| Abstract|| |
Background/Aim: The objective of the study is to clarify whether early oral refeeding (EORF) and quickly increasing diet (QID) are of benefit to patients with mild acute pancreatitis compared with a traditional oral refeeding strategy.
Materials and Methods: Studies were searched in PubMed, Cochrane library, ScienceDirect, SpringerLink, China Biology Medicine disc and Embase. A meta-analysis was then performed, using relapse of abdominal pain, nausea/vomiting, and length of hospital stay (LOHS) as the evaluation indices.
Results: Eight trials met the inclusion criteria. For the oral refeeding time group, EORF could significantly decrease the LOHS (mean deviation [MD] −1.97; 95% confidence interval (CI) −3.32 to −0.62;P = 0.004), and there was no significant difference for relapse of abdominal pain (relative risk [RR] 1.17; 95% CI 0.69–2.00;P = 0.56) or nausea/vomiting (RR 1.30; 95% CI 0.19–8.82;P = 0.79) when compared with conventional oral refeeding. For the oral refeeding material group, there was no significant difference for relapse of abdominal pain (RR 0.86; 95% CI 0.53–1.40;P = 0.54), nausea/vomiting (risk difference −0.01; 95% CI −0.19–0.18;P = 0.94), or LOHS (MD −0.88; 95% CI −2.24–0.48;P = 0.20) between the QID and stepwise increasing diet groups.
Conclusion: Pure EORF or QID caused no damage to patients with mild acute pancreatitis, and EORF could significantly decrease the LOHS.
Keywords: Abdominal pain, acute pancreatitis, oral refeeding, length of hospital stay
|How to cite this article:|
Zhang J, Zhu S, Tan D, Ma A, Yang Y, Xu J. A meta-analysis of early oral refeeding and quickly increased diet for patients with mild acute pancreatitis. Saudi J Gastroenterol 2019;25:14-9
|How to cite this URL:|
Zhang J, Zhu S, Tan D, Ma A, Yang Y, Xu J. A meta-analysis of early oral refeeding and quickly increased diet for patients with mild acute pancreatitis. Saudi J Gastroenterol [serial online] 2019 [cited 2021 Jan 24];25:14-9. Available from: https://www.saudijgastro.com/text.asp?2019/25/1/14/241426
| Introduction|| |
Acute pancreatitis is one of the most common acute abdominal pains that causes hospitalization worldwide; the annual incidence ranges from 13 to 45 per 100,000 persons. Acute pancreatitis results in nearly 250,000 hospitalizations in the United States each year, incurring costs of approximately 2.2 billion dollars., In the United Kingdom, the incidence of pancreatitis increased from 14.8 in 100,000 (1990–1994) to 31.2 in 100,000 (2010–2013) in males, and from 14.5 to 28.3 in 100,000 in females (2010–2013). It seriously threatens people's health and places a huge economic burden on society.
The majority of cases are classified as mild, and oral refeeding is an important step in the course of recovery in patients with mild acute pancreatitis, and its tolerance is the basic condition for discharge. Traditionally, the timing and method of restart of oral feeding after mild acute pancreatitis is based on experience rather than scientific research.
Some scholars have investigated oral refeeding time and materials for patients with acute pancreatitis. For the oral refeeding time, the traditional view considers that oral refeeding should not be performed before the abdominal pain is controlled, gastrointestinal function is recovered, and pancreatic enzymes are normalized. By contrast, some researchers believe that normalization of serum lipase is not obligatory  and early oral refeeding (EORF), based on returning bowel sounds, feeling of hunger, or immediate oral feeding, is feasible and safe and might accelerate recovery in mild acute pancreatitis., Most of the trials of EORF were performed in patients with mild acute pancreatitis. For patients with moderate and severe acute pancreatitis, a prospective randomized controlled clinical trial  confirmed the effectiveness and feasibility of EORF based on hunger, which could shorten the length of hospitalization.
