Acute pancreatitis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]; Tarek Nafee, M.D. [3]

Overview

The mainstay of treatment in acute pancreatitis involves pain control, bowel rest (NPO or nothing by mouth), and fluid resuscitation. Assessment of the re-introduction of feeding and nutritional support must be made subsequently based on clinical improvement and imaging findings. Serial cross sectional imaging may be used to determine the need for surgical intervention secondary to complications. Antiobiotics may only be used in cases when infection is suspected or confirmed. Clinicians must note that imaging findings almost always lag the clinical findings. Clinicians must make decisions primarily based on the patient's clinical condition.[1]

Medical Therapy

According to the American college of gastroenterology, following are the guidelines for the management of acute pancreatitis:[2][3][4][5][6][7][8][9][10][11][12][13][14][15]

Initial Management

Recommendation Evidence Level Strength of Recommendation
Aggressive hydration, defined as 250-500 ml per hour of isotonic crystalloid solution should be provided to all patients unless cardiovascular and/or renal comorbidities exist. Early aggressive intravenous hydration is most beneficial the first 12–24 h, and may have little benefit beyond Moderate Strong
In a patient with severe volume depletion, manifest as hypotension and tachycardia, more rapid repletion (bolus) may be needed Moderate Conditional
Lactated Ringer's solution may be the preferred isotonic crystalloid replacement fluid Moderate Conditional
Fluid requirements should be reassessed at frequent intervals within 6 h of admission and for the next 24–48 h. The goal of aggressive hydration should be to decrease the blood urea nitrogen Moderate Strong

Role of Antibiotics

According to the American college of gastroenterology, following are the guidelines for the use of antibiotics in acute pancreatitis:[2][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]

Recommendation Evidence Level Strength of Recommendation
Antibiotics should be given for an extrapancreatic infection, such as cholangitis, catheter-acquired infections, bacteremia, urinary tract infections, pneumonia High Strong
Routine use of prophylactic antibiotics in patients with severe acute pancreatitis is not recommended  Moderate Strong
The use of antibiotics in patients with sterile necrosis to prevent the development of infected necrosis is not recommended  Moderate Strong
Infected necrosis should be considered in patients with pancreatic or extrapancreatic necrosis who deteriorate or fail to improve after 7–10 days of hospitalization. In these patients, either (i) initial CT-guided fine needle aspiration (FNA) for Gram stain and culture to guide use of appropriate antibiotics or (ii) empiric use of antibiotics without CT FNA should be given Low Strong
In patients with infected necrosis, antibiotics known to penetrate pancreatic necrosis, such as carbapenems, quinolones, and metronidazole, may be useful in delaying or sometimes totally avoiding intervention, thus decreasing morbidity and mortality Low Conditional
Routine administration of antifungal agents along with prophylactic or therapeutic antibiotics is not recommended Low Conditional

Nutrition in Acute Pancreatitis

According to the American college of gastroenterology, following are the guidelines for the use of antibiotics in acute pancreatitis:[2][31][32][33][34][35][36][37][38]

Recommendation Evidence Level Strength of Recommendation
In mild AP, oral feedings can be started immediately if there is no nausea and vomiting, and abdominal pain has resolved Moderate Conditional
In mild AP, initiation of feeding with a low-fat solid diet appears as safe as a clear liquid diet  Moderate Conditional
In severe AP, enteral nutrition is recommended to prevent infectious complications. Parenteral nutrition should be avoided unless the enteral route is not available, not tolerated, or not meeting caloric requirements High Strong
Nasogastric delivery and nasojejunal delivery of enteral feeding appear comparable in efficacy and safety Moderate Strong

The mainstay of treatment in acute pancreatitis involves pain control, bowel rest (NPO or nothing by mouth), and fluid resuscitation. Assessment of the re-introduction of feeding and nutritional support must be made subsequently based on clinical improvement and serial imaging findings. Antibiotics may only be used in cases when infection is suspected or confirmed.[1]

Pain Control

Analgesia should not be provided by morphine because it may cause spasm of the sphincter of Oddi and worsen the pain, so the drug of choice is Meperidine.[39][2][1]

Bowel Rest

In the management of acute pancreatitis, the initial steps involve bowel rest and placing the patient as NPO (nothing by mouth).[39][2][1]

Fluid Resuscitation

Aggressive fluid therapy is of utmost importance from 12-24 hrs after onset of symptoms. There is little value beyond this point. Normal saline or Ringer's lactate should be administered at a rate of 200-500 mL/hr within the first 24 hours.[39][2] Fluid status should be monitored with hourly urine output, BUN and hematocrit. Resistence of normalization of BUN and hematocrit despite adequate fluid resuscitation is associated with a poor prognosis.[1]

