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acute pancreatitis

Etiology: 1) common causes (80-90% of cases) a) alcoholism b) gallstone disease (most common) [20] - biliary sludge or microlithiasis [3] 2) uncommon causes a) abdominal trauma - including trauma caused by ERCP [3] b) post-operative, especially coronary artery bypass (CABG) c) infections - viral: mumps, hepatitis B, coxsackie B, HIV - bacterial: Mycoplasma, Campylobacter - parasitic: ascaris, toxoplasmosis d) hyperlipidemia, hypertriglyceridemia [30] - serum triglycerides > 500 mg/dL generally accepted threshold for increased risk for acute pancreatitis - serum triglycerides > 1000 mg/dL [3]; > 2000 mg/dL - baseline risk 3 per 10,000 with serum triglycerides < 90 mg/dL - risk increases 4-fold to 12 per 10,000 with serum triglycerides of 440 mg/dL [19] e) hypercalcemia f) pharmaceutical agents (see causes of acute pancreatitis) g) vascular - ischemia - vasculitis h) biliary duct & pancreatic duct abnormalities 3) risk factors for idiopathic pancreatitis* [20] - smoking & other environmental toxins - obesity - diabetes mellitus * idiopathic acute pancreatitis increases with age [20] Epidemiology: - hospital admissions for acute pancreatitis have increased by at least 20% 2006-2016 [20] - large increases in incidence in pediatric populations - increased risk of pancreatitis tracks with the worldwide obesity epidemic and increasing rates of gallstones [20] Pathology: 1) trypsinogen activation to trypsin 2) release of intracellular lysosomal enzymes 3) disruption of zymogen granules by refluxed pancreatic juice or duodenal obstruction 4) trypsin activation of phospholipases, elastases, kallikreins, & other mediators 5) neutrophil migration & release of inflammatory cytokines 6) bacterial invasion with localized sepsis 7) pancreatic necrosis (most important prognostic factor) [3] 8) multiorgan failure Genetics: genetic predispositions - mutations in PRSS1, SPINK1, CFTR, CTRC, CASR, CLDN2 - these mutations may interact with other causal factors - claudin-2 (CLDN2) mutations synergistic with alcohol [20] Clinical manifestations: 1) acute onset upper abdominal pain, rebound tenderness suggests complications - pain may radiate to back 2) low grade fever; high fever suggests complications (not a marker of severe disease) [32] 3) signs/symptoms of shock may be present a) tachypnea b) tachycardia c) diaphoresis 5) left-sided pleural effusion (minimal) may be present 6) decreased bowel sounds secondary to paralytic ileus - absent bowel sounds suggests complications 7) melena suggests complications 8) uncommon findings a) jaundice b) abdominal distension c) Grey-Turner sign: blueish discoloration of flanks d) Cullen's sign: - blueish discoloration of periumbilical region 9) most cases are mild, 20% of patients with severe disease Diagnostic criteria: - at least 2 of 3 of the following - acute onset of upper abdominal pain - serum amulase or serum lipase increased >= 3-fold upper limit of normal - findings suggesting pancreatitis on ultrasound, CT or MRI Laboratory: 1) serum amylase a) > 3-4 times upper limit of reference interval suggests pancreatitis b) serum amylase may be elevated in other conditions 1] acute cholecystitis 2] mesenteric thrombosis 3] intestinal obstruction, 4] perforated peptic ulcer 5] inflammation of the salivary gland - mumps 6] mild elevation with renal failure, intestinal ischemia, appendicitis, parotitis c) does not correlate with prognosis (see Ranson's criteria) d) may be normal 1] chronic pancreatitis with little functional pancreatic tissue 2] hyperlipidemic pancreatitis e) pancreatic versus salivary amylase 2) urine amylase is neither sensitive nor specific, but may be useful for excluding macroamylasemia 3) serum lipase increases specificity - in connection with amylase - diagnosis requires serum lipase or serum