Early oral protein-containing diets following elective lower gastrointestinal tract surgery in adults: a meta-analysis of randomized clinical trials

Background Although current guidelines make consensus recommendations for the early resumption of oral intake after surgery, a recent comprehensive meta-analysis failed to identify any patient-centered benefits. We hypothesized this finding was attributable to pooling studies providing effective protein-containing diets with ineffective non-protein liquid diets. Therefore, the aim of this paper was to investigate the safety and efficacy of early oral protein-containing diets versus later (traditional) feeding after elective lower gastrointestinal tract surgery in adults. Methods PubMed, Embase, and the China National Knowledge Infrastructure databases were searched from inception until 1 August 2019. Reference lists of retrieved studies were hand searched to identify randomized clinical trials reporting mortality. No language restrictions were applied. Study selection, risk of bias appraisal and data abstraction were undertaken independently by two authors. Disagreements were settled by obtaining an opinion of a third author. Majority decisions prevailed. After assessment of underlying assumptions, a fixed-effects method was used for analysis. The primary outcome was mortality. Secondary outcomes included surgical site infections, postoperative nausea and vomiting, serious postoperative complications and other key measures of safety and efficacy. Results Eight randomized clinical trials recruiting 657 patients were included. Compared with later (traditional) feeding, commencing an early oral protein-containing diet resulted in a statistically significant reduction in mortality (odds ratio [OR] 0.31, P = 0.02, I2 = 0%). An early oral protein-containing diet also significantly reduced surgical site infections (OR 0.39, P = 0.002, I2 = 32%), postoperative nausea and vomiting (OR 0.62, P = 0.04, I2 = 37%), serious postoperative complications (OR 0.60, P = 0.01, I2 = 25%), and significantly improved other major outcomes. No harms attributable to an early oral protein-containing diet were identified. Conclusions The results of this systematic review can be used to upgrade current guideline statements to a grade A recommendation supporting an oral protein-containing diet commenced before the end of postoperative day 1 after elective lower gastrointestinal surgery in adults. Supplementary Information The online version contains supplementary material available at 10.1186/s13741-021-00179-3.

© 2020 Gordon S Doig, University of Sydney. All rights reserved. This publication is protected by copyright. No part of it may be reproduced for commercial purposes or distributed electronically without prior written permission of the publisher. Reproduction for personal or educational use is acceptable.  The EMTREE terms used to identify the nutritional support literature included:

Contents
diet therapy/ or nutritional support/ or nutritional disorder/ or nutritional assessment/ or nutritional deficiency/ or feeding behaviour/ or nutritional status/ or overnutrition/ These nutrition related terms were crossed with EMTREE terms to restrict the results to RCTs conducted in large bowel surgery patients: (random or clinical trial or randomised or randomized or randomized controlled trial or randomised controlled trial).mp AND (surgery or surgical or operat$ or post-operat$ or postoperat$).tw AND (lower gastrointestinal or large bowel or colectomy or colostomy or colorectal or colon or rectal or rectum).tw China National Knowledge Infrastructure search terms: The CNKI subject heading terms used to identify the nutritional support literature included: Mortality not explicitly reported. Both groups received early protein.
Clear liquid diet commenced on POD 2.
No early protein.

Binderow 3 1994
Elective laparotomy with either a colonic or ileal resection.
Regular solid food on morning of POD 1.
Mortality not explicitly reported.
No early protein.

Chatterjee 5 2012
Gastrointestinal anastomosis and uncomplicated simple biliary-enteric anastomosis (choledochoduodenosto my) on an emergency or elective basis.
"Oral liquids" (25ml/hr) were started within 24 hours of operation in group A with clamping the NGT.
Early protein possible, but not explicit in protocol. 'Oral liquids' protein content not described.

Chen 6 2015
Surgery for colorectal cancer.
Water was started on POD 1, water and a small amount of EN was taken repeatedly on POD 2. 1L of EN was taken repeatedly on POD 3 followed by a small amount of liquid food.
No early protein.
Mortality not explicitly reported.