In terms of oral refeeding material, the conventional stepwise refeeding protocol starts with a clear liquid diet, and if it is well tolerated, a light diet and full diet are introduced consecutively until the patient can tolerate a full oral diet. Some trials have shown that a full solid diet or a soft diet as the initial meal is well tolerated and may lead to a shorter total length of hospitalization compared with that achieved using a stepwise increasing diet (SID) in mild acute pancreatitis.,,,,
Although differences exist between the traditional and the latest opinions, there has been no large multicenter randomized controlled trial to determine the optimal solution. Therefore, we performed this meta-analysis to compare previous studies to identify the best schedule, which will allow clinicians to select a more effective and safe refeeding strategy for patients with mild acute pancreatitis.
| Methods|| |
Searching for studies
Two independent reviewers searched the following databases: PubMed, Cochrane library, ScienceDirect, SpringerLink, China Biology Medicine disc and Embase.
They combined the following search terms with different forms as much as possible to avoid publication bias: “pancreatitis,” “pancreatic inflammation,” “refeeding,” “oral refeeding,” and “oral nutrition.”
All published control trials in the last 10 years, written in English, comparing “oral refeeding time” or “oral refeeding material” between the traditional and the latest opinions were included. The criteria for traditional opinion for starting oral refeeding were as follows: abdominal pain was controlled, gastrointestinal function was recovered, and pancreatic enzymes became normalized (conventional oral refeeding [CORF]), a clear liquid diet should be first performed for the stepwise refeeding protocol (SID). For refeeding according to the latest opinion, oral refeeding was performed earlier (EORF) and started with a full solid diet or a soft diet (quickly increasing diet [QID]).
The selected studies were all nonrandomized comparative studies; therefore, they were evaluated using the Methodological Index for Nonrandomized Studies (MINORS), which includes 12 items: a clearly stated aim, inclusion of consecutive patients, prospective collection of data, end points appropriate to the aim of the study, unbiased assessment of the study end point, follow-up period appropriate to the aim of the study, loss to follow-up less than 5%, prospective calculation of the study size, an adequate control group, contemporary groups, baseline equivalence of groups, and adequate statistical analyses. These items are scored 0 (not reported), 1 (reported but inadequate), or 2 (reported and adequate). Publications scoring ≥18 (the maximum possible score was 24) were included.
Screening studies and extracting data
Clinical controlled trials that met the inclusion criteria were screened. All these steps mentioned above were performed independently by two reviewers and then cross-checked to rule out discrepancies; different opinions were resolved by discussion or with the aid of a senior investigator.
Relative risk (RR), risk difference (RD), mean deviation (MD), and 95% confidence interval (CI) were used as statistical indices and statistical significance was represented as P < 0.05. RevMan 5.1 provided by the Cochrane Collaboration was used to perform this meta-analysis and according to the degree of heterogeneity, a fixed or random-effect model was used. The χ2 test was used to assess heterogeneity and significance set at P < 0.10. The quantity I2, which describes the percentage of total variation that is caused by heterogeneity rather than chance, was also used to evaluate heterogeneity. An I2 value of 0–25% indicates no significant heterogeneity, 26–50% indicates low heterogeneity, 51–75% indicates moderate heterogeneity, and 76–100% indicates high heterogeneity. When I2 >50%, the random-effect model was performed. Otherwise, the fixed-effect model was used.
| Results|| |
Quantity of the included studies
A search of databases identified a total of 530 references (PubMed 56, Cochrane library 24, ScienceDirect 267, SpringerLink 159, China Biology Medicine disc 16, Embase 8).
After scanning the titles and abstracts, and removing duplications, 18 references remained for intensive reading and assessment using MINORS. Finally, eight trials remained to perform this meta-analysis [Figure 1]: four trials to analyze oral refeeding time ,,, [Table 1], and five trials to analyze oral refeeding material ,,,, [Table 2].
|Table 2: Information from the selected studies for oral refeeding material|
Click here to view
Oral refeeding time
The four analyzed trials included 388 patients in this analysis and we assessed the difference between EORF and CORF in terms of abdominal pain, nausea/vomiting, and length of hospital stay (LOHS).
