Early Seizure Prophylaxis in Traumatic Brain Injuries Revisited: A Prospective Observational Study

Pharmacological prophylaxis for early seizures following traumatic brain injury (TBI) is a recommendation in the Brain Trauma Foundation Guidelines. However, several studies have challenged the efficacy and safety of this practice, resulting in varied practice across centers around the world. The purpose of the present study was to compare the incidence of early clinical seizures following TBI, between two large centers, a US Center that practises routine seizure prophylaxis and a Chinese Center that does not use seizure prophylaxis following TBI.

This was a prospective observational study including an urban level I trauma center in the USA and a large hospital in Shenzhen, China. At the US Center, all patients received seizure prophylaxis with levetiracetam. At the Chinese Center, no seizure prophylaxis was given. All patients with blunt TBI and positive computed tomography findings for epidural hematoma, subdural hematoma, subarachnoid hemorrhage, intracerebral hemorrhage or diffuse axonal injury were included. Patients who died within 24 h of admission were excluded. The study population was monitored daily for clinical seizures for the first 7 post-injury days. Data collected included demographics, mechanism of injury, vital signs upon arrival, injury severity and emergency interventions. Primary outcome was the incidence of early seizures, defined as those occurring within 7 days of injury.

A total of 522 patients were included in the analysis: 272 patients at the US Center who received seizure prophylaxis and 250 patients at the Chinese Center who did not receive prophylaxis. Overall, 3.7% of patients who received seizure prophylaxis developed early seizures, compared to 2.8% of patients who did not receive any prophylaxis (p = 0.573). Decompressive craniectomy was associated with the highest incidence of early seizure (9.2%). In this subgroup, the seizure rate was 10.4% in the prophylaxis group and 7.1% in the no-prophylaxis group (p = 0.738). Patients with admission GCS < 9 had an overall early seizure incidence of 7.0%: 4.3% in the prophylaxis group and 14.3% in the no-prophylaxis group (p = 0.062). Analysis of the subgroup with isolated blunt TBI showed an incidence of early seizures of 3.4% in the prophylaxis group versus 2.4% in the no-prophylaxis group (p = 0.593). Further analyses of outcomes according to head AIS 3, 4 and 5 showed no significant difference in the seizure rate between the two groups: head AIS 3: 6.1% in the prophylaxis group versus 2.6% in the no-prophylaxis group, p = 0.329; head AIS 4: 0 versus 2.7%, p = 0.302; head AIS 5: 8.7 versus 4.0%, p = 0.601.

The present study failed to show any benefit of routine early seizure prophylaxis following blunt TBI. This practice should be reexamined in a large randomized clinical study.