Acute pancreatitis

Acute pancreatitis is an inflammatory condition of the pancreas most commonly caused by biliary tract disease or alcohol abuse. Damage to the pancreas causes local release of digestive proteolytic enzymes that autodigest pancreatic tissue. Acute pancreatitis usually presents with epigastric pain radiating to the back, nausea and vomiting, and epigastric tenderness on palpation. The diagnosis is made based on the clinical presentation, elevated serum pancreatic enzymes, and findings on imaging (CT, MRI, ultrasound) that suggest acute pancreatitis. Treatment is mostly supportive and includes bowel rest, fluid resuscitation, and pain medication. Enteral feeding is usually quickly resumed once the pain and inflammatory markers begin to subside. Interventional procedures may be indicated for the treatment of underlying conditions, such as ERCP or cholecystectomy in gallstone pancreatitis. Localized complications of pancreatitis include necrosis, pancreatic pseudocysts, and abscesses. Systemic complications involve sepsis, ARDS, organ failure, and shock and are associated with a considerable rise in mortality.

• Most common causes
  1. Biliary pancreatitis; (e.g., gallstones, constriction of the ampulla of Vater) ∼ 40% of cases
  2. Alcohol-induced (∼ 30% of cases)
  3. Idiopathic (∼ 15%–25% of cases)
• Other causes
  • Severe hypertriglyceridemia (> 1,000 mg/dl), hypercalcemia
  • Post-ERCP
  • Certain drugs
    • Steroids
    • Azathioprine
    • Sulfonamides
    • Loop and thiazide diuretics
    • Estrogen
    • Protease inhibitors
    • NRTIs
    • Anticonvulsants
  • Scorpion stings
  • Viral infections (e.g., coxsackievirus B, mumps)
  • Trauma (especially in children)
  • Autoimmune and rheumatological disorders (e.g., Sjögren syndrome)
  • Pancreas divisum
  • Hereditary (e.g., mutation of the trypsinogen gene, cystic fibrosis)

To remember the most common causes of acute pancreatitis, think: "I GET SMASHED" (Idiopathic, Gall stones, Ethanol, Trauma, Steroids, Mumps, Autoimmune, Scorpion poison, Hypercalcemia, Hypertriglyceridemia, ERCP, Drugs).

References:^[1][2][3]

Mechanisms of development

Sequence of events leading to pancreatitis

• Intrapancreatic activation of pancreatic enzymes: secondary to pancreatic ductal outflow obstruction (e.g., gallstones, cystic fibrosis) or direct injury to pancreatic acinar cells (e.g., alcohol, drugs)
• Increased proteolytic and lipolytic enzyme activity → destruction of pancreatic parenchyma
• Attraction of inflammatory cells (neutrophils, macrophages) → release of inflammatory cytokines → pancreatic inflammation (pancreatitis)

Sequelae of pancreatitis (depending on the severity of pancreatitis)

• Capillary leakage: release of inflammatory cytokines and vascular injury by pancreatic enzymes → vasodilation and increased vascular permeability → shift of fluid from the intravascular space into the interstitial space (third space loss) → hypotension, tachycardia → distributive shock
• Pancreatic necrosis: uncorrected hypotension and third space loss → decreased organ perfusion → multiorgan dysfunction (mainly renal) and pancreatic necrosis
• Hypocalcemia: lipase breaks down peripancreatic and mesenteric fat; → release of free fatty acids that bind calcium → hypocalcemia (fatty saponification) ^[4]

• Constant, severe epigastric pain
  • Classically radiating towards the back
  • Worse after meals and when supine
  • Improves on leaning forwards
  • Nausea, vomiting
• General physical examination
  • Signs of shock: tachycardia, hypotension, oliguria/anuria
  • Possibly jaundice in patients with biliary pancreatitis
• Abdominal examination
  • Abdominal tenderness, distention, guarding
  • Ileus with reduced bowel sounds and tympany on percussion
  • Ascites
  • Skin changes (rare)
    • Cullen's sign: periumbilical ecchymosis and discoloration (bluish-red)
    • Grey Turner's sign: flank ecchymosis with discoloration
    • Fox's sign: ecchymosis over the inguinal ligament

References:^[5][6][7]

Acute pancreatitis is diagnosed based on a typical clinical presentation, with abdominal pain radiating to the back, and either detection of highly elevated pancreatic enzymes or characteristic findings on imaging. Serum hematocrit is an easy test that should be conducted to help quickly predict disease severity.

