Highlights from #AASTAnnualMeeting - Anti-Seizure Prophylaxis

The group from Jacksonville retrospectively studied patients with TBI.  They found that the routine use of Phenytion for anti-seizure prophylaxis may actually be detrimental.  These patients had longer length of stay and lower Glasgow Outcome scores.

MORE HARM THAN GOOD: ANTI-SEIZURE PROPHYLAXIS AFTER TRAUMATIC BRAIN INJURY DOES NOT DECREASE SEIZURE RATES BUT MAY INHIBIT FUNCTIONAL RECOVERY

Indermeet Bhullar* MD, Donald Johnson PharmD, David Chesire Ph.D., Eric Frykberg* MD, University of Florida, Jacksonville

Invited Discussant: Kenji Inaba, MD

Introduction: The purpose of this study was to examine the current Brain Trauma Foundation recommendation for anti-seizure prophylaxis with Phenytoin during the first seven days after traumatic brain injury [TBI] in preventing seizures and to determine if this medication affects functional recovery as measured by Glasgow Outcome Score (GOS) at discharge.

Methods: The records of adult (age≥18) patients with blunt severe TBI (positive computed tomography [CT] scan of the head and admission Glasgow Coma Score [GCS] of [3-8]) that remained in the hospital at least 7 days after injury at a Level I trauma center were retrospectively reviewed from Jan 2008 to Jan 2010. Seizure rates during the first seven days after injury were compared for two groups based on anti-seizure prophylaxis provided: No prophylaxis (NP) vs. Phenytoin prophylaxis (PP). Phenytoin levels were checked and doses adjusted appropriately to achieve therapeutic levels. The two groups were well matched for demographic characteristics and received identical treatments based on Brain Trauma Foundation Guidelines. Length of stay in the hospital, mortality, seizure rates and functional outcome as determined by GOS were compared for the two groups. Patients with mortality due to other causes outside of brain injury were excluded. Statistical analysis was performed using mean, Fisher’s Exact test, and Mann-WhitneUy test, accepting p<0.05 as significant.

Results: 93 adult patients that met the above criteria were identified (43 [46%] NP group vs. 50 [54%] PP group). The two groups were well matched with no significant differences in age, sex, GCS, and AIS, mechanism of injury, and other demographic characteristics. Contrary to expectation, more seizures occurred in the PP group as compared to the NP group, however, this did not reach significance (PP vs. NP, 2[4%] vs. 0[0%], p=0.5). Therapeutic Phenytoin levels were present at the time of the two seizures which occured at day 5 and 6 after TBI. There was no significant difference in the two groups (PP vs. NP) as far as disposition: mortality due to head injury (4 [8%] vs. 3 [7%], p=1); discharge home (16 [32%] vs. 17 [40%], p=0.7); and discharge to Rehab (30[60%] vs. 23[53%], p=0.9). However, with Phenytoin prophylaxis there was a significantly longer hospital LOS (PP vs. NP, 36 vs. 25 days, p=0.04) and significantly worse functional outcome at discharge based on GOS (PP vs. NP, 2.9 vs. 3.4, p<0.01).

Conclusion: Anti-seizure prophylaxis with Phenytoin may be detrimental after TBI; while providing no benefit in decreasing seizure rates, Phenytoin significantly increased LOS and resulted in worse functional outcome at discharge (lower GOS score). Use
of this medication needs to be re-evaluated with current randomized trials that incorporate many of the newer management strategies (such as Diprivan [Propofol] infusion) which were not found in the original landmark study of 1990 by Temkin et al. that helped define the current Brain Trauma Foundation anti-seizure prophylaxis guideline.