Chen 7 2010
Surgery for colorectal cancer.
Liquid diet was began within 24 hours after surgery, and then gradually continued to solid diet.
Mortality not explicitly reported.
Early protein possible, but not explicit in protocol. 'Oral liquid diet' protein content not described.

Dag 9 2011
Colorectal surgery Postoperative oral feeding commencing approximately 12 hours after the operation with a "fluid diet".
Early protein possible, but not explicit in protocol. 'Fluid diet' protein content not described.

Delaney 10 2003
Patients scheduled for elective segmental intestinal or rectal resection by laparotomy.
On Postoperative Day (POD) 1, patients were encouraged to walk at least one circuit of the nursing floor (approximately 60 meters) up to five times, to sit out of bed between walks, and to do regular incentive spirometry. They were allowed noncarbonated liquids ad libitum and were offered solid food that evening if tolerating oral fluids.
Mortality not explicitly reported.
Patients began fluids on the first postoperative day and advanced to a regular diet within the next 24-48 h, as tolerated (indicated by an absence of vomiting or abdominal distension).
Early protein possible, but not explicit in protocol. 'Fluids' protein content not described.
Patients were 'allowed to drink' the day after the operation, eat a soft diet the following day regardless of the passage of flatus, and were then advanced to solid food as tolerated.
Early protein possible, but not explicit in protocol. 'Fluids' protein content not described.

Han 13 2012
Surgery for colorectal cancer.
Liquid diet was began within 6-8 hours.
Mortality not explicitly reported.

Han-Geurts 14 2001
Elective abdominal surgery including open colonic surgery and transabdominal central vascular reconstruction procedures.
Patients were assigned to a patient-controlled (PC) diet after surgery of a fixed regimen (FR). Patients in the PC group chose when to start an oral diet. There was no motivation to start early. Patients in the FR group started water on POD 0 and 1. On POD 2 a 'liquid diet' was commenced. Liquid diet was defined as water, tea, coffee, lemonade.
No early protein.
Patients were assigned to a conventional dietary regimen or a diet of their own choice. There was no motivation to start early. Patients in the conventional diet group started water on POD 0 and 1. POD 2 and 3, they continued with a 'liquid diet' defined as water, tea, coffee and lemonade.
No early protein.
Commence 'liquid diet' on POD 1, advance to regular diet when they consumed 1L in 24 h.
Early protein possible, but not explicit in protocol. Protein content of 'liquid diet' not described. He 17 2016 Elective resection for colorectal carcinoma.
Water was began on POD 1, followed by 500ml of enteral nutrition on POD 2. No early protein.
Mortality not explicitly reported. ©2020 Gordon S. Doig, University of Sydney.
Immediate post-op elemental diet via jejunostomy catheter vs. IV glucose.
Not lower GI tract surgery. Mortality not explicitly reported. Kemen 19 1995 Upper GI malignancies.
On POD 1, patients were randomized to receive either the arginine, RNA, and omega-3 fatty acids supplemented diet or an isocaloric and isonitrogenous placebo diet.
Not lower GI tract surgery. Both groups received early protein.
Patients were allowed to take water (less than 1 L) immediately after the operation. They progressed to semifluid diet on POD 1 and commenced a regular diet in 2 days after surgery.
Early protein possible, but not explicit in protocol. Protein content of 'semifluid diet' not described.
Pre-op carbohydrate and Post-op protein drink (factorial design). In the postoperative period patients were given polymeric nutritional supplement drink or placebo (600 ml/day) from the period immediately after their operation until discharge. Patients in the supplement group consumed Fortifresh (Numico, Zoetermeer, the Netherlands). All patients received "free fluids permitted immediately after surgery and a light diet as tolerated by the patient." Both groups received early protein. This trial compares 'standard' early protein (light diet from POD 1) to 'standard' early protein (light diet from POD 1) plus protein supplement drink.

