BMJ 2001;323:773-776 ( 6 October )

Papers

Early enteral feeding versus "nil by mouth" after gastrointestinal surgery: systematic review and meta-analysis of controlled trials

Editorial by Silk and Gow

Stephen J Lewis, consultant a, Matthias Egger, senior lecturer in epidemiology and public health medicine b, Paul A Sylvester, specialist registrar c, Steven Thomas, senior lecturer d. 

a Department of Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ, b MRC Health Services Research Collaboration, Department of Social Medicine, University of Bristol, Bristol BS8 2PR, c Department of Surgery, Bristol Royal Infirmary, Bristol BS2 8HW, d Department of Maxillofacial Surgery, University of Bristol, Bristol BS1 2LY

Correspondence to: S Lewis sjl{at}doctors.org.uk


    Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References

Objective: To determine whether a period of starvation (nil by mouth) after gastrointestinal surgery is beneficial in terms of specific outcomes.
Design: Systematic review and meta-analysis of randomised controlled trials comparing any type of enteral feeding started within 24 hours after surgery with nil by mouth management in elective gastrointestinal surgery. Three electronic databases (PubMed, Embase, and the Cochrane controlled trials register) were searched, reference lists checked, and letters requesting details of unpublished trials and data sent to pharmaceutical companies and authors of previous trials.
Main outcome measures: Anastomotic dehiscence, infection of any type, wound infection, pneumonia, intra-abdominal abscess, length of hospital stay, and mortality.
Results: Eleven studies with 837 patients met the inclusion criteria. In six studies patients in the intervention group were fed directly into the small bowel and in five studies patients were fed orally. Early feeding reduced the risk of any type of infection (relative risk 0.72, 95% confidence interval 0.54 to 0.98, P=0.036) and the mean length of stay in hospital (number of days reduced by 0.84, 0.36 to 1.33, P=0.001). Risk reductions were also seen for anastomotic dehiscence (0.53, 0.26 to 1.08, P=0.080), wound infection, pneumonia, intra-abdominal abscess, and mortality, but these failed to reach significance (P>0.10). The risk of vomiting was increased among patients fed early (1.27, 1.01 to 1.61, P=0.046).
Conclusions: There seems to be no clear advantage to keeping patients nil by mouth after elective gastrointestinal resection. Early feeding may be of benefit. An adequately powered trial is required to confirm or refute the benefits seen in small trials.


What is already known on this topic
Enteral feeding within 24 hours after gastrointestinal surgery is tolerated

Theoretically, early enteral feeding improves tissue healing and reduces septic complications after gastrointestinal surgery

What this study adds
There is no benefit in keeping patients "nil by mouth" after gastrointestinal surgery

Septic complications and length of hospital stay were reduced in those patients who received early enteral feeding

In patients who received early enteral feeding there were no significant reductions in incidence of anastomotic dehiscence, wound infection, pneumonia, intra-abdominal abscess, and mortality



    Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References

A period of starvation ("nil by mouth") is common practice after gastrointestinal surgery during which an intestinal anastomosis has been formed. The stomach is decompressed with a nasogastric tube and intravenous fluids are given, with oral feeding being introduced as gastric dysmotility resolves.1 The rationale of nil by mouth is to prevent postoperative nausea and vomiting and to protect the anastomosis, allowing it time to heal before being stressed by food. It is, however, unclear whether deferral of enteral feeding is beneficial.