For abdominal pain, the χ2 and I2 were 0.82 (P = 0.67 > 0.1) and 0%, respectively, suggesting homogeneity among the studies. The fixed-effect model was used and the results showed no significant difference (RR 1.17; 95% CI 0.69–2.00; P = 0.56) [Figure 2]a. The included studies were heterogeneous for the comparison of nausea/vomiting (χ2 = 3.56, P = 0.06 < 0.1; I2 = 72%). Thus, the random-effect model was used and the results revealed no significant differences (RR 1.30; 95% CI 0.19–8.82; P = 0.79) [Figure 2]b. For LOHS, the results showed that the included studies were heterogeneous (χ2 = 11.57, P = 0.009 < 0.1; I2 = 7 4%) and the use of EORF could significantly decrease the LOHS (MD −1.97; 95% CI −3.32 to −0.62; P = 0.004) [Figure 2]c.
|Figure 2: Results of meta-analysis for oral refeeding time: (a) results for abdominal pain (P = 0.56); (b) results for nausea/vomiting (P = 0.79); (c) results for length of hospital stay (P = 0.004)|
Click here to view
Oral refeeding material
Five trials including 457 patients participated in this analysis and we assessed the difference between QID and SID in terms of abdominal pain, nausea/vomiting, and LOHS.
For abdominal pain, the χ2 and I2 were 1.47 (P = 0.69 > 0.1) and 0%, respectively, suggesting homogeneity among the studies. The fixed-effect model was used and the results showed no significant difference (RR 0.86; 95% CI 0.53–1.40; P = 0.54) [Figure 3]a. The included studies were heterogeneous for nausea/vomiting (χ2 = 3.07, P = 0.08 < 0.1; I2 = 67%). Thus, the random-effect model was used and the results revealed no significant difference (RD −0.01; 95% CI −0.19–0.18; P = 0.94) [Figure 3]b. For LOHS, the results showed that the included studies were heterogeneous (χ2 = 30.14, P ≤ 0.00001; I2 = 87%); however, there was no significant difference between QID and SID (MD −0.88; 95% CI −2.24–0.48; P = 0.20) [Figure 3]c.
|Figure 3: Results of meta-analysis for oral refeeding material: (a) results for abdominal pain (P = 0.54); (b) results for nausea/vomiting (P = 0.94); (c) results for length of hospital stay (P = 0.20)|
Click here to view
| Discussion|| |
Acute pancreatitis seriously harms human health, with high morbidity and mortality rates. Indeed, the overall mortality rate could reach 5% and in the most severe cases may be as high as 30%. Thus, the present meta-analysis was performed to determine a better schedule in terms of oral refeeding time and material for patients with acute pancreatitis.
For the oral refeeding time, the results showed that EORF, based on bowel sounds being present, subjective feelings of hunger, or abdominal pain relief, could significantly decrease the LOHS and did not increase the incidence of abdominal pain or nausea/vomiting. For the oral refeeding material, the differences of abdominal pain, nausea/vomiting, and LOHS between QID and SID were not significant.
From the included articles, we observed that in the oral refeeding time group, most of the patients received SID. While in the oral refeeding material group, most of the patients started oral refeeding when the signs and symptoms of acute pancreatitis resolved, i.e., they received CORF. We assumed that EORF-combined QID could be more beneficial to patients. One article  compared Group I (standard time + stepwise increasing caloric intake), Group II (early refeeding + stepwise increasing caloric intake), Group III (standard time + immediate full caloric intake), and Group IV (early refeeding, immediate full caloric intake), and the results showed EORF-combined QID was safe and well tolerated. However, the sample size was small; thus, a large multicenter study should be performed to confirm these conclusions.
In this meta-analysis, the included patients had mild acute pancreatitis, and only one article  compared patients with moderate and severe acute pancreatitis for EORF; the results showed that EORF could shorten the LOHS in patients with moderate or severe acute pancreatitis and did not increase incidence of adverse events or complications. However, its small sample size limited its wider clinical application, and a large multicenter clinical trial is required.
