CI: Initiation of Enteral Nutrition (2012)


Doig GS, Heighes PT, Simpson F, Sweetman EA, Davies AR. 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. Intensive Care Med. 2009; 35 (12): 2, 018-2,027.

PubMed ID: 19777207
Study Design:
Meta-analysis or Systematic Review
M - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

The purpose was to determine if early standard EN has benefits to critically-ill adult patients.

Inclusion Criteria:
  • Methodologically-sound RCTs comparing delivery of EN provided within 24 hours of ICU admission, or injury to standard care
  • Trials reporting meaningful patient-oriented outcomes conducted in critically-ill adult population.
Exclusion Criteria:
  • Not an RCT (letters, observational studies, systematic reviews, narrative reviews, previous meta-analyses)
  • Presence of major methodological flaws (pseudo randomization, greater than 10% loss to follow-up)
  • No provision of a primariy comparison of timing of EN
  • Study on oral intake rather than EN
  • Not adult critically-ill population
  • Not primary nutritional support intervention
  • Cross-over trials
  • Pre-operative interventions
  • Early EN not started within 24 hours of injury or ICU admission
  • Sub-group of patients from a larger published trial.
Description of Study Protocol:
  • Search plan: Medline and EMBASE were searched using appropriately broad Medical Subject Heading and EMTREE terms for nutritional support and critical illness, crossed with phrases optimised to detect RCTs
  • Design: Meta-analysis of RCT's
  • Intervention: To be included in meta-analysis, studies had to incorporate standard EN within 24 hours of ICU admission.

Statistical Analysis

  • Fixed effects model with OR
  • Tests for heterogeneity
  • Alpha =0.05 denoted statistical significance
  • Alpha =0.05 to 0.10 indicated a trend toward significance.
Data Collection Summary:


  • Validity appraisal
  • Clinically meaningful patient-oriented outcomes
  • Complications and major ICU infections
  • Sensitivity analysis.

Dependent Variables

  • Primary Analysis
    • Hospital stay mortality
    • Discharge mortality
    • Quality of life
    • Physical function.
  • Secondary Analysis
    • Vomiting/regurgitation
    • Pneumonia
    • Bacteraemia
    • Sepsis
    • Multiple organ dysfunction syndrome.

Independent Variable

Standard EN initiated within 24 hours of admission to ICU or injury.

Description of Actual Data Sample:

Summary of Articles Reviewed Number
Number of Articles Identified and Retrieved as Potentially Relevant
Number of Articles Reviewed for More Detailed Evaluation
Number and Type of Studies Considered for Meta-Analysis
Number of Articles that Met All Criteria for Inclusion


Summary of Results:

 Key Findings

 Outcome Studies Included Incidence with Early EN (<24 Hours) Incidence with Standard Care Odds Ratio (95% CI)
Mortality (primary) N=6
Pneumonia (secondary) N=2
  • There were no other significant differences in secondary outcomes of vomiting or regurgitation, bacteremia or multiple organ dysfunction syndrome
  • No included studies had incidence of sepsis as an outcome.
Author Conclusion:
  • There is a positive observation in reduction of mortality and pneumonia in critically-ill patients on early standard enteral nutrition
  • Due to the low quality of the studies included, as well as the small size of these studies a large multi-center trial with a diverse critically-ill patient group, needs to be conducted to confirm these results.
Funding Source:
University/Hospital: Northern Clinical School, University of Sydney
Reviewer Comments:
  • Doig 2009 meta-analysis papers for mortality: Chiarelli et al, 1990; Chuntrasakul et al, 1996; Kompan et al, 1999; Pupelis et al, 2001; Kompan et al, 2004; Nguyen et al, 2008.
  • Doig authored a second meta-analysis in 2011 and the articles included for mortality were: Chuntrasakul, 1996; Kompan, 1999; Kompan, 2004; Moore, 1986.
Quality Criteria Checklist: Review Articles
Relevance Questions
  1. Will the answer if true, have a direct bearing on the health of patients? Yes
  2. Is the outcome or topic something that patients/clients/population groups would care about? Yes
  3. Is the problem addressed in the review one that is relevant to dietetics practice? Yes
  4. Will the information, if true, require a change in practice? Yes
Validity Questions
  1. Was the question for the review clearly focused and appropriate? Yes
  2. Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? Yes
  3. Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased? Yes
  4. Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible? Yes
  5. Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined? Yes
  6. Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? Yes
  7. Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described? Yes
  8. Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included? Yes
  9. Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? Yes
  10. Was bias due to the review's funding or sponsorship unlikely? Yes