Pancreapedia: Exocrine Pancreas Knowledge Base, DOI: 10.3998/panc.2015.31
As previously demonstrated, acute pancreatitis can be regarded as a hyper catabolism state and nutrition plays a key role in the treatment of this disease. When patient’s food intake is limited because of pancreatic pain, organ failure or other, an adapted nutrition support should be initiated early in the management of acute pancreatitis in order to decrease mortality and morbidity. Numerous meta-analyses addressing this issue have been published and the most appropriate modalities for artificial nutrition are now well-established. Compared to parenteral nutrition, enteral nutrition has been shown to have a greater clinical benefit in patients with acute pancreatitis reducing the risk of developing both, pancreatic infections and multiple organ failure. Enteral nutrition may attenuate the mucosal barrier breakdown and subsequent bacterial translocation. It also may increase the intestinal motility and decrease bacterial overgrowth. The international guidelines recommend that enteral nutrition in acute pancreatitis should be administered via either the nasojejunal or nasogastric route but the choice of the location should not delay the nutritional support. Either elemental or polymeric enteral nutrition formulations can be used in acute pancreatitis.
As previously demonstrated, acute pancreatitis can be regarded as a hyper catabolism situation and nutrition plays a key role in the treatment of this disease. When patients food intake is limited because of pancreatic pain, organ failure or other complications, an adapted nutrition support should be initiated early in the management of acute pancreatitis in order to decrease mortality and morbidity. Numerous studies and meta analysis are now available and the most appropriate modalities for artificial nutrition are well established (24, 47).
The importance of providing nutritional support in patients with severe acute pancreatitis has been well demonstrated and leads to decreased morbidity and mortality rates (17, 31). The main objectives are to provide adequate calories in this condition of hypercatabolism and to decrease the infection of pancreatic necrosis.
In acute pancreatitis, the concept of “pancreatic rest” was developed many decades ago in order to decrease pancreatic inflammation. It suggested prolonged fasting in cases of mild pancreatitis and parenteral nutrition in case of severe pancreatitis to prevent stimulation of exocrine function and release of proteolytic enzymes. However, it is now well known that parenteral nutrition leads to electrolyte and metabolic disturbances, gut barrier alteration, and increased intestinal permeability. Moreover, parenteral nutrition is not cost effective and may increase the risks of sepsis complications (8, 9, 23, 48).
Pancreatic infection and organ failure are determinants of severity in acute pancreatitis. Gut barrier dysfunction and increased bacterial translocation are implicated in the development of secondary infection, sepsis, multiple organ failure, and death in acute pancreatitis. Studies have shown that microorganisms responsible for sepsis and pancreatic infection originate mainly from the digestive tract. Moreover, dysfunction of the gut barrier and the translocation of digestive bacteria into the portal venous system may cause multiple organ failure. Gut barrier dysfunction is characterized by damages of the gut epithelium and intestinal cell junctions, resulting in increased intestinal permeability (3, 4, 40, 41). Splanchnic hypoperfusion and ischemia/reperfusion injury have been postulated as possible causes of this increased intestinal permeability. A decrease in splanchnic perfusion results in a concomitant decrease in oxygen delivery to the intestinal mucosa; this coupled with the consequences of reperfusion leads to histologic evidence of mucosal ischemia (21, 50). Loss of cell membrane integrity and cytoskeletal alterations during hypoperfusion results in the leakage of cytoplasmic proteins. In the literature, only enteral nutrition has been shown to have a significant clinical benefit in patients with acute pancreatitis in reducing the risk of developing both pancreatic infections and multiple organ failure. Enteral nutrition may attenuate the mucosal barrier breakdown and subsequent bacterial translocation. It also may increase the intestinal motility and decrease bacterial overgrowth thanks to a better clearance of bacteria in the digestive tract (36).