Clinicians should be wary of volume overload, particularly in patients with underlying CHF or renal dysfunction. In those patients, fluid therapy should be individualized according to renal and cardiac tolerance as well as close monitoring of clinical manifestations of fluid overload (e.g. edema, dyspnea, electrolyte imbalance, and symptoms of compartment syndrome).[39][2]

Nutritional Support

Traditionally, complete resolution of pain was a requirement prior to initiation of oral feeding. However, as of late, a low-fat soft or solid diet has been found to benefit patients with shorter durations of hospitalization than slower advancements to solid foods in patients with mild pancreatitis in the absence of organ failure or pancreatic necrosis.

Approximately 20% of patients have a relapse of pain during acute pancreatitis.[40] Approximately 75% of relapses occur within 48 hours of oral refeeding.

The incidence of relapse after oral refeeding may be reduced by post-pyloric enteral rather than parenteral feeding prior to oral refeeding.[40] IMRIE scoring may be a useful tool in assessing the optimal initiation of refeeding.[1]

TPN vs. Tube Feeding

There has been a shift in the management paradigm from TPN (total parenteral nutrition) to early, post-pyloric enteral feeding (in which a feeding tube is endoscopically or radiographically introduced to the third portion of the duodenum).[35]

The advantage of enteral feeding is that it is more physiological, prevents gut mucosal atrophy, and is free from the side effects of TPN (such as fungemia). The additional advantages of tube feeding are the inverse relationship of pancreatic exocrine secretions and distance of nutrient delivery from the pylorus, as well as reduced risk of aspiration.[41][39][2]

TPN may be utilized in the rare cases where enteral feeding is not at all tolerated and nutritional goals are not met.[39][2]

Timing of Enteric Feeding

The need for enteral feeding should be assessed by day 5, at latest, based on ongoing assessment of symptoms and the ability to tolerate oral feeds. In milder cases, oral diet should be attempted at 72 hours when symptoms improve and tube feeding only be attempted in cases when oral feeding is not tolerated for 2 to 3 days. Switching from oral to tube feeding should only be considered when oral feeding shows no improvement or worsening of symptoms at 3 to 5 day intervals.[2][1]

Types of Tube Feeding

Naso-jejunal tube feeding is known to minimize pancreatic secretions; however, nasogastric and nasoduodenal feeding are associated with similar patient outcomes.[2]

Disadvantages of a naso-enteric feeding tube include increased risk of sinusitis (especially if the tube remains in place greater than two weeks) and a still-present risk of accidentally intubating the bronchus even in intubated patients (contrary to popular belief, the endotracheal tube cuff alone is not always sufficient to prevent NG tube entry into the trachea).[1]

Antibiotics

There is no benefit for prophylactic antibiotics in patients with acute pancreatitis unless infection is suspected or confirmed.[23][22][42][43][2][39][1]

Other Measures

  • Pancreatic enzyme inhibitors are not proven to work.[44]
  • The use of octreotide has not been shown to improve outcome.[45]

Contraindicated medications

Acute pancreatitis accompanied by hyperlipidemia is considered an absolute contraindication to the use of the following medications:

