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The optimal initial fluid resuscitation strategy for obese patients with septic shock is unknown. We evaluated fluid resuscitation strategies across BMI groups.Retrospective analysis of 4157 patients in a multicenter activation pathway for treatment of septic shock between 2014 and 2016.1293 (31.3%) patients were obese (BMI ≥ 30). Overall, higher BMI was associated with lower mortality, however this survival advantage was eliminated in adjusted analyses. Patients with higher BMI received significantly less fluid per kilogram at 3 h than did patients with lower BMI (p ≤0.001). In obese patients, fluid given at 3 h mimicked a dosing strategy based on actual body weight (ABW) in 780 (72.2%), adjusted body weight (AdjBW) in 95 (8.8%), and ideal body weight (IBW) in 205 (19.0%). After adjusting for condition- and treatment-related variables, dosing based on AdjBW was associated with improved mortality compared to ABW (OR 0.45; 95% CI [0.19, 1.07]) and IBW (OR 0.29; 95% CI [0.11,0.74]).Using AdjBW to calculate initial fluid resuscitation volume for obese patients with suspected shock may improve outcomes compared to other weight-based dosing strategies. The optimal fluid dosing strategy for obese patients should be a focus of future prospective research.For initial fluid resuscitation in septic shock, obese patients received less fluid per kilogram than did lower BMI patientsInitial fluids based on adjusted body weight was associated with improved mortality compared to other strategies.