CI: Enteral Nutrition vs. Parenteral Nutrition (2012)

Simpson F and Doig GS. Parenteral vs. enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle. Intensive Care Med. 2005; 31: 12-23.
PubMed ID: 15592814
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:

Intestigate the effect of trial quality on overall conclusions surrounding use of parenteral nutrition (PN) in critical illness.

Inclusion Criteria:

Characteristics of Included Articles

Patient characteristics

  • PN and EN did not contain supplemental glutamine, arginine or other immune-enhancing ingredients
  • Published in the English language prior to April 30, 2003
  • Patients were recruited in ICU and the majority were receiving invasive mechanical ventilatory support
  • Average ICU length of stay (LOS) was longer than two days
  • Severity of illness was reported and commensurate with patients being critically ill
  • Patients were suffering from a condition usually requiring care in ICU (burns over 40% to 50% of total body surface, multi-trauma requiring urgent laparotomy).

Methodological article quality

Reporting of three key methodological components including:

  • Intent-to-treat analysis
  • Maintenance of allocation concealment during randomization
  • Appropriate use of blinding (participants, investigators, outcome adjudicators).
Exclusion Criteria:

Papers were excluded if they did not meet criteria for patient inclusion, article quality or had more than 10% loss of patients to follow-up.

Description of Study Protocol:

Search Procedures

  • Database search included Medline and EMBASE
  • Reference lists of overviews and evidence-based guidelines hand-searched
  • Contacted experts and industry representatives to ensure trials were not missed
  • The final closure data for search process was April 30, 2003.

Study Quality

  • Patients recruited into trials were critically ill, as defined per inclusion criteria
  • Positive methodological quality, as defined per inclusion criteria (presence of intent-to-treat analysis, maintenance of allocation concealment during randomization and appropriate use of blinding, less than 10% of patients lost to follow-up).

Populations Included

Critically ill (included patients with burns over 40% of body).

Data Collection Summary:
  • Infectious complications (sepsis, pneumonia, UTI, wound infections, peritonitis)
  • Mortality
  • Timing of feeding on clinically meaningful outcomes.

Method for Synthesis of Information

  • Meta-analysis with fixed-effect model, using odds ratio metric
  • Herterogeneity assessed with X2 statistic and I2 measure
  • Formal test of treatment-sub-group interactions.
Description of Actual Data Sample:
  • 465 articles were identified and retrieved as potentially relevant
  • 329 RCTs were reviewed for more detailed evaluation
  • 124 RCTs were considered for meta-analysis
  • 22 RCTs compared EN to PN
  • 11 RCTs met all criteria for inclusion.
Summary of Results:

Key Findings

  • There were six studies for early EN with 224 subjects; five studies for late EN with 121 subjects
    • When PN compared to early EN (started within 24 hours), no effect on mortality (OR, 1.07; 97% CI, 0.39 to 2.05; P=0.89)
    • Mortality was significantly less with PN compared to delayed EN (start time of greater than 24 hours; OR, 0.29; 95% CI, 0.12 to 0.70; P=0.006).
  • For infectious complications, there were three studies that reported a number of patients with infections (N=136) and three studies reporting a total number of infections (N=89 subjects): Use of PN resulted in a trend toward more infectious complications compared to early EN (OR, 1.47; 95% CI, 0.90 to 2.38; P=0.12).

Other Findings

Infectious complications in early vs. delayed EN was not analyzed due to inadequate studies to include in the meta-analysis: Two studies.

Author Conclusion:

Although there is an association with increased infectious complications with PN use, PN should be used in patients for whom EN cannot be initiated within 24 hours or ICU admission or injury.


Funding Source:
New Zealand Intensive Care Foundation (industry-supported)
Pharmaceutical/Dietary Supplement Company:
Other: NorthCare Foundation
Reviewer Comments:
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