II. 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)
III. Causes
- See Pancreatitis Causes
- See Medication Causes of Pancreatitis
- Adult common causes
- Alcohol Abuse (35% of cases)
- Cholelithiasis (40% of cases)
- Children common causes
- Infection (e.g. Mumps, Viral Hepatitis, Coxsackievirus, Ascariasis, Mycoplasma)
- Abdominal Trauma (e.g. handlebar injury)
IV. Symptoms
-
Abdominal Pain
- Mid-Epigastric Pain, Left Upper Quadrant Abdominal Pain or Periumbilical Abdominal Pain
- Radiation into the chest or mid-back
- Worse with eating and drinking (especially fatty foods) and in supine position
- Boring pain that starts episodically and advances to become constant
- Pancreatitis may be painless in some cases (e.g. toxin-induced)
- Associated gastrointestinal symptoms
- Nausea or Vomiting
- Indigestion
- Abdominal Bloating, distention or fullness
- Clay-colored stool
- Other associated symptoms
- Decreased Urine Output
- Hiccups
- Tactile warmth
V. Signs
-
General
- Low grade fever
- Altered Mental Status (severe cases)
- Cardiopulmonary Exam
- Tachycardia
- Hypotension
- Hypoxemia (25%)
- Left basilar rales (Pleural Effusion)
- Abdominal Exam
- Abdominal tenderness and guarding in the upper quadrants
- Peritoneal signs may be present (e.g. abdominal rigidity or Rebound Tenderness
- Bowel sounds decreased
- Palpable upper abdominal mass
- Ecchymosis (non-specific, and found in only 3% of cases)
- Cullen's Sign
- Periumbilical discoloration with subcutaneous Ecchymosis and edema
- Grey Turner's Sign
- Flank discoloration with Ecchymosis
- References
- Cullen's Sign
- Skin Exam
- Erythematous skin Nodules (Subcutaneous Fat Necrosis)
- Jaundice (severe cases)
VI. Labs
- Serum Lipase elevated (preferred first-line study)
- Serum Lipase >540-1000 U/L, depending on specific lab (>3 times normal)
- Test Sensitivity for Pancreatitis: 96% (and LR+ 30)
- Test Specificity for Pancreatitis: 96% (and LR- 0.03)
- Other conditions (e.g. Gastroenteritis, Diverticulitis) result in more mild Lipase elevations
- Returns to normal in 7-14 days
- Serum Lipase >540-1000 U/L, depending on specific lab (>3 times normal)
-
Serum Amylase elevated
- Replaced by Serum Lipase, which has higher Test Sensitivity and Test Specificity
- Serum Amylase>360 U/L, depending on specific lab (>3 times normal)
- Test Sensitivity for Pancreatitis: 95% (and LR+ 21)
- Test Specificity for Pancreatitis: 95% (and LR- 0.05)
- Returns to normal in 48-72 hours
- Precautions
- Normal amylase does not exclude Pancreatitis
- Level of elevation does not predict disease severity
- Some clinicians obtain Serum Amylase and serum Lipase simultaneously on initial evaluation
- Serum Electrolytes
-
Complete Blood Count (CBC)
- White Blood Cells increased to 15k-20k
- Hematocrit repeated within 2 hours of initial 2 L bolus is a marker of adequate initial fluids if <44%
-
Fasting Serum Triglycerides
- May be obtained with emergency department labs as often patients have had minimal oral intake at presentation
- Hypertriglyceridemia (15%)
- Very severe Hypertriglyceridemia (>1000 mg/dl) is responsible for 2-4% of Pancreatitis cases
- Consider acute Serum Triglyceride lowering with Insulin Infusion, plasmapheresis
- Urinary trypsinogen-2 Level
- May help predict Pancreatitis severity, but not widely available
- Urinary trypsinogen-2 >50 ng/ml
- Test Sensitivity for Pancreatitis: 92% (and LR+ 13.1)
- Test Specificity for Pancreatitis: 93% (and LR- 0.09)
-
Liver Function Tests
- Gallstone Pancreatitis (acute biliary Pancreatitis)
- Serum Bilirubin elevated
- Alkaline Phosphatase elevated
- Aspartate Aminotransferase (AST) elevated
- Alcoholic Pancreatitis
- Aspartate Aminotransferase (AST) elevated increased more than Alanine Aminotransferase (ALT)
- Gallstone Pancreatitis (acute biliary Pancreatitis)
- Prognostic indicators
- Hypoalbuminemia
