Critical norepinephrine dose to predict early mortality during circulatory shock in intensive care: a retrospective study in 3423 ICU patients over 4-year period

Introduction: The maximal norepinephrine (NE) dose >1 μg/kg/min during circulatory shock apparently is associated with higher mortality, but this threshold needs confirmation. This study aimed at investigating whether NE infusion at a dose >1 μg/kg/min could predict early intensive care unit (ICU) mortality (first 5 days). The secondary objective was to assess the day-by-day relationship between NE dose during the first 4 days of ICU stay and subsequent mortality. Methods: We conducted a retrospective analysis of data from ICU patients receiving NE for circulatory shock at the Nimes University Hospital (France) from January 2016 to December 2019. Results: A total of 5,735 patients were admitted, 3,693 were screened, and 3,423 were analyzed. NE infusion at a dose >1 μg/kg/min was associated with day-5 mortality (hazards ratio: 7.40, P 1 μg/kg/min. The calculated threshold of 1.13 μg/kg/min for maximal NE was the best prognostic value (sensitivity: 67%, specificity: 80%, positive predictive value: 45%). When the 1.2 μg/kg/min threshold was crossed either on the first, second, third, or fourth day of ICU stay, the probability of subsequent death was 47%, 49%, 60%, and 40%, respectively. Along the first 4 days of ICU stay, the risk of death increased with increasing NE infusion dose. Conclusions: An NE infusion rate >1.13 μg/kg/min predicts day-5 mortality in ICU patients with circulatory shock. The time to reach maximal NE infusion rate was shorter in survivors than in nonsurvivors.