• DOI:10.7326/M16-2533
• Corpus ID: 2025443

Early Versus Delayed Feeding in Patients With Acute Pancreatitis

@article{Vaughn2017EarlyVD,
  title={Early Versus Delayed Feeding in Patients With Acute Pancreatitis},
  author={Valerie M. Vaughn and Dmitry Shuster and Mary A M Rogers and Jason Mann and Marisa L. Conte and Sanjay Saint and Vineet Chopra},
  journal={Annals of Internal Medicine},
  year={2017},
  volume={166},
  pages={883-892}
}

• Valerie M. Vaughn, D. Shuster, +4 authors V. Chopra
• Published 16 May 2017
• Medicine
• Annals of Internal Medicine

Acute pancreatitis is a common cause of hospitalization worldwide (1), and recent data suggest that incidence is increasing (2). Treatment of pancreatitis usually consists of early recognition, aggressive intravenous hydration, pain control, and supportive monitoring. Oral intake during an episode of acute pancreatitis is believed to stimulate pancreatic exocrine activity and potentially prolong recovery. For this reason, bowel rest, including nothing-by-mouth status (NPO), has been the standard of care since at least 1950 (3). Keeping patients NPO, however, necessitates prolonged hospitalization or other forms of nutrition, both of which may increase risk for adverse events. Data suggest that enteral nutrition helps stimulate the gut and maintain its protective barrier, thus reducing bacterial overgrowth and preventing bacterial translocation and sepsis (46). Several reviews of patients with pancreatitis suggest that those who receive enteral feeding have fewer infections, shorter hospital stays, and lower mortality than those who receive total parenteral nutrition (711). In addition, enteral feeding in patients with acute pancreatitis may reduce length of hospital stay when given early (12). Despite these data, whether to feed patients with pancreatitis during an active phase of inflammation or to delay feeding until the acute phase has subsided remains controversial. Recent trials comparing early versus delayed feeding have yielded mixed results, and available guidelines are vague and contradictory (13, 14). Physician practice varies, with up to 94% of patients being placed NPO at admission (15, 16). The aim of this systematic review of randomized clinical trials was to evaluate whether early feeding affects length of hospital stay, symptoms, and clinical outcomes compared with delayed feeding in patients hospitalized with acute pancreatitis. Methods We developed a protocol (PROSPERO: CRD42015016193) and followed the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) recommendations (17). Data Sources and Searches Between 25 March 2015 and 6 January 2017, a medical librarian (M.L.C.) performed serial literature searches for randomized controlled trials in the following databases: MEDLINE via Ovid (start date, 1950), EMBASE (start date, 1946), the Cochrane Library (start date, 1948), CINAHL (start date, 1960), and Web of Science (start date, 1996). Searches designed for each database included controlled vocabulary terms (for example, Medical Subject Headings) when available, combined with keywords to represent concepts, including pancreatitis, fast, NPO, delayed feeding, and enteral nutrition (see the Appendix for all search details). No restrictions were placed on publication date, language, or completion status. We also searched ClinicalTrials.gov (23 December 2016), hand-searched bibliographies of trials and reviews, and contacted content experts. Study Selection Randomized controlled trials were eligible for inclusion if they compared early versus delayed enteral nutrition in adults hospitalized with a diagnosis of acute pancreatitis. In keeping with prior reviews and guidelines (18, 19), we defined early feeding as feeding initiated at or within 48 hours of hospitalization and delayed feeding as feeding initiated more than 48 hours after hospitalization. Studies were excluded if they compared enteral versus parenteral nutrition, compared one form of enteral nutrition with another without varying timing of feeding, or compared one type of feeding formula with another. We considered studies published in any language and in full-text, abstract, or poster form eligible for inclusion. Two authors (V.M.V. and D.S.) independently determined study eligibility; when necessary, differences in opinion were resolved by a third author (V.C.). Interrater agreement for study eligibility and data abstraction was assessed using the Cohen coefficient. Study authors were contacted to ascertain study eligibility or clarify data. Data Extraction and Quality Assessment Data were extracted from included studies independently and in duplicate by 2 authors (V.M.V. and D.S.) using a template adapted from the Cochrane Collaboration (20). Information on the number and type of patients, definitions of early and delayed feeding, type of feeding, and outcomes (length of hospital stay, mortality, readmission, and symptoms) was extracted. Two authors (V.M.V. and D.S.) independently assessed risk of bias in included trials for the outcome of length of stay by using the Cochrane Collaboration tool (20). Studies that met low-risk criteria in each of the 6 domains were designated as having low risk of bias. Studies were classified as having