What may be the ideal nutritional strategy in acute pancreatitis?

Introduction

Acute pancreatitis runs a relatively mild course in most patients and responds rapidly to supportive therapy, including adequate pain relief, intravenous fluids, and oral intake when feasible. However, the severe form of the disease is characterized by organ failures and leads to a protracted and often complicated clinical course. Nutritional support is crucial and can be challenging to the bedside intensive care physician. The optimal nutritional strategy in acute pancreatitis has been intensely debated, with a distinct change in paradigms over the years. 

How early to feed?

In mild acute pancreatitis, intravenous hydration alone may be adequate, because rapid recovery is common, and oral intake is possible within a week. However, in moderate to severe acute pancreatitis, nutritional support is usually required as early oral intake is usually not possible. 

Mild disease

Conventionally, it was widely believed that enteral feeding may lead to worsening of pain and exacerbate acute pancreatitis. Gastric feeding may stimulate the release of pancreatic enzymes, worsen autodigestion, and aggravate the disease process. Hence, conventional management has been to place patients on strict bowel rest and use parenteral nutrition to bypass the stimulatory effects of oral feeding. Current evidence suggests a low-fat diet is safe and well-tolerated in most patients with acute pancreatitis. Hence, oral nutrition is advisable as tolerated when abdominal pain eases off, and there is a subjective feeling of hunger, regardless of complete resolution of pain and normalization of pancreatic enzyme levels.

Moderate to severe disease

Severe pancreatitis leads to reduced contractility of the small bowel leading to bacterial overgrowth. Besides, reduced splanchnic blood flow increases intestinal permeability. Early commencement of enteral nutrition may have a trophic effect on gut wall integrity and may help reduce the inflammatory response. In the PYTHON trial, patients predicted to have severe acute pancreatitis were randomized to receive either early enteral nutrition through a nasoenteral feeding tube within 24 hours after presentation to the emergency department or placed on a nil-per-mouth regime for 72 hours followed by an oral diet. If oral intake was insufficient after this period, a feeding tube was inserted, and enteral nutrition commenced. The primary endpoint was a composite of major infection (infected pancreatic necrosis, bacteremia, or pneumonia) or death during 6 months of follow-up. There was no difference in these outcomes between the two groups (30% in the early vs. 27% in the later feeding group).¹

A recent systematic review of 11 randomized controlled trials (RCT) compared early vs. delayed feeding in acute pancreatitis.² This review suggested a reduced hospital length of stay with early enteral nutrition. None of the included studies showed a significant increase in the incidence of adverse events or worsening of symptoms with early feeding, regardless of disease severity.

Enteral vs. parenteral nutrition

Previously, parenteral nutrition was administered routinely in acute pancreatitis to prevent pancreatic stimulation. The traditional belief was that nutrition delivered proximal to the ligament of Treitz would stimulate the pancreas and worsen the severity of acute pancreatitis. Hence, parenteral nutrition seemed ideal for adequate nutritional support in acute pancreatitis.

Enteral feeding may have immunomodulating effects, including preservation of the integrity of the gut mucosa; it may also stimulate intestinal motility, thereby reducing bacterial overgrowth. Besides, enteral feeding may also enhance splanchnic blood flow. All these may reduce bacterial translocation from the gut, which is one of the key factors that lead to infection in acute pancreatitis. Although there is no strong corroboratory evidence, enteral nutrition may prevent infection of the necrosis and reduce mortality.

Two major RCTs have been carried comparing enteral with total parenteral nutrition. Wu et al., in a randomized controlled trial of 208 patients, showed a lower incidence of organ failure, infected necrosis, surgical intervention, and mortality with enteral nutrition.³ A smaller RCT of 70 patients also showed a lower incidence of infected necrosis, reduced organ failures, and lower mortality with enteral compared to parenteral nutrition.⁴ Three recent meta-analyses have also concluded that enteral nutrition significantly reduces infections, organ failure, and mortality in patients with acute pancreatitis compared with parenteral nutrition.^5–7 Meta-analyses are limited by heterogeneous patient groups; inclusion of patients with mild disease may have resulted in reduced mortality. Despite these limitations, early enteral nutrition is recommended in acute pancreatitis; total parenteral nutrition is indicated only if enteral nutrition is not tolerated.  

Nasojejunal vs. nasogastric feeding

Placement of a feeding tube beyond the ligament of Treitz is considered to reduce the risk of reflux of feeds back into the stomach and prevent stimulation of pancreatic enzyme release. However, it has been shown that pancreatic stimulation may be preventable only when enteral nutrition is given in the mid-distal jejunum.⁸ Three trials compared nasojejunal with nasogastric nutrition in patients with severe acute pancreatitis.^9–11 These studies suggested that nasogastric feeding may be easier, well-tolerated, and equally efficacious as nasojejunal feeding. Infectious complications and duration of stay in hospital were also comparable. There was no difference in pain on refeeding, intestinal permeability, and endotoxemia. These studies were limited by small sample sizes, and included patients at different stages of the disease, with varying severity. A meta-analysis of these three randomized trials showed no differences in mortality, the incidence of tracheal aspiration, and attainment of calorie targets between the two groups.¹²

Although the quality of the evidence is limited, when tolerated, nasogastric nutrition appears to be safe. When nasogastric nutrition is not tolerated, or when the caloric requirement cannot be attained, nasojejunal feeding beyond the ligament of Treitz is recommended.

