Prehospital Norepinephrine and Early Mortality in Traumatic Shock

The Association of Norepinephrine Use in Pre-hospital Transport and Early Mortality in Hemorrhagic Shock

The effect of early, prehospital norepinephrine use in patients with traumatic shock on mortality is unknown. Recent existing observational evidence from single system data (US, France, Japan) are conflicting. The investigators hypothesize that prehospital norepinephrine is associated with decreased mortality when used in patients with traumatic shock.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury; Hemorrhagic Shock; Hypotension and Shock; Traumatic Shock
• Intervention / Treatment: Drug: Norepinephrine

Detailed Description

Prehospital hypotension is associated with worse clinical outcomes in patients who sustain traumatic injuries. Administration of vasoactive medications, including norepinephrine, is not advocated in North American trauma systems due to the belief that vasopressors will worsen clinical outcomes and increase mortality. However, in European trauma systems prehospital vasopressor administration is included as part of the guidelines for the management of hypotension and hemorrhagic shock. There are multiple physiologic explanations for why prehospital vasopressor administration may be useful in patients with traumatic shock, such as providing adequate blood pressure to maintain vital signs until arrival at the trauma center, allowing adequate organ perfusion in the setting of low blood flow, and supplementing decreased hormone production in the later stages of hemorrhagic shock.

The purpose of this retrospective study is to investigate if prehospital norepinephrine administration is associated with decreased mortality in patients with traumatic shock. The investigators will collect patient data from previously collected sources of information and trauma databases from three separate locations: the TRAUMABase consortium in Paris, France; TRENAU trauma database from Grenoble, France; and the R Adams Cowley Shock Trauma Center in Baltimore, MD, USA. The investigators will perform statistical modeling to propensity score match patients that received prehospital vasopressors with patients that did not receive prehospital vasopressors and assess the association with 24-hour and 28-day mortality.

• Study Type: Observational
• Enrollment (Actual): 2164

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will be collected from the previously collected trauma database at three separate locations, as previously described. These databases are collected, maintained, and managed by professional medical staff.

Description

Inclusion Criteria:

• Age 18-90 years
• Blunt traumatic mechanism of injury
• Admitted to the trauma center from the scene of injury
• Systolic blood pressure during prehospital transport or at admission to the trauma center <100 mmHg

Exclusion Criteria:

• Penetrating mechanism of injury
• No vital signs at the scene of injury
• Prehospital cardiac arrest
• Transferred to the trauma center from another hospital

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prehospital norepinephrine; Trauma patients that received norepinephrine in the prehospital setting or in the resuscitation unit .	Drug: Norepinephrine; Trauma patients with prehospital or arrival to the trauma center hypotension, defined as a systolic blood pressure <100 mmHg, that received norepinephrine during prehospital transport or in the resuscitation unit.
Prehospital no norepinephrine; Trauma patients that did not receive norepinephrine in the prehospital setting or in the resuscitation unit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early mortality	Death within 24-hours of admission to the trauma center	Admission to the trauma center to 24-hours after admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day mortality	Death occurring within 28-days from admission to the trauma center	Admission to the trauma center to 28-days after admission

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: Beaujon Hospital; University Grenoble Alps
• Investigators: Study Director: Tobias Gauss, MD, Hospital Beujon; Study Director: Pierre Bouzat, MD, PhD, University Grenoble Alps; Principal Investigator: Justin E Richards, MD, R Adams Cowley Shock Trauma Center

Publications and helpful links

General Publications

• Gupta B, Garg N, Ramachandran R. Vasopressors: Do they have any role in hemorrhagic shock? J Anaesthesiol Clin Pharmacol. 2017 Jan-Mar;33(1):3-8. doi: 10.4103/0970-9185.202185.
• Beloncle F, Meziani F, Lerolle N, Radermacher P, Asfar P. Does vasopressor therapy have an indication in hemorrhagic shock? Ann Intensive Care. 2013 May 22;3(1):13. doi: 10.1186/2110-5820-3-13.
• Gauss T, Gayat E, Harrois A, Raux M, Follin A, Daban JL, Cook F, Hamada S; TraumaBase Group; Prehospital Traumabase Group Ile de France, SAMU=Service d'Aide Medicale Urgente. Effect of early use of noradrenaline on in-hospital mortality in haemorrhagic shock after major trauma: a propensity-score analysis. Br J Anaesth. 2018 Jun;120(6):1237-1244. doi: 10.1016/j.bja.2018.02.032. Epub 2018 Apr 14.
• Sims CA, Holena D, Kim P, Pascual J, Smith B, Martin N, Seamon M, Shiroff A, Raza S, Kaplan L, Grill E, Zimmerman N, Mason C, Abella B, Reilly P. Effect of Low-Dose Supplementation of Arginine Vasopressin on Need for Blood Product Transfusions in Patients With Trauma and Hemorrhagic Shock: A Randomized Clinical Trial. JAMA Surg. 2019 Nov 1;154(11):994-1003. doi: 10.1001/jamasurg.2019.2884.
• Harrois A, Baudry N, Huet O, Kato H, Dupic L, Lohez M, Ziol M, Vicaut E, Duranteau J. Norepinephrine Decreases Fluid Requirements and Blood Loss While Preserving Intestinal Villi Microcirculation during Fluid Resuscitation of Uncontrolled Hemorrhagic Shock in Mice. Anesthesiology. 2015 May;122(5):1093-102. doi: 10.1097/ALN.0000000000000639.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: July 29, 2020
• First Submitted That Met QC Criteria: July 29, 2020
• First Posted (Actual): August 4, 2020

Study Record Updates

• Last Update Posted (Actual): February 10, 2022
• Last Update Submitted That Met QC Criteria: January 27, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: norepinephrine; hypotension; traumatic shock
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Hemorrhage; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Shock; Brain Injuries, Traumatic; Shock, Hemorrhagic; Hypotension; Shock, Traumatic; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine
• Other Study ID Numbers: HP-00082182

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No