High blood pressure-targeted management associated with reduced benefits of higher body mass index in elderly patients with septic shock: a post hoc analysis of a multicenter randomized controlled trial.

Abstract

Background: Body mass index (BMI) is an important prognostic factor in sepsis, and an obesity paradox has been reported. A higher mean arterial pressure (MAP) target has been associated with worse outcomes in elderly patients with septic shock. However, whether MAP target strategy alters the association between BMI and outcomes in this population is unknown.

Methods: We conducted a post hoc analysis of the OPTPRESS trial, a multicenter randomized controlled trial at 29 Japanese centers reporting worse outcomes with a high MAP target in elderly patients with septic shock. A total of 489 patients aged ≥65 years with septic shock were assigned to a control MAP target of 65-70 mmHg (n = 245) or high target of 80-85 mmHg (n = 244). Patients were categorized using Asian BMI cutoffs into underweight (<18.5 kg/m²), normal-weight (18.5-22.9 kg/m²), and higher-BMI (≥23 kg/m²) categories. The primary outcome was 90-day mortality. The primary analysis assessed the interaction between BMI category and MAP target strategy.

Results: In the control group, mortality decreased across increasing BMI categories (P = 0.03 for the trend), while no trend was observed in the high-target group (P = 0.26 for the trend). After adjustment for age, sex, APACHE II score, Clinical Frailty Scale, and site of infection, MAP target strategy significantly interacted with the higher-BMI category (P = 0.02), but not with underweight (P = 0.41). In the high-target group, both underweight and higher-BMI patients had higher mortality than those with normal BMI (underweight, adjusted HR 1.74 [95% CI 1.02-2.98], P = 0.04; higher BMI, adjusted HR 1.72 [95% CI 1.02-2.87], P = 0.04). Fluid volume per body weight decreased across increasing BMI categories in both groups. The proportion of patients receiving vasopressin increased across BMI categories only in the control group, whereas the body weight-adjusted vasopressin dose among recipients showed no significant trend in either group.

Conclusions: In elderly patients with septic shock, mortality decreased across increasing BMI categories under a standard MAP target, whereas patients in the higher-BMI category had higher mortality under a high MAP target. High MAP targets may attenuate the survival benefit of higher BMI, possibly in association with BMI-related patterns in fluid and vasopressor management.

Trial registration: Not registered. The original OPTPRESS trial was registered at UMIN Clinical Trials Registry (UMIN000041775) on 13 September 2020.