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Forsmark CE, Vege SS, Wilcox M (November 17,2016). "Acute Pancreatitis". The New England Journal of Medicine: 1972–1981. doi:10.1056/NEJMra1505202. Retrieved November 25,2016. Check date values in: |access-date=, |date= (help)
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 Tenner S, Baillie J, DeWitt J, Vege SS, American College of Gastroenterology (2013). "American College of Gastroenterology guideline: management of acute pancreatitis". Am J Gastroenterol. 108 (9): 1400–15, 1416. doi:10.1038/ajg.2013.218. PMID 23896955.
  3. ↑ Steinberg W, Tenner S (1994). "Acute pancreatitis". N. Engl. J. Med. 330 (17): 1198–210. doi:10.1056/NEJM199404283301706. PMID 7811319.
  4. ↑ Tenner S (2004). "Initial management of acute pancreatitis: critical issues during the first 72 hours". Am. J. Gastroenterol. 99 (12): 2489–94. doi:10.1111/j.1572-0241.2004.40329.x. PMID 15571599.
  5. ↑ Banks PA, Freeman ML (2006). "Practice guidelines in acute pancreatitis". Am. J. Gastroenterol. 101 (10): 2379–400. doi:10.1111/j.1572-0241.2006.00856.x. PMID 17032204.
  6. ↑ Mounzer R, Langmead CJ, Wu BU, Evans AC, Bishehsari F, Muddana V, Singh VK, Slivka A, Whitcomb DC, Yadav D, Banks PA, Papachristou GI (2012). "Comparison of existing clinical scoring systems to predict persistent organ failure in patients with acute pancreatitis". Gastroenterology. 142 (7): 1476–82, quiz e15–6. doi:10.1053/j.gastro.2012.03.005. PMID 22425589.
  7. ↑ Brown A, Orav J, Banks PA (2000). "Hemoconcentration is an early marker for organ failure and necrotizing pancreatitis". Pancreas. 20 (4): 367–72. PMID 10824690.
  8. ↑ Kerner T, Vollmar B, Menger MD, Waldner H, Messmer K (1996). "Determinants of pancreatic microcirculation in acute pancreatitis in rats". J. Surg. Res. 62 (2): 165–71. doi:10.1006/jsre.1996.0190. PMID 8632634.
  9. ↑ Bassi D, Kollias N, Fernandez-del Castillo C, Foitzik T, Warshaw AL, Rattner DW (1994). "Impairment of pancreatic microcirculation correlates with the severity of acute experimental pancreatitis". J. Am. Coll. Surg. 179 (3): 257–63. PMID 8069418.
  10. ↑ Inoue K, Hirota M, Beppu T, Ishiko T, Kimura Y, Maeda K, Ogawa M (2003). "Angiographic features in acute pancreatitis: the severity of abdominal vessel ischemic change reflects the severity of acute pancreatitis". JOP. 4 (6): 207–13. PMID 14614201.
  11. ↑ Wu BU, Hwang JQ, Gardner TH, Repas K, Delee R, Yu S, Smith B, Banks PA, Conwell DL (2011). "Lactated Ringer's solution reduces systemic inflammation compared with saline in patients with acute pancreatitis". Clin. Gastroenterol. Hepatol. 9 (8): 710–717.e1. doi:10.1016/j.cgh.2011.04.026. PMID 21645639.
  12. ↑ Takeda K, Mikami Y, Fukuyama S, Egawa S, Sunamura M, Ishibashi T, Sato A, Masamune A, Matsuno S (2005). "Pancreatic ischemia associated with vasospasm in the early phase of human acute necrotizing pancreatitis". Pancreas. 30 (1): 40–9. PMID 15632698.
  13. ↑ Gardner TB, Vege SS, Chari ST, Petersen BT, Topazian MD, Clain JE, Pearson RK, Levy MJ, Sarr MG (2009). "Faster rate of initial fluid resuscitation in severe acute pancreatitis diminishes in-hospital mortality". Pancreatology. 9 (6): 770–6. doi:10.1159/000210022. PMID 20110744.
  14. ↑ Cho YS, Lim H, Kim SH (2007). "Comparison of lactated Ringer's solution and 0.9% saline in the treatment of rhabdomyolysis induced by doxylamine intoxication". Emerg Med J. 24 (4): 276–80. doi:10.1136/emj.2006.043265. PMC 2658235. PMID 17384382.
  15. ↑ Eckerwall G, Olin H, Andersson B, Andersson R (2006). "Fluid resuscitation and nutritional support during severe acute pancreatitis in the past: what have we learned and how can we do better?". Clin Nutr. 25 (3): 497–504. doi:10.1016/j.clnu.2005.10.012. PMID 16337067.
  16. ↑ Beger HG, Rau B, Isenmann R (2003). "Natural history of necrotizing pancreatitis". Pancreatology. 3 (2): 93–101. doi:10.1159/000070076. PMID 12774801.
