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CI: Timing of Enteral Nutrition (2006)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To determine the effect of early vs. delayed enteral feedings of immune-enhancing formula on outcomes [length of hospital stay (LOS) and ICU stay, infectious complications] in a population of severe closed–head-injured patients.

Inclusion Criteria:
  • Patients suffering from severe closed-head injuries at Regional Medical Center at Memphis as indicated by a Glasgow Coma (GCS) score greater than three and less than 11 within six hours post-injury
  • Informed consent from family or legal guardian
  • Absence of any of the conditions stated in the exclusion criteria.
Exclusion Criteria:
  • Age less than 18 or more than 65 years
  • Weight less than 85% or more than 200% ideal body weight (IBW)
  • Pregnancy
  • Patient not expected to survive
  • Abdominal trauma requiring laparotomy
  • Use of steroids more than 24 hours on admission
  • Known HIV-positive patient
  • Current chemotherapy or radiation treatment
  • Class III or IV heart failure
  • Sepsis
  • Severe renal failure
  • Pulmonary failure requiring  more than 15cm PEEP and FI02 more than 0.6 within 24 hours of injury
  • Hemodynamic instability or use of pressors.
Description of Study Protocol:

Recruitment

  • Patients were recruited if they were eligible according to inclusion and exclusion criteria
  • It is not clear if all patients who entered the hospital were considered or the timeframe for the recruitment period.

Design

  • Prospective
  • RCT.
Intervention
  • Patients were randomly assigned to receive early (within 60 hours of injury) or delayed (after gastroparesis resolved) enteral feeding
  • Resolved gastroparesis was considered resolved when nasogastric tube output was less than 500ml per day with no abdominal distention or vomiting for 24 hours after the tube was removed
  • All patients received Impact as the EN formula with a goal rate of 21 non-protein kcal per kg per day and 0.3g nitrogen per kg per day for up to 14 days 
  • After day 15, all patients who still required EN received a standard enteral formula
  • Patients were followed daily for 14 days
  • The protocol per the neurosurgery service was followed for care of patients.

Statistical Analysis

  • Demographic and outcome variable differences between early and late groups was assessed using Student's T-tests and Chi square tests
  • Spearman correlation coefficients were used to determine associations between demographic and outcome variables
  • Survival estimates for time in days to a GCS of 14 were estimated using the Kaplan-Meier method for:
    • Early vs. late nutrition
    • Having or not having infections strata.
Data Collection Summary:

Primary Variables 

  • Length of ICU stay
  • Hospital stay
  • Infectious complications (e.g., pneumonia).

All Other Variables

  • Patient demographics
  • Associated injury
  • Injury Severity Score
  • Type of head injury
  • GCS scores
  • Number of ventilator days
  • Number of days to GCS score of 14
  • Feeding complications (e.g., vomiting, diarrhea, aspiration and abdominal distention).
Description of Actual Data Sample:
  • Initial N: 30 (unknown gender)
  • Attrition (final N): 27 (19 males, 8 female)
    • N=12 early feeding group
    • N=15 delayed feeding group (control)
    • The three dropped subjects were two early feeding subjects because of inability to place a nasoenteric tube and one delayed feeding patient who died within 72 hours of injury
  • Age (years): 30±13 early; 36±11 delayed
  • Location: Memphis, TN (Level 1 Hospital)
  • ISS score: 31±13 early; 30±11 delayed
  • Admission GCS: 7±1 early; 7±2 delayed
  • GCS Day 14: 9±4 early; 10±5 delayed
  • Mortality: One (8%) early; four (27%) delayed; not statistically significant.
Summary of Results:

 

Variable Early Delayed Significance
Length of stay in ICU (days)1 18.5±8.8 11.3+6.1 Not significant
Length of stay in hospital (days)1 30.0±14.7 21.3+13.7 Not significant
Ventilator days (days) 15.1±7.5 10.4+6.1 Not significant
Significant infections per patient (#) 0.8±0.8 0.6+0.8 Not significant
Number of patients with pneumonia (%) 6 (50%) 7 (47%) Not significant
Time feeding initiated (hours) 33±15 84+41 P<0.0004
Average kcal per day 1,509±45 1,174±425 P<0.02
Days fed 13±3.7 8±4.5 Not significant
Number of patients with more than 50% goal met for at least five days 10/12 7/15 Not significant
Vomiting N (%) 1 (8) 3 (20) Not significant 
Aspiration N (%) 0 2 (13) Not significant 
Diarrhea N (%) 11 (92) 8 (53) Not significant 
Distention N (%) 5 (42) 8 (53) Not significant 
Intolerance N (%) 5 (42) 7 (47) Not significant 

1 Due to a higher mortality rate in the control group, the trend actually appears to show a trend towards longer hospitalization and ICU stay in the early feeding group. 

Mortality

A greater mortality rate existed in the delayed (control) group; however, this finding was not significant.

Infective Complications

No significant difference existed between the two groups in the number of infections suffered by each patient.

Correlation Analysis

  • The only independent predictor of major infection was admission GCS score (R=-0.6, P<0.003)
  • GCS score also predicted length of hospital stay (P<0.02), ICU (P<0.03) and ventilator days (P<0.007).

Strata

  • Rapid neurologic recovery, as measured by number of days to GCS of 14, was not related to timing of the feeding but was significantly different between patients who developed major infections and those who did not 
  • Fewer patients with infections reached a GCS of 14 during their hospital stay, and those who reached a GCS of 14 took longer to do so than patients without infections (P<0.02).
Author Conclusion:
  • Timing of feeding of enteral nutrition in severe head-injured patients fed an immune-enhanced formula does not appear to have a significant impact on patient length of stay, number of infectious complications or mortality when compared with patients. GCS scores seemed to be the only indicator of these outcomes. Patients with infections also took longer to reach a GCS of 14, if at all.
  • Early enteral feedings in head-injured patients appears safe; however, this does not appear to offer any additional benefits than those patients receiving enteral nutrition after the patient’s gastric ileus resolves.
Funding Source:
Industry:
Novartis Nutrition Corporation
Pharmaceutical/Dietary Supplement Company:
Reviewer Comments:
  • Strengths:
    • Randomized, controlled trial
    • Attrition reported (10%)
  • Limitations:
    • No information pertaining to the method of randomization
    • Small sample size
    • Initiated enteral feeding within 60 hours of injury may not be early enough to demonstrate benefit
    • No reporting of statistical adjustment for multiple T-tests and Chi-square tests.
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) ???
  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? 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? 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? N/A
  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? N/A
  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? 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