Does Obesity Protect Against Death in Sepsis? A Retrospective Cohort Study of 55,038 Adult Patients

Objectives: Observational studies suggest obesity is associated with sepsis survival, but these studies are small, fail to adjust for key confounders, measure body mass index at inconsistent time points, and/ or use administrative data to define sepsis. To -estimate the relationship between body mass index and sepsis mortality using detailed clinical data for case detection and risk adjustment. Design: Retrospective cohort analysis of a large clinical data repository. Setting: One- hundred thirty- nine hospitals in the United States. Patients: Adult inpatients with sepsis meeting Sepsis- 3 criteria. Exposure: Body mass index in six categories: underweight (body mass index < 18.5 kg/m2), normal weight (body mass index = 18.5- 24.9 kg/m2), overweight (body mass index = 25.029.9 kg/m2), obese class I (body mass index = 30.0- 34.9 kg/m2), obese class II (body mass index = 35.0- 39.9 kg/m2), and obese class III (body mass index = 40 kg/m2). Measurements: Multivariate logistic regression with generalized estimating equations to estimate the effect of body mass index category on short- term mortality (in- hospital death or discharge to hospice) adjusting for patient, infection, and hospital- level factors. Sensitivity analyses were conducted in subgroups of age, gender, Elixhauser comorbidity index, Sequential Organ Failure Assessment quartiles, bacteremic sepsis, and ICU admission. Main Results: From 2009 to 2015, we identified 55,038 adults with sepsis and assessable body mass index measurements: 6% underweight, 33% normal weight, 28% overweight, and 33% obese. Crude mortality was inversely proportional to body mass index category: underweight (31%), normal weight (24%), overweight (19%), obese class I (16%), obese class II (16%), and obese class III (14%). Compared with normal weight, the adjusted odds ratio (95% CI) of mortality was 1.62 (1.50- 1.74) for underweight, 0.73 (0.70- 0.77) for overweight, 0.61 (0.570.66) for obese class I, 0.61 (0.55- 0.67) for obese class II, and 0.65 (0.59- 0.71) for obese class III. Results were consistent in sensitivity analyses. Conclusions: In adults with clinically defined sepsis, we demonstrate lower short- term mortality in patients with higher body mass indices compared with those with normal body mass indices (both unadjusted and adjusted analyses) and higher short- term mortality in those with low body mass indices. Understanding how obesityimproves survival in sepsis would inform prognostic and therapeutic strategies.