CI: Body Weight and Outcomes: Mixed ICU Patients (2007)


O’Brien JM, Welsh CH, Fish RH, Ancukiewicz M, Kramer AM. Excess body weight is not independently associated with outcome in mechanically ventilated patients with acute lung injury. Ann Intern Med. 2004; 140:338-345.

PubMed ID: 14996675
Study Design:
Meta-analysis or Systematic Review
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To evaluate interaction between assigned ventilator protocol and BMI to determine whether the beneficial effect of lower tidal volume extends to obese patients with acute lung injury.


Inclusion Criteria:
Patients who participated in the NHLBI's multicenter, randomized trials of the ARDS Network.
Exclusion Criteria:
Patients who did not participate in the NHLBI multicenter RCT of the ARDS network.

Patients who participated in the NHLBI multicenter RCT of the ARDS network and for whom complete data did not exist

Description of Study Protocol:

Recruitment: review of existing records

Design: Secondary data analysis from RCT; included intent-to-treat analysis

 Blinding used- no

 Intervention- patients assigned to lower or higher tidal volume

Statistical Analysis-

Unadjusted analyses by comparing values for patients across the 3 BMI categories (normal vs overweight vs obese) for outcome variables of intrest. Used 2-sided Fisher exact test for dichotomous variables; a 2-sided likelihood ratio chi-square test for nondichotomous categorical variables; Kruskal-Wallis test, analysis of variance, or Wilcoxon rank-sum test for continuous variables. Correlation matrices constructed to guide regression estimation. Logistic regression used for dichotomous outcome variables and linear regression for continuous outcome variables. To estimate base regressions, variables for inclusion selected on basis of significant differences in unadjusted analyses and clinical relevance. To minimize multicollinearity, variables with correlation greater than 0.5, only one variable was considered. Base model included variables of strong clinical relevance that had statistically significant unadjusted effect (P<.05).

Data Collection Summary:

Dependent Variables

  • Mortality (death within 28 days after study enrollment)
  • Achievement of unassisted ventilation by day 28 (unassisted ventilation defined as liberation from mechanical ventilation for ≥ 48 consecutive hours
  • Ventilator free days (number of days of unassisted ventilation from day 1 to day 28)
  • Survival to home or to 180 days which was duration of the study

Independent Variables

  • Tidal volume: Adjustment to higher (12 mL/kg of predicted weight) or lower (6 mL/kg of predicted weight) tidal volume ventilation strategies with specified weaning protocols.
  • Some patients received ketoconazole, lisofylline, or placebo by factorial design.

Control Variables

  •  BMI
Description of Actual Data Sample:


Initial N: 902 mechanically ventilated patients

Attrition (final N): not applicable

Age: mean 51.5 ± 17.4 yrs

Ethnicity: not described

Other relevant demographics: mean APACHE III score 74.6 ± 27.7

Anthropometrics: Obese and overweight patients were more likely to have had indirect cause of lung injury including trauma p=.0039.

Location: 10 US medical centers that participate in the NHLBI acute respiratory distress syndrome (ARDS) network.


Summary of Results:

Excess body weight was not independently associated with clinical outcomes.


Factors independently associated with death at 28 days
Odds Ratio (95% CI)
P value
BMI category
    Over wt BMI vs normal BMI
     Obese BMI vs normal BMI
1.96 (0.711-1.690)
1.111 (0.693-1.782)
Older age
1.037 (1.025-1,050)
Higher APACHE II score
1.020 (1.013-1.027)
Assignment to 12 mL/kg tidal volume protocol
1.688 (1.166-2.444)
Lower baseline ratio of Pao2 to Fio2
0.996 (0.993-0.999)
Higher pre-enrollment peak airway pressure
1.025 (1.003-1.048)


Author Conclusion:
After risk adjustment, outcomes for overweight and obese patients with acute lung injury are similar to those of patients with normal BMI. Patients with normal, overweight, or obese BMI all benefit from lower tidal volume ventilation for acute lung injury.
Funding Source:
Reviewer Comments:
This secondary analysis of data from a previous study had a very detailed description of the elaborate and well-designed statistical testing scheme. Study funded, reviewed, and approved by NHLBI prior to publishing.
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? 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? 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.) 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? Yes
  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? 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