Norepinephrine administration not tied to 24-hour mortality in patients of blunt trauma and hemorrhagic shock: JAMA

France: A recent original investigation of Emergency medicine published in the JAMA Network Open, evaluated the "non-significant association" between norepinephrine administration and 24-hour or in-hospital mortality in patients of blunt trauma and hemorrhagic shock.

The most common cause of preventable death after the injury is hemorrhagic shock (uncontrolled hemorrhage. Hypovolemia triggers the complicated neurohormonal response. Hypotension is not related to hypovolemia alone but is associated with sympathoinhibitory-induced vasodilation. Vasopressor administration in such cases may treat vasoplegia and sustain adequate perfusion pressure. Norepinephrine is a β-1 and α-1 agonist and plays an essential role in maintaining regional blood flow in cases of bleeding and hypoperfusion. Recent data showed improved survival after norepinephrine infusion, irrespective of a lower or higher blood pressure goal.

The literature mentions that vasopressor infusion leads to increase mortality in trauma patients. Emerging data support the plausibility of norepinephrine for patients with trauma and hemorrhagic shock, but few data show contradictory results. On one side, vasopressor infusion is discouraged or uncommon in North America; on the other, it is the criteria for managing bleeding in European guidelines.

Considering this, Dr. Tobias Gauss, MD in Anesthesia and Critical Care at Grenoble Alpes University Hospital, led the retrospective cohort study with a team of 12 researchers and hypothesized that norepinephrine administration is not significantly associated with 24-hour mortality among patients with blunt trauma and hemorrhagic shock.

The hemorrhagic shock was defined as a systolic blood pressure of less than 100 mm Hg and evidence of acute hemorrhage, requirement of hemorrhage emergency control, prehospital transfusion, massive transfusion of packed red blood cells (RBC) and death from hemorrhage. Blunt trauma is exposure to nonpenetrating kinetic energy, collision, or deceleration.

The exposure included continuous administration of norepinephrine in the prehospital environment or resuscitation room before hemorrhage control. The primary outcome was 24-hour mortality, and the secondary outcome was in-hospital mortality. The Rubin causal model was used to study the mean association of norepinephrine with 24-hour mortality as ATE or Average Treatment Effect estimation with five distinct analytical strategies with models of no correction, regression adjustment, weighted regression adjustment, matching by covariable and matching by cohort.

The critical points of the study are:

• The data was collected from 3 registries, TraumaBase, TRENAU, and RACSTC (the US and France ), from January 1, 2013, to December 31, 2018, and the statistical analysis was performed from January 15, 2021, to February 22, 2022.

• Total 52 568 patients were screened for inclusion criteria, and 7037 patients were included.

• 2164 patients had a history of acute hemorrhage, with 70% men of mean age 46 years and a median Injury Severity Score of 29.

• Of these, 1497 patients required emergency hemorrhage control, and 128 patients received a prehospital transfusion of packed RBC.

• 543 patients received a massive transfusion.

• 1498 patients received Norepinephrine administration, while 666 patients did not receive norepinephrine.

• The distribution of norepinephrine was 1212 patients in the TraumaBase cohort, 286 in the TRENAU cohort, and none in the RACSTS cohort.

• 24-hour mortality was 17.8% (385 of 2164);

• 24-hour mortality was comparable between RACSTC, TRENAU, and TraumaBase as 16 %, 17 %, and 19%, respectively.

• The rate of in-hospital mortality was 35.6%.

• There was no significant association of norepinephrine with in-hospital mortality in all 5 strategies of no correction, after regression adjustment, weighted regression adjustment, matching by covariable, and matching by cohort with ATE values of 3.3, 4.5, 5.3, -1.3, and 0.5, respectively. All 95 % CI crossed the numerical zero value in all 5 strategies.

• There was no significant association between norepinephrine with 24-hour mortality in all the five strategies with ATE values of -2.1, 1-9, 2.1, -4.6, and -3.1, respectively.

The co-researcher Dr. Justin E Richards from Program in Trauma of R Adams Cowley Shock Trauma Center at University of Maryland School of Medicine wrote, "To our knowledge, our study is the largest investigation on vasopressors usage after traumatic and hemorrhagic shock. "

The team wrote that our study added to the literature the data on early norepinephrine administration for patients with trauma and hypotension.

Further investigations are required on early norepinephrine administration among patients with trauma and hypotension to further assess the safety.

The team of researchers concluded that our study did not evaluate organ function, multiple organ failure, and the association of blood pressure threshold with mortality.

Further reading:

Gauss T, Richards JE, Tortù C, et al. Association of Early Norepinephrine Administration With 24-Hour Mortality Among Patients With Blunt Trauma and Hemorrhagic Shock. JAMA Netw Open. 2022;5(10):e2234258