Association of Early Norepinephrine Administration With 24-Hour Mortality Among Patients With Blunt Trauma and Hemorrhagic Shock
Authors: Gauss Tobias , Richards Justin E. , Tortù Costanza , Ageron François-Xavier , Hamada Sophie , Josse Julie , Husson François , Harrois Anatole , Scalea Thomas M. , Vivant Valentin , Meaudre Eric , Morrison Jonathan J. , Galvagno Samue , Bouzat Pierre ,   French Trauma Research Initiative, Albasini François , Briot Olivier , Chaboud Laurent , Chateigner Coelsch Sophie , Chaumat Alexandre , Comlar Thomas , Debas Olivier , Debaty Guillaume , Dupré-Nalet Emmanuelle , Gay Samuel , Ginestie Edouard , Girard Edouard , Grèze Jules , Haesevoets Marc , Hallain Marie , Haller Etienne , Hoareau Christophe , Lanaspre Bernard , Lespinasse Safia , Levrat Albrice , Mermillod-Blondin Romain , Nicoud Philippe , Rancurel Elisabeth , Thouret Jean-Marc , Vallenet Claire , Vallot Cécile , Zerr Bénédicte , Abback Paér-Sélim , Audibert Gérard , Boutonnet Mathieu , Clavier Thomas , Cook Fabrice , Eljamri Mohamed , Floch Thierry , Gaertner Elisabeth , Garrigue Delphine , Geeraerts Thomas , Gette Sebastien , Godier Anne , Gosset Pierre , Hanouz Jean-Luc , Moyer Jean-Denis , Langeron Olivier , Leone Marc , Pottecher Julien , Portaz Jonathan , Raux Mathieu , Scotto Marion , Willig Mathieu , Hardy Alexia 
Published: October 2022

Importance

Hemorrhagic shock is a common cause of preventable death after injury. Vasopressor administration for patients with blunt trauma and hemorrhagic shock is often discouraged.

Objective

To evaluate the association of early norepinephrine administration with 24-hour mortality among patients with blunt trauma and hemorrhagic shock.

Design, Setting, and Participants

This retrospective, multicenter, observational cohort study used data from 3 registries in the US and France on all consecutive patients with blunt trauma from January 1, 2013, to December 31, 2018. Patients were alive on admission with hemorrhagic shock, defined by prehospital or admission systolic blood pressure less than 100 mm Hg and evidence of hemorrhage (ie, prehospital or resuscitation room transfusion of packed red blood cells, receipt of emergency treatment for hemorrhage control, transfusion of &amp;gt;10 units of packed red blood cells in the first 24 hours, or death from hemorrhage). Blunt trauma was defined as any exposure to nonpenetrating kinetic energy, collision, or deceleration. Statistical analysis was performed from January 15, 2021, to February 22, 2022.

Exposure

Continuous administration of norepinephrine in the prehospital environment or resuscitation room prior to hemorrhage control, according to European guidelines.

Main Outcomes and Measures

The primary outcome was 24-hour mortality, and the secondary outcome was in-hospital mortality. The average treatment effect (ATE) of early norepinephrine administration on 24-hour mortality was estimated according to the Rubin causal model. Inverse propensity score weighting and the doubly robust approach with 5 distinct analytical strategies were used to determine the ATE.

Results

A total of 52 568 patients were screened for inclusion, and 2164 patients (1508 men [70%]; mean [SD] age, 46 [19] years; median Injury Severity Score, 29 [IQR, 17-36]) presented with acute hemorrhage and were included. A total of 1497 patients (69.1%) required emergency hemorrhage control, 128 (5.9%) received a prehospital transfusion of packed red blood cells, and 543 (25.0%) received a massive transfusion. Norepinephrine was administered to 1498 patients (69.2%). The 24-hour mortality rate was 17.8% (385 of 2164), and the in-hospital mortality rate was 35.6% (770 of 2164). None of the 5 analytical strategies suggested any statistically significant association between norepinephrine administration and 24-hour mortality, with ATEs ranging from –4.6 (95% CI, –11.9 to 2.7) to 2.1 (95% CI, –2.1 to 6.3), or between norepinephrine administration and in-hospital mortality, with ATEs ranging from –1.3 (95% CI, –9.5 to 6.9) to 5.3 (95% CI, –2.1 to 12.8).

Conclusions and Relevance

The findings of this study suggest that early norepinephrine infusion was not associated with 24-hour or in-hospital mortality among patients with blunt trauma and hemorrhagic shock. Randomized clinical trials that study the effect of early norepinephrine administration among patients with trauma and hypotension are warranted to further assess whether norepinephrine is safe for patients with hemorrhagic shock.