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
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Glauser T, Shinnar S, Gloss D, Alldredge B, Arya R, Bainbridge J, Bare M, Bleck T, Dodson WE, Garrity L, Jagoda A, Lowenstein D, Pellock J, Riviello J, Sloan E, Treiman DM. 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. Available at: https://journals.sagepub.com/doi/10.5698/1535-7597-16.1.48?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed&
Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, Laroche SM, Riviello JJ Jr, Shutter L, Sperling MR, Treiman DM, Vespa PM; Neurocritical Care Society Status Epilepticus Guideline Writing Committee. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012 Aug;17(1):3-23. Available at: https://link.springer.com/article/10.1007%2Fs12028-012-9695-z
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