“Effect of weight-based versus absolute norepinephrine dosing on mortality risk in obese patients with septic shock: an observational, multicohort, retrospective study”

Background: Norepinephrine dose is used as an indicator of severity and a decision-making tool in septic shock management, influencing the initiation of adjuvant therapies, life support limitation and mortality estimation. However, weight-based dosing may impact its accuracy, particularly given the rising global incidence of obesity. Our objective was to assess how body mass index (BMI) influences the relationship between norepinephrine dosing strategy (absolute vs. weight-based) and observed mortality in patients with septic shock. Methods: Retrospective analysis of six open-access datasets encompassing more than 300 intensive care units (ICU) in four countries. The relationship with ICU mortality of both absolute and weight-based norepinephrine dosing was analyzed in the same set of septic shock patients using non-parametric generalized additive models, adjusted by disease severity. Results: Among 386,792 critically ill patients screened, 10,246 septic shock patients were identified. Patients had a SOFA score of 7 [5, 10], required a norepinephrine dose of 0.1 [0.05, 0.2] μg/kg/min (7 [3.4, 15.8] μg/min) and presented lactate levels of 3.0 [2.3, 4.8] mmol/l at diagnosis. 2,858 (28%) patients had a BMI above 30 kg/m 2 . SOFA-adjusted estimated mortality using weight-based norepinephrine dosing was significantly affected by BMI, with a mean difference in predicted mortality of 14.5% (95% CI 13.7 to 15.3%, p Analysis of Deviance <0.001) between obese and non-obese patients. At higher norepinephrine doses (>0.3 µg/kg/min), weight-based dosing led to a progressive mortality underestimation with increasing BMI, reaching mortality divergences of up to 26% at doses of 1 µg/kg/min between patients with BMIs of 20 and 50 kg/m 2 . In contrast, mortality estimation by absolute norepinephrine dosing was not affected by BMI (mean difference in predicted mortality between obese and non-obese 0.3% [95% CI, -0.1 to 0.6%], p Analysis of Deviance =0.715). Conclusion: Weight-based norepinephrine dosing may underestimate ICU mortality in obese patients with septic shock, especially at higher doses, distorting risk stratification and potentially influencing clinical decision making. Absolute dosing offers a simpler, consistent approach across BMI categories and dose ranges.