How
In order to address the question of how to feed patients with AP, this section encompasses mode of introduction (oral vs. enteral tube) and compares nasogastric versus nasojejunal routes of administration.
Reintroduction of oral intake is critical to the gut mucosal barrier and a cornerstone of AP treatment; the next step is determining how to reintroduce nutrition. The initial meal given to patients with AP is vital in determining whether reintroduction of oral intake is tolerated [30]. One of the goals to consider during reintroduction of nutrition is to minimize OFI and gut disuse, as this can precipitate villous atrophy and may prolong hospitalization. In keeping with this aim, a widely supported approach is timely introduction of low rates of enteral feed. Pupelis et al. [31] enrolled 129 patients with severe AP (without severely impaired intestinal motility) to receive early oral feeding composed of small oral boluses of standard enteral formula, usually within 48–72 hours of admission. After two days of tolerance, the enteral formula was supplemented with light food and then gradually advanced to a full diet. Volume and frequency of enteral feed boluses were increased according to each individual’s tolerance. This was followed up by a larger study in which 129 patients received early low‐volume oral (ELVO) feeds containing 248–330 kcal daily to help stimulate gastrointestinal function. Patients receiving ELVO feeding within 72 hours of admission were allocated to Group I, whereas those receiving ELVO feeds after 72 hours were allocated to Group II. The study concluded that ELVO feeding provides physiological stimulation and promotes recovery of bowel function. C‐reactive protein (CRP) levels at seven days were significantly lower in Group I; CRP levels had normalized in both groups at 14 days. The rate of infection and need for surgical intervention were significantly higher in Group II, as was length of hospitalization [31]. These authors posit that it is the supply of nutrients to the gut that is important in recovery, rather than the amount of food or nutritional status. In the MIMOSA trial [32], 35 patients with mild to moderate AP were allocated to receive either nasogastric feeding within 24 hours or kept nil by mouth until oral feeding, according to conventional protocol. Patients who received early enteral tube feeding had a significantly reduced risk of OFI, reduced need for opiates, and reduced abdominal pain. Lastly, however, the PYTHON study seemed to refute these results. In this multicenter randomized controlled trial, patients were randomly allocated to receive EN within 24 hours through a nasojejunal catheter, or given an on‐demand oral diet over the first four days (and only started EN if oral diet was not tolerated). This Dutch study did not find a significant difference between the two groups, and interpreted results as favoring feeding at three to four days after admission as an equally effective nutritional strategy. Approximately 20% of patients in this study were admitted to the intensive care unit (ICU), and around 8% had persistent MOF (>48 hours). Hence, the patients in this study might have had somewhat limited benefit from tube feeding, in terms of the composite primary end point (mortality and infection complications). Of interest, in this study of early versus late enteral tube feeding, less than one‐third of patients in the control group ultimately required tube feeding. The potential benefit of initiating early tube feeding in patients with predicted severe acute pancreatitis is supported by other evidence, including direct head‐to‐head randomized comparison of early versus late tube feeding [33], indirect meta‐analysis of randomized controlled trials, and retrospective cohort studies. The International Association of Pancreatology (IAP)/American Pancreatic Association (APA) guidelines do not have recommendations for early enteral feeding per se, but do remark that enteral tube feeding should be the primary therapy in patients with predicted severe acute pancreatitis who require nutritional support, and that patients who can eat do not require additional EN via a feeding tube. It stands to reason that the strongest evidence for impact of nutrition therapy on patient outcome is in severe AP [5]. Other guidelines also suggest early initiation of oral intake if tolerated, and tube feeding if not tolerated, but vary on the timing of initiation [23,34–36].
The IAP/APA guidelines remark that patients may not tolerate nasogastric tube feeding due to delayed gastric emptying [23]. Nasogastric tube feeding could also theoretically stimulate more pancreatic secretion. However, while the placement of a nasogastric tube is a simple routine procedure, nasojejunal tubes must be radiologically or endoscopically placed, which may cause a delay in the start of early enteral feeding. With the advent of a commercial tube including an electromagnetic GPS imaging system, post‐pyloric placement of nasoenteric tubes has become much less onerous, though a specially trained technician must be available for placement. Eatock et al. [37] were the first to consider these concerns in a prospective pilot study and found that nasogastric feeding is overall safe and well tolerated. This was followed by two randomized controlled trials that compared nasogastric and nasojejunal feeding, and which concluded that there were no differences in length of stay, surgery, and mortality rate between the two groups [38,39]. A subsequent meta‐analysis involving 157 patients concluded that there were no significant differences in terms of mortality, aspiration events, diarrhea, exacerbation of pain, or meeting caloric requirements between nasogastric and nasojejunal feeding [40]. Therefore, post‐pyloric or jejunal placement of the nasoenteric tube tip is no longer considered necessary in feeding AP patients [41–43]. Overall, nasogastric feeding, or nasoduodenal feeding tube placed by a technician, seem the most feasible options in clinical practice as they are least likely to delay initiation of EN.
All international guidelines [24,41–44] state that nutritional support in severe AP should be given by enteral feeding. EN is to be preferred to TPN even if complications such as fistulas, ascites, and pseudocysts are present [42,43]. EN is feasible and recommended even after surgery for pancreatitis (by intraoperative jejunostomy) and even in cases of gastric outlet obstruction (tube tip should be placed distal to obstruction). Prolonged paralytic ileus is a relative contraindication to EN; however, even in this case, the European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines recommend combining PN with a small amount of EN (10–30 ml/hour) continuously perfused to the jejunum [42].
What to Feed
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