3. Indications of Artificial Nutrition
In mild pancreatitis, artificial nutrition is often not initiated. After pain relief, oral nutrition can be indicated. Usually, patients recover and are discharged after a few days. The recently published International Association of Pancreatology guidelines recommend oral feeding in predicted mild pancreatitis once abdominal pain is decreasing and inflammatory markers are improving (47). A clinical trial showed that immediate oral refeeding with a normal diet is safe in predicted mild pancreatitis and leads to a shorter hospital stay (4 vs 6 days) (15). Feeding can be started with a full solid diet without needing to first start with a liquid or soft diet (28). A normalization of lipase levels before restarting oral feeding is not required (44). Finally, international guidelines from gastroenterologic and pancreatic societies, state that, regardless of disease severity, nutrition support is indicated when patients are not able to tolerate oral food for up to 7 days (5, 47).
Patients who can eat do not require additional enteral nutrition via a feeding tube. However artificial nutrition support can be supplemented in specific situation of mild pancreatitis, notably in case of severe malnutrition, which is frequent in alcoholic patients. This nutrition support has to be performed by nasoenteric tube feeding to minimize i.v. catheter infections and should be added to the per os intake.
In patients with predicted severe pancreatitis, nutritional support should be the primary therapy and may begin within 48 hours. A recent clinical trial in 60 patients found improved outcomes when nutrition was started within 48h as compared to after 7 days of fasting (43).
4. Type of Artificial Nutrition: Parenteral Versus Enteral Nutrition
Previously parenteral nutrition used to be the preferred option for the treatment of acute pancreatitis, but it placed patients on strict bowel rest and bypassed the stimulatory effects of oral feeding. The lack of the stimulatory effects of oral feeding results in gastro-intestinal atrophy with decreased villous thickness in the intestinal tract, which leads to bacterial translocation across the gut barrier, sepsis, and organ failure.
The comparison of total parenteral nutrition and total enteral nutrition in patients with predicted severe acute pancreatitis was studied in more than eight randomized controlled trials (1, 14, 16, 18, 20, 37, 38, 46). Several meta-analyses have demonstrated the benefits of enteral over parenteral nutrition: a significant 2.0-fold reduction in the risk of systemic and pancreatic infectious complications, a decrease of multi-organ failure, a reduction of the need for surgical interventions and finally a 2.5-fold reduction in the risk of mortality in patients receiving exclusively enteral nutrition (2, 26, 34, 35, 39, 49).
Regarding the international guidelines published recently parenteral nutrition can be used in acute pancreatitis as second-line therapy if nasojejunal tube feeding is not tolerated and nutritional support is required (47). However, the authors proposed that parenteral nutrition should only be started if the nutritional goals cannot be reached with oral or enteral feeding. A delay up to 5 days in initiation of parenteral nutrition may be appropriate to allow for restarting of oral or enteral feeding (2, 27).
5. Optimal Route of Enteral Nutrition Delivery
This issue has been debated regarding the “pancreatic rest” theory. It was suggested that prepyloric delivery would stimulate pancreatic secretion and, consequently increase the severity of acute pancreatitis. However, a postpyloric tube (mainly naso jejunal location) usually requires the help of an endoscopic or a radiological procedure. This may delay the nutritional support and can impact on the clinical outcome. In contrast, a nasogastric feeding tube can be inserted in every day practice immediately and does not require specific assistance. A prepyloric feeding (gastric location) can be started without delay (31).
Pancreatic Exocrine Function and Route of Enteral Nutrition Delivery
In healthy patients studies have demonstrated that all types of oral feeding stimulate exocrine pancreatic secretion. In enteral nutrition it was shown that the exocrine pancreatic response was different regarding the location of the nutrition delivery. Trypsin and lipase secretion was significantly lower in response to nutrition delivered into the jejunum in comparison with the duodenum; this secretion was not different in the group of patients with distal jejunum delivery and in the fasting group (30, 31).
In acute pancreatitis it was shown that pancreatic exocrine function is not normal and the level of pancreatic secretions decreased compared with healthy subjects. This pancreatic “stunning” is correlated with pancreatitis severity and a lower secretion of trypsin and lipase was found in patients with severe pancreatitis. These data suggest that during acute pancreatitis acinar cells are not able to respond normally to a secretory stimulus. It explains why no study demonstrated that nasogastric tube could increase inflammation and the severity of acute pancreatitis (7).
