Valproate and levetiracetam are available as intravenous preparations, making them suitable for administration in status, but their role in this circumstance has not been extensively studied. Another dependable approach is infusion of either pentobarbital, starting with 5 mg/kg, or phenobarbital, at a rate of 100 mg/min until the seizures stop or a total dose of 20 mg/kg is reached; a long period of stupor must be anticipated after. Hypotension often limits the continued use of the barbiturates, but Parviainen and colleagues were able to manage this problem by fluid infusions, dopamine, and neosynephrine.
If none of these measures controls the seizures, a more aggressive approach is taken to subdue all brain electrical activity by the use of general anesthesia. The preferred medications for this purpose have been pentobarbital or propofol, which, despite their moderate efficacy as primary anticonvulsants, are easier to manage than the alternative inhalational anesthetic agents. An initial intravenous dose of 5 mg/kg pentobarbital or 2 mg/kg propofol is given slowly to induce an EEG burst-suppression pattern, which is then maintained by the administration of pentobarbital, 0.5 to 2 mg/kg/h, or propofol, up to 10 mg/kg/h. Every 12 to 24 h, the rate of infusion is slowed to determine whether the seizures have stopped. The experience of Lowenstein and Aldredge, like our own, is that most instances of status epilepticus that cannot be controlled with the combination of standard anticonvulsants and midazolam will respond to high doses of barbiturates or to propofol, but that these infusions cause hypotension and cannot be carried out for long periods. Even a ketogenic diet, more commonly employed in childhood epilepsy as discussed further on, has been suggested as an ancillary treatment in these difficult cases of truly refractory status epilepticus as discussed by Thakur and colleagues.
Should the seizures continue, either clinically or electrographically, despite all these medications, one is justified in the assumption that the convulsive tendency is so strong that it cannot be checked by reasonable quantities of medications. However, a few patients in this predicament have survived and awakened, even at times with minimal neurologic damage depending on the underlying cause.
The volatile anesthetic agent isoflurane has also been used in these circumstances with good effect, as we have reported (Ropper et al), but the continuous administration of inhalational anesthetic agents is impractical in most critical care units. Halothane has been relatively ineffective as an anticonvulsant, but ether, although impractical, has in the past been effective in some. In the end, in patients with truly intractable status, one usually depends on phenytoin, phenobarbital (smaller doses in infants and children than are shown in Table 15-8), and on measures that safeguard the patient’s vital functions. Ketamine infusions have been a last resort, in combination with a midazolam infusion. A few times over the years, we have also resorted to inducing ketosis in adults by manipulating the nutrition given through a nasogastric tube. As a cautionary note, a series reported by Sutter and colleagues (2014) suggested that adverse events such as infection as well as mortality are higher in patients receiving intravenous anesthetic drugs compared to those who did not receive them but the possibility of confounding by the severity of illness must be taken into account before accepting a causal relationship.