After peeling your unrestrained passenger from an MVC rollover off the pavement, you’re running down the usual trauma checklist: circulation, airway, breathing, and focused assessment. It’s probably safe to assume that your patient has a traumatic brain injury, so at what point in your treatment pathway do you reach for an antiepileptic drug (AED)? Are you carrying antiepileptics on your truck or aircraft? To give an AED or not to give an AED, that is the question. (Bet you thought you left Shakespeare in high school).
Why give antiepileptic drugs in traumatic brain injury?
Antiepileptic drugs such as levetiracetam (Keppra), phenytoin (Dilantin), fosphenytoin (Cerebryx), valproic acid (Depakote), and lacosamide (Vimpat) are at the cornerstone of inpatient TBI treatment. Why are TBI patients at higher risk of seizures?
Mechanical damage to brain cells, tissue, cerebral vessels and disruption of the blood-brain barrier occurs immediately due to the force of impact exerted on the head. Within minutes, inflammatory processes kick off the development of ischemia and edema.
The presence of blood and inflammatory by-products irritate and excite the cells within the brain and decrease the seizure threshold – think about it like your friend with the contagious laugh starts to giggle and suddenly the entire group is infected with laughter.
Why are seizures dangerous for the TBI patient?
Seizure activity increases inflammatory processes in the brain, which potentiates the injury already sustained by the TBI. Repeated seizure activity can permanently alter cognitive and motor function. As with all seizure patients, there is a risk of secondary injury such as a fall, other physical injury, or aspiration sustained during the active seizure.
The greater the amount of cerebral injury/inflammation, the more likely it is the patient will begin to seize. Because of this, TBI patients are given antiepileptic medications prophylactically for seven days following their injury. Current literature demonstrates that the seven-day seizure prophylaxis is effective in reducing the risk in mild and moderate TBI patients. Patients with severe TBIs may require longer term anti-seizure medication regimens.
Use of antiepileptic drugs in the prehospital setting?
Should antiepileptics be a cornerstone in the prehospital treatment of a suspected TBI patient? The existing evidence is inconclusive at best. Antiepileptic drugs are well-studied in the hospital setting but the literature on their use in the prehospital environment is extremely limited.
Prehospital administration of antiepileptic drugs should be prioritized when the patient has received paralytics. Typical seizure symptoms such as myoclonic jerking, decrease in level of consciousness, or involuntary, rhythmic movements are masked by neuromuscular blocking agents. Airway management is obviously the priority, but following airway securement, a loading dose of antiepileptics should be considered for management of subclinical seizures (seizure activity occurring without changes in clinical assessment).
Which antiepileptic drug should I give to a suspected TBI patient?
Of all the AEDs available in IV form, Keppra is likely the safest for prehospital administration. Keppra is FDA approved for the treatment of myoclonic, partial, and generalized tonic-clonic seizures. However, it is commonly used off-label for seizure prophylaxis in traumatic brain injury.
Keppra has relatively few contraindications, with hypersensitivity reactions being the most notable. This lack of contraindications makes it infinitely safer for prehospital use, where patient history is limited at best. Keppra is also well-tolerated during pregnancy and poses a low risk of teratogenicity.
Another advantage to Keppra is the ease of administration. A loading dose of Keppra can be given as an IV push or mixed into 100mL of normal saline and infused over 10-15 minutes. This “mix it and forget it” method of administration can be particularly helpful in situations where you need 10 pairs of hands to resuscitate your patient adequately. Keppra can also be given as an IV push, but use caution with rapid administration as it can cause hypotension.
Prehospital Takeaways
To give AEDs or not to give AEDs in prehospital TBI patients? As with all things in medicine, this answer is not black and white. Although there is a lack of research on the prehospital management of TBI, seizure prophylaxis is initiated in most inpatient TBI patients for at least seven days.
Treatment priorities remain the same as any trauma patient: circulation, airway, breathing, and prevent of trauma triad.
Special consideration for seizure prophylaxis in the TBI who has been chemically paralyzed
When treating suspected TBI patients in the prehospital arena, Keppra is the most prudent choice as it is generally well-tolerated with few adverse effects and is easy to administer.
References
Hazama A, Ziechmann R, Arul M, Krishnamurthy S, Galgano M, Chin LS. The Effect of Keppra Prophylaxis on the Incidence of Early Onset, Post-traumatic Brain Injury Seizures. Cureus. 2018 May 23;10(5):e2674. doi: 10.7759/cureus.2674. PMID: 30050729; PMCID: PMC6059528.
Kumar, A., Maini, K., & Kadian, R. (2023). Levetiracetam. StatPearls. Retrieved August 8, 2024, from https://www.ncbi.nlm.gov/books/NBK499890
Pease, M., Mittal, A., Merkaj, S., et al. (2024). Early seizure prophylaxis in mild and moderate traumatic brain injury: A systematic review and meta-analysis. JAMA Neurology, 81(5):507–514. https://doi.org/10.1001/jamaneurol.2024.0689
Tani, J., Wen, YT., Hu, CJ., et al. (2022). Current and potential pharmacologic therapies for traumatic brain injury. Pharmaceuticals,15: 838. https://doi.org/10.3390/ph15070838