Laboratory tests

• Tests to confirm clinical diagnosis
  • ↑ Serum pancreatic enzymes
    • Lipase: if ≥ 3 x the upper reference range → highly indicative of acute pancreatitis
    • Amylase (nonspecific)
    • The enzyme levels are not directly proportional to severity or prognosis!
• Tests to assess severity
  • Hematocrit (Hct)
    • Should be conducted at presentation as well as 12 and 24 hours after admissions
    • ↑ Hct (due to hemoconcentration) indicates third space fluid loss and inadequate fluid resuscitation
    • ↓ Hct indicates the rarer acute hemorrhagic pancreatitis
  • WBC count
  • Blood urea nitrogen
  • ↑ CRP and procalcitonin levels
  • ↑ ALT
• Tests to determine etiology
  • Alkaline phosphatase, bilirubin levels (evidence of gallstone pancreatitis)
  • Serum calcium levels
  • Serum triglyceride levels (fasting)

Determining calcium values is very important: Hypercalcemia may cause pancreatitis, which may then, in turn, cause hypocalcemia!

Imaging

• Ultrasound (most useful initial test): indicated in all patients with acute pancreatitis
  • Main purpose: detection of gallstones and/or dilatation of the biliary tract (indicating biliary origin)
  • Signs of pancreatitis
    • Indistinct pancreatic margins (edematous swelling)
    • Peripancreatic build-up of fluid ; evidence of ascites in some cases
    • Evidence of necrosis, abscesses, pancreatic pseudocysts
• CT scan: not routinely indicated
  • Indications
    • At admission: only when the diagnosis is in doubt (e.g., not very highly elevated pancreatic enzymes, non-specific symptoms)
    • > 72 hours of symptom onset: if complications such as necrotizing pancreatitis or pancreatic abscess (e.g., persistent fever and leukocytosis, no clinical improvement or evidence of organ failure > 72 hours of therapy) are suspected
  • Findings
    • Enlargement of the pancreatic parenchyma with edema; indistinct pancreatic margins with surrounding fat stranding
    • Necrotizing pancreatitis: lack of parenchymal enhancement or presence of air in the pancreatic tissue
    • Pancreatic abscess: circumscribed fluid collection
• MRCP and ERCP
  • Indications: suspected biliary or pancreatic duct obstructions
  • MRCP is noninvasive but less sensitive than ERCP
  • ERCP can be combined with sphincterotomy and stone extraction; but may worsen pancreatitis.
• Conventional x-ray
  • Sentinel loop sign: dilatation of a loop of small intestine in the upper abdomen (duodenum/jejunum)
  • Colon cut off sign: gaseous distention of the ascending and transverse colon that abruptly terminates at the splenic flexure
  • Evidence of possible complications: pleural effusions, pancreatic calcium stones; helps rule out intestinal perforation with free air

References:^{[5][6][7][8][9][10][11][12][13][14][15][16][17]}

• Intestinal manifestations
  • Acute peritonitis
  • Appendicitis
  • Acute mesenteric ischemia
  • Acute cholecystitis
  • Acute cholangitis
  • Peptic ulcer disease
  • Biliary colic
  • Abdominal aorta aneurism
• Extraintestinal manifestations
  • Myocardial infarction
  • Bacterial pneumonia
• See Differential diagnoses of acute abdomen

The differential diagnoses listed here are not exhaustive.

General measures

• Admission to hospital and assessment of disease severity (consider ICU admission)
• Fluid resuscitation: aggressive hydration with crystalloids (e.g., lactated Ringer's solution , normal saline)
• Analgesia: IV opioids (e.g., fentanyl)
• Bowel rest (NPO)and IV fluids are recommended until the pain subsides
• Nasogastric tube insertion: not routinely recommended; indicated in patients with vomiting and/or significant abdominal distention
• Nutrition
  • Begin enteral feeding (oral/nasogastric/nasojejunal) as soon as the pain subsides
  • Total parenteral nutrition: only in patients who cannot tolerate enteral feeds (e.g., those with persistent ileus and abdominal pain)

Drug therapy

• Analgesics: fentanyl or hydromorphone; consider pump administration (patient controlled analgesia = PCA)
• Antibiotics
  • Prophylactic antibiotic therapy is not recommended.
  • Antibiotics should only be used in patients with evidence of infected necrosis.
• Fenofibrates: in hyperlipidemia-induced acute pancreatitis

Procedures/surgery

• Biliary pancreatitis
  • Urgent ERCP and sphincterotomy (within 24 hours): in patients with evidence of choledocholithiasis and/or cholangitis; followed by cholecystectomy
  • Cholecystectomy (preferably during same admission once the patient is stabilized; or within 6 weeks): in all patients with biliary pancreatitis

The most important therapeutic measure is adequate fluid replacement (minimum of 3–4 liters of crystalloids per day)!