Contrary to widespread opinion, evidence from clinical studies and animal experiments suggests that initiating feeding early is advantageous. Postoperative dysmotility predominantly affects the stomach and colon, with the small bowel recovering normal function 4-8 hours after laparotomy.1 Feeding within 24 hours after laparotomy is tolerated and the feed absorbed. 2 3 Gastrointestinal surgery is often undertaken in patients who are malnourished,4-6 which in severe cases is known to increase morbidity.7 In animals, starvation reduces the collagen content in anastomotic scar tissue 8 9 and diminishes the quality of healing, 9 10 whereas feeding reverses mucosal atrophy induced by starvation11 and increases anastomotic collagen deposition and strength.12 Experimental data in both animals and humans suggest that enteral nutrition is associated with an improvement in wound healing.13 Finally, early enteral feeding may reduce septic morbidity after abdominal trauma14 and pancreatitis.15

Several clinical trials directly comparing strategies of early feeding with nil by mouth after elective gastrointestinal surgery have been performed. These studies, however, have not been systematically reviewed. We performed a systematic review and meta-analysis of randomised trials to assess the evidence on benefit and harm of early enteral feeding.


    Methods
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Abstract
Introduction
Methods
Results
Discussion
References

Eligibility criteria and literature search---Clinical trials were eligible if patients had undergone elective gastrointestinal surgery and were randomly allocated to receive either enteral feeding (within 24 hours after surgery) or the traditional management of nil by mouth and intravenous fluids with introduction of enteral fluids and diet as tolerated.

Data extraction and outcomes---From each study we collected data on the site of surgery, whether an intestinal anastomosis was formed, whether the pathology was benign or malignant, the type of feed used, and the method of administration of the feed. The site of surgery was classified as pancreatic, hepatobiliary, upper gastrointestinal (proximal to the jejunum), or lower gastrointestinal (distal to the duodenum). Outcomes potentially related to feeding included anastomotic dehiscence, infection of any type, wound infection, pneumonia, intra-abdominal abscess, vomiting, mortality, and length of hospital stay. The unplanned reinsertion of a nasogastric tube was recorded.

Analysis---We combined results from individual studies on the relative risk scale using fixed effects meta-analysis.16 Data on length of hospital stay were pooled with non-standardised mean differences. We used a chi 2 test to test for homogeneity of relative risks. We used funnel plots to determine the presence of publication bias and related biases and performed a statistical test of funnel plot asymmetry.17


    Results
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Abstract
Introduction
Methods
Results
Discussion
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Characteristics of trials, patients, and interventions
We identified 13 randomised controlled trials, all of which were published in English. 13 18-29 We excluded two of these trials because no information on relevant outcomes was given. 28 29 We obtained additional unpublished data for six of the studies.19-27

Patients had a wide variety of gastrointestinal conditions. Table 1 gives details of the 11 trials that we included.


                              
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Table 1. Characteristics of eleven trials of early enteral feeding after elective gastrointestinal surgery

Methodological quality of trials
Reporting on concealment of allocation of treatment and blinding was poor. In three trials allocation was concealed with sealed envelopes, 21 22 24 and one trial used an open table with random numbers,18 but in the remaining studies the exact method of randomisation was unclear. In the study by Heslin et al the outcomes were assessed by "a physician not associated with the surgical team."24 In all other studies outcome assessment was probably open, although this was explicitly stated in only one report.26

Outcomes
The effects of early feeding on anastomotic dehiscence, infections, vomiting, and mortality are detailed in table 2 and summarised in the figure. Seven trials showed that early feeding led to a reduction in risk of anastomotic dehiscence with a combined relative risk of 0.53 (95% confidence interval 0.26 to 1.08, P=0.080) and no evidence of heterogeneity between studies (chi 2=2.10, P=0.96). Results were similar when 31 patients in whom no anastomosis had been formed were excluded from the denominator of five trials (combined relative risk 0.54, 0.26 to 1.09). 18 20 22 23 25 There was little evidence that results differed between the two studies in which the anastomosis was known to be proximal to the site of feeding 24 26 and the six trials in which it was distal (P=0.42). 13 19 20 23 25 27


                              
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Table 2. Relative risk (95% CI) of anastomotic dehiscence, infection, and death in eleven randomised trials of early enteral nutrition



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  		Risk of anastomotic dehiscence, infections, vomiting, and death after elective gastrointestinal surgery: results from meta-analyses of randomised trials comparing early enteral feeding with regimen of nil by mouth

The risk of any type of infection was obtained in all but two trials (table 2). 19 26 The combined relative risk was 0.72 (0.53 to 0.98), indicating a significant (P=0.036) reduction in the risk of infection, with little evidence of heterogeneity between trials (chi 2=10.7, P=0.22). Similar reductions were observed for wound infection and pneumonia (figure). There was an increase in the risk of vomiting among patients fed early (1.27, 1.01 to 1.61, P=0.045).