- Lactate Dehydrogenase (LDH) elevated
- Venous Blood Gas (or Arterial Blood Gas)
- Serum Calcium level
- C-Reactive Protein
- Interleukin-6 (IL-6) and Interleukin-8 (IL-8) if available
- Urinalysis
VII. Diagnostics
-
Electrocardiogram
- May demonstrate non-specific ST Segment abnormality or T Wave abnormality
- Evaluates differential diagnosis in undifferentiated Epigastric Pain (referred Chest Pain)
VIII. Imaging: First-Line Studies
- Right Upper Quadrant Transabdominal Ultrasound (preferred imaging in early Pancreatitis to evaluate biliary tract)
- First-line study in Acute Pancreatitis evaluation (but limited by body habitus and overlying bowel gas)
- May demonstrate Pancreas enlargement or edema
- Evaluate for Cholelithiasis! (Gallstone Pancreatitis is most common cause, and requires surgical management)
- Gallstones or gallbladder sludge is sufficient to make diagnosis of Gallstone Pancreatitis
- Gallstone Test Sensitivity 87-98%
- CholedocholithiasisTest Sensitivity is only 25-60%
-
CT Abdomen with contrast (preferred imaging later in Acute Pancreatitis to evaluate for complications)
- Indications
- Severe Abdominal Pain (esp. undifferentiated Abdominal Pain)
- Critical Illness
- Pancreatic necrosis suspected
- Other complications suspected (e.g. mass, Hemorrhage; obstruction of bile tract, vessels, Small Bowel)
- Findings in Acute Pancreatitis
- Peripancreatic inflammation and fat stranding (but may be absent early in course)
- Pancreatic edema
- Pancreatic necrosis
- Necrotic pancreatic tissue has decreased contrast enhancement (<30 HU at 40 seconds)
- Normal pancreatic tissue has contrast enhancement (100-150 HU at 40 seconds)
- Extrapancreatitc changes including fluid accumulation
- Acute Necrotic Collection
- Pancreatitic parenchymal fluid collection <4 weeks from symptom onset
- No discrete wall around collection
- Walled-Off Necrosis
- Pancreatitic parenchymal fluid collection >4 weeks from symptom onset
- Discrete wall around collection
- Pancreatic Pseudocyst
- Peripancreatitc fluid collection that is homogenous and non-enhancing
- Contrast enhancing wall
- Acute Necrotic Collection
- Efficacy
- Test Sensitivity for severe Pancreatitis: 78% (and LR+ 5.57)
- Test Specificity for severe Pancreatitis: 86% (and LR- 0.26)
- Predicts and evaluates Pancreatitis complications, length of hospital stay and prognosis
- See CT Severity Index in Pancreatitis (Balthazar Computed Tomography Severity Index)
- CT does not change outcomes or management in first 72 hours of symptoms of Acute Pancreatitis
- May defer CT Abdomen in early, uncomplicated typical Pancreatitis
- Indications
IX. Imaging: Cholangiography
-
Magnetic Resonance Cholangiopancreatography (MRCP)
- Consider in cases where ERCP not possible
- Similar efficacy to CT in identifying Pancreatitis
- Detects Common Bile Duct Stones in 81-100% of cases
- Negative Predictive Value: 98%
- Positive Predictive Value: 94%
- May miss Gallstones <4mm
- Endoscopic Ultrasonography
- Gallstone Test Sensitivity 100%, Specificity 91%
-
ERCP Indications
- Evaluate atypical causes of Pancreatitis
- Microlithiasis
- Sphincter of Oddi Dysfunction
- Pancreas divisium
- Pancreatic duct strictures
- Urgent intervention
- Biliary Sepsis
- Biliary obstruction and severe Pancreatitis
- Ascending Cholangitis
- Progressive Jaundice or Hyperbilirubinemia
- Evaluate atypical causes of Pancreatitis
X. Imaging: Other studies
- Abdominal XRay (non-specific abnormalities in 50%)
- Total or partial ileus (Sentinel loop)
- Spasm of transverse colon
- MRI Abdomen
- Indications
- IV contrast contraindicated
- Unclear diagnosis
- Refractory Acute Pancreatitis course after 2-3 days of conservative management
- May better defining peripancreatic changes
- Pancreatitis Test Sensitivity 83%, Specificity 91%
- Test Sensitivity for Pancreatitis: 79%, and for severe Pancreatitis, 83%
