CI: Supplemental Intravenous Glutamine (2011)


Fuentes-Orozco C, Anaya-Prado R, González-Ojeda A, Arenas-Márquez H,Cabrera-Pivaral C, Cervantes-Guevara G, Barrera-Zepeda LM. L-alanyl-L-glutamine-supplemented parenteral nutrition improves infectious morbidity in secondary peritonitis. Clin Nutr. 2004 Feb; 23(1): 13-21.

PubMed ID: 14757388
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

The purpose of this study was to investigate whether the provision of glutamine-enriched TPN after surgical and medical treatment of secondary peritionitis improves infectious morbidity.

Inclusion Criteria:

Patients with diagnosis of secondary peritonitis who required TPN.

Exclusion Criteria:
  • Patients with:
    • Renal failure (creatinine more than 180µmol per L)
    • Hepatic failure (bilirubin more than 40µmol per L, alanine aminotransferase more than 100 U per L and aspartate aminotransferase more than 100 U per L)
    • Severe neutropenia (less than 500 cells per mm3)
    • Hemodynamic instability, resistant to aggressive fluid resuscitation
  • Patients receiving:
    • Cytoxic
    • Radiation
    • Steroid therapy.
Description of Study Protocol:


Patients with diagnosis of secondary peritonitis who required TPN were enrolled.


All patients underwent surgical correction of the infectious focus and had placement of a central venous catheter at the time of surgery. Patients were randomly assigned to receive either standard TPN or GLN-supplemented TPN. This was started the day after surgery and ran continuously for 10 consecutive days.

Blinding Used

Pharmacy prepared solutions and all investigators, patients and their relatives remained blind to the randomization until the 10-day follow-up had been completed.


  • Standard TPN solution
  • GLN-supplemented TPN solution.

Statistical Analysis

  • Comparison between means was assessed by ANOVA test or using the unpaired Student's T-test
  • When data were not distributed normally, comparisons were made with the Mann-Whitney U-test, X2 test or Fisher's exact test to determine the significance when comparing proportions.
Data Collection Summary:

Timing of Measurements

May 1999 to April 2001.

Dependent Variables

  • Primary efficacy variables: Infectious morbidity, nitrogen balance, leukocytes, lymphocytes, sub-populations CD4 and CD8, Immunoglobulin A (IgA), total proteins and albumin
  • Secondary efficacy parameters: Length of hospital stay, days at ICU, length of ventilatory support and mortality.

Independent Variables

  • GLN-supplemented TPN: L-alanyl-L-glutamine, 0.40g per kg per day (Dipeptiven®, Fresenius Kabi, Bad Homburg, Germany) plus 8.5% standard amino acids (1.1g per kg per day)
  • Standard TPN: 30kcal per kg per day. The non-protein calories were given as carbohydrates, 50% hypertonic glucose and lipids (20% fatty acids) in a ratio of approximately 60:40. The protein calories were given as 8.5% amino acids (1.1g per kg per day).

Control Variables

  • Control and GLN-PN formulas were isonitrogenous and isocaloric
  • Nitrogen balance: Fluid balance chart was maintained. Total urinary nitrogen was determined using the Micro-Kjeldahl method. The amount of nitrogen administered in the TPN was calculated by multiplying the measured administered volume by the nitrogen concentration of the product. Insensible nitrogen losses were assume to be 0.02g nitrogen per kg per day, using the formula of Daily nitrogen balance = (nitrogen administered - calculated total urinary nitrogen - estimated insensible nitrogen losses).
Description of Actual Data Sample:
  • Initial N: 33 (66% male)
  • Age:
    • Standard TPN: 48.93±16.30
    • GLN-enriched TPN: 53.64±16.86
  • Other relevant demographics: Illness Severity (using Mannheim Index):
    • Standard TPN: 23.4±4.4
    • GLN-enriched TPN: 23.8±5.44
  • Location:
    • All patients were treated at the ICU after surgery
    • Medical Research Unit in Clinical Epidemiology at Western Medical Center, Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico.
Summary of Results:

Key Findings


GLN Group (N=17)

Control Group (N=16)


Infection rate (incidences)

4 12


Hospital stay (days) 16.69±7.04 16.52±8.9 NS P>0.05
ICU stay (days) 7.25±4.46 7.17±9.2 NS P>0.05
Mortality 3 (18.75%) 2 (11.7%) NS P>0.05
Ventilatory support (days) 4.47±4.4 4.88±8.2 NS P>0.05

Other Findings

  • There were NS differences in total leukocytes, total lymphocytes, lymphocyte sub-populations CD4 or CD8
  • Subjects who received the GLN PN had significantly more positive nitrogen balance (P=0.003) and immunoglobulin A (P=0.029).
Author Conclusion:

L-alanyl-L-glutamine-supplemented PN improved the infectious morbidity of patients with secondary peritonitis. GLN supplementation to parental nutrition may be an alternative for enhancing host defenses and improving infectious morbidity.

Funding Source:
Government: Mexican Institute of Social Security, Institutional Grant No. 0038/240
In-Kind support reported by Industry: Yes
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? ???
  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")? Yes
4. Was method of handling withdrawals described? Yes
  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%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? Yes
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? Yes
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? N/A
  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? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? Yes
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)? N/A
  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