amylase > 3-4 times upper limit of reference interval [20] 4) complete blood count (CBC) a) may show leukocytosis (neutrophilia, not a marker of severe disease) [32] b) may show anemia or drop in hemoglobin/hematocrit 5) serum chemistries a) serum glucose b) electrolytes c) liver function tests 1] serum ALT (for Ranson criteria) - serum ALT > 3x upper limit of normal suggests gallstone pancreatitis [9] 2] serum lactate dehydrogenase (for Ranson criteria) d) urea nitrogen - serial urea nitrogen predicts disease severity [3] - level > 20 mg/dL is poor prognostic indicator [3] - best predictor of severe disease [3,32] e) elevated serum creatinine is poor prognostic indicator [3] f) serum Ca+2 (for Ranson criteria) g) serum triglycerides (> 1000-2000 mg/dL) [29] 6) arterial blood gas 7) serum procalcitonin can improve antibiotic stewardship [27] 7) testing in research phase [3] a) trypsin-activating polypeptide in urine b) pancreatitis-associated protein in serum 8) see ARUP consult [11] Special laboratory: 1) endoscopic retrograde cholangiopancreatography (ERCP) a) avoid in acute pancreatitis unless evidence of cholestasis or cholangitis or worsening of symptoms in the context of abnormal liver function tests [3,7] - within 24 hours [2] - avoid in 1st 72 hours unless cholangitis [34] b) evaluation of the pancreatic & common bile ducts 1] microlithiasis 2] stenosis of the sphincter of Oddi 3] traumatic pancreatitis c) identification fluid collection prior to drainage - IL8 elevated in pancreatic fluid, but does not distinguish pancreatic carcinoma [6] d) sphincterotomy* if dilated common bile duct [28] e) pancreatic carcinoma 2) culture of fine-needle aspiration fluid obtained under CT guidance (see radiology) * sphincter of Oddi Radiology: 1) abdominal ultrasound a) all patients unless cause is obvious [3] b) preferred imaging modality to evaluate biliary cause of acute pancreatitis c) gallbladder: gallstones or sludge suggests gallstone pancreatitis [9] d) size of common bile duct (biliary obstruction) e) avoids risks of intravenous contrast material [32] f) endoscopic ultrasound or MRI if diagnosis unclear [34] 2) computed tomography (CT) of abdomen (IV contrast-enhanced) a) indications - confirmation of diagnosis of acute pancreatitis (1st line) [3] - serum lipase not diagnostic - diagnosis of complications or extensive pancreatic necrosis when the patient continues to deteriorate after 48 hours - inability to adequately visualize pancreas with ultrasound [3] b) IV contrast may constrict pancreatic & renal micro-circulation & worsen pancreatic injury c) IV contrast puts patients at risk for contrast nephropathy d) useful for assessing 1] size of pancreas 2] extent of pancreatic necrosis 3] fluid collections e) CT-guided fine-needle aspiration for culture [16] f) peripancreatic edema resulting from pancreatic inflammation blurs the margins of the pancreas on CT (not a marker of severe pancreatitis) [32] 3) magnetic resonance imaging or CT required for diagnosis [20] 4) plain film of the abdomen (KUB) a) perforated peptic ulcer b) intestinal obstruction c) non-specific signs 1] dilated loop of jejunum (sentinel loop) 2] dilated transverse colon (colon cutoff sign) Complications: 1) pancreatic pseudocyst a) most common complication [3] b) generally take at least 4 weeks to form c) generally resolve spontaneously d) if asymptomatic & not mucinous pseudosyt, requires no further testing or treatment 2) repeated episodes may lead to chronic pancreatitis 3) pancreatic necrosis (non-infectious) or phlegmon a) may become infected - antibiotics essential for infected pancreatic necrosis - fine-needle aspiration should not be performed [34] b) diabetes mellitus if necrosis is extensive 4) pancreatic abscess 5) may increase risk of pancreatic cancer [23] 6) gastrointestinal hemorrhage 7) splenic vein thrombosis - anticoagulation not recommended 8) systemic inflammatory response syndrome 9) pancreatitis may cause exudative ascites 10) multiorgan failure 11) mortality 5% [3] Management: 1) NPO (nothing by mouth) until pain subsides - consider oral feeding when pain has improved [3] 2) intravenous fluids to maintain circulatory volume & electrolyte balance - 10 mL/kg bolus only if hypovolemic, then 1.5 mL/kg/hour infusion with additional boluses if hypovolemic [26,34] - formerly 20 mL/kg bolus followed by 3 mL/kg/hour superior to a lower rate in mild acute pancreatitis [21] - most beneficial in 1st 12-24 hours, may be harmful after this [3] - lactated Ringer's within 1st 24 hours may be associated with diminished risk of moderate-severe pancreatitis vs normal saline [33] 3) nasogastric tube (NGT) aspiration of stomach contents 4) parenteral analgesics to relieve pain - meperidine (Demerol) 75-100 mg IM every 3-4 hours 5) broad spectrum antibiotics a) indications: 1] routine use not indicated unless evidence of extrapancreatic infection 2] severe biliary pancreatitis (cholangitis) 3] infected pancreatic necrosis [3] 4] infected pseudocyst b) antibiotics 1] imipenem-cilastatin, meropenem, doripenem, or piperacillin-tazobactam 2] metronidazole plus cefepime, ceftazidime, ciprofloxacin, or levofloxacin 3] ceftazidime, amikacin & metronidazole 4] ofloxacin & metronidazole 5] cefuroxime (alone) 6] add vancomycin (if MRSA suspected) [8] 6) surgery a) most fluid collections resolve without intervention [3] b) abscess suspected c) unstable patients with infected pancreatic necrosis despite appropriate antimicrobial therapy [3,16] d) diagnosis not clear e) no relief with conservative measures - pancreatic pseudocyst f) gallstone pancreatitis (see laboratory & radiology) 1] cholecystectomy after pancreatitis subsides - laparoscopic cholecystectomy within 48 hours of admission (before discharge) for mild pancreatitis [12] 2] endoscopic papillotomy with stone extraction g) traumatic pancreatitis 1] partial pancreatectomy distal to avulsed duct identified by ERCP for severe injury 2] drainage of cyst resulting from trauma 7) newer, controversial or untested pharmaceuticals a) octreotide b) platelet-activating factor (PAF) antagonists 8) nutritional support a) resume feeding with low fat diet when asymptomatic - a low-fat diet started on admission results in hospital discharge ~5 days earlier than if feeding is delayed [25] b) enteral feeding within 72 hours if oral feeding not tolerated [3] - elemental or peptide-based enteral feeding via nasojejunal route for moderate to severe disease [3,4] c) regular oral intake at 72-96 hours after admission is an acceptable strategy in patients with predicted severe acute pancreatitis [15] d) do not withhold oral feeding for persistent elevations of serum amylase or serum lipase [3] e) mild pancreatitis does not benefit from nutritional support f) total parenteral nutrition - enteral feeding not feasible - may increase risk of sepsis [16] - not an initial recommendation [16] - monitor lipid intake - maintain serum triglycerides < 400 mg/dL [3] g) optimal timing & route of feeding in patients with acute pancreatitis remains controversial [22] 9) prognostic information provided by a) Ranson criteria b) modified Glasgow criteria c) severity index for acute pancreatitis d) bedside index for severity in acute pancreatitis e) pancreatis necrosis most important prognostic factor [3] f) serial serum urea nitrogen provides the most reliable routine laboratory test to predict mortality [3] 10) prevention - a diet high in vegetables is associated with reduced risk of non-gallstone related acute pancreatitis [10] - rectal indomethacin for individuals at high risk for post-ERCP pancreatitis [34] - pancreatic duct stents for patients at high risk for post-ERCP pancreatitis receiving rectal indomethacin.

