EAL

CI: Immune-Modulating Enteral Nutrition (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

Study the effect of Immunonutrition on the clinical outcome of a heterogeneous ICU population receiving enteral nutrition for more than 2 days.

Inclusion Criteria:

All patients admitted to the ICU who were expected to receive enteral nutrition (EN) for more than 2days.

Exclusion Criteria:

Patients <18 years of age
Chronic renal patients requiring dialysis

Description of Study Protocol:

Study conducted between October 1998 and June 2000
All patients admitted to the ICU expected to receive EN for more than 2 days were eligible.
Patients were randomized to receive either the Immunonutrition (IMN) or a control formula.
IMN formula was high-protein, enteral tube feed enriched with glutamine, arginine, n3-fatty acid, antioxidants, and fibers.
The control formula was isocaloric. Protein content was chosen to keep at a standard level (16% of energy from total energy content).
Goal feeding regimen: 500ml on day one, 1000ml on day two, 1500ml on day three, and 2000ml or required volume on day 4.

Statistical Analysis

Differences in continous variables were determined by the Student's t test for independent samples or the Mann-Whitney U test, depending on their distribution. Differences in binomial variables were determineed by Fisher's exact test. Kaplan-Meier analysis (log-rank test) was used to correct LOS for mortality by censoring for death at time of event. Two-tailed statistical analysis was performed, and differecnes were regarded as significant if p values were below 0.05.

Data Collection Summary:

Patient Demographics were determined on admission

Age, gender, weight, height, and body mass index
Acute Physiology and Chronic Health Evaluation II score (APACHE II)
Type of diagnosis
Daily energy requirement

Primary Outcome Parameters

ICU Length of Stay (LOS)

Secondary Outcome Parameters

ICU mortality, In-hospital mortality, 28-day mortality
Hospital LOS
Complication Rate (Infection, Respiratory Dysfunction, Renal dysfunction, Hepatic dysfunction, Hematological dysfunction, Hypotension)
Duration of Ventilation

Description of Actual Data Sample:

Patient Totals:

N = 597 (390 men & 207 women) patients were included in the Intention-To-Treat (ITT) analysis.
N= 473 (303 men & 170 women) patients were included in Per Protocol (PP) analysis. 123 did not meet the inclusion criteria or receive EN for 2days or less (control 54 vs. IMN 69)

Age: ITT control 68 years (55-74), ITT IMN 66 years (49-74); PP control 67 years (55-74, PP IMN 65 years (47-75)

Summary of Results:

Table 1. Patient characteristics and clinical outcome (IMN Immunonutrition, APACHE Acute Physiology and Chronic Health Evaluation, HB Harris-benedict Equation, LOS length of stay, IQR interquartile range).

	Intention to Treat	Intention to Treat		Per Protocol	Per Protocol
	Control (n=295)	IMN (n=302)	P Value	Control (n=241)	IMN(n=232)	P Value
Mortality ICU In-Hosp 28-days	78 (26.8%) 106 (36.4%) 82 (30.4%)	84 (28%) 114 (38.5%) 93 (33.7%)	0.713 0.610 0.411	61 (25.3%) 84 (34.9%) 71 (30.0%)	75 (32.3%) 95 (40.9%) 81 (35.1%)	0.104 0.185 0.278
LOS (days) ICU Hospital	8 (5-16) 20 (10-34)	7 (4-14) 20 (10-35)	0.085 0.550	9 (6-17) 21 (10-35)	9 (5-16) 21 (10-36.8)	0.282 0.697
Infection	123 (41.7%)	130 (43.0%)	0.741	115 (47.7%)	119 (51.3%)	0.462
Ventilation	6 (3-12.0)	6.0 (3.0-12.0)	0.69	6.0(3.0-12.0)	6.0(3.0-12.0)	0.703

Table 2 Patient characteristics and clinical outcome in moderately sick (APACHE <20) and severely Sick (APACHE II>20) patients.

	Moderately Sick	Moderately Sick		Severely Sick	Severely Sick
	Control (n=168)	IMN (n=168)	P Value	Control (n=68)	IMN(n=55)	P Value
Mortality ICU In-Hosp 28-days	39 (23.2%) 52 (31.0%) 42 (25.1%)	50 (29.8%) 64 (38.1%) 55 (32.7%)	0.216 0.207 0.148	20 (29.4%) 30 (44.1%) 27 (41.5%)	23 (41.8%) 27 (49.1%) 23 (41.8%)	0.184 0.591 1.000
LOS (days) ICU Hospital	9 (5-16) 13 (10-34)	7 (4-14) 20 (10-35)	0.085 0.550	9 (6-17) 21 (10-35)	9 (5-16) 21 (10-36.8)	0.282 0.697
Infection	31 (48.2%)	87 (51.8%)	0.585	33 (48.5)	27 (49.1%)	1.000
Ventilation	6.0 (3-12.8)	7.0 (3.0-12.8)	0.922	7.0(3.0-11.0)	5.0(3.0-11)	0.357

Other Findings

No statistical significant difference in Mortality, LOS, Complications, and days on Ventilation when patients separated in to surgical and nonsurgical.

Author Conclusion:

No statistical significant differences in clinical outcome were observed between Immune Enhancing Nutrition and control groups in Intention to treat or Per Protocol analyses or within subgroups of surgical, trauma, and medical patients.

Funding Source:

Industry:

Numico Research

Food Company:

University/Hospital:

Isala Clinic (Netherlands), Catharina Hospital (Netherlands),

Reviewer Comments:

This is a large well designed study.

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)	N/A
	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.)	N/A
	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?	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?		???
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	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.)	N/A
	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?	Yes
	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)?	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?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	???
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