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Since it has been established that prolonged nil by mouth is to be avoided (if possible) in all cases of AP, the next issue at hand is what form of nutrition should administered. According to guidelines from the American College of Gastroenterology (ACG) [15], American Gastroenterology Association (AGA) [36], and IAP/APA [23], enteral tube feeding should be the primary therapy in patients with predicted severe acute pancreatitis who require nutritional support. Parenteral nutrition should be avoided, unless the enteral route is not available, not tolerated, or not meeting caloric requirements [15,23,36]. Patients who can eat do not require additional EN via feeding tubes.

A meta‐analysis including 20 randomized controlled trials determined that there is no specific type of EN or immune nutrition that improves outcomes in acute pancreatitis [45,46]. Likewise, a 2015 Cochrane review [47] showed no beneficial effects of one specific EN formulation over another. Cochrane also specifically looked at immune nutrition formulations compared with control and found a reduction in all‐cause mortality. However, when analysis was stratified only for studies comparing it to other EN formulations, this effect could not be confirmed, and the authors remarked that all these findings are based on low‐quality evidence. With regard to safety issues of probiotic provision to critically ill patients, cases of fungemia in ICU patients associated with the use of Saccharomyces boulardii, as well as worsened clinical outcomes in severe pancreatitis, have been reported [48,49]. POPATRIA, a randomized controlled trial that investigated the use of a multispecies probiotic with Bifidobacterium in AP patients, was stopped early due to increased rate of bowel ischemia and MOF [48]. Based on the risk of adverse events, routine probiotic use cannot be recommended in the treatment of AP at this time [42].

A systematic review and meta‐analysis of the literature regarding EN formulations in AP found that the use of polymeric, compared with semi‐elemental, formulations does not lead to a significantly higher risk of feeding intolerance, infectious complications, or death in patients with acute pancreatitis [45]. Neither the supplementation of EN with probiotics, nor the use of immune nutrition, significantly improve clinical outcomes [45]. A separate meta‐analysis that investigated the effect of immune nutrition only also corroborated its lack of effectiveness [46]. Though underpowered, one small randomized prospective pilot study comparing semi‐elemental formula with polymeric formula in AP found that both formulas were similarly well tolerated (no difference in pain, bloating, or analgesic consumption). However, the semi‐elemental formula was associated with decreased weight loss and reduction in length of stay [50]. The study population was composed of patients with moderately severe pancreatitis; the authors remarked that it would not be expected that these patients would have pancreatic exocrine insufficiency, nor any difficulty tolerating a polymeric formula. Theoretically, the patients expected to benefit from an elemental formulation are those with severe pancreatitis. A retrospective cohort study using a Japanese national administrative database compared patients who received elemental formula with a control group, which received either semi‐elemental or polymeric formulation. The study found that there was no significant difference observed for in‐hospital mortality and all secondary outcomes, including sepsis, readmission, and cost [51]. The American Society for Parenteral and Enteral Nutrition and the Society of Critical Care Medicine recommend using a standard polymeric formula when initiating EN in the ICU setting [52]. ESPEN [42] and the International Consensus Guidelines [43] recommend a peptide‐based medium‐chain triglyceride oil formula to improve tolerance, which is in line with the fact that most human studies have been carried out utilizing a peptide‐based formula [53–59]. In clinical practice, it is reasonable to start EN using a standard formula and then, if not tolerated, switching to a peptide‐based formula, given the higher expense of the latter.

In terms of when patients can be weaned from EN, most AP patients on EN have more severe pancreatitis and may have ongoing MOF and/or peripancreatic fluid collections, with a higher likelihood of OFI. Oral feeding can be progressively attempted once concern for gastric outlet obstruction has resolved, provided it does not result in pain, and provided that complications are under control [42]. Tube feeds can be gradually withdrawn as intake improves.