CI: Immune-Modulating Enteral Nutrition (2006)

Study Design:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To determine whether early enteral feeding in a septic intensive care unit (ICU) population, using formula supplemented with arginine, mRNA, and omega-3 fatty acids from fish oil (IMPACT), improves clinical outcomes, when compare with a common use, high protein enteral feed without these nutrients.
Inclusion Criteria:
  • Men and nonpregnant women >14years old.
  • Septic-defined as a positively cultured or clinically diagnosed infection with two or more of the following:
    • Body temperature of .38 degrees or less than 36 degrees
    • Heart rate >90 beat/min
    • Respiratory rate of >20 breaths/min or a PaCO2 of <32 torr
    • White blood count of >12,000 cells/mm3 or <4,000 cells/mm3
  • APACHE II score >=10 at time of admission to ICU
Exclusion Criteria:
  • Previous radio therapy
  • Treatment with immunosuppressive drugs
  • AIDS
  • Neoplasia
  • Metastases
  • Already received immune-enhancing enteral or parenteral (branched-chain amino acids, omega 3 fish oil, glutamines, or nucleotides) nutrition.
Description of Study Protocol:

Pt were randomized to receive control solution (Precitene Hiperproteico) or experimental solution (IMPACT), unblended, via nasoenteric, nasogastric, gastrostomy, or jejunostomy tube.

Calorie needs were determined using HBE formula, using ht, IBW, and stress factor of 1.3.

Enteral nutrition was started within 36 hours and total intake caloric needs to be reached by day 4 after entry in to the study.

both formulas were similar in from. The treatment feed had slightly higher nitrogen content because of the additional nitrogen found in arginine.

Data Collection Summary:
  • Frequency, type, organism, localization, adn required treatment for infection recorded.
  • LOS in ICU.
  • Digestive complications.
Description of Actual Data Sample:

Initial N: 181 (87 control, 94 treatment)

Attrition (final N): 176 (87 control, 86 treatment)

Five pt in the treatment group were excluded from the intention-to-treat analysis.

No significant differences between patient groups in terms of age height, ideal wt, gender, and ICU admission APACHE II score.

Summary of Results:
  • Control group received more calories.
  • No difference in amount of Nitrogen received, nor Nitrogen balance between the two groups.
  • Mortality rate of treatment group was less than control group.
  • Number of acquired bacteremias in treatment group was also less than that in the control group.
  • LOS was higher for treatment group-difference not significant.
  • At APACHE scores of 10-15 the relative risk of death is lower for the treatment group.
  • No significant difference in relative risk at the higher APACHE scores.
  • No difference in rates of diarrhea or digestive complications.


Author Conclusion:
Overall, compared to a standard enteral formula, immunonutrition enriched with arginine, nucleotides, and omega-3 fish oils seems to reduce the mortality rates as well as the recurrence rate of bacteremias for septic ICU patients. Benefit to the mortality rate seems to be more pronounced for the less ill patients, patients with lower APACHE II scores of 10-15.
Funding Source:
Novus Nutrition
Food Company:
Foundation associated with industry:
Reviewer Comments:

Not blinded

Sufficient Power

No significant benefit in mortality rate in those with APACHE scores greater than 15.

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? N/A
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? N/A
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) N/A
Validity Questions
1. Was the research question clearly stated? N/A
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? N/A
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? N/A
  1.3. Were the target population and setting specified? N/A
2. Was the selection of study subjects/patients free from bias? N/A
  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? N/A
  2.2. Were criteria applied equally to all study groups? N/A
  2.3. Were health, demographics, and other characteristics of subjects described? N/A
  2.4. Were the subjects/patients a representative sample of the relevant population? N/A
3. Were study groups comparable? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  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? 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? N/A
  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? N/A
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  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? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  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? N/A
  7.1. Were primary and secondary endpoints described and relevant to the question? N/A
  7.2. Were nutrition measures appropriate to question and outcomes of concern? N/A
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? N/A
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? N/A
  7.5. Was the measurement of effect at an appropriate level of precision? N/A
  7.6. Were other factors accounted for (measured) that could affect outcomes? N/A
  7.7. Were the measurements conducted consistently across groups? N/A
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? N/A
  8.1. Were statistical analyses adequately described and the results reported appropriately? N/A
  8.2. Were correct statistical tests used and assumptions of test not violated? N/A
  8.3. Were statistics reported with levels of significance and/or confidence intervals? N/A
  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? N/A
  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? N/A
  9.1. Is there a discussion of findings? N/A
  9.2. Are biases and study limitations identified and discussed? N/A
10. Is bias due to study's funding or sponsorship unlikely? N/A
  10.1. Were sources of funding and investigators' affiliations described? N/A
  10.2. Was the study free from apparent conflict of interest? N/A