Meta Analysis Early enteral nutrition, provided within 24 h of injury or intensive care unit admission, significantly reduces mortality in critically ill patients: a meta-analysis of randomised controlled trials
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Summary
Posted By:	Elizabeth Sweetman
E-Mail:	esweetman@med.usyd.edu.au
Posted Date:	23.09.11
Title:	Early enteral nutrition, provided within 24 h of injury or intensive care unit admission, significantly reduces mortality in critically ill patients: a meta-analysis of randomised controlled trials
Authors:	Doig GS, Heighes PT, Simpson F, Sweetman EA, Davies AR.
Reference:	Intensive Care Med. 2009 Dec;35(12):2018-27
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract:	PURPOSE: To determine whether the provision of early standard enteral nutrition (EN) confers treatment benefits to critically ill patients. METHODS: Medline and EMBASE were searched. Hand citation review of retrieved guidelines and systematic reviews were undertaken, and academic and industry experts were contacted. Methodologically sound randomised controlled trials (RCTs) conducted in critically ill patient populations that compared the delivery of standard EN, provided within 24 h of intensive care unit (ICU) admission or injury, to standard care were included. The primary analysis was conducted on clinically meaningful patient-oriented outcomes. Secondary analyses considered vomiting/regurgitation, pneumonia, bacteraemia, sepsis and multiple organ dysfunction syndrome. Meta-analyses were conducted using the odds ratio (OR) metric and a fixed effects model. The impact of heterogeneity was assessed using the I (2) metric. RESULTS: Six RCTs with 234 participants were analysed. The provision of early EN was associated with a significant reduction in mortality [OR = 0.34, 95% confidence interval (CI) 0.14-0.85] and pneumonia (OR = 0.31, 95% CI 0.12-0.78). There were no other significant differences in outcomes. A sensitivity analysis and a simulation exercise confirmed the presence of a mortality reduction. CONCLUSION: Although the detection of a statistically significant reduction in mortality is promising, overall trial quality was low, trial size was small, and the findings may be restricted to the patient groups enrolled into included trials. The results of this meta-analysis should be confirmed by the conduct of a large multi-centre trial enrolling diverse critically ill patient groups.
Are the Results Valid?
1. Did the overview address a focused clinical question?
	Yes. The authors stated that the purpose of their project was to determine whether the provision of early (with 24 hours) standard EN confers treatment benefits to critically ill patients compared with standard care.
2. Were the criteria used to select articles for inclusion appropriate?
	Yes. The authors stated that they would identify all RCT's evaluating primary feeding interventions in critically ill patients. The authors RCT selection process for this project was defined as; - Early EN was the provision of EN formula by any feeding route with 24 hrs of initial injury or ICU admission. - Standard EN formula was considered to be any formula not supplemented with additional glutamine, arginine or other immune-enhancing ingredients. - Comparison groups were accepted to include all forms of standard EN provided later than 24 hours after injury or ICU admission. - RCT's reporting clinically meaningful patient orientated outcomes conducted in critically ill populations were considered for inclusion.
3. Is it unlikely that important, relevant studies were missed?
	Yes. The authors conducted a comprehensive search for RCT's which included; searching Medline, EMBASE, contacting Academic and Industry experts and hand searching reference lists and evidence based guidelines.
4. Was the validity of the included studies appraised?
	Yes the authors did appraise the validity of the included RCT's. Validity appraisal was based on the reporting of three key methodological criteria; 1. The maintenance of allocation concealment, 2. The use of any form of blinding and 3. The completeness of patient follow-up. Validity appraisal of the included studies is presented in the results section of this paper.
5. Were assessments of studies reproducible?
	Yes. Three authors reviewed all potentially eligible abstracts on topic. The selection process for this project was also outlined in figure 1.
6. Were the results similar from study to study?
	There was no heterogeneity for either of the two outcomes analysed (mortality & pneumonia). Both outcomes had an I2 = 0% as per figure 2 and 3 in the paper.
What are the Results?
1. What are the overall results of the overview?
	Mortality (figure 2): meta-analysis of RCTs revealed a statisically significant reduction in mortality in favour of early standard EN (within 24 hrs),(OR = 0.34, P = 0.02). Pneumonia (figure 3): The meta-analysis of the 2/6 trials that reported the outcome pneumonia demonstrated a significantly significant reduction in pneumonia in favour of early standard EN (within 24 hrs),(OR = 0.31, P = 0.01).
2. How precise were the results?
	The 95% confidence interval (CI) around the esitmate of; mortality reduction was: 0.14–0.85 pneumonia reduction was: 0.12-0.78
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care
	Yes. NG tubes are inserted at time of admission in the majority of our ICU patients. There are no barriers in our system to prevent us from commencing enteral feeds slightly earlier.
2. Were all clinically important outcomes considered?
	Yes, all clinically important outcomes were considered by the authors of this meta-analysis however not all outcomes were published in the clinical trials reviewed. We would like to see QOL, physical function costs but unfortunately many of the trials published are not reporting these yet.
3. Are the benefits worth the harms and costs?
	Starting EN earlier (within 24 hours) of admission or injury may be of real benefit to patients as shown in this paper. The authors reported no harms associated with early EN. The trials did not report costs.
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