Choices in Refractory Status Epilepticus

FIGURE 11.1 Algorithm for the management of status epilepticus. ABC, airway, breathing, circulation; CSF, cerebrospinal fluid; ED, emergency department; EEG, electroencephalography; ICU, intensive care unit; MV, mechanical ventilation.

* The risk of propofol infusion syndrome is substantial and this complication may be fatal.

SE should be considered refractory after failure of two antiepileptic agents. In our practice, the diagnosis of refractory generalized SE means we will need to start a continuous infusion of an anesthetic agent. This decision demands endotracheal intubation for mechanical ventilation and continuous electroencephalographic (EEG) monitoring. There are some exceptions to this rule. In cases of complex partial status epilepticus we try one or two more anticonvulsants before using anesthetics because in these patients there is less evidence that uncontrolled complex partial seizures can produce irreversible brain damage, at least in the short term. For the same reasons, in patients with epilepsia partialis continua we try to avoid intubation and potent anesthetic drugs.

Among anesthetic agents we favor midazolam because of its better safety profile Table 11.1. Midazolam can be effective in aborting status epilepticus when used in high doses. We start with a bolus of 0.2 mg per kilogram of body weight and an infusion of 0.2 mg/kg/hr. However, we rapidly increase the infusion dose until we achieve suppression of the seizures and have reached doses as high as 5 mg/kg/hr in the most recalcitrant cases. Even these very high doses are well tolerated by most patients, although support with vasopressor drugs may be needed. Tachyphylaxis develops quickly with benzodiazepines in general and midazolam in particular. This phenomenon may demand using even higher doses if the infusion needs to be maintained over time.

Propofol is a very effective antiepileptic anesthetic, but we have found it unsafe in the doses necessary to control refractory SE (often higher than 100 micrograms per kg per minute). The main risk is the development of propofol infusion syndrome. This syndrome –albeit rare– is manifested by lactic acidosis, rhabdomyolysis, myocardial depression, and, when most severe, cardiovascular collapse and cardiac arrest. In our experience, even careful monitoring of metabolic changes (serial lactic acid, arterial blood gases, and creatine kinase levels) may fail to recognize the beginning of a fatal form of this complication. Therefore, we rarely use propofol for the treatment of SE and when we do we strictly avoid infusing large doses. More than 80 μg/kg per minute or 3 mg/kg per hour for longer than 48 hours should be avoided.

Continuous infusion of barbiturates, such as pentobarbital, is very effective in aborting SE. Unfortunately, adverse side effects are many and often severe. Hypotension is ubiquitous and requires vasopressors. Infections, especially pneumonia, ileus, and liver toxicity occur in the majority of patients treated with a barbiturate drip for more than 2 days. Consequently, we tend to reserve this option for those patients who fail to be controlled with midazolam.

TABLE 11.1 Doses and Side Effects of Therapeutic Options for Refractory Status Epilepticus