EAL

CI: Calorie/Energy Needs (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine the effects of withholding intravenous fat emulsion (IVFE) infusions in trauma patients requiring total parenteral nutrition (TPN) during a 10 day study period.

Inclusion Criteria:

trauma patients between ages of 18 and 50 years of age who requiried TPN

Exclusion Criteria:

Patients were excluded if

they were able to tolerate more than 10% of their caloric requirement as enteral feeding at the time of randomization
had clinical evidence of fatty acid deficiency
had hepatic cirrhosis, HIV, or a concurrent malignancy
were receiving steroids or nonsteroidal anti-inflammatory agents.

Description of Study Protocol:

Recruitment: trauma patients requiring TPN after admission to the Trauma Surgery Service between September 1992 and July of 1994; entry criteria not well defined

Design: prospective, randomized trial

Blinding used: not applicable

Intervention:

Patients were randomized on or after their fifth post-injury day. IVFE infusions (Intralipid) were withheld until after randomization. The TPN regimen was similar for all patients, with the exception of the difference in fat emulsion administration.

Standard TPN was formulated based on ideal body weight with the goal of providing 30 nonprotein kcal/kg/day with 25% of the calories provided as fat-- (fat emulsions as IVFE withheld in no lipid patients) and 1.5g/kg/day of amino acids (both groups received the same carbohydrate and amino acid dose). Caloric requirements were estimated using the Harris-Benedict formula. TPN was administered by continuous infusion and was started at one half the goal rate and advanced to full rate on the second day. Patients in the lipid group received the standard TPN formulation including the IVFE; patients in the no lipid group received the same regimen of TPN except IVFE was withheld for the 10-day study period.

For the patients randomized to the no lipid group, calories lost due to the lack of IVFE infusion were not replaced with additional carbohydrates. Thus, patients in the no lipid group received a hypocaloric nutritional regimen and were underfed compared with patients in the lipid group who received a standard number of calories.

Clinical outcome parameters were measured.

T-cell function was assessed by measuring lymphokine activated killer (LAK) and natural killer (NK) cell activity.

Statistical Analysis

Continuous variables were compared using Student's t tests

Dichotomous variables were compared using a X² Fisher's Exact Test

Immune function activity measurements (LAK and NK) were not normally distributed, analyzed using a Mann-Whitney U rank sum test; PGE₂ levels and CD₄/CD₈ ratios were analyzed using repeated measures analysis of variance

Statistical significance was defined p < 0.05

Data Collection Summary:

Timing of Measurements

At baseline, demographics were collected for each participant. The demographics included:

Age
Gender
Mechanism of injury
Injury Severity Score
Acute Physiology and Chronic Health Evaluation II score (APACHE II)
Presence of shock on presentation (defined as a systolic blood pressure of 90 mm Hg or less)
Total number of blood transfusions

During the study, clinical outcomes were measured for each patient. These included:

Length of hospital stay and length of stay in the intensive care unit
Number of days on mechanical ventilation
Infectious complications

Laboratory

A 24-hour urine collection was collected for total nitrogen was obtained at baseline to determine nitrogen balance between the third and fifth day of TPN infusion.

Number of days patients were hyperglycemic (glucose > 200 mg/dl); total amount of insulin administered and overall fluid balance for the 10-day study period were also tabulated.

T-cell function as a measure of immune function was assessed my measuring lymphokine activated killer cell activity (LAK) and natural killer cell activity (NK) at the time of randomization and on the fifth day postrandomization using standardized protocols. All assays were performed in triplicate and averaged. The peripheral blood lyphocytes were harvested; variability of the incubated PBLs was confirmed by trypan blue exclusion and noted to be > 98%. PGE₂ levels in the supernatants of cultured PBLs were determined using a enzyme immunoassay test with a sensitivity of 1.5 pg/mL. T-cell phenotypes were determined using phycoerythrin-labeled monoclonal antibodies to CD₄ (Leu-3a) and CD₈ (Leu-2a) receptors.

Along with every patient LAK and NK assay, a normal subject was run as a control.

Dependent Variables

length of ICU and hospital stay
length of mechanical ventilation
infection complications (pneumonia, line sepsis, wound infections, acalculous cholecystitis, bacteremia)
immune function: measured by T-cell function (LAK and NK activities)

Independent Variables

TPN with or without IVFE infusions (2 patient groups)

Description of Actual Data Sample:

Initial N: 60 polytrauma patients requiring TPN randomized to receive standard TPN including IVFE (lipid group) or to receive the same TPN formula without the IVFE infusion (no lipid group)

Attrition: 57 patients (lipid group = 30, 80% males; no lipid group = 27, 85% males);2 patients died (no lipid group), 1 patient ineligible due to medical complications

Mean Age: lipid group: 33 ± 10 years; no lipid group: 32 ± 9 years

Ethnicity: not discussed

Anthropometrics--presented as not significantly different in two groups

Location: University of California, a level I trauma center

Summary of Results:

Both groups were comparable in terms of demographics, Injury Severity Score, distribution of head and chest injuries, and Acute Physiology and APACHE II (22 +/- 5).

Clinical Outcomes

Variable	lipid group (n=30)	no lipid group (n=27)	p-value
mechanical ventilation (days)	27 ± 21	15 ± 12	0.01
ICU length of stay (days)	29 ± 22	18 ± 12	0.02
hospital length of stay (days)	39 ± 24	27 ± 18	0.03
pneumonia: No. of patients with at least one episode (total episodes)	22	13	0.05
line sepsis: No. of patients with at least one episode (total episodes)	13	5	0.04

Other Findings

No significant differences between groups in mortality rate.

Nitrogen balance, number of days patients were hyperglycemic and total insulin administered were similar for the two groups

The lipid group had a total of 72 (mean 2.4 per patient) infections compared with 39 (mean 1.4 per patient) in the no lipid group. Significant differences in pneumonia and line sepsis; however, were not significantly different for bacteremia (p=0.68), abdominal abscess (p=0.99), superficial wound infections (p=0.3) or other wound infections (urinary tract, acalculous cholecystitis, sinusitis, etc. p=0.35).

T-cell function (both LAK and NK) improved from baseline values during the first 5 days of TPN in the no lipid group, but was depressed in the lipid group. PGE₂ production and CD₄/ CD₈ ratios did not differ significantly between the two groups.

Author Conclusion:

TPN with lipid emulsion infusions was associated with increased days on mechanical ventilation and greater length of stay both in the ICU and in the hospital. It was unclear whether the less favorable outcomes were associated with the lipids or with hypocaloric feedings. IVFE should be used sparingly, if at all, early after surgery, in patients with multiple injuries.

Funding Source:

Government:

NIH

Reviewer Comments:

Limitations include:

conducted for only 10 days
questionable generalizability; study included a sample of critically injured patients who are fairly homogeneous; high percentage male (>80%)
major deficiency in the design is that the control group received fewer calories; there is a question of whether the results could therefore be ascribed to this difference in calories

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?	No
	2.2.	Were criteria applied equally to all study groups?	???
	2.3.	Were health, demographics, and other characteristics of subjects described?	No
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
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?		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?	No
	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?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	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.)	No
	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?	???
	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?	No
	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?	???
	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?	???
	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)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	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