Use benzodiazepines first-line in status epilepticus

Continue to use injectable benzodiazepines first. Give adequate doses such as lorazepam 4 mg IV in adults. Repeat in 5 mins if needed....

As a hospital pharmacist, you will see more emphasis on the management of status epilepticus due to new guidelines from the American Epilepsy Society. We know seizures lasting more than five minutes are hard to stop. Create a stepwise protocol and order set to ensure fast and seamless treatment of your status epilepticus patients...

Continue to use injectable benzodiazepines first. Give adequate doses such as lorazepam 4 mg IV in adults. Repeat in 5 mins if needed. Feel comfortable with these higher doses, the risk of respiratory depression is greater with the ongoing seizure than from benzodiazepines "see table 1".

Table (1). Intermittent drug dosing in SE
Drug Initial dosing Administration rates and alternative dosing recommendations Serious adverse effects Considerations
Diazepam 0.15 mg/kg IV up to 10 mg per dose, may repeat in 5 min Up to 5 mg/min (IVP)
Peds: 2–5 years, 0.5 mg/kg (PR); 6–11 years, 0.3 mg/kg (PR); greater than 12 years, 0.2 mg/kg (PR)
Hypotension
Respiratory depression
Rapid redistribution (short duration), active metabolite, IV contains propylene glycol
Lorazepam 0.1 mg/kg IV up to 4 mg per dose, may repeat in 5–10 min Up to 2 mg/min (IVP) Hypotension
Respiratory depression
Dilute 1:1 with saline
IV contains propylene glycol
Midazolam 0.2 mg/kg IM up to maximum of 10 mg Peds: 10 mg IM (>40 kg); 5 mg IM (13–40 kg); 0.2 mg/kg (intranasal); 0.5 mg/kg (buccal) Respiratory depression
Hypotension
Active metabolite, renal elimination, rapid redistribution (short duration)
Fosphenytoin 20 mg PE/kg IV, may give additional 5 mg/kg Up to 150 mg PE/min; may give additional dose 10 min after loading infusion Hypotension
Arrhythmias
Compatible in saline, dextrose, and lactated ringers solutions
Peds: up to 3 mg/kg/min
Lacosamide 200–400 mg IV 200 mg IV over 15 min
No pediatric dosing established
PR prolongation
Hypotension
Minimal drug interactions
Limited experience in treatment of SE
Levetiracetam 1,000–3,000 mg IV
Peds: 20–60 mg/kg IV
2–5 mg/kg/min IV Minimal drug interactions
Not hepatically metabolized
Phenobarbital 20 mg/kg IV, may give an additional 5–10 mg/kg 50–100 mg/min IV, may give additional dose 10 min after loading infusion Hypotension
Respiratory depression
IV contains propylene glycol
Phenytoin 20 mg/kg IV, may give an additional 5–10 mg/kg Up to 50 mg/min IV; may give additional dose 10 min after loading infusion
Peds: up to 1 mg/kg/min
Arrhythmias
Hypotension
Purple glove syndrome
Only compatible in saline
IV contains propylene glycol
Topiramate 200–400 mg NG/PO 300–1,600 mg/day orally (divided 2–4 times daily)
No pediatric dosing established
Metabolic acidosis No IV formulation available
Valproate sodium 20–40 mg/kg IV, may give an additional 20 mg/kg 3–6 mg/kg/min, may give additional dose 10 min after loading infusion
Peds: 1.5–3 mg/kg/min
Hyperammonemia
Pancreatitis Thrombocytopenia
Hepatotoxicity
Use with caution in patients with traumatic head injury; may be a preferred agent in patients with glioblastoma multiforme
IM intramuscular; IV intravenous; IVP intravenous push; min minute; NG nasogastric; PE phenytoin equivalents; PEDs pediatric; PO by mouth; PR rectal administration; PRIS propofol related infusion syndrome

Choose an IV SECOND-line therapy based on specific factors. Consider phenytoin (Epilog, etc) or fosphenytoin next.

  • But lean toward fosphenytoin "NOT available in Egypt" if there's no shortage. Both seem to work equally well, but fosphenytoin may have fewer administration side effects like arrhythmias, injection site pain, phlebitis, etc.
  • Plus, cost difference can be minimal since both are now generic.
  • Recommend 20 mg/kg for phenytoin or fosphenytoin, the popular 1-gram dose won't cut it for most status epilepticus patients. Remember to dilute phenytoin in normal saline not D5%W.

Think of valproate sodium (Depakine, etc) for known generalized epilepsy. It may be more effective than other agents. Use up to 40 mg/kg. Try levetiracetam (Keppra, Tiratam, etc) if interactions are a concern or there are delays with other agents. Keep in mind, loading doses of 3 to 4.5 grams may be needed. Levetiracetam now has a sister drug, brivaracetam (Briviact). But brivaracetam hasn't been studied in status epilepticus yet.

Try phenobarbital if other second-line agents don't work. It works well but has side effects such as hypotension, sedation, etc. Save lacosamide (Vimpat, Lacovimp, Andovimpamide) for last-line when refractory-status medications (Propofol, etc) can't be used, "see table 2". It has limited evidence in status epilepticus.

Table (2). Refractory SE dosing recommendations
Drug Initial dose Continuous infusion dosing recommendations-titrated to EEG Serious adverse effects Considerations
Midazolam 0.2 mg/kg; administer at an infusion rate of 2 mg/min 0.05–2 mg/kg/hr CI
Breakthrough SE: 0.1–0.2 mg/kg bolus, increase CI rate by 0.05–0.1 mg/kg/hr every 3–4 h
Respiratory depression
Hypotension
Tachyphylaxis occurs after prolonged use
Active metabolite, renally eliminated, rapid redistribution (short duration), does NOT contain propylene glycol
Pentobarbital 5–15 mg/kg, may give additional 5–10 mg/kg; administer at an infusion rate ≤50 mg/min 0.5–5 mg/kg/h CI
Breakthrough SE: 5 mg/kg bolus, increase CI rate by 0.5–1 mg/kg/h every 12 h
Hypotension
Respiratory depression
Cardiac depression
Paralytic ileus
At high doses, complete loss of neurological function
Requires mechanical ventilation
IV contains propylene glycol
Propofol Start at 20 mcg/kg/min, with 1–2 mg/kg loading dose 30–200 mcg/kg/min CI
Use caution when administering high doses (>80 mcg/kg/min) for extended periods of time (i.e., >48 h)
Peds: Use caution with doses >65 mcg/kg/min; contraindicated in young children
Breakthrough SE: Increase CI rate by 5–10 mcg/kg/min every 5 min or 1 mg/kg bolus plus CI titration
Hypotension (especially with loading dose in critically ill patients)
Respiratory depression
Cardiac failure
Rhabdomyolysis
Metabolic acidosis
Renal failure (PRIS)
Requires mechanical ventilation
Must adjust daily caloric intake (1.1 kcal/ml)
Thiopental 2–7 mg/kg, administer at an infusion rate ≤50 mg/min 0.5–5 mg/kg/h CI
Breakthrough SE: 1–2 mg/kg bolus, increase CI rate by 0.5–1 mg/kg/h every 12 h
Hypotension
Respiratory depression
Cardiac depression
Requires mechanical ventilation
Metabolized to pentobarbital
CI continuous infusion; EEG electroencephalogram; h hour; IM intramuscular; IV intravenous; IVP intravenous push; min minute; PRIS propofol related infusion syndrome


References

  1. Glauser T, Shinnar S, Gloss D, 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;16(1):48-61.
  2. Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17(1):3-23.