Safety and Tolerance of Enteral Nutrition Delivery Route
Several randomized controlled trials and the latest published meta-analyses have demonstrated the equivalence of nasogastric and nasojejunal tube feeding regarding safety and tolerance (10, 12, 13, 18, 19, 22, 25, 29, 32, 42).
In a recently published review, nasogastric and nasojejunal tube feeding were compared. Four randomized controlled trials and a cohort study were included and represented 131 patients who received nasogastric tube feeding for severe pancreatitis. In 107/131 (82%) patients, a total nasogastric nutrition was performed without withdrawal. In 18% of the patients, enteral nutrition was stopped because of gastric ileus, diarrhea or repeatedly dislocated feeding tubes. In a meta-analysis restricted to randomized studies, 82 patients with nasogastric administration and 75 patients with nasojejunal feeding were included. The risk of mortality and the number of nutrition-associated adverse events were similar between the two groups. In this review, nasogastric tube feeding was not associated with an increased risk of aspiration pneumonia (29).
Most recently, a meta-analysis reported data of 3 randomized controlled trials, involving a total of 157 patients. There were no significant differences in mortality, tracheal aspiration, diarrhea, exacerbation of pain and energy balance between the two groups. Nasogastric feeding was not inferior to nasojejunal feeding (10).
The international guidelines recommend that enteral nutrition in acute pancreatitis can be administered via either the nasojejunal or nasogastric route (47). The choice of the location should not delay the nutritional support. Nasogastric tube feeding is probably easier than nasojejunal tube feeding, however some patients will not tolerate nasogastric feeding because of delayed gastric emptying. It is known that patients with severe acute pancreatitis frequently present with gastric ileus because the pancreatic inflammation is close to the stomach. In addition, inflammation can lead to a transient duodenal stenosis (partial or complete). In this specific case, a nasojejunal tube feeding can be used and the tube should be placed endoscopically.
6. Type of Enteral Nutrition Formulations
More than 100 different enteral nutrition formulations are available, classified into three categories: elemental or semi-elemental, polymeric and immunoenhanced (immunonutrition and probiotics). In acute pancreatitis, (semi)elemental nutrition is usually preferred over polymeric formulation because this formulation is supposed to have a superior absorption from the intestine, less stimulation of pancreatic secretions and a better tolerance (11). A meta-analysis compared the safety and the tolerance of different enteral nutrition formulations used in acute pancreatitis. Twenty randomized controlled trials, including 1070 patients, were selected. No significant difference was observed between the formulations regarding feeding tolerance: the use of (semi)elemental versus polymeric formulation or versus supplementation of enteral nutrition with probiotics or immunonutrition. The risk of infectious complications and death did not differ significantly in any of the comparisons. The relatively inexpensive polymeric feeding formulations were associated with similar feeding tolerance and appeared as beneficial as the more expensive (semi)elemental formulations in reducing the risks of infectious complications and mortality (33, 45). Probiotics should not be used in acute pancreatitis because they were associated with a higher complication rate and mortality in one randomized trial (6).
International published guidelines recommend that either elemental or polymeric enteral nutrition formulations can be used in acute pancreatitis (47).
Nutrition plays a key role in the treatment of acute pancreatitis. When patients food intake is impaired, an adapted nutritional support is required early in the management of the disease in order to decrease the mortality and morbidity. Several meta-analyses have been published and the most appropriate modalities of artificial nutrition are well-established. Compared to parenteral nutrition enteral nutrition has been shown to have a greater clinical benefit in patients with acute pancreatitis reducing the risk of developing both, pancreatic infection and multiple organ failure. The international guidelines recommend that enteral nutrition in acute pancreatitis can be administered via either the nasojejunal or nasogastric route but the choice of administration route should not delay the nutritional support. Either elemental or polymeric enteral nutrition formulations can be used in acute pancreatitis.
- Abou-Assi S, Craig K, O'Keefe SJ. Hypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative study. Am J Gastroenterol. 97(9):2255-2262, 2002. PMID: 12358242.