"PANCREAS" - Perfusion (fluid replacement), Analgesia, Nutrition, Clinical (observation), Radiology (imaging), ERC (endoscopic stone extraction), Antibiotics, Surgery (surgical intervention, if necessary).

References:^{[18][19][20][21][22][23][24]}

• IV access with two large-bore peripheral IV lines
• Identify and treat sepsis, if present.
• Aggressive IV fluid resuscitation ^[25]
• Electrolyte repletion
• Early enteral nutrition (if able to tolerate PO) ^[26]
• Acute pain management: parenteral analgesics with NSAIDs (e.g., ketorolac ) and/or opioids (e.g., morphine ) ^[27]
• IV antiemetics (e.g., ondansetron )
• Assess severity (e.g., Ranson criteria)
• Consider an early general surgery consult if pancreatitis is severe or pancreatic necrosis is present.
• Vitals and urine output every 1–2 hours
• Serial abdominal examination
• Serial BMP, electrolytes, and CBC every 6–12 hours
• Consider continuous telemetry if electrolyte abnormalities are present or the patient is critically ill.
• Transfer to ICU if there is evidence of multiorgan dysfunction.
• Identify and treat the underlying cause.
  • Gallstone pancreatitis ^[26]
    • Urgent GI and general surgery consult
    • Early ERCP is only recommended in patients with acute cholangitis and/or evidence of complete obstruction of the biliary tract.
    • Cholecystectomy during the same admission
  • Lipid profile for hypertriglyceridemia: If present, initiate fibrate therapy at discharge.
  • Alcohol use: alcohol cessation counseling

Localized

• Bacterial superinfection of necrotic tissue → fever
  • Diagnosis: CT-guided percutaneous drainage + culture of the aspirate
  • Treatment: surgical debridement, antibiotics
  • High mortality rate; multiple organ failure in ∼ 50% of cases
• Pancreatic pseudocysts
• Pancreatic abscess
  • Walled-off infected necrotic tissue; or pancreatic pseudocyst; typically develops > 4 weeks after an attack of acute pancreatitis
  • Abdominal CT: visible contrast-enhanced abscess capsule with evidence of fluid (pus)
  • Ultrasound: complex cystic, fluid collection with irregular walls and septations
  • Treatment: cannulation and drainage; necrosectomy if other measures are not effective
• Pleural effusion
• Abdominal compartment syndrome
• Blood vessel erosion with bleeding

Systemic

• SIRS, sepsis, DIC
• Pneumonia, respiratory failure, ARDS
• Shock
• Prerenal failure due to volume depletion
• Hypocalcemia
• Pleural effusion, pancreatic ascites
• Paralytic ileus

References:^{[7][14][18][28]}

We list the most important complications. The selection is not exhaustive.

• Mortality
  • In patients without organ failure: < 1%
  • In patients with organ failure: ∼ 30%
  • Higher mortality in patients with biliary pancreatitis than in patients with alcoholic pancreatitis
• Important predictors of severity
  • Age > 55
  • Gastrointestinal bleeding
  • Abnormal hematocrit within 48 hours
    • Acute hemorrhagic pancreatitis: ↓ Hct
    • Third space fluid loss: ↑ Hct
  • Hypocalcemia and/or hyperglycemia
  • Inflammatory markers: ↑↑ CRP, ↑ IL-6, ↑ IL-8
  • Evidence of shock and/or organ failure
    • ↑ AST, ↑ ALT
    • ↑ BUN, creatinine
    • ↑ LDH
    • ABG: pO₂ < 60 mmHg, metabolic acidosis with a base deficit > 4 mmol/L
  • CT findings: pancreatic edema, peripancreatic fluid collection, and/or necrosis of > 33% of the pancreas

Amylase and lipase, which are used for the diagnosis of pancreatitis, cannot be used to predict the prognosis!

