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

Shock. 2024 Aug 28. doi: 10.1097/SHK.0000000000002454. Online ahead of print.

Abstract

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 four 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: 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 (Hazard Ratio: 7.40, p < 0.0001). The area under the receiver operating characteristic was 0.79 to predict day-5 mortality in ICU for maximal NE > 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 four days of ICU stay, the risk of death increased with increasing NE infusion dose.

Conclusions: A 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 non-survivors.