- Al-Omran M, Albalawi ZH, Tashkandi MF, Al-Ansary LA. Enteral versus parenteral nutrition for acute pancreatitis. Cochrane Database Syst Rev 1):CD002837, 2010. PMID: 20091534.
- Ammori BJ. Gut barrier dysfunction in patients with acute pancreatitis. J Hepatobiliary Pancreat Surg 9(4):411-412, 2002. PMID: 12483261.
- Ammori BJ, Leeder PC, King RF, Barclay GR, Martin IG, Larvin M, et al. Early increase in intestinal permeability in patients with severe acute pancreatitis: correlation with endotoxemia, organ failure, and mortality. Gastrointest Surg May-Jun;3(3):252-262, 1999. PMID: 10481118.
- Banks PA, Freeman ML. Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol 101(10):2379-2400, 2006. PMID: 17032204.
- Besselink MG, van Santvoort HL, Buskens E, Boermeester MA, van Goor H, Timmerman HM et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, Placebo-controlled trial. Lancet 371:651-659, 2008. PMID: 18279948.
- Boreham B, Ammori BJ. A prospective evaluation of pancreatic exocrine function in patients with acute pancreatitis: correlation with extent of necrosis and pancreatic endocrine insufficiency. Pancreatology 3(4):303-308, 2003. PMID: 12890992.
- Brandtzaeg P, Halstensen TS, Kett K, Krajci P, Kvale D, Rognum TO, et al. Immunobiology and immunopathology of human gut mucosa: humoral immunity and intraepithelial lymphocytes. Gastroenterology 97(6):1562-1584, 1989. PMID: 2684725.
- Capurso G, Zerboni G, Signoretti M, Valente R, Stigliano S, Piciucchi M, et al. Role of the gut barrier in acute pancreatitis. J Clin Gastroenterol 46 Suppl:S46-S51, 2012. PMID: 22955357.
- Chang YS, Fu HQ, Xiao YM, Liu JC. Nasogastric or nasojejunal feeding in predicted severe acute pancreatitis: a meta-analysis. Crit Care 17(3):R118, 2013. PMID: 23786708.
- Duerksen DR, Bector S, Parry D, Yaffe C, Vajcner A, Lipschitz J. A comparison of the effect of elemental and immune-enhancing polymeric jejunal feeding on exocrine pancreatic function. J Parenter Enteral Nutr 26(3):205-208, 2002. PMID: 12005463.
- Eatock FC, Brombacher GD, Steven A, Imrie CW, McKay CJ, Carter R. Nasogastric feeding in severe acute pancreatitis may be practical and safe. Int J Pancreatol 28(1):23-29, 2000. PMID: 11185707.
- Eatock FC, Chong P, Menezes N, Murray L, McKay CJ, Carter CR, et al. A randomized study of early nasogastric versus nasojejunal feeding in severe acute pancreatitis. Am J Gastroenterol (2):432-439, 2005. PMID: 15667504.
- Eckerwall GE, Axelsson JB, Andersson RG. Early nasogastric feeding in predicted severe acute pancreatitis: A clinical, randomized study. Ann Surg 244(6):959-965, 2006. PMID: 17122621.
- Eckerwall GE, Tingstedt BB, Bergenzaun PE, Andersson RG. Immediate oral feeding in patients with mild acute pancreatitis is safe and may accelerate recovery--a randomized clinical study. Clin Nutr 26(6):758-763, 2007. PMID: 17719703.
- Gupta R, Patel K, Calder PC, Yaqoob P, Primrose JN, Johnson CD. 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 ≥ 6). Pancreatology 3(5):406-413, 2003. PMID: 14526151.
- Ioannidis O, Lavrentieva A, Botsios D. Nutrition support in acute pancreatitis. JOP 9(4):375-90, 2008. PMID: 18648127.
- Jiang K, Chen XZ, Xia Q, Tang WF, Wang L. Early nasogastric enteral nutrition for severe acute pancreatitis: a systematic review. World J Gastroenterol 13(39):5253-5260, 2007. PMID: 17876897.