• Numerous scoring systems exist (e.g, Ranson criteria) for assessing the severity and predicting the prognosis of acute pancreatitis

References:^{[8][29][30][31][32]}

1. Vege SS. Etiology of acute pancreatitis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/etiology-of-acute-pancreatitis?source=search_result&search=acute%20pancreatitis&selectedTitle=3~150#H17.Last updated: May 7, 2015. Accessed: February 11, 2017.
2. Fogel EL, Sherman S. Pancreas divisum: Clinical manifestations and diagnosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/pancreas-divisum-clinical-manifestations-and-diagnosis?source=search_result&search=pancreas%20divism&selectedTitle=1~150.Last updated: February 24, 2016. Accessed: February 11, 2017.
3. Vege SS, Whitcomb DC, Grover S. Pathogenesis of Acute Pancreatitis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/pathogenesis-of-acute-pancreatitis.Last updated: August 10, 2016. Accessed: November 7, 2017.
4. Ahmed A, Azim A, Gurjar M, Baronia A. Hypocalcemia in acute pancreatitis revisited. Indian J Crit Care Med. 2016; 20 (3): p.173. doi: 10.4103/0972-5229.178182 . | Open in Read by QxMD
5. Tenner S, Baillie J, Dewitt J, Vege SS. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013; 108 (9): p.1400-1415. doi: 10.1038/ajg.2013.218 . | Open in Read by QxMD
6. Agabegi SS, Agabegi ED. Step-Up To Medicine. Lippincott Williams & Wilkins ; 2013
7. Le T, Bhushan V, Bagga HS. First Aid for the USMLE Step 2 CK. McGraw-Hill Medical ; 2009
8. Vege SS. Clinical manifestations and diagnosis of acute pancreatitis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-acute-pancreatitis?source=search_result&search=acute%20pancreatitis&selectedTitle=2~150#H2.Last updated: December 14, 2015. Accessed: February 12, 2017.
9. Gardner TB. Acute Pancreatitis. In: BS Anand, Acute Pancreatitis. New York, NY: WebMD. http://emedicine.medscape.com/article/181364. Updated: September 12, 2016. Accessed: February 12, 2017.
10. Gelrud D, Gress FG. Approach to the patient with elevated serum amylase or lipase. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/approach-to-the-patient-with-elevated-serum-amylase-or-lipase?source=machineLearning&search=amylase&selectedTitle=1~150§ionRank=2&anchor=H4#H4.Last updated: February 3, 2017. Accessed: February 12, 2017.
11. Banks PA, Freeman ML, Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol. 2006; 101 (10): p.2379-2400. doi: 10.1111/j.1572-0241.2006.00856.x . | Open in Read by QxMD
12. Sentinel loop. https://radiopaedia.org/articles/sentinel-loop. Updated: February 12, 2017. Accessed: February 12, 2017.
13. Colon cut-off sign. https://radiopaedia.org/articles/colon-cut-off-sign. Updated: February 12, 2017. Accessed: February 12, 2017.
14. Pickhardt PJ. The colon cutoff sign. Radiology. 2000; 215 (2): p.387-389. doi: 10.1148/radiology.215.2.r00ma18387 . | Open in Read by QxMD
15. Clancy TE. Pancreatic Debridement. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/pancreatic-debridement.Last updated: May 9, 2017. Accessed: October 28, 2017.
16. Acute Pancreatitis. https://radiopaedia.org/articles/acute-pancreatitis. Updated: January 1, 2017. Accessed: October 28, 2017.
17. Acute Pancreatitis. http://www.gastro.org/guidelines/acute-pancreatitis. Updated: March 4, 2014. Accessed: October 28, 2017.
18. Munoz A. Diagnosis and management of acute pancreatitis. Am Fam Physician. 2000; 62 (1): p.164-174.
19. Vege SS. Management of acute pancreatitis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/management-of-acute-pancreatitis.Last updated: November 19, 2015. Accessed: February 12, 2017.
20. Pain Management in Acute Pancreatitis.
21. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013; 13 (4): p.e1-e15. doi: 10.1016/j.pan.2013.07.063 . | Open in Read by QxMD
22. Quinlan JD. Acute pancreatitis.. Am Fam Physician. 2014; 90 (9): p.632-9.
23. Forsmark CE, Baillie J. AGA Institute Technical Review on Acute Pancreatitis. Gastroenterology. 2007; 132 (5): p.2022-2044. doi: 10.1053/j.gastro.2007.03.065 . | Open in Read by QxMD
