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Summary of The Use of Benzodiazepines for Emergent Therapy of SE

Jimmy September 29, 2021

Summary of Benzodiazepines for Emergent Therapy

DrugRoute of Administration and Corresponding DoseAdverse EffectsPearls
LorazepamIntravenous: 0.1 mg/kg with a maximum single dose of 4mgHypoventilation, Hypotension, and Cardiac Rhythm DisturbanceBest agent for SE patients with IV access
MidazolamIntramuscular: 0.2 mg/kg, with maximum single dose of 10mg

Intranasal: 5 – 10 mg (0.2 mg/kg)
Pain on injection site, Hypoventilation, Hypotension, and Cardiac Rhythm DisturbanceDrug of choice for patients for SE patients with no IV access

IM Midazolam shows similar response rate to IV Lorazepam in that pharmacologic effect of both for the cessation of seizure happens at the same time
DiazepamIntravenous: 10 mg, may repeat q5-10 minutes with a maximum cumulative dose of 30mg

Intrarectal: 5 – 20 mg
Withdrawal Symptoms, Hypotension, and Cardiovascular CollapseRapidly re-distributes into adipose

Short-lived efficacy

Several factors remain relevant for an effective initial therapy of SE: the pharmacologic agent, adequacy of dose, and timing. For Emergent Therapy of SE, treatment focuses on the rapid termination of seizure activity to relatively minimize systemic dysfuction, neurological injury, pharmacoresistance, and ultimately morbidity and mortality. All of which are associated with uncontrolled SE.

Benzodiazepines are the standard of care for emergency treatment of SE with IV Lorazepam as the drug of choice for initial emergency therapy. 

For maximum benefits for the patient, Benzodiazepine therapy must be dosed appropriately and in a timely manner. Lorazepam given at doses of 0.1mg/kg with the maximum single dose of 4mg shows satisfactory seizure cessation. For patients where intravenous access is deemed unavailable, IM Midazolam given at 10mg for patients weighing more than 40kg is as efficacious and beneficial as IV Lorazepam.

If seizure persists after Benzodiazepine treatment, consider a repeat or following with an anti-epileptic drug (AED).

For stabilization from hyperexcitability, the initial therapy phase should begin when the seizure duration reaches 5 minutes and should conclude by the 20-minute mark. By this time, response from initial therapy should be apparent, whether it is responsive or non-responsive. It should be noted that in SE, a progressive decrease of the γ2 subunit is associated with benzodiazepine resistance and reduction to benzodiazepine drug potency reduces up to 20-fold if seizures persists for more than 30 minutes so a response from the initial therapy is necessary for assessment of the second stage of therapy.