- Test Specificity for Pancreatitis: 92%, and for severe Pancreatitis 91%
- Indications
XI. 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
XII. Differential Diagnosis
- Intra-Abdominal Causes
- Bowel perforation (Peptic Ulcer perforation)
- Acute Cholecystitis or Ascending Cholangitis
- Chronic Pancreatitis
- Acute Intestinal Obstruction
- Mesenteric Ischemia
- Renal Colic
- Gastric outlet obstruction
- Acute Hepatitis
- Pancreatic Cancer
- Tubo-Ovarian Abscess
- Referred Pain and Systemic Conditions
XIII. 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)
- Test Sensitivity 85 to 100% for severe disease on Day 1 of hospital admission
- Negative Predictive Value 98 to 100% for excluding severe disease
- Singh (2009) Clin Gastroenterol Hepatol 7(11): 1247-51 [PubMed]
-
BALI Score
- Simple scoring system (4 criteria), but requires Interleukin-6 (IL-6) level
-
CT Severity Index in Pancreatitis (Balthazar Computed Tomography Severity Index)
- Superior to Ranson Criteria and APACHE 2 Score in its predictive value
- Bollen (2012) Am J Gastroenterol 107(4): 612-9 [PubMed]
XIV. Management: Emergency Department Approach
- Protocol Indications
- 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)
- Serum Lipase >3 times upper limit normal (threshold approaches 1000, depending on lab used)
- RUQ Ultrasound (preferred) or CT Abdomen (if severe Pancreatitis and delayed diagnosis)
- Initial Management
- Lactated Ringers (LR) 2 Liter bolus at 10 ml/kg/h, followed by LR at 250 ml/hour
- Most important initial single measure
- See fluid Resuscitation below regarding indications for additional fluid boluses
- Other measures
- Antiemetics (e.g. Ondansetron)
- Opioid Analgesics (e.g. Hydromorphone)
- Lactated Ringers (LR) 2 Liter bolus at 10 ml/kg/h, followed by LR at 250 ml/hour
- Determine underlying cause
- Gallstone Pancreatitis
- Surgical consult for Cholecystectomy
- Suspected Common Bile Duct Stone (bile duct dilitation, increased Liver Function Tests)
- Alcoholic Pancreatitis
- Alcohol cessation
- Alcohol Withdrawal Protocol
- Give Thiamine, Multivitamin, Folic Acid, Magnesium
- Hypertriglyceridemia (Serum Triglycerides >500)
- Evaluate for Diabetes Mellitus (e.g. Hemoglobin A1C)
- Very high Serum Triglycerides (>1000 mg/dl)
- Admit to ICU and aggressive Triglyceride lowering
- Early and aggressive Serum Triglyceride lowering is associated with better outcomes
- Insulin Infusion 0.25 units/kg/h with dextrose infusion unless hyperglycemic
- Plasmapheresis (consult nephrology) if Insulin Infusion is not effective or Pancreatitis is refractory
- Idiopathic Pancreatitis
- See Medication Causes of Pancreatitis
- Consult gastroenterology
- Consult pharmacy for medication causes
- Review patient history for toxin exposures
- Gallstone Pancreatitis
- Later evaluation and management
- 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
- Non-toxic appearance
- Normal Vital Signs
- Tolerating oral intake
- Pain controlled on Oral Analgesics
- No serious cause of Acute Pancreatitis (e.g. Gallstone Pancreatitis, severe Hypertriglyceridemia >1000)
XV. Management: Specific Measures
- Gastrointestinal rest
- Nothing by mouth for first 24 hours
- ParenteralAntacid
- H2 Blocker (e.g. Ranitidine) or
- Proton Pump Inhibitor (e.g. Pantoprazole)
- Transition back to oral intake
- Early oral intake is preferred
- Start within 24 hours of admission (or of Cholecystectomy or other procedure)
- Re-initiate oral clear liquids, then
- Advance to low fat full liquids, then
- Advance to low fat, low-residue, soft solid diet
- Older guidelines recommended delayed oral intake
- Previously waited until pain well controlled without Opioid Analgesics (typically day 3-6)
- However, early enteral feeding is associated with fewer complications
- Al-Omran (2010) Cochrane Database Syst Rev (1): CD002837 [PubMed]