Nutritional supplements

Probiotics

Probiotic bacteria may prevent infectious complications by inhibiting the overgrowth of pathogenic bacteria in the small bowel, restoration of gastrointestinal barrier function, and immune modulation. Hence, probiotic administration may potentially prevent pancreatic and extra-pancreatic bacterial infections. This was particularly of interest following the failure of prophylactic antibiotic therapy to prevent infections. 

The PROPATRIA trial compared probiotic prophylaxis using six different strains of freeze-dried, viable bacteria with placebo in 298 patients who were predicted to have severe acute pancreatitis.¹³ No difference was observed in the incidence of infectious complications. Besides, there was a significant increase in mortality with the use of probiotics. Nine patients suffered non-occlusive mesenteric ischemia in the probiotic group compared to none in the placebo group. A subsequent retrospective study used the same type of probiotics in patients with acute pancreatitis without organ failure.¹⁴ This study revealed no evidence of benefit or harm, suggesting that the harmful effects of probiotics may occur in patients with evidence of organ failure. Based on these findings, the current recommendation is against the use of probiotics in acute pancreatitis. 

Other supplements

The use of glutamine and omega-3 fatty acids are not recommended in acute pancreatitis. Vitamin C, N-acetylcysteine, and selenium administration have also shown no benefit. Although antioxidant vitamins, including Vitamin C, could theoretically attenuate the inflammatory reaction, no clinical benefit has been demonstrated in acute pancreatitis. 

The bottom line 

• In mild acute pancreatitis, intravenous hydration alone may suffice if oral intake is not feasible due to pain or intolerance. A low-fat diet is usually possible within a week once symptoms begin to subside.
• In severe disease, nutritional support is essential; early enteral nutrition is recommended, although the optimal timing of commencement is uncertain. 
• Nasogastric feeding may be as efficacious as feeding through the nasojejunal route; the latter is preferred if there is intolerance to gastric feeds.
• Enteral nutrition is always preferred compared to total parenteral nutrition; prolonged paralytic ileus may be an indication for parenteral nutritional support. 
• Nutritional supplements, including probiotics, glutamine, omega-3 fatty acids, and Vitamin C have not been shown to be useful.    

References

1.        Bakker OJ, van Brunschot S, van Santvoort HC, et al. Early versus On-Demand Nasoenteric Tube Feeding in Acute Pancreatitis. N Engl J Med. 2014;371(21):1983-1993. doi:10.1056/NEJMoa1404393

2.         Vaughn VM, Shuster D, Rogers MAM, et al. Early Versus Delayed Feeding in Patients With Acute Pancreatitis: A Systematic Review. Ann Intern Med. 2017;166(12):883. doi:10.7326/M16-2533

3.         Wu X-M, Ji K-Q, Wang H-Y, Li G-F, Zang B, Chen W-M. Total Enteral Nutrition in Prevention of Pancreatic Necrotic Infection in Severe Acute Pancreatitis: Pancreas. 2010;39(2):248-251. doi:10.1097/MPA.0b013e3181bd6370

4.         Petrov MS, Kukosh MV, Emelyanov NV. 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. 2006;23(5-6):336-345. doi:10.1159/000097949

5.         Yi F, Ge L, Zhao J, et al. Meta-analysis: Total Parenteral Nutrition Versus Total Enteral Nutrition in Predicted Severe Acute Pancreatitis. Intern Med. 2012;51(6):523-530. doi:10.2169/internalmedicine.51.6685

6.         Al-Omran M, AlBalawi ZH, Tashkandi MF, Al-Ansary LA. Enteral versus parenteral nutrition for acute pancreatitis. 2010:44.

7.         Petrov MS, van Santvoort HC, Besselink MGH, van der Heijden GJMG, 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 Chic Ill 1960. 2008;143(11):1111-1117. doi:10.1001/archsurg.143.11.1111

8.         Vu MK, van der Veek PP, Frölich M, et al. Does jejunal feeding activate exocrine pancreatic secretion? Eur J Clin Invest. 1999;29(12):1053-1059. doi:10.1046/j.1365-2362.1999.00576.x

9.         Eatock FC, Chong P, Menezes N, et al. A randomized study of early nasogastric versus nasojejunal feeding in severe acute pancreatitis. Am J Gastroenterol. 2005;100(2):432-439. doi:10.1111/j.1572-0241.2005.40587.x

10.       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. 2006;40(5):431-434. doi:10.1097/00004836-200605000-00013

11.       Singh N, Sharma B, Sharma M, et al. Evaluation of Early Enteral Feeding Through Nasogastric and Nasojejunal Tube in Severe Acute Pancreatitis: A Noninferiority Randomized Controlled Trial. Pancreas. 2012;41(1):153-159. doi:10.1097/MPA.0b013e318221c4a8

12.       Chang Y, Fu H, Xiao Y, Liu J. Nasogastric or nasojejunal feeding in predicted severe acute pancreatitis: a meta-analysis. Crit Care Lond Engl. 2013;17(3):R118. doi:10.1186/cc12790

13.       Besselink MG, van Santvoort HC, Buskens E, et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet Lond Engl. 2008;371(9613):651-659. doi:10.1016/S0140-6736(08)60207-X

14.       van Baal MC, Kohout P, Besselink MG, et al. Probiotic treatment with Probioflora in patients with predicted severe acute pancreatitis without organ failure. Pancreatology. 2012;12(5):458-462. doi:10.1016/j.pan.2012.08.004