Lucha 23 2005
Elective open GI surgery. Over half procedures were lower GI.
Early management consisted of bowel rest for 8 hours after completion of surgery followed by a regular diet. Traditional management consisted of bowel rest until the passage of flatus, followed by 24 hours of clear liquids and advancement to a regular diet.
Mortality not explicitly reported.
Both groups received early protein. This trial compares 'normal' early protein (normal diet from POD 1) to 'normal' early protein (normal diet from POD 1) plus protein supplement drink.
Early feeding after surgery was initiated by filtrate liquids within 24 h after surgery. Over the next 24 h, the liquid diet was replaced by a normal diet in case tolerance was desirable.
Early protein possible, but not explicit in protocol. Protein content of 'filtrate liquids' not described. Normal diet introduced later than 24 h after surgery. Nessim 26 1999 Patients without stoma who underwent anorectal reconstructive surgery.
Study intervention (bowel confinement) patients received a clear liquid diet with loperamide 4 mg by mouth three times per day for three days, with codeine phosphate 30 mg by mouth four times per day for three postoperative days after the operation. Patients in the regular diet group began a regular diet on the day of surgery.
Mortality not explicitly reported.
Patients in the early feeding group began a clear liquid diet on the first postoperative day and advanced to a regular diet within the next 24 to 48 hours, as tolerated (absence of vomiting or abdominal distention). Control group received NPO until resolution of ileus.
No early protein.
Clear liquid diet started at the 24 hour mark after surgery. Full fluid diet offered within 48 h and solid diet over next 24 h.
No early protein.
Water was began within 2 hours of surgery and then a small amount of enteral nutrition was began after 2 hours, with total amount less than 600ml.
Mortality not explicitly reported.
Water was began on POD 1, followed by water and 500ml of enteral nutrition on POD 2.
Mortality not explicitly reported. No early protein. Ryan 31 1981 Elective colectomy.
Mortality not explicitly reported.

Sagar 32 1979
Major GI surgery. (>70% lower GI tract surgery) Starting POD 1, for the first 24 hours elemental solution (Flexical) was infused at half strength solution at 25 ml/hour. Thereafter, undiluted Flexical was infused at 25 ml/hour on the second postoperative day, 50 ml/hour on the third postoperative day, and 100 ml/hour on the fourth and fifth days. Conventional patients received NPO for two days.
Mortality not explicitly reported.
Pre-op carbohydrate and Post-op protein drink (factorial design). Protocol does not prescribe early normal diet or early protein drink intake. All patients received standard postoperative care with commencement of free fluids and reintroduction of normal diet without interference by the study team or protocol. Patients randomized to standard diet plus supplement were encouraged to drink Fortisip (Nutricia) ad libitum in small, frequent quantities between meals.
No early protein.

Soliani 36 2001
Major surgery of the abdomen and pelvis.
Compares early PN vs. early EN vs. early immunoenhanced EN. No differences in time to receiving protein between groups (ePN, eEN and eEIN).
All three groups received early protein.
Water was began on POD 1, followed by water and 500ml of enteral nutrition on POD 2 Mortality not explicitly reported. No early protein.
POD 1: Began small amount of water orally; POD 2: progressed to Enteral Nutrition (Jevity, Abbott) 500 ml and water; POD 3: EN 1000 ml and Liquid diet on the third POD (Jevity, Abbott) 1000 ml , added Liquid diet on the fourth, and continued on the fifth POD .
No early protein. Both groups received early protein.

Xu 43 2012
Postoperative colorectal cancer Water was began within 6 hours after surgery, enteral nutrition was started on POD 1.
Mortality not explicitly reported.

Yang 44 2013
Postoperative colorectal cancer Oral intake of 30ml to 50ml Ensure (US Abbott) 6 to 12 hours postsurgery at 1-to 2-hours intervals. Progressed to 100ml to 200ml Ensure at 2-to 3-hours intervals on POD 2. POD 3 to 4; started with liquid diet and gradually changed to a regular diet .
Mortality not explicitly reported.
Early feeding patients were provided immediately water and gradually to a liquid fiberless diet after one day, and a semi-liquid fiber diet after three days. Control patients commenced nutrition after passage of flatus.
Mortality not explicitly reported. Early protein possible, but not explicit in protocol. Protein content of 'liquid fiberless diet' not described. CNKI: Identfied by searching China National Knowledge Infrastructure, EN: enteral nutrition, PN: refers to a parenteral nutrition solution containing protein.