One size does not fit all in severe infection: obesity alters outcome, susceptibility, treatment, and inflammatory response

Abstract

Introduction: Obesity is an increasingly common comorbidity in critically ill patients. Whether obesity alters sepsis outcome, susceptibility, treatment, and response is not completely understood.

Methods: We conducted a retrospective analysis comparing three group of septic shock patients based on the intervals of actual body mass index (BMI) in patients enrolled in the VASST (Vasopressin and Septic Shock Trial) cohort. Primary outcome measurement was 28-day mortality. We tested for differences in patterns of infection by comparing the primary site of infection and organism. We also compared the treatments (fluids and vasopressors) and inflammatory response, measuring adipose tissue-related cytokine concentrations (interleukin [IL]-6, monocyte chemotactic protein [MCP]-1, tumor necrosis factor [TNF]-α, and resistin) in plasma in a subset of 382 patients. Of the 778 patients in VASST, 730 patients who had body weight and height measurements were analyzed. Patients with BMI<25 kg/m2 (n=276) were grouped as a reference and compared to 'overweight' (25<BMI<30 kg/m2, n=209) and 'obese' (BMI>30 kg/m2, n=245) patients.

Results: Obese patients had the lowest 28-day mortality followed by overweight patients while patients with BMI<25 kg/m2 had the highest mortality (p=0.02). Compared to the patients with BMI<25 kg/m2, obese and overweight patients also had a different pattern of infection with less lung (obese 35%, overweight 45%, BMI<25 kg/m2 50%, p=0.003) and fungal infection (obese 8.2%, overweight 11%, and BMI<25 kg/m2 15.6%, p=0.03). Per kilogram, obese and overweight patients received less fluid during the first four days (p<0.05) and received less norepinephrine (obese 0.14, overweight 0.21, BMI<25 kg/m2 0.26 µg/kg/min, p<0.0001) and vasopressin (obese 0.28, overweight 0.36, BMI<25 kg/m2 0.43 µU/kg/min, p<0.0001) on day 1 compared to patients with BMI<25 kg/m2. Obese and overweight patients also had a lower plasma IL-6 concentration at baseline (obese 106 [IQR 34-686], overweight 190 [IQR 44-2339], BMI<25 kg/m2 235 [IQR 44-1793] pg/mL, p=0.046).

Conclusions: Overall obesity was associated with improved survival in septic shock and differences in pattern of infection, fluids, and vasopressors. Importantly, the magnitude of inflammatory IL-6 response is muted in the obese.

Figure 1

Kaplan-Meier curves of 28-day survival compared by actual body mass index (BMI) across three groups of patients with septic shock. Obese patients with septic shock had a significantly lowest 28-day mortality following overweight patients, whereas the septic shock patients with a BMI of less than 25 kg/m² had a highest 28-day mortality (P = 0.02, log-rank analysis). *P <0.05, compared among three groups.

Figure 2

Serum vasopressin level during septic shock compared across the three patient groups. At 24 and 72 hours after vasopressin infusion, the overweight and obese patients had a trend toward lower mean vasopressin concentrations compared with those with body mass index (BMI) of less than 25 kg/m² (P = 0.08, one-way repeated-measures analysis of variance). Error bars indicate standard error of the mean.

Figure 3

Plasma interleukin-6 (IL-6) expression differences at the initial phase of septic shock compared across the three patient groups. Compared with patients with a body mass index (BMI) of less than 25 kg/m², overweight and obese patients had significantly lower IL-6 (P = 0.046) plasma levels at the initial phase of septic shock. P values were calculated by using the Kruskal-Wallis test. Error bars indicate interquartile range. *P <0.05.