CI: Supplemental Enteral Glutamine (2010)


Schulman AS, Willcutts KF, Claridge JA, O'Donnell KB, Radigan AE, Evans HL, McElearney ST, Hedrick TL, Lowson SM, Schirmer BD, Young JS, Sawyer RG. Does enteral glutamine supplementation decrease infectious morbidity? Surg Infect. 2006 Feb; 7(1): 29-35.

PubMed ID: 16509783
Study Design:
Non-Randomized Controlled Trial
C - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To investigate the role of enteral glutamine supplementation in reducing infectious morbidity in critically ill surgical patients. 

Inclusion Criteria:

Patients who were expected to receive enteral feedings for more than 48 hours  in the surgical trauma intensive care unit (STICU) at the University of Virginia.

Exclusion Criteria:

None stated.

Description of Study Protocol:


Patients in the surgical trauma intensive care unit.


Prospective, non-randomized clinical trial; subjects were assigned to groups sequentially.


  • Group 1: Standard 1kcal per ml feeding with added protein powder
  • Group 2: Standard feedings with glutamine 0.6g per kg per day (20 to 40g per day)
  • Group 3: Immune-modulated feedings with a similar amount of glutamine.

Statistical Analysis 

  • Categorical data analyzed using the chi-square statistic
  • Fisher exact test used for any calculations with cell values less than five
  • Continuous data summarized by mean and standard error of the mean and compared using the Student T-test (assuming equal or unequal variance based on the F-test for variance). All P-values are considered significant if P≤0.05.


Data Collection Summary:

Timing of Measurements  

  • January 1999 to January 2002
  • Patients were followed from hospital entry to hospital discharge
  • Infection data was collected throughout the hospital stay. In particular, every other day information would be collected via chart reviews, discussions with house staff and evaluation of antibiotic usage. 

Dependent Variables

Infection occurrence based on the CDC criteria or catheter-related infections (15 or more colony-forming units from the catheter tip). 

Independent Variables

Diet type:

  • Group 1: Standard 1kcal per ml with added protein
  • Group 2: Standard feeding  with 20 to 40g of glutamine
  • Group 3: Immune-modulated formula with a similar amount of glutamine.
Description of Actual Data Sample:
  • Initial N: 185 patients (41% male)
  • Attrition (final N): 185 patients
  • Age: Patients were 40 to less than 50 years
  • Other relevant demographics:
    • ISS NS different; 27.3 to 30.1
    • APACHE II scores were significantly higher for GlN/immune-modulated group [20.6±0.9 (P=0.03) compared to control (17.9 ±0.9) and GLN only 18.6±0.9]
  • Location: Charlottesville, VA, University of Virginia.
Summary of Results:

Key Findings

  • Mortality: NS differences between groups
  • Infections: NS differences between groups; 64% of N=119 patients developed a total of 343 infections
    • Among all the groups, the lungs were the most commonly infected site, followed by a smaller percent of total infections for the blood, urine, catheter and peritoneum locations
    • There were no differences among the three groups in antibiotic treatment usage or duration (mean number of treatment days). 
Author Conclusion:

Supplemental enteral glutamine in the doses provided in this study did not influence the acquisition or characteristics of infection in patients admitted to a mixed surgical trauma intensive care unit. 

Funding Source:
University/Hospital: Univ of VA
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? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  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%.) N/A
  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? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? No
  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.) No
  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? No
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  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)? N/A
  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? N/A
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