Acute Pancreatitis

See Also

Chronic Pancreatitis

Epidemiology

Among the three most common gastrointestinal emergency requiring hospitalization in United States
Incidence United States: 20-40 per 100,000 (estimates vary up to 5 to 80 per 100,000)

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. Ecchymosis (non-specific, and found in only 3% of cases)
  1. Cullen's Sign
    1. Periumbilical discoloration with subcutaneous Ecchymosis and edema
  2. Grey Turner's Sign
    1. Flank discoloration with Ecchymosis
  3. References
    1. Dickson (1984) Surg Gynecol Obstet 159(4): 343-7 [PubMed]
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 Serum Triglycerides
1. May be obtained with emergency department labs as often patients have had minimal oral intake at presentation
2. 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, but not widely available
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 (acute biliary Pancreatitis)
  1. Serum Bilirubin elevated
  2. Alkaline Phosphatase elevated
  3. Aspartate Aminotransferase (AST) elevated
2. Alcoholic Pancreatitis
  1. Aspartate Aminotransferase (AST) elevated 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. Gallstones or gallbladder sludge is sufficient to make diagnosis of Gallstone Pancreatitis
  2. Gallstone Test Sensitivity 87-98%
  3. Choledocholithiasis Test Sensitivity is only 25-60%
CT Abdomen with contrast (preferred imaging later in Acute Pancreatitis to evaluate for complications)
1. Indications
  1. Severe Abdominal Pain (esp. undifferentiated Abdominal Pain)
  2. Critical Illness
  3. Pancreatic necrosis suspected
  4. Other complications suspected (e.g. mass, Hemorrhage; obstruction of bile tract, vessels, Small Bowel)
2. Findings in Acute Pancreatitis
  1. Peripancreatic inflammation and fat stranding (but may be absent early in course)
  2. Pancreatic edema
  3. Pancreatic necrosis
    1. Necrotic pancreatic tissue has decreased contrast enhancement (<30 HU at 40 seconds)
    2. Normal pancreatic tissue has contrast enhancement (100-150 HU at 40 seconds)
  4. Extrapancreatitc changes including fluid accumulation
    1. Acute Necrotic Collection
      1. Pancreatitic parenchymal fluid collection <4 weeks from symptom onset
      2. No discrete wall around collection
    2. Walled-Off Necrosis
      1. Pancreatitic parenchymal fluid collection >4 weeks from symptom onset
      2. Discrete wall around collection
    3. Pancreatic Pseudocyst
      1. Peripancreatitc fluid collection that is homogenous and non-enhancing
      2. Contrast enhancing wall
3. Efficacy
  1. Test Sensitivity for severe Pancreatitis: 78% (and LR+ 5.57)
  2. Test Specificity for severe Pancreatitis: 86% (and LR- 0.26)
4. Predicts and evaluates Pancreatitis complications, length of hospital stay and prognosis
  1. See CT Severity Index in Pancreatitis (Balthazar Computed Tomography Severity Index)
  2. CT does not change outcomes or management in first 72 hours of symptoms of Acute Pancreatitis
    1. May defer CT Abdomen in early, uncomplicated typical Pancreatitis

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, Serum Amylase or serum Lipase (>540-1000 U/L, depending on lab)
Characteristic imaging findings

Differential Diagnosis

Intra-Abdominal Causes
1. Bowel perforation (Peptic Ulcer perforation)
2. Acute Cholecystitis or Ascending Cholangitis
3. Chronic Pancreatitis
4. Acute Intestinal Obstruction
5. Mesenteric Ischemia
6. Renal Colic
7. Gastric outlet obstruction
8. Acute Hepatitis
9. Pancreatic Cancer
10. Tubo-Ovarian Abscess
Referred Pain and Systemic Conditions

