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
To assess the influence of enteral glutamine on the incidence of severe sepsis and death in critically ill patients.
- All adults who were admitted to the ICU at Royal Perth Hospital and received nutritional support between May 1996 and January 2001
- Informed consent.
- 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.
- 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.
- 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.
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.
- 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).
Glutamine-supplemented enteral formula (20g per L glutamine added) or isocaloric/isonitrogenous control enteral formula.
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.
- Initial N: 363 randomized, (N=122 glutamine group, 68% male) (N=125 control group, 68% male)
- Attrition (final N): 363 (all subjects completed study).
- 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.
Percent mortality (death within six months)
RR (95% CI)
0.95 (0.71 to 1.28)
Percent incidence of severe sepsis
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|
Glutamine supplementation did not enhance survival or diminish incidence of severe sepsis.
|Government:||National Health and Medical Research Council of Australia|
Quality Criteria Checklist: Primary Research
|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|
|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|