CI: Supplemental Intravenous Glutamine (2011)


Goeters C, Wenn A, Mertes N, Wempe C, Van Aken H, Stehle P, Bone HG. Parenteral L-alanyl-L-glutamine improves SIX-month outcome in critically ill patients. Crit Care Med. 2002 Sep; 30 (9): 2,032-2,037.

PubMed ID: 12352037
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

Investigate whether adding GLN to PN can improve clinical outcomes.

Inclusion Criteria:
  • Randomization within THREE days after admission to ICU and before start of balanced nutritional therapy
  • Indication for total parenteral nutrition (failure or contraindication of enteral nutrition)
  • Expected stay on ICU for at least five days.
Exclusion Criteria:
  • Primary Exclusion Factors:
    • Age <16 years old
    • Pregnancy or breast feeding
    • Inborn disorders of amino acid metabolism.
  • Secondary Exclusion Factors:
    • Discharge or death before completing study protocol for five days.


Description of Study Protocol:


Admission to ICU


Prospective, open, randomized trial

Blinding used

Nutrition support was surveyed by a nutritional team with nutrition scientists not involved in the clinical care of the patients.


  • Control Group: 1.5g per kg per day usual amino acid solution
  • Ala-Gln Group: 0.3g per kg per day ALA-GLN and 1.2g per kg of usual amino acid solution (total of 1.5g per kg per day).

Statistical Analysis

  • Nominal scale variables were described by relative and absolute frequencies, and differences between groups were assessed by the chi-square test
  • All values with interval or rational scales are given as mean±SD
  • Student's T-test for independent variables or a repeated measures analysis of variance was performed (P≤0.05 was considered significant)
  • The effect of glutamine supply on dichotomous outcome variables (mortality, length of stay) was analyzed by Cox regression.


Data Collection Summary:

Timing of Measurements


  • Nutritional and medical treatment, vital variables and routine laboratory data were recorded
  • Urinary nitrogen excretion and nitrogen losses by continuous venovenous filtration were determined by chemoluminescence procedure. Nitrogen balances were calculated as well.

Before Start of Treatment:

  • Blood samples were taken to analyze plasma proteins and amino acids.
    • Before feeding
    • Feeding for three to five days
    • Feeding for six to nine days
  • APACHE II score was calculated assuming a Glasgow Coma Scale score of 15 (sedated and ventilated patients) and without chronic health points
  • PINI was calculated.

Two Times a Week:

  • Blood samples for plasma proteins and amino acids
  • PINI.

Six-month Outcomes:

Telephone interviews with the patients relatives or treating physician

Dependent Variables

  • Mortality (death within 30 days or six months)
  • Hospital and ICU LOS.

Independent Variables

  • Usual amino acid solution vs. ALA-GLN solution nutrition therapy treatment groups
    • ALA-GLN: Continuously infused as long as a central venous access was necessary for other medical reasons.

Control Variables

  • Caloric Support: managed by metabolic variables (glucose [≤10mmol/L] and triglyceride plasma concentrations [≤2.8mmol/L])
    • Target values for daily energy supply were 3g per kg per day carbohydrates and 1g per kg per day fat
    • Nitrogen balance
    • Enteral Feeding: If successfully tolerating 700mL (enteral input minus reflux) parenteral protein was reduced. Formulas used were not enriched with glutamine.
  • Variation of medical treatment by limiting duration of study to two years
  • Medical Treatment Subgroups: Trauma, visceral, cardiovascular and miscellaneous surgery.


Description of Actual Data Sample:
  • Initial N: 95 (65% male)
  • Attrition (final N):
    • 95 patients remained in ICU at least five days
    • 63 patients remained in ICU at least nine days
  • Age:
    • 48.9±16.3 GLN group
    • 53.6±18.0 control group
  • Anthropometrics: BMI
    • 26.3±4.0 GLN group
    • 25.0±4.0 control group
  • Demographics: SICU patients with APACHE II score
    • 14.2±5.4 GLN group
    • 14.9±7.6 control group
  • Location:
    • University of Munster,Germany
    • Raphaelsklinik-Munster, Germany
    • University of Bonn, Germany.
Summary of Results:

Key Findings

Variable GLN (N=33) Control (N=35) P-Value
Mortality (death within 30 days) 7 11 NS
Mortality (death within six months) 11 21 P<0.05
ICU LOS (days) 21.3±13.5 20.8±9.1 NS
Hospital LOS (days) 40.6±49.1 39.4±31.1 NS


Author Conclusion:

Providing glutamine to correct deficiency may lead to decreased mortality.

Funding Source:
University/Hospital: Dept of Anesthesiology and Intensive Care - Univ of Muenster, Germany
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? 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.) 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? No
  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? Yes
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