24. Oláh A, Jr LR. Enteral nutrition in acute pancreatitis: A review of the current evidence. World J Gastroenterol. 2014; 20 (43): p.16123. doi: 10.3748/wjg.v20.i43.16123 . | Open in Read by QxMD
25. Browne GW. Pathophysiology of pulmonary complications of acute pancreatitis. World J Gastroenterol. 2006; 12 (44): p.7087. doi: 10.3748/wjg.v12.i44.7087 . | Open in Read by QxMD
26. Carroll JK, Herrick B, Gipson T. Acute Pancreatitis: Diagnosis, Prognosis, and Treatment. Am Fam Physician. 2007; 75 (10): p.1513-1520.
27. Mofidi R, Patil PV, Suttie SA, Parks RW. Risk assessment in acute pancreatitis. Br J Surg. 2009; 96 (2): p.137-150. doi: 10.1002/bjs.6431 . | Open in Read by QxMD
28. Vege SS. Predicting the severity of acute pancreatitis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/predicting-the-severity-of-acute-pancreatitis.Last updated: July 14, 2016. Accessed: February 12, 2017.
29. Meher S, Mishra TS, Sasmal PK, et al. Role of Biomarkers in Diagnosis and Prognostic Evaluation of Acute Pancreatitis. J Biomark. 2015; 2015 . doi: 10.1155/2015/519534 . | Open in Read by QxMD
30. Crockett et al. American Gastroenterological Association Institute Guideline on Initial Management of Acute Pancreatitis. Gastroenterology. 2018; 154 (4): p.1096-1101. doi: 10.1053/j.gastro.2018.01.032 . | Open in Read by QxMD
31. D Jeffrey. Acute Pancreatitis. AAFP. 2014 .
32. Vege SS, DiMagno MJ, Forsmark CE, Martel M, Barkun AN. Initial Medical Treatment of Acute Pancreatitis: American Gastroenterological Association Institute Technical Review. Gastroenterology. 2018; 154 (4): p.1103-1139. doi: 10.1053/j.gastro.2018.01.031 . | Open in Read by QxMD
33. Basurto Ona et al. Opioids for acute pancreatitis pain. Cochrane Database of Systematic Reviews. 2013 . doi: 10.1002/14651858.cd009179.pub2 . | Open in Read by QxMD
34. Dupuis CS, Baptista V, Whalen G, et al. Diagnosis and management of acute pancreatitis and its complications. Gastrointest Interv. 2013; 2 (1): p.36-46. doi: 10.1016/j.gii.2013.03.001 . | Open in Read by QxMD
35. Tao Le, Vikas Bhushan, Deol M, Reyes G. First Aid for the USMLE Step 2 CK, Tenth Edition. McGraw-Hill Education ; 2018
36. Foster BR, Jensen KK, Bakis G, Shaaban AM, Coakley FV. Revised Atlanta Classification for Acute Pancreatitis: A Pictorial Essay. RadioGraphics. 2016; 36 (3): p.675-687. doi: 10.1148/rg.2016150097 . | Open in Read by QxMD
37. Banks, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2012; 62 (1): p.102-111. doi: 10.1136/gutjnl-2012-302779 . | Open in Read by QxMD
38. Baillie J. AGA Institute Medical Position Statement on Acute Pancreatitis. Gastroenterology. 2007; 132 (5): p.2019-2021. doi: 10.1053/j.gastro.2007.03.066 . | Open in Read by QxMD
39. Leppäniemi A, et al. 2019 WSES guidelines for the management of severe acute pancreatitis. World Journal of Emergency Surgery. 2019; 14 (1). doi: 10.1186/s13017-019-0247-0 . | Open in Read by QxMD
40. Mikhail N, et al. Treatment of severe hypertriglyceridemia in nondiabetic patients with insulin. The American Journal of Emergency Medicine. 2005; 23 (3): p.415-417. doi: 10.1016/j.ajem.2005.02.036 . | Open in Read by QxMD
41. Acute Pancreatitis. https://acsearch.acr.org/docs/69468/Narrative/. Updated: November 1, 2019. Accessed: January 30, 2020.
42. Garg R, Rustagi T. Management of Hypertriglyceridemia Induced Acute Pancreatitis. BioMed Research International. 2018; 2018 : p.1-12. doi: 10.1155/2018/4721357 . | Open in Read by QxMD
43. Carroll MF, Schade DS. A practical approach to hypercalcemia.. Am Fam Physician. 2003; 67 (9): p.1959-66.
44. Rao SA, Kunte AR. Interleukin-6: An Early Predictive Marker for Severity of Acute Pancreatitis. Indian Journal of Critical Care Medicine. 2017; 21 (7): p.424-428. doi: 10.4103/ijccm.ijccm_478_16 . | Open in Read by QxMD
45. Cui J, et al. Serum lactate dehydrogenase is predictive of persistent organ failure in acute pancreatitis. J Crit Care. 2017; 41 : p.161-165. doi: 10.1016/j.jcrc.2017.05.001 . | Open in Read by QxMD
46. Jenssen C, et al. Endoscopic Ultrasound in Acute Pancreatitis. Video Journal and Encyclopedia of GI Endoscopy. 2013; 1 (2): p.554-559. doi: 10.1016/s2212-0971(13)70241-3 . | Open in Read by QxMD