CI: Supplemental Intravenous Glutamine (2011)


Estívariz CF, Griffith DP, Luo M, Szeszycki EE, Bazargan N, Dave N, Daignault NM,Bergman GF, McNally T, Battey CH, Furr CE, Hao L, Ramsay JG, Accardi CR, CotsonisGA, Jones DP, Galloway JR, Ziegler TR. Efficacy of parenteral nutrition supplemented with glutamine dipeptide to decrease hospital infections in critically ill surgical patients. JPEN J Parenter Enteral Nutr. 2008 Jul-Aug; 32 (4): 389-402.

PubMed ID: 18596310
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 primary aim was to evaluate the efficacy of alanyl-GLN-supplemented PN to reduce hospital (nosocomial) infections in adults requiring post-operative SICU care and PN. 

Inclusion Criteria:
  • Signed informed consent
  • Age 18-80 years
  • SICU care required after five types of operation (pancreatic necrosis surgery, coronary artery bypass grafting (CABG), cardiac valve surgery, non-neurologic vascular surgery, or colonic surgery)
  • Subject deemed likely to required PN for at least seven subsequent days.
Exclusion Criteria:
  • Study PN not given for five or more consecutive days after initiation of study
  • Evidence of developing acute hepatic failure
  • Evidence of acute, uncontrolled infection or history of clinical sepsis in previous 24 hours
  • Evidence of active malignancy, significant hepatic dysfunction or significant renal dysfunction. 
Description of Study Protocol:


Hospital patients who consented


Double-blind, randomized, controlled trial

Blinding used 



Isocaloric, isonitrogenous, GLN dipeptide-supplemented PN (GLN-PN)

Statistical Analysis

Data were analyzed with the chi square test or Fisher exact test and Poisson regression as appropriate to compare the clinical outcome end points and other dichotomized factors between control and experimental groups. T-tests were used to compare other data and continuous factors that were measured only once.  Variables measured serially over time were compared between groups using two-way repeated-measures ANOVA followed by Tukey pairwise comparisons. 


Data Collection Summary:

Timing of Measurements

Clinical, metabolic, and biochemical data were entered daily during hospitalization. PN intake was recorded on days when any study PN was received. 

Dependent Variables

  • Total number of new nosocomial infections diagnosed during the entire hospitalization after initiation of PN and number of patients with multiple hospital infections
  • Site of infection
  • Days on mechanical ventilation
  • Development of ARDS
  • SICU and hospital LOS
  • Hospital mortality
  • Antibiotic days.

Independent Variables

  • PN Formulation
    • GLN-PN, given at a dose of 1.5g per kg per day. The GLN-PN group received PN containing 0.5g per kg per day alanyl-GLN dipeptide added to 1.0g per kg per day 15% Clinisol AA solution (total 1.5g per kg per day), providing 23g of L-GLN daily for a 70kg subject. 
    • Control PN provided 1.5g per kg per day AA with no GLN.
Description of Actual Data Sample:
  • Initial N: 63 randomized
  • Attrition (final N):
    • 59-29 STD-PN (21 males) 
    • 30 GLN-PN (19 males)
  • Age: STD-PN 57±3, GLN-PN 56±3
  • Ethnicity: Not described
  • Other relevant demographics:
    • APACHE II scores STD-PN 13.1±1.2; GLN-PN 13.4±1.4
    • APACHE II scores pancreatic necrosis surgery 9.8±1.1; nonpancreatic surgery 14.8±1.4 (P<0.05)
  • Location: Emory University, Atlanta GA.


Summary of Results:

 Key Findings


STD-PN (control)

GLN-PN P-Value
New infections-all patients (N=59) 65 (N=29) 38 (N=30) P=0.06
New infections-pancreatic surgery (N=32) 29 (N=17) 25 (N=15) P=0.67
New infections-non-pancreatic surgery (N=27) 36 (N=12) 13 (N=15) P=0.03
Mortality-all patients (N=59) 17% (N=29)  3% (N=30) NS
Mortality-pancreatic surgery (N=32)  0/32 (0%)  0/15 (0%) NS
Mortality-non-pancreatic surgery (N=27) 5/12 (42%) 1/15 (7%) P=0.06

Days on ventilator-pancreatic surgery (N=32)

8±4 6±3 NS
Days on ventilator-non-pancreatic surgery (N=27) 21±5


SICU LOS-pancreatic surgery (N=32) 10±4 11±4 NS
SICU LOS-non-pancreatic surgery (N=27) 23±6 12±2 NS
Hospital LOS-pancreatic surgery (N=32) 31±5 32±4 NS
Hospital LOS-non-pancreatic surgery (N=27) 30±6 20±2 NS


Author Conclusion:

Supplementation of PN with alanyl-GLN dipeptide was well tolerated, with decreased nosocomial infections, and improved organ function indices in adult patient requiring both PN and prolonged SICU care after cardiac, abdominal vascular and colonic surgery.

Beneficial effects were not observed in patients who required SICU care and PN after major pancreatic surgery for pancreatic necrosis. 

Daily blood glucose concentrations were maintained between 145 and 154mg/dL within individual patient subgroups, and these were not different between subgroups. Thus, differences in blood glucose control between study groups cannot explain the outcomes observed. 

Funding Source:
Government: NIH
Pharmaceutical/Dietary Supplement Company:
University/Hospital: Emory General Clinical Research Center
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? 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? N/A
  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? 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? 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)? N/A
  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? 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