unclear risk of bias if methodological data were missing. Because blinding of patients and clinicians was not feasible and blinding of data collectors and outcome adjudicators was unlikely to affect length of stay, we considered all studies to be at low risk of bias for the blinding domain. Data Synthesis and Analysis We qualitatively synthesized results of studies that included patients with mild to moderate pancreatitis separately from those that included patients with severe pancreatitis. Our main outcomes of interest were length of hospital stay, mortality, and readmission. Secondary outcomes included feeding intolerance, nausea, vomiting, recurrent abdominal pain, and necrotizing pancreatitis. We reported length of stay using the summary statistic (mean or median) provided by individual studies. One study (21) had 2 early-feeding groups, so the means and SDs of the groups were combined (20). For this study, the number of patients in each group was not provided, so an equal split was assumed. For the remaining outcomes, risk differences were calculated as the difference in the proportion of patients in each group who developed an adverse event. Because of clinical heterogeneity of patient populations, feeding protocols, and reported outcomes, meta-analysis was not performed. Role of the Funding Source No funding was received for the preparation of this manuscript. Dr. Chopra is supported by a career development award from the Agency for Healthcare Research and Quality (1-K08-HS022835-01), which had no role in study design; collection, analysis, or interpretation of data; or writing of the report. Results Search Results and Study Details A total of 1212 citations were retrieved by our search. An additional 107 studies were obtained through review of references and ClinicalTrials.gov. Of these 1319 citations, 8 peer-reviewed randomized clinical trials (2229) and 3 conference abstracts (21, 30, 31) that included 948 patients met eligibility criteria (Figure 1). Interrater agreement for study eligibility was 0.86. Eight studies were conducted in Europe, and the other 3 were done in New Zealand, the United States, and China. Figure 1. Flow diagram of study selection. RCT= randomized clinical trial. Four of the 11 trials were determined to have low risk of bias using the Cochrane tool (Table 1 and Appendix Table) (24, 26, 28, 29). The Cohen coefficient for adjudication of study bias was 0.87. Table 1. Characteristics of Included Randomized Clinical Trials Appendix Table. Risk of Bias in Studies Comparing Early Versus Delayed Feeding in Patients With Acute Pancreatitis Patient Characteristics Acute pancreatitis was uniformly defined across studies as 2 or more of the following: typical abdominal pain, a serum lipase or amylase level at least 3 times the upper limit of normal, and characteristic findings on imaging. Patients with chronic (24, 26, 28, 29), recurrent (25), postendoscopic retrograde cholangiopancreatography (24, 28), or tumor-related (24, 28) pancreatitis were variably excluded from studies. Most studies (24, 2630) followed the usual standard of care (for example, intravenous fluids or pain control) for patients with pancreatitis; however, 3 studies (22, 23, 25) included intravenous antibiotics, and 1 (23) included intermittent parenteral nutrition. Total parenteral nutrition was permitted at the treating physician's discretion in 3 of the 11 studies (23, 24, 28). Severity of pancreatitis was variably defined and included such assessments as the Atlanta criteria, APACHE (Acute Physiology and Chronic Health Evaluation) score, Ranson criteria, computed tomography classification, or organ failure; however, APACHE II scores were used most frequently (Table 1) (2226). Four studies included patients with predicted moderate to severe (25) or severe (2224) pancreatitis. The incidence of severe pancreatitis in these studies varied from 27% to 100%, and mean APACHE II scores varied from 9.8 to 11 (22, 24, 25). The 7 remaining studies included patients with mild (21, 26, 27, 29, 31) or mild to moderate (28, 30) pancreatitis. Route of Feeding For studies of patients with mild to moderate pancreatitis, the route of feeding in the early group varied: 4 administered oral feeding (26, 27, 29, 31), and 2 administered nasogastric feeding (28, 30). One study (21) randomly assigned patients in the early group to either early oral or early nasoenteric feeding. All control groups in studies of patients with mild to moderate pancreatitis were fed orally. In contrast, all 4 studies of patients with predicted severe pancreatitis provided the early group with nasojejunal feeding, whereas the delayed group received either oral (22, 24, 25) or nasojejunal feeding (23). Oral diets varied from white bread with jam and tea (27) to regular diet. One study randomly assigned patients in each group to receive a full-calorie diet or stepwise increases in nutrition (29). Generally, patients who did not tolerate an oral diet were kept NPO or were provided nasoenteric or parenteral nutrition at the treating physician's discretion. In general, enteral feeding had no minimum duration; however, in the largest trial (25), patients who received early enteral nutrition were required to receive it for 7 days per