CI: Monitoring Delivery of Energy (2006)

Citation:

Bower, RH, Cerra FB, Bershadsky B, Licari, JJ, Hoyt DB, Jensen GL, Van Buren CT, Rothkpf MM, Daly JM, Adelsberg BR. Early enteral administration of a formula (Impact Registered Trademark) supplemented with arginine, nucleotides, and fish oil intensive care unit patients: Results of a multicenter, prospective, randomized, clinical trial. Critical Care Medicine, Volue 23(3) March 1995 pp 436-449.

PubMed ID: 7874893
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To determine if early enteral feeding, in an intensive care unit (ICU) patient population, using a formula supplemented with arginine, dietary nucleotides, and fish oil (Impact) results in a shorter hospital stay and a reduced frequency of infectious complications, when compared with feeding a common use enteral formula (Osomolite HN).
Inclusion Criteria:

Men and women between the ages of 18-80 years who had experienced a defined event (trauma, operation, or new onset of infection that necessitated ICU treatment. Must have Acute Physiology and Chronic Hdalth Evaluation II of > = 10 or a Therapeutic Intervention Severity Score of > = 20 and had to be considered appropriated candidates to receive enteral nutrition for at least 7 days. Study entry had to occur within 48 hrs of qualifying event.

Exclusion Criteria:
  • Immunosuppresive drug therapy within the previous 6 months
  • Immunosuppressive condition
  • Autoimmune disorder
  • Organ transplantation
  • Radiation therapy and chemotherapy within the previous 6 months
  • Cancer with a clinically important, post procedural, residual tumor burden
  • IDDM
  • Morbid obesity >200% of IBW or BMI > 40
  • Isolated severe head injury, Glasgow Coma Score of <5
  • Chronic Obstructive pulmonary disease with PCO2 > 45 torr on admission
  • Cardiac disease class III or IV
  • Clinically important renal disease, requiring peritonieal or hemodialysis or with admission serum creatinine concentration of >2.5 mg/dL
  • Hepatic dysfunction, with biopsy-proven cirrhosis or a serum total bilirubin >3.0 mg/dL on admission.
Description of Study Protocol:

Pt were randomized to receive either the experimental formula (Impact) that contained arginine, RNA, and Omega 3 fatty acids or the common use control formula Osomolite HN enterally for 7 days. Stratified by age (<60 or >= to 60 years of age) and disease (systemic inflammatory response syndrome or septic). Received enteral formula within 48 hours of the event necessitating ICU admissions and 60 mL/hr of formula within 96 hrs.

Data Collection Summary:

Length of stay after study entry.

Infections acquired after ICU admission .

A multivariate model for analyzing the effects of relevant, dependent variables on hospital length of stay was developed. The model assumes that length of stay is affected by the severity of the injury, the frequency of infections, and the use of the experimental feeding formula.  The model tested for direct and indirect effects of the feeding formula on length of stay.

Description of Actual Data Sample:

326 Pt randomized into trial, 296 met entrance criteria, 279 were fed (n=147/23 for experimental/died, n=13/10 for control/died)

Summary of Results:

No statistical differences in deaths between groups or subgroups

Of the 279 fed eligible patients 200 were successfully fed and and received at least 5750 mL of formula (n=100 for both experimental and control) by the end of the early feeding period.

Of the 279 fed pts there were no statistically significant differences in between exp and control groups in LOS and infections per patient. There was a significant difference in LOS (21days for experimental, 29 for control) in a subgroup of pt (exp n=39, control n=46) who received > = 1150 mL formula in 96 hours, fed at least 7 days, >= 5 consecutive days at 1150 mL during early feeding, and >=5750 mL by end of 7 days.

In the 89 pt that were stratified as septic there were significant reductions in: a) median LOS (control 28 to experimental 18days) b) per patient frequency of the total number of acquired infections ( 0.88+ 0.95 for control versus 0.36 + 0.60 for experimental) and c) bacteremias (control 7 vs experimental 0). In this subgroup of patients, those in the experimental group received less formula and calories than the control group.

Multivariate analysis—

In the pts stratified as septic at study entrance: a) the probability of a prolonged length of stay was increased by acquired infections and directly decreased by the use of experimental feeding; b) the probability of an acquired infection was increased by a high admission APACHE II score and decreased by the experimental feeding formula; c) the probability of an infection during the early feeding was increased by a high severity of injury.  Thus the experimental formula had an indirect benefit of reducing the length of stay by decreasing the probability of an acquired infection during the feeding interval.

The probability of a significant reduction in length of stay was substantially increased with the use of experimental formula

Author Conclusion:

The patients who were randomized to receive the experimental formula, who were stratified as septic on entrance to the study, and who were fed, experienced a significant reduction in hospital length of stay and a significant reduction in the rate of acquired infections. Although there was a relevant trend toward similar end points in the patients with systemic inflammatory response syndrome, the difference in end points did not reach statistical significance at the p <0.05 level. In a subgroup of patients who received a mean of 821 mL of formula per day (the group that was fed the most consistent) the LOS was significantly less in the experimental group.

The multivariate analysis demonstrated that the experimental formula abrogated the affect of injury severity by reducing the probability of an acquired infection during the feeding interval. This effect was manifested by a reduction in antibiotic use and LOS.

Pts who received adequate doses of formula, particularly if they were septic on admission to the study, demonstrated fewer infections and reduced LOS with the experimental formula than the common use formula.

Funding Source:
Reviewer Comments:

Formulas not isocaloric or isonitrogenous.

Pt receiving experimental formula received more nitrogen

Significance decreases in LOS and number of infections demonstrated only in subgroup fed consistently and greater than 821 mL/day. Subgroup experimental n= 14, control n=20.

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