Standard procedure	The treatment algorithm in Fig. 1 demonstrates the approach for treating acute repetitive seizures and status epilepticus. To terminate an acute prolonged seizure of 5 minutes or greater duration, initially administer intravenous lorazepam, 0.1 mg/kg (typically 1–2 mg in adults), with an additional 2 mg/min until seizure cessation or maximum of 8 mg is reached [82–84]. Lorazepam is the initial drug of choice for status given its greater lipid solubility and a longer duration of antiseizure effect than diazepam [83–85]. If seizure activity continues despite lorazepam, intravenous fosphenytoin (an esterified phenytoin prodrug safe for intravenous or intramuscular administration [86–88]) remains the drug of choice for status epilepticus. Infuse fosphenytoin at 100 to 150 mg phenytoin equivalents (PE)/min to a maximum of 18 mg/kg PE. Maintenance doses of 314± 61.2 mg/d support target-free phenytoin levels between 1 and 2 µg/mL (~10–20 µg/mL total phenytoin) [89]. Precautions during intravenous infusion include necessary blood pressure and ECG monitoring. Alternatively, intramuscular fosphenytoin may be administered if there is limited or no intravenous access. Measure levels 2 h following intravenous infusion and 4 h following intramuscular injection. As alternatives, intravenous valproate, 1,000 to 3,000 mg; levetiracetam, 1,000 to 3,000 mg; or lacosamide, 200 to 600 mg, may be considered for patients who are hemodynamically unstable.
Contraindications	Hypersensitivity to lorazepam, phenytoin, or other aromatic amine compounds. Relative contraindications include severe hepatic or bone marrow dysfunction, although the priority of prompt convulsive seizure termination by these proven effective drugs trumps other safety concerns in emergency situations. Be prepared to intubate patient to protect airway or mechanically ventilate in status epilepticus.
Main drug interactions	Blood levels and therapeutic effect of numerous medications metabolized by hepatic cytochrome P450 may be reduced by lorazepam and fosphenytoin, which are enzymatic inducers, and highly protein bound medications may be displaced by lorazepam or phenytoin, increasing their free unbound fraction.
Main side effects/complications	Genital pruritus is a common and transient adverse effect of fosphenytoin. Respiratory depression occurs with higher doses of lorazepam. Rash, including serious hypersensitivity allergic reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) are possible. Hepatic insufficiency or failure and hematologic dyscrasias, including aplastic anemia, rarely occur.
Special points	Increased clearance and earlier peak phenytoin concentrations are seen in patients with active hepatic or renal disease, likely due to decreased plasma protein concentrations and binding in these disease states, resulting in increased unbound fosphenytoin fractions [90]. Phenytoin half-life is decreased in uremia, so doses should be administered every 8 h at minimum [91]. Additionally, phenytoin reduces plasma cyclosporine concentration [85] and can also alter the metabolism of corticosteroids [65]. Management of refractory status epilepticus is beyond the scope of this review, but alternatives for management include infusions of additional 10 mg/kg PE fosphenytoin; midazolam or propofol; ketamine; phenobarbital, pentobarbital, or pentothal; or administration of inhalation anesthetics such as isoflurane [92].
Cost	Inexpensive (lorazepam); moderate (fosphenytoin); expensive (valproate).