Related

bedside index for severity in acute pancreatitis (BISAP) causes of acute pancreatitis chronic pancreatitis modified Glasgow criteria Ranson criteria severity index for acute pancreatitis

Specific

acute necrotizing pancreatitis gallstone pancreatitis

General

pancreatitis acute inflammation

References

  1. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 514-517
  2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 379-81
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Journal Watch 24(15):122, 2004 Marik PE, Zaloga GP. Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute pancreatitis. BMJ. 2004 Jun 12;328(7453):1407. Epub 2004 Jun 02. Review. PMID: 15175229 - Marik PE & Zaloga GP, BMJ. 2004 Jun 12;328(7453):1407 http://bmj.bmjjournals.com/cgi/content/full/328/7453/1407
  5. Prescriber's Letter 11(12): 2004 Acute Pancreatitis: Enteral or Parenteral Nutritional Support? Detail-Document#: 201221 (subscription needed) http://www.prescribersletter.com
  6. Noh KW et al, Do cytokine secretions in pancreatic juice predict the presence of pancreatic disease? Clin Gastroenterol Hepatol 2006, 4:782 PMID: 16713745
  7. van Santvoort HC et al Early endoscopic retrograde cholangiopancreatography in predicted severe acute biliary pancreatitis: A prospective multicenter study. Ann Surg 2009 Jul; 250:68. PMID: 19561460
  8. Prescriber's Letter 17(3): 2010 CHART: Antibiotics for Complicated Intra-Abdominal Infections GUIDELINES: Diagnosis and Management of Complicated Intra- abdominal Infections Detail-Document#: 260321
  9. Trna J et al. Lack of significant liver enzyme elevation and gallstones and/or sludge on ultrasound on day 1 of acute pancreatitis is associated with recurrence after cholecystectomy: A population-based study. Surgery 2012 Feb; 151:199 PMID: 21975288
  10. Oskarsson V et al Vegetables, fruit and risk of non-gallstone-related acute pancreatitis: a population-based prospective cohort study Gut, June 27 2012 PMID: 22740517 http://gut.bmj.com/content/early/2012/06/08/gutjnl-2012-302521.abstract
  11. ARUP Consult: Acute Pancreatitis The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/pancreatitis-acute - ARUP consult: Idiopathic and Hereditary Pancreatitis Testing https://arupconsult.com/ati/idiopathic-and-hereditary-pancreatitis-testing
  12. Falor AE et al. Early laparoscopic cholecystectomy for mild gallstone pancreatitis: Time for a paradigm shift. Arch Surg 2012 Nov; 147:1031 PMID: 22801992 http://archsurg.jamanetwork.com/article.aspx?articleid=1216541
  13. Wu BU, Johannes RS, Sun X, Conwell DL, Banks PA. Early changes in blood urea nitrogen predict mortality in acute pancreatitis. Gastroenterology. 2009 Jul;137(1):129-35. PMID: 19344722
  14. Banks PA, Freeman ML; Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol. 2006 Oct;101(10):2379-400. PMID: 17032204
  15. Bakker OJ et al. Early versus on-demand nasoenteric tube feeding in acute pancreatitis. N Engl J Med 2014 Nov 20; 371:1983 PMID: 25409371
  16. Tenner S, Baillie J, DeWitt J, Vege SS American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 2013 Jul 31; 108:1400. PMID: 23896955
  17. Banks PA, Bollen TL, Dervenis C et al Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 Jan;62(1):102-11. Epub 2012 Oct 25. PMID: 23100216
