Refractory Status Epilepticus - #PHARMFAX

Status epilepticus (SE) is associated with significant morbidity and mortality, especially when not terminated early.

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Status epilepticus (SE) is associated with significant morbidity and mortality, especially when not terminated early. Persistent, abnormal electrical brain activity can contribute toward neurologic ischemia and cellular brain damage.

Seizures are driven by an imbalance of inhibitory and excitatory neurotransmitters. Status epilepticus is defined by sequential seizures without returning to baseline or those lasting more than 5 minutes. Aggressively identifying and reversing seizure triggers should be completed throughout the initial presentation.

Benzodiazepines are first line therapy. The American Epilepsy Society Guidelines recommend lorazepam 0.1 mg/kg IV (max 4 mg), midazolam 0.2 mg/kg (max 10 mg), and diazepam 5 to 10 mg IV. Lorazepam is preferred if you have IV access. If no IV access is available, midazolam intramuscular is preferred given its rapid onset compared to other benzodiazepines. Literature indicates that benzodiazepines are underdosed in up to 90% of cases.

Patients who continue to seize through benzodiazepines require secondary anticonvulsants. We're now in refractory status epilepticus. Common options are levetiracetem 60 mg/kg max 4500, fosphenytoin 20mg/kg (max 1500), and valproic acid 20 mg/kg (3000). These doses have been shown to be safe with a roughly 50% incidence of seizure termination. Lacosamide has been used in retrospective, lower quality trials with a similar termination rate around 50%. Doses range from 200 - 400 mg intravenously.

Failure of secondary anticonvulsants with persistent seizures need to have the airway secured. The team's setting up for endotracheal intubation. What's your plan to slow down the brain before ischemia develops?

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Recommended Read/Watch

ESETT Secondary Anticonvulsants Overview: https://www.instagram.com/p/CpOgF9kJpwM/

ESETT Secondary Anticonvulsants Safety: https://www.instagram.com/p/CpQoQfivLvT/

Vimpat (lacosamide) Overview: https://www.instagram.com/p/Cpkviu6M6UX/

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References

1. Glauser et al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016 Jan-Feb;16(1):48-61. doi: 10.5698/1535-7597-16.1.48.

2. Kapur et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. N Engl J Med. 2019 Nov 28;381(22):2103-2113.

3. Kienitz et al. Benzodiazepines in the Management of Seizures and Status Epilepticus: A Review of Routes of Delivery, Pharmacokinetics, Efficacy, and Tolerability. CNS Drugs. 2022; 36(9): 951–975.

4. Strzelczyk et al. Lacosamide in status epilepticus: Systematic review of current evidence. Epilepsia. 2017 Jun;58(6):933-950. doi: 10.1111/epi.13716.

1. Glauser et al. Epilepsy Curr. 2016 Jan-Feb;16(1):48-61.

2. Kapur et al. N Engl J Med. 2019 Nov 28;381(22):2103-2113.

3. Kienitz et al. CNS Drugs. 2022; 36(9): 951–975.