4. Pain controlled on Oral Analgesics
5. No serious cause of Acute Pancreatitis (e.g. gallstone Pancreatitis, severe Hypertriglyceridemia >1000)

Management
Specific Measures

Gastrointestinal rest
1. Nothing by mouth for first 24 hours
2. Parenteral Antacid
  1. H2 Blocker (e.g. Ranitidine) or
  2. Proton Pump Inhibitor (e.g. Pantoprazole)
3. Transition back to oral intake
  1. Early oral intake is preferred
    1. Start within 24 hours of admission (or of Cholecystectomy or other procedure)
    2. Re-initiate oral clear liquids, then
    3. Advance to low fat full liquids, then
    4. Advance to low fat, low-residue, soft solid diet
  2. Older guidelines recommended delayed oral intake
    1. Previously waited until pain well controlled without Opioid Analgesics (typically day 3-6)
4. Consider nasojejunal Enteral Nutrition if no oral intake within first 48 hours
  1. Preferred over parenteral nutrition
    1. Decreased secondary infections
    2. Surgical interventions
    3. Shorter hospital stays
  2. May not be tolerated in severe ileus or very low oncotic pressure
  3. Marik (2004) BMJ 328:1407-10 [PubMed]
Intravenous hydration
1. Early aggressive intravenous hydration speeds recovery in even mild Acute Pancreatitis
  1. Buxbaum (2017) Am J Gastroenterol 112(5):797-803 [PubMed]
2. Initial: 2 L (or 20 ml/kg) Lactated Ringers at 5-10 ml/kg/hour
  1. Lactated Ringers is preferred in Acute Pancreatitis (decreased systemic inflammation)
  2. Consider Normal Saline instead if Hypercalcemia is present
  3. Wu (2011) Clin Gastroenterol Hepatol 9(8):710-7 [PubMed]
3. Next: Fluid Resuscitation up to 250 ml/hour for up to 48 hours to maintain Urine Output >0.5 ml/kg/h
  1. Obtain Hematocrit within 2 hours of initial fluid bolus (and consider again at 6 hours)
    1. Hematocrit <44% suggests adequate initial fluid Resuscitation (no need to re-bolus)
    2. Hematocrit >44% is an indication to rebolus LR 2 Liters over 2 hours
  2. Other markers of hydration status and Resuscitation effectiveness
    1. IVC Ultrasound for Volume Status
    2. Blood Urea Nitrogen
Opioid Analgesics
1. Start with parenteral agents
  1. Hydromorphone (Dilaudid) or Morphine Sulfate
  2. Historically Meperidine (Demerol) was used (but has fallen out of favor due to associated risks)
2. Transition to oral Opioid Analgesics when tolerating oral fluids
  1. Oral Hydromorphone, Oxycodone or Hydrocodone
Monitoring
1. Vital Signs and Urine Output recorded every 1-2 hours initially
  1. Transfer patients to Intensive Care for Hypotension, Hypoxemia or Oliguria despite aggressive rehydration
2. Physical examination every 4 to 8 hours
  1. Observe for Altered Mental Status
  2. Abdominal exam for marked abdominal firmness (Abdominal Compartment Syndrome, third spacing)
3. Laboratory tests every 6 to 12 hours
  1. Comprehensive metabolic panel
  2. Complete Blood Count
  3. Serum Calcium
  4. Serum Magnesium
  5. Serum Glucose
  6. Blood Urea Nitrogen
4. Imaging
  1. Consider repeat CT Abdomen for clinical worsening or signs of complications
Electrolyte disturbance
1. Hypocalemia (related to saponification)
  1. Replace Serum Calcium as needed
Antibiotics
1. Antibiotics are not indicated in acute Alcoholic Pancreatitis without necrosis
2. Absolutely indicated only for concurrent infection (infected Pancreatic Pseudocyst, Pancreatic Abscess)
  1. Obtain abscess cultures to guide antibiotic therapy
3. Controversial whether to use in pancreatic necrosis
  1. Infections occur in one third of necrotizing Pancreatitis cases
  2. AGA as of 2018 recommends NO prophylactic antibiotics regardless of necrosis severity
    1. Prophylactic antibiotics were previously recommended for necrosis of >30% of Pancreas
    2. Crockett (2018) gastroenterology 154:1096-1101 +PMID:29409760 [PubMed]
4. Antibiotic regimens (if indicated) for infected Pancreatic Pseudocyst or Pancreatic Abscess
  1. Piperacillin-Tazobactam 3.375 g IV every 6 hours
  2. Imipenem/Cilastin (Primaxin) 0.5 to 1 g IV every 6 hours
    1. Villatoro (2010) Cochrane Database Syst Rev (5): CD002941 [PubMed]
  3. Meropenem 1 g IV every 8 hours
  4. Moxifloxacin 400 mg IV every 24 hours
  5. (2018) Sanford Guide
5. Do not use Probiotics (contraindicated in Acute Pancreatitis)
  1. Besselink (2008) Lancet 371(9613): 651-9 [PubMed]
Surgical debridement indications
1. Gallstone Pancreatitis
  1. Cholecystectomy is contraindicated in necrotizing Pancreatitis until inflammation improves
  2. Early Cholecystectomy shortens hospital stay without increased surgical complications
    1. Aboulian (2010) Ann Surg 251(4): 615-9 [PubMed]
  3. Consider ERCP with sphincterotomy
    1. Indicated in severe gallstone Pancreatitis (especially if Acute Cholangitis is present or unresolved obstruction)
    2. Sharma (1999) Am J Gastroenterol 94(11): 3211-14 [PubMed]
    3. Ayub (2004) Cochrane Database Syst Rev (4): CD003630 [PubMed]
2. Non-Gallstone related
  1. Surgical indications
    1. Infected pancreatic necrosis
    2. Pancreatic necrosis with clinical deterioration
    3. Severe Pancreatitis and persistent fluid collections (e.g. >2 weeks after onset)
  2. Approach
    1. Minimally invasive techniques are preferred (e.g. percutaneous CT guided aspiration)

