Propranolol monotherapy versus combined propranolol-gabapentin for prevention of paroxysmal sympathetic hyperactivity after moderate-severe traumatic brain injury: a randomized controlled trial

Abstract

BACKGROUND: Paroxysmal sympathetic hyperactivity (PSH) is a serious complication of traumatic brain injury (TBI), characterized by episodic hypertension (HTN), tachycardia, hyperthermia, hyperhidrosis, and dystonia. It is associated with prolonged mechanical ventilation (MV), extended ICU and hospital stays, and worse outcomes. Current guidelines lack prophylactic recommendations. METHODOLOGY: This single-center randomized controlled trial (NCT05427474) enrolled 90 adults with moderate-to-severe TBI glasgow coma scale (GCS 3-12). Participants were randomized to: standard care (Group I, n = 30); standard care plus propranolol (40 mg/12 h, Group II, n = 30); or standard care plus propranolol (40 mg/12 h) and gabapentin (100 mg/8 h, Group III, n = 30). The primary endpoint was PSH incidence. Secondary endpoints included ventilator days, ICU and hospital length of stay (LOS), and mortality. RESULTS: PSH incidence was lowest in Group III (10%) vs. Group II (33.3%) and Group I (60%) (p < 0.001). Group II showed the shortest MV duration (5.92 ± 5.15 days) vs. Group III (9.42 ± 6.99 days, p = 0.047) and Group I (12.92 ± 5.98 days, p < 0.001). ICU LOS was shortest in Group II (9.6 ± 5.32 days) vs. Group III (14.69 ± 8.35 days, p = 0.017) and Group I (19.5 ± 8.19 days, p < 0.001). Mortality and GCS improvement did not differ significantly (p > 0.05). CONCLUSION: Prophylactic propranolol significantly reduces PSH incidence, shortens MV duration, and decreases ICU stay in moderate-to-severe TBI. Although adding gabapentin further reduces PSH, it prolongs recovery time, suggesting a trade-off between efficacy and sedative effects. These findings suggest that propranolol monotherapy is a promising prophylactic strategy, with gabapentin potentially reserved for refractory cases. However, given the study's limitations, these results should be considered hypothesis-generating and warrant confirmation in larger, multicenter trials. Mortality and neurological outcomes were comparable across groups. TRIAL REGISTRATION: The trial was prospectively registered at ClinicalTrials.gov (NCT05427474) on June 22, 2022.