  18. Mounzer R, Langmead CJ, Wu BU et al Comparison of existing clinical scoring systems to predict persistent organ failure in patients with acute pancreatitis. Gastroenterology. 2012 Jun;142(7):1476-82; Epub 2012 Mar 13. PMID: 22425589
  19. Pedersen SB et al. Nonfasting mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis. JAMA Intern Med 2016 Nov 7 PMID: 27820614 http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2580722
  20. Forsmark CE, Vege SS, Wilcox CM Acute Pancreatitis N Engl J Med 2016; 375:1972-1981 November 17, 2016 PMID: 27959604 http://www.nejm.org/doi/full/10.1056/NEJMra1505202
  21. Buxbaum JL, Quezada M, Da B et al. Early aggressive hydration hastens clinical improvement in mild acute pancreatitis. Am J Gastroenterol 2017 May; 112:797 PMID: 28266591 https://www.nature.com/ajg/journal/v112/n5/full/ajg201740a.html
  22. Vaughn VM et al. Early versus delayed feeding in patients with acute pancreatitis: A systematic review. Ann Intern Med 2017 May 16; PMID: 28505667 - Roberts KM, Conwell D. Acute Pancreatitis: How soon should we feed patients? Ann Intern Med 2017 May 16; PMID: 28505666
  23. Sadr-Azodi O et al. Pancreatic cancer following acute pancreatitis: A population-based matched cohort study. Am J Gastroenterol 2018 Oct 12; PMID: 30315287
  24. Mederos MA, Reber HA, Girgis MD Acute Pancreatitis. JAMA. 2021;325(4):382-390. Jan 26 PMID: 33496779 https://jamanetwork.com/journals/jama/fullarticle/2775452
  25. Ramirez-Maldonado E, Gordo SLOP, Pueyo EM et al. Immediate oral refeeding in patients with mild and moderate acute pancreatitis: A multicenter, randomized controlled trial (PADI trial). Ann Surg 2021 Aug; 274:255 PMID: 33196485
  26. de-Madaria E et al. Aggressive or moderate fluid resuscitation in acute pancreatitis. N Engl J Med 2022 Sep 15; 387:989. PMID: 36103415 https://www.nejm.org/doi/10.1056/NEJMoa2202884
  27. Siriwardena AK et al. A procalcitonin-based algorithm to guide antibiotic use in patients with acute pancreatitis (PROCAP): A single-centre, patient-blinded, randomised controlled trial. Lancet Gastroenterol Hepatol 2022 Oct; 7:913. PMID: 35863358 Clinical Trial. https://www.thelancet.com/journals/langas/article/PIIS2468-1253(22)00212-6/fulltext
  28. NEJM Knowledge+ Gastroenterology
  29. NEJM Knowledge+ Endocrinology
  30. Carr RA, Rejowski BJ, Cote GA et al Systematic review of hypertriglyceridemia-induced acute pancreatitis: A more virulent etiology? Pancreatology. 2016 Jul-Aug;16(4):469-76. PMID: 27012480 Review.
  31. NEJM Knowledge+ Nephrology/Urology
  32. Crockett SD, Wani S, Gardner TB, et al American Gastroenterological Association Institute guideline on initial management of acute pancreatitis. Gastroenterology. 2018;154:1096-1101. PMID: 29409760
  33. Lee PJ et al. Lactated ringers use in the first 24 hours of hospitalization is associated with improved outcomes in 999 patients with acute pancreatitis. Am J Gastroenterol 2023 Jul 20; [e-pub] PMID: 37428139 https://journals.lww.com/ajg/abstract/9900/lactated_ringers_use_in_the_first_24_hours_of.810.aspx
  34. Tenner S et al. American College of Gastroenterology guidelines: Management of acute pancreatitis. Am J Gastroenterol 2024 Mar; 119:419-437. PMID: 38857482 https://journals.lww.com/ajg/fulltext/2024/03000/american_college_of_gastroenterology_guidelines_.14.aspx
  35. NIDDK: Pancreatitis https://www.niddk.nih.gov/health-information/digestive-diseases/pancreatitis