Mortality was reported in all but two studies, 19 26 but deaths occurred in only five (table 2). There were four deaths in the early feeding groups compared with 10 deaths in control groups (relative risk 0.48, 0.18 to 1.29, P=0.15). Length of hospital stay was reported in all 11 studies. The mean length of stay ranged from 6.2 days to 14.0 days in early feeding groups and from 6.8 days to 19.0 days in control groups. Combined results showed a significant reduction by 0.84 day (0.36 to 1.33 days, P=0.001), with some evidence of heterogeneity between studies (chi 2=16.2, P=0.094).

Funnel plots
We examined funnel plots for all nine outcomes (the seven shown in table 2 plus length of stay and replacement of nasogastric tubes). There was no clear evidence of asymmetry in any of these plots (P>0.10 by regression test17), except for mortality (P=0.068).


    Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References

This meta-analysis yielded three principal findings. Firstly, there does not seem to be a clear advantage in keeping patients nil by mouth after elective gastrointestinal resection. Secondly, in these patients early feeding may be beneficial. Thirdly, we believe these results indicate the necessity for an adequately powered clinical trial to assess early enteral feeding in patients undergoing elective gastrointestinal surgery.

Complications after operation
Anastomotic dehiscence is a major complication of gastrointestinal surgery with considerable morbidity and mortality.30 The combined estimate of the effects of early feeding failed to reach conventional levels of significance but eight out of nine studies that reported anastomotic dehiscence indicated benefit. A significant relative reduction in the risk of infection of any type was observed for patients receiving early enteral nutrition, with the greatest reduction seen in the frequency of wound infections. In most of the trials assessed infections were not clearly defined. In absolute terms results were heterogeneous, with the number of patients who would need to be treated to prevent one infection of any type ranging from three22 to 58.24

The length of hospital stay after surgery was reduced in eight of the eleven studies. Overall the reduction corresponds to about one day, which is economically important. Reduction in complication rates may explain this observation, as might a faster return of gastrointestinal function. Early postoperative feeding after non-gastrointestinal surgery has also been shown to reduce length of stay in hospital. 31 32

Quality of trials and heterogeneity
The 11 randomised trials identified were clinically heterogeneous and most of them were small and of doubtful methodological quality. It is noteworthy that the effect of early nutrition seemed to be homogeneous across a set of trials that were clearly heterogeneous in clinical terms. Our ability to detect heterogeneity between trials, however, was limited by the small number of trials and by the often inadequate reporting.

Conclusion
There is little evidence from these trials that keeping patients nil by mouth is beneficial after elective gastrointestinal resection. Although the data are clearly insufficient to conclude that early feeding is of proved benefit, we believe that there is a good case for an adequately powered clinical trial to assess early enteral feeding in such patients.

    Acknowledgments

We thank the authors who provided additional data: R Beier-Holgersen, B Stewart, S Wexner, J E Fischer, M F Brennan, and H Ortiz. We also thank the following manufacturers of enteral feeds for assisting in the collection of data: Nutricia, Fresenius Kabi, Novartis Nutrition UK, Ross Products, Clintec Nutrition, Nestlé (Clinical Nutrition), SHS International, Mead Johnson Nutrition.

    Footnotes

Funding: None.

Competing interests: None declared.

The full version of this paper appears on the BMJ's website


    References
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Abstract
Introduction
Methods
Results
Discussion
References

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(Accepted 30 May 2001)

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