Evaluation
Severity scoring systems

Ranson Criteria
BISAP Score
Revised Atlanta Criteria for Acute Pancreatitis Severity
Acute Physiology and Chronic Health Evaluation (APACHE Score, now in version 4)
Modified Glasgow Severity Criteria for Pancreatitis (Imrie Scoring System for Pancreatitis, PANCREAS Score)
Systemic Inflammatory Response Syndrome (SIRS Criteria)
1. Test Sensitivity 85 to 100% for severe disease on Day 1 of hospital admission
2. Negative Predictive Value 98 to 100% for excluding severe disease
3. Singh (2009) Clin Gastroenterol Hepatol 7(11): 1247-51 [PubMed]
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 2 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. ParenteralAntacid
  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)
    2. However, early enteral feeding is associated with fewer complications
    3. Al-Omran (2010) Cochrane Database Syst Rev (1): CD002837 [PubMed]
    4. Song (2018) Medicine 97(34): e11871 [PubMed]
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]
Intravenout Hydration: Mild to Moderate Pancreatitis
1. Aggressive intravenous hydration in mild pacreatitis does not appear to modify outcomes and risks overhydration
  1. de-Madaria (2022) N Engl J Med 387(11): 989-1000 +PMID: 36103415 [PubMed]
2. Follow a more moderate fluid Resuscitation approach in mild to moderate Pancreatitis
  1. Fluid bolus in Dehydration at presentation (e.g. LR 1 L or 10 ml/kg)
  2. Fluid maintenance with LR 100 to 125 ml/hour (or 1.5 ml/kg/hour) until taking oral fluids
  3. Titrate based on hydration markers as below (e.g. Hematocrit, BUN, IVC Ultrasound for Volume Status)
Intravenous Hydration: Severe Pancreatitis
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. Goal Heart Rate < 120 bpm
  3. Goal Mean Arterial Pressure (MAP) >65 to 85 mmHg
  4. Goal Urinary output >0.5 to 1 ml/kg/hour
  5. Goal Hematocrit 35 to 44%
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
  1. Infected Pancreatic Pseudocyst, Pancreatic Abscess, fever or bacteremia
  2. Emphysematous changes in necrosis, fever (imaging with pancreatic necrosis with gas formation)
  3. 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. Third Generation Cephalosporin AND Metronidazole (Flagyl)
  6. Fourth Generation Cephalosporin (e.g. Cefepime) AND Metronidazole (Flagyl)
  7. (2018) Sanford Guide
5. Do not use Probiotics (contraindicated in Acute Pancreatitis)
  1. Associated with increased mortality
  2. Besselink (2008) Lancet 371(9613): 651-9 [PubMed]
Surgical 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
    2. Especially if Acute Cholangitis is present or unresolved obstruction
    3. Sharma (1999) Am J Gastroenterol 94(11): 3211-14 [PubMed]
    4. 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. Common bile duct obstruction (acute biliary Pancreatitis)
  1. Typically causes Acute Pancreatitis, rather than a complication
2. Ileus
3. Abdominal Compartment Syndrome
  1. Associated with severe Pancreatitis on Mechanical Ventilation
  2. Sustained intraabdominal pressures >20 mmHg (via Bladder probe)
4. Vascular Complications
  1. Shock
  2. Pancreatic arterial pseudoaneurysm
  3. Gastrointestinal Bleeding (including from gastric Varices)
  4. Splenic Rupture
  5. Bowel infarction
  6. Venous Thrombosis of splenic vein, Portal Vein, superior mesenteric vein (up to 24% of Acute Pancreatitis)
    1. Mesenteric Venous Thrombosis
    2. Splenic venous thrombosis (Splenic infarction)
5. Systemic Inflammatory response
  1. Adult Respiratory Distress Syndrome (ARDS)
  2. Disseminated Intravascular Coagulation (DIC)
6. Acute Renal Failure
  1. Due to Hypovolemia with third spacing of fluid or intrarenal injury
7. Extra-abdominal complications
Late Complications
1. Pancreatic Phlegmon
2. Pancreatic Pseudocyst
  1. Pocket of pancreatic fluid walled off by an inflammatory capsule
  2. Matures over a 4 week period from onset of Acute Pancreatitis
3. Pancreatic necrosis (20% of Acute Pancreatitis cases)
  1. Typically walls off with an inflammatory capsule by 4 weeks
  2. Risk of secondary infection with gas formation (Emphysematous change)
    1. Pancreatitic necrosis when secondarily infected, is associated with a 20-30% mortality
4. Pancreatic Abscess
5. Pancreatic Ascites
  1. Consider splanchnic vein thrombosis with Portal Hypertension
  2. Consider pancreatic duct disruption
6. Portal Hypertension
  1. Results from splanchnic vein obstruction (thrombosis, pseudocyst-related mass effect)
  2. Risk of Esophageal Varices development
7. Pleural Effusion
8. Chronic Pancreatitis
  1. Presents with recurrent upper Abdominal Pain, weight loss, malabsorption and Insulin deficiency

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 (APACHE Score)
See Modified Glasgow Severity Criteria for Pancreatitis (Imrie Scoring System for Pancreatitis, PANCREAS Score)
Most Acute Pancreatitis resolves without complication
Overall mortality of Acute Pancreatitis: 5%
Findings that most increase mortality risk
1. Hemorrhagic Pancreatitis
2. Multiorgan dysfunction or failure
3. Necrotizing Pancreatitis (especially with concurrent infection or abscess)
  1. Necrosis occurs in up to 20% of Acute Pancreatitis cases
  2. Pancreatitic necrosis when secondarily infected, is associated with a 20-30% mortality
4. References
  1. Dervenis (1999) Int J Pancreatol 25(3): 195-210 [PubMed]

References

(2023) Presc Lett 30(1)
Broder (2021) Crit Dec Emerg Med 35(2):16-7
Mitchell (2003) Lancet 361:1447-55 [PubMed]
Oppenlander (2022) Am Fam Physician 106(1): 44-50 [PubMed]
Swaroop (2004) JAMA 291:2865-8 [PubMed]
Tenner (2004) Am J Gastroenterol 99:2489-94 [PubMed]
Quinlan (2014) Am Fam Physician 90(9): 632-9 [PubMed]