  17. ↑ Beger HG, Bittner R, Block S, Büchler M (1986). "Bacterial contamination of pancreatic necrosis. A prospective clinical study". Gastroenterology. 91 (2): 433–8. PMID 3522342.
  18. ↑ Petrov MS, Kukosh MV, Emelyanov NV (2006). "A randomized controlled trial of enteral versus parenteral feeding in patients with predicted severe acute pancreatitis shows a significant reduction in mortality and in infected pancreatic complications with total enteral nutrition". Dig Surg. 23 (5–6): 336–44, discussion 344–5. doi:10.1159/000097949. PMID 17164546.
  19. ↑ Besselink MG, Verwer TJ, Schoenmaeckers EJ, Buskens E, Ridwan BU, Visser MR, Nieuwenhuijs VB, Gooszen HG (2007). "Timing of surgical intervention in necrotizing pancreatitis". Arch Surg. 142 (12): 1194–201. doi:10.1001/archsurg.142.12.1194. PMID 18086987.
  20. ↑ Pederzoli P, Bassi C, Vesentini S, Campedelli A (1993). "A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem". Surg Gynecol Obstet. 176 (5): 480–3. PMID 8480272.
  21. ↑ Sainio V, Kemppainen E, Puolakkainen P, Taavitsainen M, Kivisaari L, Valtonen V, Haapiainen R, Schröder T, Kivilaakso E (1995). "Early antibiotic treatment in acute necrotising pancreatitis". Lancet. 346 (8976): 663–7. PMID 7658819.
  22. ↑ 22.0 22.1 Dellinger EP, Tellado JM, Soto NE, Ashley SW, Barie PS, Dugernier T, Imrie CW, Johnson CD, Knaebel HP, Laterre PF, Maravi-Poma E, Kissler JJ, Sanchez-Garcia M, Utzolino S (2007). "Early antibiotic treatment for severe acute necrotizing pancreatitis: a randomized, double-blind, placebo-controlled study". Ann. Surg. 245 (5): 674–83. doi:10.1097/01.sla.0000250414.09255.84. PMC 1877078. PMID 17457158.
  23. ↑ 23.0 23.1 Isenmann R, Rünzi M, Kron M, Kahl S, Kraus D, Jung N, Maier L, Malfertheiner P, Goebell H, Beger HG (2004). "Prophylactic antibiotic treatment in patients with predicted severe acute pancreatitis: a placebo-controlled, double-blind trial". Gastroenterology. 126 (4): 997–1004. PMID 15057739.
  24. ↑ de Vries AC, Besselink MG, Buskens E, Ridwan BU, Schipper M, van Erpecum KJ, Gooszen HG (2007). "Randomized controlled trials of antibiotic prophylaxis in severe acute pancreatitis: relationship between methodological quality and outcome". Pancreatology. 7 (5–6): 531–8. doi:10.1159/000108971. PMID 17901714.
  25. ↑ Jiang K, Huang W, Yang XN, Xia Q (2012). "Present and future of prophylactic antibiotics for severe acute pancreatitis". World J. Gastroenterol. 18 (3): 279–84. doi:10.3748/wjg.v18.i3.279. PMC 3261546. PMID 22294832.
  26. ↑ Trikudanathan G, Navaneethan U, Vege SS (2011). "Intra-abdominal fungal infections complicating acute pancreatitis: a review". Am. J. Gastroenterol. 106 (7): 1188–92. doi:10.1038/ajg.2010.497. PMID 21731015.
  27. ↑ Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM, Nieuwenhuijs VB, Bollen TL, van Ramshorst B, Witteman BJ, Rosman C, Ploeg RJ, Brink MA, Schaapherder AF, Dejong CH, Wahab PJ, van Laarhoven CJ, van der Harst E, van Eijck CH, Cuesta MA, Akkermans LM, Gooszen HG (2008). "Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial". Lancet. 371 (9613): 651–659. doi:10.1016/S0140-6736(08)60207-X. PMID 18279948.
  28. ↑ Hartwig W, Maksan SM, Foitzik T, Schmidt J, Herfarth C, Klar E (2002). "Reduction in mortality with delayed surgical therapy of severe pancreatitis". J. Gastrointest. Surg. 6 (3): 481–7. PMID 12023003.
  29. ↑ Runzi M, Niebel W, Goebell H, Gerken G, Layer P (2005). "Severe acute pancreatitis: nonsurgical treatment of infected necroses". Pancreas. 30 (3): 195–9. PMID 15782093.
  30. ↑ Mouli VP, Sreenivas V, Garg PK (2013). "Efficacy of conservative treatment, without necrosectomy, for infected pancreatic necrosis: a systematic review and meta-analysis". Gastroenterology. 144 (2): 333–340.e2. doi:10.1053/j.gastro.2012.10.004. PMID 23063972.
  31. ↑ Eckerwall GE, Tingstedt BB, Bergenzaun PE, Andersson RG (2007). "Immediate oral feeding in patients with mild acute pancreatitis is safe and may accelerate recovery--a randomized clinical study". Clin Nutr. 26 (6): 758–63. doi:10.1016/j.clnu.2007.04.007. PMID 17719703.