- Jiyong J, Tiancha H, Huiqin W, Jingfen J. Effect of gastric versus post-pyloric feeding on the incidence of pneumonia in critically ill patients: observations from traditional and Bayesian random-effects meta-analysis. Clin Nutr 32(1):8-15, 2013. PMID: 22853861.
- Kalfarentzos F, Kehagias J, Mead N, Kokkinis K, Gogos CA. Enteral nutrition superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Br J Surg 84(12):1665-1669, 1997. PMID: 9448611.
- Kovacs GC, Telek G, Hamar J, Furesz J, Regoly-Merei J. Prolonged intestinal mucosal acidosis is associated with multiple organ failure in human acute pancreatitis: gastric tonometry revisited. World J Gastroenterol 12(30):4892-2896, 2006. PMID: 16937476.
- Kumar A, Singh N, Prakash S, Saraya A, Joshi YK. Early enteral nutrition in severe acute pancreatitis: a prospective randomized controlled trial comparing nasojejunal and nasogastric routes. J Clin Gastroenterol 40(5):431-434, 2006. PMID: 16721226.
- Liu H1, Li W, Wang X, Li J, Yu W. Early gut mucosal dysfunction in patients with acute pancreatitis. Pancreas 36(2):192-196, 2008. PMID: 18376312.
- Loveday BP, Srinivasa S, Vather R, Mittal A, Petrov MS, Phillips AR, et al. High quantity and variable quality of guidelines for acute pancreatitis: a systematic review. Am J Gastroenterol 105(7):1466-1476, 2010. PMID: 20606652.
- Marik PE, Zaloga GP. Gastric versus post-pyloric feeding: a systematic review. Crit Care 7(3):R46-R51, 2003. PMID: 12793890.
- McClave SA, Chang WK, Dhaliwal R, Heyland DK. Nutrition support in acute pancreatitis: a systematic review of the literature. J Parenter Enteral Nutr 30(2):143-156, 2006. PMID: 16517959.
- Mirtallo JM, Forbes A, McClave SA, Jensen GL, Waitzberg DL, Davies AR. International Consensus Guideline Committee Pancreatitis Task Force. International consensus guidelines for nutrition therapy in pancreatitis. J Parenter Enteral Nutr 36(3):284-291, 2012. PMID: 22457421.
- Moraes JM, Felga GE, Chebli LA, Franco MB, Gomes CA, Gaburri PD, et al. 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):517-522, 2010. PMID: 20054282.
- Nally DM, Kelly EG, Clarke M, Ridgway P. Nasogastric nutrition is efficacious in severe acute pancreatitis: a systematic review and meta-analysis. Br J Nutr 112(11):1769-1778, 2014. PMID: 25333639.
- O'Keefe SJ, Lee RB, Anderson FP, Gennings C, Abou-Assi S, Clore J, et al. Physiological effects of enteral and parenteral feeding on pancreaticobiliary secretion in humans. Am J Physiol Gastrointest Liver Physiol 284(1):G27-G36, 2003. PMID: 12488233.
- O'Keefe SJ, McClave SA. Feeding the injured pancreas. Gastroenterology 129(3):1129-1130, 2005. PMID: 16143153.
- Petrov MS, Correia MI, Windsor JA. Nasogastric tube feeding in predicted severe acute pancreatitis. A systematic review of the literature to determine safety and tolerance. JOP 9(4):440-448, 2008. PMID: 18648135.
- Petrov MS, Loveday BP, Pylypchuk RD, McIlroy K, Phillips AR, Windsor JA. Systematic review and meta-analysis of enteral nutrition formulations in acute pancreatitis. Br J Surg 96(11):1243-1252, 2009. PMID: 19847860.
- Petrov MS, van Santvoort HC, Besselink MG, van der Heijden GJ, Windsor JA, Gooszen HG. Enteral nutrition and the risk of mortality and infectious complications in patients with severe acute pancreatitis: a meta-analysis of randomized trials. Arch Surg 143(11):1111-1117, 2008. PMID: 19015471.