- Song (2018) Medicine 97(34): e11871 [PubMed]
- Early oral intake is preferred
- Consider nasojejunal Enteral Nutrition if no oral intake within first 48 hours
- Preferred over Parenteral nutrition
- Decreased secondary infections
- Surgical interventions
- Shorter hospital stays
- May not be tolerated in severe ileus or very low oncotic pressure
- Marik (2004) BMJ 328:1407-10 [PubMed]
- Preferred over Parenteral nutrition
- Intravenout Hydration: Mild to Moderate Pancreatitis
- Aggressive intravenous hydration in mild pacreatitis does not appear to modify outcomes and risks overhydration
- Follow a more moderate fluid Resuscitation approach in mild to moderate Pancreatitis
- Fluid bolus in Dehydration at presentation (e.g. LR 1 L or 10 ml/kg)
- Fluid maintenance with LR 100 to 125 ml/hour (or 1.5 ml/kg/hour) until taking oral fluids
- Titrate based on hydration markers as below (e.g. Hematocrit, BUN, IVC Ultrasound for Volume Status)
- Intravenous Hydration: Severe Pancreatitis
- Early aggressive intravenous hydration speeds recovery in even mild Acute Pancreatitis
- Initial: 2 L (or 20 ml/kg) Lactated Ringers at 5-10 ml/kg/hour
- Lactated Ringers is preferred in Acute Pancreatitis (decreased systemic inflammation)
- Consider Normal Saline instead if Hypercalcemia is present
- Wu (2011) Clin Gastroenterol Hepatol 9(8):710-7 [PubMed]
- Next: Fluid Resuscitation up to 250 ml/hour for up to 48 hours to maintain Urine Output >0.5 ml/kg/h
- Obtain Hematocrit within 2 hours of initial fluid bolus (and consider again at 6 hours)
- Hematocrit <44% suggests adequate initial fluid Resuscitation (no need to re-bolus)
- Hematocrit >44% is an indication to rebolus LR 2 Liters over 2 hours
- Other markers of hydration status and Resuscitation effectiveness
- Obtain Hematocrit within 2 hours of initial fluid bolus (and consider again at 6 hours)
-
Opioid Analgesics
- Start with Parenteral agents
- Hydromorphone (Dilaudid) or Morphine Sulfate
- Historically Meperidine (Demerol) was used (but has fallen out of favor due to associated risks)
- Transition to oral Opioid Analgesics when tolerating oral fluids
- Oral Hydromorphone, Oxycodone or Hydrocodone
- Start with Parenteral agents
- Monitoring
- Vital Signs and Urine Output recorded every 1-2 hours initially
- Transfer patients to Intensive Care for Hypotension, Hypoxemia or Oliguria despite aggressive rehydration
- Goal Heart Rate < 120 bpm
- Goal Mean Arterial Pressure (MAP) >65 to 85 mmHg
- Goal Urinary output >0.5 to 1 ml/kg/hour
- Goal Hematocrit 35 to 44%
- Physical examination every 4 to 8 hours
- Observe for Altered Mental Status
- Abdominal exam for marked abdominal firmness (Abdominal Compartment Syndrome, third spacing)
- Laboratory tests every 6 to 12 hours
- Comprehensive metabolic panel
- Complete Blood Count
- Serum Calcium
- Serum Magnesium
- Serum Glucose
- Blood Urea Nitrogen
- Imaging
- Consider repeat CT Abdomen for clinical worsening or signs of complications
- Vital Signs and Urine Output recorded every 1-2 hours initially
-
Electrolyte disturbance
- Hypocalemia (related to saponification)
- Replace Serum Calcium as needed
- Hypocalemia (related to saponification)
-
Antibiotics
- Antibiotics are not indicated in acute Alcoholic Pancreatitis without necrosis
- Absolutely indicated only for concurrent infection
- Infected Pancreatic Pseudocyst, Pancreatic Abscess, fever or bacteremia
- Emphysematous changes in necrosis, fever (imaging with pancreatic necrosis with gas formation)
- Obtain abscess cultures to guide Antibiotic therapy
- Controversial whether to use in pancreatic necrosis
- Infections occur in one third of necrotizing Pancreatitis cases
- AGA as of 2018 recommends NO prophylactic Antibiotics regardless of necrosis severity
- Prophylactic Antibiotics were previously recommended for necrosis of >30% of Pancreas
