CI: Supplemental Enteral Glutamine (2010)


Hall JC, Dobb G, Hall J, de Sousa R, Brennan L, McCauley R. A prospective randomized trial of enteral glutamine in critical illness. Intensive Care Med. 2003 Oct; 29(10): 1,710-1,716.

PubMed ID: 12923621
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To assess the influence of enteral glutamine on the incidence of severe sepsis and death in critically ill patients.

Inclusion Criteria:
  • All adults who were admitted to the ICU at Royal Perth Hospital and received nutritional support between May 1996 and January 2001
  • Informed consent.
Exclusion Criteria:
  • Acute liver disease or liver failure
  • Presence of either hepatic encephalopathy or a prothombin international normalized ratio greater than 1.5 combined with a total bilirubin level greater than twice the upper limit of normal.
Description of Study Protocol:


  • All adults admitted to the ICU at Royal Perth Hospital between May 1996 and January 2001 were eligible for enrollment into the study if they received nutritional support
  • Patients entered the trial once consent had been obtained.  


Randomized controlled trial:

  • Non-stratifed two-armed clinical trial
  • Patients were allocated to a group using computer-generated random number arranged into blocks with a cell size of 10.


  • Triple blind 
  • Data collected by an independent research nurse and all assessments were performed without knowledge of the specific enteral regimen being administered to that patient. 


  • Isocaloric and isonitrogenous solutions
  • 20g per L glutamine added to treatment formula
  • 20g per L glycine added to control formula.

Statistical Analysis

  • Power analysis estimated sample at 352 based on a one-tailed test on proportion for an expected decrease in the mortality and severe sepsis rates from 20% to 10% with the probability of a type I error set at 5% and the power of 80%
  • Two-tailed X2 test to compare proportion of patients who died or had severe sepsis
  • Data analyzed on intent-to-treat basis.
Data Collection Summary:

Timing of Measurements

Monitored daily in ICU and two times weekly throughout hospital stay for outcomes, or circumstances that involved the unplanned cessation of study nutrients.

Dependent Variables

  • Death (within six months of discharge from ICU)
  • Severe sepsis (defined by the American College of Chest Physicians and the Society of Critical Care as sepsis associated with organ dysfunction, hypoperfusion or hypotension)
  • Length of hospital stay (days)
  • Positive microbiological cultures (measured daily).

Independent Variables

Glutamine-supplemented enteral formula (20g per L glutamine added) or isocaloric/isonitrogenous control enteral formula.

Control Variables

Enteral formulas were isocaloric/isonitrogenous with 55g per L protein (20g per L study protein) with an energy/N ratio of 110kcal per g N.

Description of Actual Data Sample:
  • Initial N: 363 randomized, (N=122 glutamine group, 68% male) (N=125 control group, 68% male)
  • Attrition (final N): 363 (all subjects completed study).


Mean (range):

  • Glutamine group: 47 (27 to  62)
  • Control group: 44 (28 to 63).


BMI 25 with NS differences between groups. 


  • APACHE II mean 14 (nine to 18 with NS difference between groups)
  • ISS (trauma patient) mean  28.5 (NS difference between groups).


Royal Perth Hospital in Australia.

Summary of Results:

Key Findings


Glutamine Group


Control Group



Percent mortality (death within six months)

RR (95% CI)




0.95 (0.71 to 1.28)



Percent incidence of severe sepsis

(95% CI)


0.94 (0.72 to 1.22)



Length of Stay in ICU

(mean days, range)

11 (seven to 19)

13 (eight to 19)


Length of stay in hospital (mean days, range) 25 (16 to 42) 30 (19 to 45) P>0.05



Author Conclusion:

Glutamine supplementation did not enhance survival or diminish incidence of severe sepsis.

Funding Source:
Government: National Health and Medical Research Council of Australia
Reviewer Comments:
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? No
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes