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 affect its accuracy, particularly given the rising global incidence of obesity. The 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 data sets encompassing more than 300 intensive care units (ICUs) 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 nonparametric 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 Sequential Organ Failure Assessment score of 7 [25th and 75th percentiles, 5 and 10], required a norepinephrine dose of 0.1 [25th and 75th percentiles, 0.05 and 0.2] μg · kg -1 · min -1 (7 [25th and 75th percentiles, 3.4 and 15.8] μg/min), and presented lactate levels of 3.0 [25th and 75th percentiles, 2.3 and 4.8] mmol/l at diagnosis. A total of 2,858 (28%) patients had a BMI above 30 kg/m 2 . Sequential Organ Failure Assessment-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%; PAnalysis of Deviance < 0.001) between obese and nonobese patients. At higher norepinephrine doses (greater than 0.3 μg · kg -1 · min -1 ), 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 -1 · min -1 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 nonobese 0.3% (95% CI, -0.1 to 0.6%; PAnalysis of Deviance = 0.715). CONCLUSIONS: 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.