Course

Restart clear liquids on day 3-6
Most cases subside in 3-7 days (90%)

Complications

Early Complications
1. Shock
2. Gastrointestinal Bleeding (including from gastric Varices)
3. Common bile duct obstruction
4. Ileus
5. Bowel infarction
6. Abdominal Compartment Syndrome
7. Mesenteric Venous Thrombosis
8. Splenic venous thrombosis (Splenic infarction)
9. Pancreatic arterial pseudoaneurysm
10. Splenic Rupture
11. Disseminated Intravascular Coagulation (DIC)
12. Subcutaneous Fat Necrosis
13. Adult Respiratory Distress Syndrome (ARDS)
14. Pleural Effusion
15. Hematuria
16. Acute Renal Failure
Late Complications
1. Pancreatic Phlegmon
2. Pancreatic Pseudocyst
3. Pancreatic necrosis
4. Pancreatic Abscess
5. Pancreatic Ascites
6. Pleural Effusion
7. Chronic Pancreatitis

Prognosis

See Ranson Criteria
See BALI Score
See BISAP Score
See Revised Atlanta Criteria for Acute Pancreatitis Severity
See CT Severity Index in Pancreatitis (Balthazar Computed Tomography Severity Index)
See Acute Physiology and Chronic Health Evaluation II (APACHE II Score)
See Modified Glasgow Severity Criteria for Pancreatitis (Imrie Scoring System for Pancreatitis, PANCREAS Score)
Findings that most increase mortality risk
1. Hemorrhagic Pancreatitis
2. Multiorgan dysfunction or failure
3. Necrotizing Pancreatitis (especially with concurrent infection or abscess)
4. Dervenis (1999) Int J Pancreatol 25(3): 195-210 [PubMed]

References