Title:
The relationship among obesity, nutritional status, and mortality in the critically ill.

Abstract:
The association between obesity and mortality in critically ill patients is unclear based on the current literature. To clarify this relationship, we analyzed the association between obesity and mortality in a large population of critically ill patients and hypothesized that mortality would be impacted by nutritional status.
We performed a single-center observational study of 6,518 adult patients treated in medical and surgical ICUs between 2004 and 2011. All patients received a formal, in-person, and standardized evaluation by a registered dietitian. Body mass index was determined at the time of dietitian consultation from the estimated dry weight or hospital admission weight and categorized a priori as less than 18.5 kg/m (underweight), 18.5-24.9 kg/m (normal/referent), 25-29.9 kg/m (overweight), 30-39.9 kg/m (obesity class I and II), and more than or equal to 40.0 kg/m (obesity class III). Malnutrition diagnoses were categorized as nonspecific malnutrition, protein-energy malnutrition, or well nourished. The primary outcome was all-cause 30-day mortality determined by the Social Security Death Master File. Associations between body mass index groups and mortality were estimated by bivariable and multivariable logistic regression models. Adjusted odds ratios were estimated with inclusion of covariate terms thought to plausibly interact with both body mass index and mortality. We utilized propensity score matching on baseline characteristics and nutrition status to reduce residual confounding of the body mass index category assignment.
In the cohort, 5% were underweight, 36% were normal weight, 31% were overweight, 23% had class I/II obesity, and 5% had class III obesity. Nonspecific malnutrition was present in 56%, protein-energy malnutrition was present in 12%, and 32% were well nourished. The 30-day and 90-day mortality rate for the cohort was 19.1 and 26.6%, respectively. Obesity is a significant predictor of improved 30-day mortality following adjustment for age, gender, race, medical versus surgical patient type, Deyo-Charlson index, acute organ failure, vasopressor use, and sepsis: underweight odds ratio 30-day mortality is 1.09 (95% CI, 0.80-1.48), overweight 30-day mortality odds ratio is 0.93 (95% CI, 0.80-1.09), class I/II obesity 30-day mortality odds ratio is 0.80 (95% CI, 0.67-0.96), and class III obesity 30-day mortality odds ratio is 0.69 (95% CI, 0.49-0.97), all relative to patients with body mass index 18.5-24.9 kg/m. Importantly, there is confounding of the obesity-mortality association on the basis of malnutrition. Adjustment for only nutrition status attenuates the obesity-30-day mortality association: underweight odds ratio is 0.74 (95% CI, 0.54-1.00), overweight odds ratio is 1.05 (95% CI, 0.90-1.23), class I/II obesity odds ratio is 0.96 (95% CI, 0.81-1.15), and class III obesity odds ratio is 0.81 (95% CI, 0.59-1.12), all relative to patients with body mass index 18.5-24.9 kg/m. In a subset of patients with body mass index more than or equal to 30.0 kg/m (n = 1,799), those with either nonspecific or protein-energy malnutrition have increased mortality relative to well-nourished patients with body mass index more than or equal to 30.0 kg/m: odds ratio of 90-day mortality is 1.67 (95% CI, 1.29-2.15; p < 0.0001), fully adjusted. In a cohort of propensity score matched patients (n = 3,554), the body mass index-mortality association was not statistically significant, likely from matching on nutrition status.
In a large population of critically ill adults, the association between improved mortality and obesity is confounded by malnutrition status. Critically ill obese patients with malnutrition have worse outcomes than obese patients without malnutrition.