- Crockett (2018) gastroenterology 154:1096-1101 +PMID:29409760 [PubMed]
- Antibiotic regimens (if indicated) for infected Pancreatic Pseudocyst or Pancreatic Abscess
- Piperacillin-Tazobactam 3.375 g IV every 6 hours
- Imipenem/Cilastin (Primaxin) 0.5 to 1 g IV every 6 hours
- Meropenem 1 g IV every 8 hours
- Moxifloxacin 400 mg IV every 24 hours
- Third Generation Cephalosporin AND Metronidazole (Flagyl)
- Fourth Generation Cephalosporin (e.g. Cefepime) AND Metronidazole (Flagyl)
- (2018) Sanford Guide
- Do not use Probiotics (contraindicated in Acute Pancreatitis)
- Associated with increased mortality
- Besselink (2008) Lancet 371(9613): 651-9 [PubMed]
- Surgical Indications
- Gallstone Pancreatitis
- Cholecystectomy is contraindicated in necrotizing Pancreatitis until inflammation improves
- Early Cholecystectomy shortens hospital stay without increased surgical complications
- Consider ERCP with sphincterotomy
- Indicated in severe Gallstone Pancreatitis
- Especially if Acute Cholangitis is present or unresolved obstruction
- Sharma (1999) Am J Gastroenterol 94(11): 3211-14 [PubMed]
- Ayub (2004) Cochrane Database Syst Rev (4): CD003630 [PubMed]
- Non-Gallstone related
- Surgical indications
- Infected pancreatic necrosis
- Pancreatic necrosis with clinical deterioration
- Severe Pancreatitis and persistent fluid collections (e.g. >2 weeks after onset)
- Approach
- Minimally invasive techniques are preferred (e.g. percutaneous CT guided aspiration)
- Surgical indications
- Gallstone Pancreatitis
XVI. Course
- Restart clear liquids on day 3-6
- Most cases subside in 3-7 days (90%)
XVII. Complications
- Early Complications
- Common bile duct obstruction (acute biliary Pancreatitis)
- Typically causes Acute Pancreatitis, rather than a complication
- Ileus
- Abdominal Compartment Syndrome
- Associated with severe Pancreatitis on Mechanical Ventilation
- Sustained intraabdominal pressures >20 mmHg (via Bladder probe)
- Vascular Complications
- Shock
- Pancreatic arterial pseudoaneurysm
- Gastrointestinal Bleeding (including from gastric Varices)
- Splenic Rupture
- Bowel infarction
- Venous Thrombosis of splenic vein, Portal Vein, superior mesenteric vein (up to 24% of Acute Pancreatitis)
- Mesenteric Venous Thrombosis
- Splenic venous thrombosis (Splenic infarction)
- Systemic Inflammatory response
- Acute Renal Failure
- Due to Hypovolemia with third spacing of fluid or intrarenal injury
- Extra-abdominal complications
- Common bile duct obstruction (acute biliary Pancreatitis)
- Late Complications
- Pancreatic Phlegmon
- Pancreatic Pseudocyst
- Pocket of pancreatic fluid walled off by an inflammatory capsule
- Matures over a 4 week period from onset of Acute Pancreatitis
- Pancreatic necrosis (20% of Acute Pancreatitis cases)
- Typically walls off with an inflammatory capsule by 4 weeks
- Risk of secondary infection with gas formation (Emphysematous change)
- Pancreatitic necrosis when secondarily infected, is associated with a 20-30% mortality
- Pancreatic Abscess
- Pancreatic Ascites
- Consider splanchnic vein thrombosis with Portal Hypertension
- Consider pancreatic duct disruption
- Portal Hypertension
- Results from splanchnic vein obstruction (thrombosis, pseudocyst-related mass effect)
- Risk of Esophageal Varices development
- Pleural Effusion
- Chronic Pancreatitis
- Presents with recurrent upper Abdominal Pain, weight loss, malabsorption and Insulin deficiency
XVIII. 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
- Hemorrhagic Pancreatitis
- Multiorgan dysfunction or failure
- Necrotizing Pancreatitis (especially with concurrent infection or abscess)
- Necrosis occurs in up to 20% of Acute Pancreatitis cases
- Pancreatitic necrosis when secondarily infected, is associated with a 20-30% mortality
- References
XIX. 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]