For other studied oral refeeding materials, like pancreatic enzymes, glutamine, or placebo supplementation,, large-scale studies are required to obtain more reliable results for clinical application.
| Conclusion|| |
Pure EORF or QID causes no harm to patients with mild acute pancreatitis, and EORF could significantly decrease the LOHS. Combined EORF and QID for patients with mild disease, and EORF for patients with moderate and severe disease, appear to be safe and well tolerated and could shorten LOHS; however, a larger sample size is needed to obtain more accurate results.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology 2013;144:1252-61.
Fagenholz PJ, Fernández-del Castillo C, Harris NS, Pelletier AJ, Camargo CA Jr. Direct medical costs of acute pancreatitis hospitalizations in the United States. Pancreas 2007;35:302-7.
Lowenfels AB, Maisonneuve P, Sullivan T. The changing character of acute pancreatitis: Epidemiology, etiology, and prognosis. Curr Gastroenterol Rep 2009;11:97-103.
Hazra N, Gulliford M. Evaluating pancreatitis in primary care: A population-based cohort study. Br J Gen Pract 2014;64:e295-301.
Meier R, Beglinger C, Layer P, Gullo L, Keim V, Laugier R, et al.
ESPEN guidelines on nutrition in acute pancreatitis. European society of parenteral and enteral nutrition. Clin Nutr 2002;21:173-83.
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 2010;39:1088-92.
Lariño-Noia J, Lindkvist B, Iglesias-García J, Seijo-Ríos S, Iglesias-Canle J, Domínguez-Muñoz JE, et al.
Early and/or immediately full caloric diet versus standard refeeding in mild acute pancreatitis: A randomized open-label trial. Pancreatology 2014;14:167-73.
Li J, Xue GJ, Liu YL, Javed MA, Zhao XL, Wan MH, et al.
Early oral refeeding wisdom in patients with mild acute pancreatitis. Pancreas 2013;42:88-91.
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 2007;26:758-63.
Pupelis G, Snippe K, Plaudis H, Rudakovska M. Early oral feeding in acute pancreatitis: An alternative approach to tube feeding. Preliminary report. Acta Chir Belg 2006;106:181-6.
Zhao XL, Zhu SF, Xue GJ, Li J, Liu YL, Wan MH, et al.
Early oral refeeding based on hunger in moderate and severe acute pancreatitis: A prospective controlled, randomized clinical trial. Nutrition 2015;31:171-5.
Rajkumar N, Karthikeyan VS, Ali SM, Sistla SC, Kate V. Clear liquid diet vs. soft diet as the initial meal in patients with mild acute pancreatitis: A randomized interventional trial. Nutr Clin Pract 2013;28:365-70.
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 2010;44:517-22.
Sathiaraj E, Murthy S, Mansard MJ, Rao GV, Mahukar S, Reddy DN, et al.
Clinical trial: Oral feeding with a soft diet compared with clear liquid diet as initial meal in mild acute pancreatitis. Aliment Pharmacol Ther 2008;28:777-81.
Jacobson BC, Vander Vliet MB, Hughes MD, Maurer R, McManus K, Banks PA, et al.
A prospective, randomized trial of clear liquids versus low-fat solid diet as the initial meal in mild acute pancreatitis. Clin Gastroenterol Hepatol 2007;5:946-51.
Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J, et al.
Methodological index for non-randomized studies (minors): Development and validation of a new instrument. ANZ J Surg 2003;73:712-6.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.
Janisch NH, Gardner TB. Advances in management of acute pancreatitis. Gastroenterol Clin North Am 2016;45:1-8.
Kahl S, Schütte K, Glasbrenner B, Mayerle J, Simon P, Henniges F, et al.
The effect of oral pancreatic enzyme supplementation on the course and outcome of acute pancreatitis: A randomized, double-blind parallel-group study. JOP 2014;15:165-74.
Singh N, Mishra SK, Sachdev V, Sharma H, Upadhyay AD, Arora I, et al.
Effect of oral glutamine supplementation on gut permeability and endotoxemia in patients with severe acute pancreatitis: A randomized controlled trial. Pancreas 2014;43:867-73.
Prof. Jiyang Xu
Clinical Medical College of Yangzhou University, Subei People's Hospital, Nantong West Road, 98Yangzhou 225001, Jiangsu Province
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]