Midazolam

A loading dose of 0.2 mg/kg (repeated up to a maximum of 2 ms/kEg) followed by a continuous infusion of 0.05 to 2 mg/kg/h is recommended in RSE. 2_ The dose must be adjusted during prolonged infusions, especially in patients with renal impairment, as the active metabolite can accumulate.3 Breakthrough seizures are common with midazolam infusions and usually respond to a bolus and a 20% increase in the rate. Despite this, tachyphylaxis can occur and the patient should be switched to another agent if seizures continue.

Propofol

The anesthetic agent propofol can be started with loading doses of 1 mg/kg repeated every 3 to 5 minutes until a clinical response is achieved, after which the infusion can be initiated at 2 to 4 mg/kg/h. Propofol can cause hypotension, especially with loading doses. Long-term, high-dose (greater than 5 mg/kg/h) propofol infusions are associated with rhabdomyolysis, acidosis, and cardiac arrhythmias (propofol infusion syndrome), especially in children.36 Propofol has a very short serum half-life and should be tapered off slowly to avoid withdrawal seizures. High-dose propofol infusions can also provide a considerable amount of calories (1 kcal/mL [4.2 kJ/mL]) over time, so other sources of nutrition may have to be adjusted accordingly.

Pentobarbital

Barbiturate infusions have been reported to be highly successful in treating RSE, but their side effects are considerable. They can cause significant hypotension, myocar-dial and respiratory depression, ileus, and infection (especially gram-positive organisms). As a result, patients often require mechanical ventilation, IV vasopressor therapy, invasive hemodynamic monitoring, and total parenteral nutrition while undergoing "barbiturate coma." On the other hand, barbiturates are beneficial in patients with elevated intracranial pressure (ICP) problems.

Pentobarbital is commonly loaded at a dose of 10 to 15 mg/kg over 1 to 2 hours, followed by a continuous infusion of 0.5 to 4 mg/kg/h. Therapy can be tapered off after 12 to 24 hours of seizure control as evident on the EEG. 8 One meta-analysis reported a lower incidence of treatment failure with pentobarbital (3%) when compared to midazolam (21%) or propofol (20%), although the risk of hypotension re-

quiring vasopressor therapy was higher with pentobarbital. This relative efficacy for pentobarbital must be considered together with its complications when determining which agent to use. Patients who fail midazolam and/or propofol infusions should be switched over to pentobarbital therapy.

Levetiracetam

Although not FDA approved for SE, levetiracetam is a newer antiepileptic that has ideal characteristics since it does not have the significant cardiopulmonary, hepatic, and sedative side effects seen with the other agents nor does it have potentially harmful drug interactions. Both IV and oral formulations have been used in RSE patients as add-on therapy with some success, although it is unclear if levetiracetam would be effective as a single agent in these cases.40 Loading doses of up to 2,000 mg over 15 to 30 minutes in the critically ill have been documented with very little toxicity noted.41

Other Agents

Ketamine, topiramate, and inhaled anesthetics have also been used to treat RSE. Ketamine is an NMDA-receptor antagonist that has been given orally43 and IV44 for RSE in children. Topiramate is a newer oral antiepileptic agent with multiple mechanisms of action that may have some benefit in RSE. The dose in adults ranges from 300 to 1,600 mg/day.45 Children have also been administered topiramate at a starting dose of 2 to 3 mg/kg/day and titrated to a maintenance dose of 5 to 6 mg/kg/day4

Topiramate can induce metabolic acidosis, and this should be monitored carefully. The

inhaled anesthetics, desflurane and isoflurane, are normally delivered in an operating room, and require special equipment for administration in an ICU. Future studies will determine their place in therapy.

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