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Assessing risk factors associated with breakthrough early post-traumatic seizures in patients receiving phenytoin
Eugene Generoso1, Calvin Diep1, Carolyn Hua1
1Department of Pharmacy, Stanford Health Care, Palo Alto, CA, United States.
Insights
Older age, higher Marshall scores, and neurosurgery increase the risk of breakthrough post-traumatic seizures (PTS) in traumatic brain injury (TBI) patients on phenytoin. Many seizures occurred despite therapeutic phenytoin levels, indicating potential prophylaxis gaps.
Area of Science:
- Neuroscience
- Critical Care Medicine
- Pharmacology
Background:
- Post-traumatic seizures (PTS) are a significant complication following traumatic brain injury (TBI).
- Phenytoin is commonly used for seizure prophylaxis in TBI patients.
- Identifying risk factors for breakthrough seizures is crucial for optimizing patient care.
Purpose of the Study:
- To identify risk factors associated with breakthrough early post-traumatic seizures (PTS) in traumatic brain injury (TBI) patients receiving phenytoin prophylaxis.
- To analyze the incidence of early PTS and associated clinical factors.
- To evaluate the impact of early PTS on patient outcomes.
Main Methods:
- A single-centered retrospective study was conducted.
- Included adult patients admitted to the ICU with TBI, receiving phenytoin prophylaxis within 24 hours.
- Primary outcome: incidence and factors of early PTS (seizure within 7 days of TBI on continuous EEG).
Main Results:
- 105 patients were analyzed. Early PTS patients were older (65 vs. 48 years), had higher Marshall scores (5 vs. 2), and more neurosurgeries (57% vs. 19%).
- Among patients with early PTS, 57% had a phenytoin level drawn, with 87.5% of those being therapeutic.
- Early PTS was associated with longer ICU stays (14.7 vs. 5.9 days) and higher in-hospital mortality (21% vs. 2%).
Conclusions:
- Higher age, Marshall score, and neurosurgical procedures are linked to breakthrough early PTS despite phenytoin prophylaxis.
- Many early PTS cases occurred with therapeutic phenytoin levels, suggesting potential limitations in current prophylaxis strategies.
- Further research is needed to refine seizure prevention protocols in TBI patients.
Objective:
Post-traumatic seizure (PTS) is a well-known complication of traumatic brain injury (TBI). The objective of this study was to identify risk factors associated with breakthrough early PTS in TBI patients receiving phenytoin prophylaxis.
Methods:
This was a single-centered retrospective study including adult patients admitted to the intensive care unit (ICU), had a TBI, and started on phenytoin for seizure prophylaxis within 24 h of admission. The primary outcome was the incidence and factors associated with early PTS, defined as a confirmed seizure on a continuous electroencephalogram within 7 days of TBI. Secondary outcomes included the association between early post-traumatic seizures and ICU length of stay, hospital length of stay, and in-hospital mortality.
Results:
A total of 105 patients were included in the final analysis. Patients with early PTS were older (65 vs. 48 years old, p = 0.01), had a higher Marshall score (5 vs. 2, p = 0.01), were more likely to have a Marshall score > 2 (73 vs. 37%, p = 0.01), and had more neurosurgeries for hematoma evacuation (57 vs. 19%, p = 0.01). In patients with early PTS, 57% had a level at the time of seizure, and of those, 87.5% had a therapeutic level (>10 mcg/mL). Patients with early PTS had a longer ICU length of stay (14.7 vs. 5.9 days, p = 0.04) and a greater proportion of hospital mortality (21 vs. 2%, p = 0.02).
Conclusion:
Patients with higher age, Marshall score, and neurosurgical procedures for hematoma evacuation had higher incidences of breakthrough early PTS despite the use of phenytoin prophylaxis. The majority of patients with early PTS had therapeutic phenytoin levels at the time of seizure when a level was available; however, approximately half (43%) did not have a level.
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