Efficacy and Safety of Enalapril and Propranolol on Neurologic Recovery After Isolated Severe Traumatic Brain Injury: A Randomized Clinical Trial

Objective

It has been hypothesized that propranolol and enalapril can provide cardiovascular stability without any negative impact on neurologic recovery after severe traumatic brain injury (TBI). Although propranolol and enalapril have been proposed to have beneficial effects as cardiovascular stabilizers in TBI, many neurologic effects remain obscure. We hypothesized which of the following drugs could improve The Glasgow Outcome Scale-extended (GOS-E) in severe TBI patients.

Methods

This single-blinded randomized, clinical trial was conducted in 2 university hospitals from 2020 to 2021. All the patients age >18 years with severe isolated TBI who had legal consent to participate (by guardians) were enrolled. G1 (propranolol), G2 (enalapril), G3 (propranolol + enalapril), and G4 (no medication) were defined. The GOS-E was the primary outcome. Secondary outcomes included the Apraxia of Speech Rating Scale, cardiovascular stability, mortality rate, ventilator dependency, and hospital length of stay. P ≤ 0.05 was defined as significant.

Results

One hundred and forty patients were reviewed in the final analysis. The mean patient age was 36.91 ± 16.19 years, and the median Glasgow Coma Scale (GCS) score was 5. Baseline vital signs and TBI severity indices were distributed equally among the 4 groups (P > 0.05). Multivariate regression analysis showed that GOS-E was directly associated with discharge GCS in all groups (P < 0.001, β = 0.199, 0.16 ≤ confidence interval [CI] ≤ 0.22). Multivariate regression analysis showed better on-discharge GCS in G1 (P < 0.001; β = 2.26; 0.58 ≤ CI ≤ 3.9).

Conclusion

Regarding neurologic recovery and other outcomes, enalapril and propranolol, both alone and in combination, are effective and safe after severe isolated TBI. Considering long-term outcomes, propranolol showed more promising results in GOS-E during the follow-up period.