  32. ↑ Louie BE, Noseworthy T, Hailey D, Gramlich LM, Jacobs P, Warnock GL (2005). "2004 MacLean-Mueller prize enteral or parenteral nutrition for severe pancreatitis: a randomized controlled trial and health technology assessment". Can J Surg. 48 (4): 298–306. PMC 3211537. PMID 16149365.
  33. ↑ Casas M, Mora J, Fort E, Aracil C, Busquets D, Galter S, Jáuregui CE, Ayala E, Cardona D, Gich I, Farré A (2007). "[Total enteral nutrition vs. total parenteral nutrition in patients with severe acute pancreatitis]". Rev Esp Enferm Dig (in Spanish; Castilian). 99 (5): 264–9. PMID 17650935.
  34. ↑ Gupta R, Patel K, Calder PC, Yaqoob P, Primrose JN, Johnson CD (2003). "A randomised clinical trial to assess the effect of total enteral and total parenteral nutritional support on metabolic, inflammatory and oxidative markers in patients with predicted severe acute pancreatitis (APACHE II > or =6)". Pancreatology. 3 (5): 406–13. doi:73657 Check |doi= value (help). PMID 14526151.
  35. ↑ 35.0 35.1 Yi F, Ge L, Zhao J, Lei Y, Zhou F, Chen Z, Zhu Y, Xia B (2012). "Meta-analysis: total parenteral nutrition versus total enteral nutrition in predicted severe acute pancreatitis". Intern. Med. 51 (6): 523–30. PMID 22449657.
  36. ↑ Jacobson BC, Vander Vliet MB, Hughes MD, Maurer R, McManus K, Banks PA (2007). "A prospective, randomized trial of clear liquids versus low-fat solid diet as the initial meal in mild acute pancreatitis". Clin. Gastroenterol. Hepatol. 5 (8): 946–51, quiz 886. doi:10.1016/j.cgh.2007.04.012. PMC 2034288. PMID 17613280.
  37. ↑ Moraes JM, Felga GE, Chebli LA, Franco MB, Gomes CA, Gaburri PD, Zanini A, Chebli JM (2010). "A full solid diet as the initial meal in mild acute pancreatitis is safe and result in a shorter length of hospitalization: results from a prospective, randomized, controlled, double-blind clinical trial". J. Clin. Gastroenterol. 44 (7): 517–22. doi:10.1097/MCG.0b013e3181c986b3. PMID 20054282.
  38. ↑ Singh N, Sharma B, Sharma M, Sachdev V, Bhardwaj P, Mani K, Joshi YK, Saraya A (2012). "Evaluation of early enteral feeding through nasogastric and nasojejunal tube in severe acute pancreatitis: a noninferiority randomized controlled trial". Pancreas. 41 (1): 153–9. doi:10.1097/MPA.0b013e318221c4a8. PMID 21775915.
  39. ↑ 39.0 39.1 39.2 39.3 39.4 39.5 39.6 Working Group IAP/APA Acute Pancreatitis Guidelines (2013). "IAP/APA evidence-based guidelines for the management of acute pancreatitis". Pancreatology. 13 (4 Suppl 2): e1–15. doi:10.1016/j.pan.2013.07.063. PMID 24054878.
  40. ↑ 40.0 40.1 Petrov MS, van Santvoort HC, Besselink MG, Cirkel GA, Brink MA, Gooszen HG (2007). "Oral Refeeding After Onset of Acute Pancreatitis: A Review of Literature". doi:10.1111/j.1572-0241.2007.01357.x. PMID 17573797.
  41. ↑ Al-Omran M, Albalawi ZH, Tashkandi MF, Al-Ansary LA (2010). "Enteral versus parenteral nutrition for acute pancreatitis". Cochrane Database Syst Rev (1): CD002837. doi:10.1002/14651858.CD002837.pub2. PMID 20091534. Review in: Ann Intern Med. 2010 Jul 20;153(2):JC1-6
  42. ↑ Lim CL, Lee W, Liew YX, Tang SS, Chlebicki MP, Kwa AL (2015). "Role of antibiotic prophylaxis in necrotizing pancreatitis: a meta-analysis". J Gastrointest Surg. 19 (3): 480–91. doi:10.1007/s11605-014-2662-6. PMID 25608671.
  43. ↑ Villatoro E, Mulla M, Larvin M (2010). "Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis". Cochrane Database Syst Rev (5): CD002941. doi:10.1002/14651858.CD002941.pub3. PMID 20464721.
  44. ↑ DeCherney, Alan H. (2003). Current Obstetric & Gynecologic Diagnosis & Treatment. McGraw-Hill Professional. ISBN 0838514014. Unknown parameter |coauthors= ignored (help)
  45. ↑ Peitzman, Andrew B. (2007). The Trauma Manual: Trauma and Acute Care Surgery. Lippincott Williams & Wilkins. ISBN 0781762758. Unknown parameter |coauthors= ignored (help); line feed character in |publisher= at position 20 (help)


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