EAL

CI: Initiation of Enteral Nutrition (2012)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate trauma patients receiving early immune enhancing diet (IED) vs. isocaloric isonitrogenous enteral diet (ISO) on clinical outcomes and to prospectively analyze a control group that was not immediately fed (late unfed control group without randomization).

Inclusion Criteria:

18 years to 65 years of age
ISS of at least 21, ATI of at least 25
Glasgow Coma Scale of at least seven
Candidate for enteral feeding.

Exclusion Criteria:

Pregnancy
Any genetic immune or autoimmune disorder
Recipient of an organ transplant
Known IDDM
Hepatic dysfunction with serum total bili over 2.5mg per dL or known history of cirrhosis
Hx COPD
Prior positive test for HIV
Confirmed sepsis or suspected infection or sepsis at study entry
Metastatic cancer
Systemic steroids more than 48 hours
Immuosuppressive drugs, chemotherapy or radiation therapy within the previous six months
CHF; complicated heart disease
Existing renal disease
Head injury with Glasgow Coma Scale below seven at 24 hours post-injury
Mentally incompetent
Imprisoned individuals.

Description of Study Protocol:

Recruitment: Patients admitted between March 1994 and June 1995 to the Presley Memorial Trauma Center at The University of Tennessee, Memphis
Design: Prospective randomized clinical trial
Blinding Used: Not described

Intervention

35 patients with early enteral access were randomized to study diet (IED) or ISO diets within eight hours of operation
Patients eligible by severity of injury, but without early enteral access, served as controls (non-randomized)
Experimental diet (Immun-Aid) was compared with ISO diet (four cans of Promote with 22g added protein and 50ml water)
Controls had specialized nutrition only after consultation by the trauma team
Nitrogen needs were calculated at a rate of 0.32g to 0.38g nitrogen per kg per day
Prophylactic antibiotics were used for 24 hours
NG decompression was done for three days.

Statistical Analysis

Categoric variables tested with Fisher’s exact test or chi-square test of homogeneity
Continuous variables tested with Wilcoxon’s rank sum test or median test
Statistical power analysis determined 40 patients would have been needed in both the ISO Group and Control to reach statistical significance.

Data Collection Summary:

Timing of Measurements

The following data was collected at zero and seven days:

Albumin
Prealubumin
Blood urea nitrogen
Creatinine
Potassium
Glucose
Triglyceride
Magnesium
Phosphorus
Transferrin
Bilirubin
Leukocyte.

Dependent Variables

IED, ISO or control diet.

Independent Variables

Septic complications: Intra-abdominal abscess, IAA with colon injury, pneumonia, bacteremia, wound infection, UTI, sepsis syndrome.

Controls

Two patients received nutrition before diagnosis of infection: One received one day of 25ml-per-hour gastric feeding and one received three days of TPN and two days gastric feeding
Remaining patients received IV dextrose and no nutrition support before developing infection.

[Note: At time of hospital discharge, all charts reviewed by PI for confirmation of infection, LOS, number of vent days, number of TF days, blood administration and antibiotic usage.]

Description of Actual Data Sample:

Initial N

N=54

17 received IED: One died (data excluded); 34.3 years old; 15 males, one female
18 received ISO: One died (data excluded); 31.8 years old; 15 males, two females
19 unfed controls: 35.7 years old; 10 males, nine females.

Attrition

There was one subject from each of the two enterally-fed groups that died from progressive multiple organ failure.

Ethnicity

Not described.

Location

University of Tennessee, Memphis.

Summary of Results:

Significant Differences

More females in Control than other two groups
More duodenal injuries in IED patients than Control. More colon injuries in Control than ISO.
IED patients had fewer total septic complications than controls (P=0.03) or ISO (P=0.06)
IED had significantly less pneumonia and abscess compared to ISO (P=0.02) and Control (P=0.002)
IED significantly reduced empiric antibiotic usage (P=0.02), compared to ISO or Control (P=0.002)
IED significantly reduced hospital stay, compared with ISO (P=0.03) or Control (P=0.03).

No Significant Differences

Groups’ ages, ISS, ATI, mechanism of injury or Glasgow Coma Scale
Blood administration in ISO or IED patients (controls received less blood than ISO or IED)
Albumin, prealbumin, transferrin, bilirubin, leukocytes, BUN, creatinine, glucose, triglyceride, magnesium, phosphorus or potassium
ICU stay and vent days (highest in unfed controls; P=0.10 and P=0.09, respectively)
Hospital charges (P=0.10), but highest charges were for unfed controls.

[Note: Feedings started at 1.63±0.16 days in IED and at 1.97±0.23 for ISO.]

Author Conclusion:

Specialized enteral formula (IED) significantly reduces septic complications while reducing hospital charges, compared with isonitrogenous standard diets
Use of the specialized diet also significantly improves outcome, compared with patients receiving minimal (if any) early nutrition intervention
An IED is the preferred diet for early enteral feeding after severe blunt and penetrating trauma in patients at risk of subsequent septic complications
Unfed patients have the highest complication rate (hospital stay, infectious complications hospital cost and antibiotic usage was highest in the Unfed Group).

Funding Source:

Industry:

McGaw Pharmaceuticals Inc,

Pharmaceutical/Dietary Supplement Company:

University/Hospital:

U of Tennesse

Reviewer Comments:

Description of diet composition
No description of diet tolerance
Limited presentation of demographic data
Late (Unfed Group) had the most difficult hospital course, including complications from infection, LOS and increased cost
Marginal outcome differences between ISO and unfed Control Group
Small sample size
No power calculation presented
No description of randomization scheme.

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?		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?		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?	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?	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?	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?	No
	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?	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