- Petrov MS, Whelan K. Comparison of complications attributable to enteral and parenteral nutrition in predicted severe acute pancreatitis: a systematic review and meta-analysis. Br J Nutr 103(9):1287-1295, 2010. PMID: 20370944.
- Powell JJ, Murchison JT, Fearon KC, Ross JA, Siriwardena AK. Randomized controlled trial of the effect of early enteral nutrition on markers of the inflammatory response in predicted severe acute pancreatitis. Br J Surg 87(10):1375-1381, 2000. PMID: 11044164.
- Pupelis G, Austrums E, Jansone A, Sprucs R, Wehbi H. Randomised trial of safety and efficacy of postoperative enteral feeding in patients with severe pancreatitis: preliminary report. Eur J Surg 166(5):383-387, 2000. PMID: 10881949.
- Pupelis G, Selga G, Austrums E, Kaminski A. Jejunal feeding, even when instituted late, improves outcomes in patients with severe pancreatitis and peritonitis. Nutrition 17(2):91-94, 2001. PMID: 11240334.
- Quan H, Wang X, Guo C. A meta-analysis of enteral nutrition and total parenteral nutrition in patients with acute pancreatitis. Gastroenterol Res Pract 2011:698248, 2011. PMID: 21687619.
- Rahman SH, Ammori BJ, Holmfield J, Larvin M, McMahon MJ. Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis. J Gastrointest Surg 7(1):26-35; discussion 35-6, 2003. PMID: 12559182.
- Ralls MW, Demehri FR, Feng Y, Woods Ignatoski KM, Teitelbaum DH. Enteral nutrient deprivation in patients leads to a loss of intestinal epithelial barrier function. Surgery 157(4):732-742, 2015. PMID: 25704423.
- Singh N, Sharma B, Sharma M, Sachdev V, Bhardwaj P, Mani K, et al. Evaluation of early enteral feeding through nasogastric and nasojejunal tube in severe acute pancreatitis: a noninferiority randomized controlled trial. Pancreas 41(1):153-159, 2012. PMID: 21775915.
- Sun JK, Mu XW, Li WQ, Tong ZH, Li J, Zheng SY. Effects of early enteral nutrition on immune function of severe acute pancreatitis patients. World J Gastroenterol 19(6):917-922, 2013. PMID: 23431120.
- Teich N, Aghdassi A, Fischer J, Walz B, Caca K, Wallochny T, et al. Optimal timing of oral refeeding in mild acute pancreatitis: results of an open randomized multicenter trial. Pancreas 39(7):1088-1092, 2010. PMID: 20357692.
- Tiengou LE, Gloro R, Pouzoulet J, Bouhier K, Read MH, Arnaud-Battandier F, et al. Semi-elemental formula or polymeric formula: is there a better choice for enteral nutrition in acute pancreatitis? Randomized comparative study. JPEN J Parenter Enteral Nutr 30(1):1-5, 2006.
- Windsor AC, Kanwar S, Li AG, Barnes E, Guthrie JA, Spark JI, et al. Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis. Gut 42(3):431-435, 1998. PMID: 9577354.
- Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology 13(4 Suppl 2):e1-e15, 2013. PMID: 24054878.
- Wu LM, Sankaran SJ, Plank LD, Windsor JA, Petrov MS. Meta-analysis of gut barrier dysfunction in patients with acute pancreatitis. Br J Surg 101(13):1644-1656, 2014. PMID: 25334028.
- Yi F, Ge L, Zhao J, Lei Y, Zhou F, Chen Z, et al. Meta-analysis: total parenteral nutrition versus total enteral nutrition in predicted severe acute pancreatitis. Intern Med 51(6):523-530, 2012. PMID: 22449657.
- Zou XP, Chen M, Wei W, Cao J, Chen L, Tian M. Effects of enteral immunonutrition on the maintenance of gut barrier function and immune function in pigs with severe acute pancreatitis. J Parenter Enteral Nutr 34(5):554-566, 2010. PMID: 20852186.