Obesity paradox of sepsis in long-term outcome: The differential effect of body composition

Background: The obesity paradox has been widely studied recently; however, its impact on the long-term prognosis of sepsis and the protective mechanism of body mass have not yet been sufficiently revealed.

Methods: We retrospectively evaluated the association between obesity and 1-year survival after sepsis in a single university-affiliated hospital and examined the differential effects of muscle mass and adiposity.

Results: Adult patients with sepsis or septic shock (n = 1492)were classified into obese (n = 300) and nonobese (n = 1192) groups. One-year mortality due to sepsis was lower in the obese than in the nonobese (52.0 % vs. 64.8 %; p < 0.001). In multivariate Cox analysis, one-year mortality due to sepsis was independently associated with body mass index (BMI) (hazard ratio 0.96). In the subgroup analysis, 705 were divided into four groups according to the psoas muscle index (PMI) and body fat percentage (BFP) to assess the differential impact of body fat and muscle mass on the one-year outcome of sepsis. One-year mortality was significantly different among the four groups (high BFP/low PMI, 60.6 %; high BFP/high PMI, 42.1 %; low BFP/high PMI, 34.8 %; low BFP/low PMI, 63.2 %; p = 0.002). The adjusted hazards ratio of one-year mortality of sepsis, which was normalized to the low BFP/high PMI group, were 1.2 (p = 0.585), 2.2 (p = 0.016), and 2.3 (p = 0.009) in groups of high BFP/high PMI, high BFP/low PMI, and low BFP/low PMI, respectively.

Conclusion: An obesity paradox has been observed in the long-term outcomes of patients with sepsis, and muscle mass may be more critical than fat mass as a protective mechanism against obesity.

Implications for clinical practice: A high BMI is linked to a more favorable long-term prognosis in sepsis, with muscle mass playing a more critical role than fat mass. A proactive nutritional and conditioning program may benefit patients anticipating major procedures and potential ICU admission. Such preparation could enhance their resilience and improve outcomes when facing critical illness, including sepsis.