Third-Line Agents

For refractory status epilepticus, defined by failure of seizure cessation after a second-line medication, options include propofol, midazolam (0.2 mg/kg IV, then infusion of 0.05–2 mg/kg/hr), ketamine (0.5–3 mg/kg IV, then infusion of 0.3–4 mg/kg/hr), lacosamide (400 mg IV over 15 minutes, then maintenance of 200 mg q12h PO/IV), and phenobarbital (15–20 mg/kg IV at 50–75 mg/min) in consultation with an intensivist.

Underlying Cause

A concurrent search for the underlying cause of the seizure should be pursued. Always start by considering any immediate life-threatening conditions that require immediate treatment with specific antidotes (in parentheses below). These include:

• Vital sign extremes: hypoxemia (oxygen), hypertensive encephalopathy (labetalol, etc.), and severe hyperthermia (cooling)
• Metabolic: hypoglycemia (glucose), hyponatremia (hypertonic saline), hypomagnesemia (magnesium sulphate), and hypocalcemia (calcium gluconate or calcium chloride)
• Toxicologic: anticholinergics (bicarbonate), isoniazid (pyridoxine), lipophilic drug overdose (lipid emulsion), etc.
• Eclampsia: typically after 20 weeks of pregnancy and up to eight weeks postpartum (magnesium sulphate)

After such conditions have been identified/treated or excluded, it is useful to divide other possible causes into intracranial versus systemic. Imaging and lumbar punctures may be indicated.

With this approach, you can lower the risk of anoxic brain injury, multiorgan failure, and death as a result of refractory status epilepticus in your patients with status epilepticus.

And if you can’t remember all the details and remember only one thing in the heat of the moment, remember this: Go big, go early.

References

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10. Dalziel SR, Borland ML, Furyk J, et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial. Lancet. 2019;393(10186):2135-2145.
11. Lyttle MD, Rainford NEA, Gamble C, et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019;393(10186):2125-2134.
12. Zhang Q, Yu Y, Lu Y, et al. Systematic review and meta-analysis of propofol versus barbiturates for controlling refractory status epilepticus. BMC Neurol. 2019;19(1):55
13. Farkas J. PulmCrit – Resuscitationist’s guide to status epilepticus. PulmCrit (EMCrit) website.
14. Kapur J, Elm J, Chamberlain JM, et al. Randomized trial of three anticonvulsant medications for status epilepticus. N Engl J Med. 2019;381(22):2103-2113.
15. Wieck A, Jones S. Dangers of valproate in pregnancy. BMJ. 2018;361:k1609.