EAL

CI: Supplemental Intravenous Glutamine (2011)

Citation:

Cai G, Yan J, Zhang Z, Yu Y. Immunomodulatory effects of glutamine enriched nutritional support in elderly patients with severe sepsis: A prospective, randomized, controlled study. J Organ Dysfunction. 2008, 4: 31-37.

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

The purpose was to try to elucidate the effects of Gln-enriched nutritional support on immunological and clinical outcomes in elderly patients with severe sepsis in an intensive care unit.

Inclusion Criteria:

Elderly subjects with severe sepsis, such as:

APACHE-II score≥16, but≤28
D-related human leukocyte antigen (HLA-DR) expression on peripheral blood CD14 monocytes≤50%.

Exclusion Criteria:

Criteria for exclusion were:

Lack of agreement to accept the routine intense treatment of the ICU, such as early antimicrobial therapy, early goal-directed therapy, mechanical ventilation and intensive insulin treatment.

Description of Study Protocol:

Recruitment

Elderly subjects were recruited from the ICU from May 2003 to October 2006 in the Zhejiang Hospital, China

Design

Prospective, randomized, controlled study

Blinding used

Intervention

The experimental group received the standard nutritional support treatment as well as an IV injection of Gln (10 grams per day).

Statistical Analysis

All data were expressed as means ± standard deviation
Comparisons between groups were made using the Students T-test and the chi square test
All statistical tests were two-tailed at a 5% significance level.

Data Collection Summary:

Timing of Measurements

May 2003 to October 2006. On days one, seven and 14 of treatment, blood samples were collected for routine biochemical measurements.

Dependent Variables

Pro-albumin
C-reactive protein
Analysis of lymphocyte subsets
Various clinical outcomes (length of stay in ICU, duration of mechanical ventilation and the 28-day survival rate).

Independent Variable

IV injection of GLN (10 grams per day)

Control Variables

All the subjects were elderly individuals with severe sepsis

Description of Actual Data Sample:

Initial N: 110
- 95 males
- 15 females
Attrition (final N): 110 (none) excluded from analysis
Age: 68-92 years of age
- 81.3±6.8 years (control) vs. 79.8±7.2 years P=0.8
Ethnicity: Chinese
Other relevant demographics:
- APACHE II score 21.37±4.36 (control) vs. 20.48 ±4.15 (Gln) P=0.3
- MODS score 10.73±3.26 (control) vs. 11.85 ±3.45 (Gln) P=0.2
Anthropometrics:
- Energy intake 25.4±3.45kcal per kg per day (control) vs. 26.6±3.6kcal per kg per day (Gln) P=0.7
- Basic Nitrogen intake 0.23±0.03g per kg per day (control) vs. 0.25±0.04g per kg per day (Gln) P=0.2
Location: Hangzhuo, China.

Summary of Results:

Key Findings

Variables	Gln (10g per day) Group	Control Group	Statistical Significance of Group Difference
Mortality (28-day survival)	69.1	63.6	P=0.8
LOS-ICU (days)	22.1±4.9	23.8±5.1	P=0.7
Mechanical ventilator days	15.6±5.7	17.2±5.9	P=0.4
Pro-albumin	309±68	256±58	P=0.02
C-reactive protein	15.6±4.2	25.8±4.9	P=0.001
Total lymphocyte count x 10⁹/l	1.91±0.33	1.35±0.25	P=0.001

Other Findings

The percentage of CD14 monocytes expressing HLA-DR in the GLN group was significantly higher than that in the control group on Day 14 of hospitalization (55.3% ± 6.3% vs. 37.3% ± 4.7%) P=0.001.

Author Conclusion:

The administration of Gln-enriched nutritional support can improve immunoparalysis in elderly patients with severe sepsis.

Funding Source:

University/Hospital:

Zhejiang Hospital, Hangzhuo, China

Reviewer Comments:

The authors did not include a limitation section, but there were a few weak points to their article. They did not include any anthropometric information, but they did verify that the subjects in both groups were approximately the same in health/well-being regarding sepsis. The clinicians were not blinded.

The ICU was not identified by any particular classification.

Strengths

The patients received a standard, isonitrogenous, isocaloric nutrition support treatment.

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