Refractory status epilepticus

In a prospective study of 48 patients with status epilepticus refractory to benzodiazepines, intravenous valproate (30 mg/ kg, 6 mg/kg per hour was not associated with systemic or local adverse effects [402 ]. 

Refractory status epilepticus (patient must have a protected airway)... 

Compare the pharmacotherapeutic options for refractory status epilepticus. 

Refractory status epilepticus is seizure activity that is not controlled by first-fine and second-line therapies, including benzodiazepines and antiepileptic drugs. 

Midazolam, propofol, and pentobarbital infusions can be used for refractory status epilepticus but may require intensive monitoring and supportive care. 

Bleck TP. Refractory status epilepticus. Curr Opin Crit Care 2005 11 117-120. 

Claassen J, Hirsch LJ, Emerson RG, et al. Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam a systemic review. Epilepsia 2002 43 146-153. 

Mayer SA, Claassen J, Lokin J, et al. Refractory status epilepticus. Arch Neurol 2002 59 205-210. 

TABLE 56-3 1 Medications Used to Treat Refractory Generalized Convulsive Status Epilepticus ... 

Parenteral Adjunct in status epilepticus and severe recurrent convulsive seizures. Rectal For selected, refractory patients on stable regimens of anti-epileptic agents who require intermittent use of diazepam to control bouts of increased seizure activity. 

Refractory status epilepticus that has failed to respond to one of these treatments, and has continued for more than 20-30 min, requires urgent action. The accepted strategy is to paralyze and ventilate the patient and administer an antiepileptic drug in sufficient dosage to suppress EEG evidence of seizure activity. The barbiturate anaesthetic thiopental (thiopentone), the benzodiazepine midazolam, and the anaesthetic propofol have all been used. What little comparative evidence there is remains inconclusive. Such treatment can only be carried out with facilities for artificial ventilation and intensive care, and effects can only be monitored by EEG recording. 

Thiopentone is a very potent anticonvulsant and continuous infusions have been used to control refractory status epilepticus. 

Two men, aged 7 and 17 years, presented with refractory status epilepticus. Both were treated with high-dose propofol infusions to achieve burst suppression on the electroencephalogram. During the second day of propofol infusion there was progressive severe lactic acidosis, hypoxia, pyrexia, and rhabdomyolysis, followed by hypotension, bradydysrhythmias, and renal dysfunction, leading to death. The total doses of propofol were 1275 mg/ kg over 2.7 days and 482 mg/kg over 2 days. 

Roberts, D.M., Dissanayake, W., Sheriff, M.H.R., Eddleston, M., 2004. Refractory status epilepticus following self-poisoning with the organochlorine pesticide endosulfan. J. Clin. Neurosci. 11, 760-762. 

In 27 children with refractory generalized convulsive status epilepticus, midazolam 0.2 mg/kg as a bolus followed by 1-5 (mean 3.1) micrograms/kg/minute as a continuous infusion achieved complete control of seizures in 26 children within 65 minutes (14). There were no adverse effects, such as hypotension, bradycardia, or respiratory depression. In one patient with acute meningoencephalitis, status epilepticus could not be controlled. Five patients died of the primary disorders, one with progressive encephalopathy. 

Parent JM, Lowenstein DH. Treatment of refractory generalized status epilepticus with continuous infusion of midazolam. Neurology 1994 44(l ()) l 837 K). 

Fountain NB, Adams RE. Midazolam treatment of acute and refractory status epilepticus. Clin Neuropharmacol 1999 22 26f-7. 

Five patients developed severe symptoms after receiving cefepime (31). The patients, three men and two women, aged 16-75 years, received 2 g/day (n — 3) A g/day n = 1) or 9 g/day n — 1). The symptoms started 12-16 days after the start of therapy. In all cases, the initial neurological symptoms (disorientation, confusion, and reduced consciousness) were progressive and were attributed to the infection. Facial or multifocal myoclonic movements occurred subsequently and were rapidly followed by convulsive or non-convulsive status epilepticus. The dose of cefipime had not been adjusted for renal function in any of the patients. Cefepime serum concentrations were measured in three cases, and were 72, 73, and 134 gg/ml. All the patients underwent hemodialysis, and the serum concentrations of cefepime fell to 4.3, 21, and 25 gg/ml respectively. In the other two patients, the serum concentrations after dialysis were 14 and 54 gg/ml, suggesting high concentrations before dialysis. There was complete recovery in four of the patients. One, a 73-year-old woman, died of multiorgan failure with refractory status epilepticus and coma. The authors referred to four... 

Tiagabine 0.45-40.57 mg/kg/day was associated with longstanding non-convulsive status epilepticus in three girls, two aged 12 years and one aged 17 years, with refractory localization-related epilepsy (17). Resolntion followed withdrawal of tiagabine or a reduction in dosage. 

Bleck TP. Advances in the management of refractory status epilepticus. Crit Care Med 1993 21 955-957. 

Crawford TO, Mitchell WG, Fishman LS, Snodgrass SR. Very-high-dose phenobarbital for refractory status epilepticus in children. Neurology 1988 38 1035-1040. 

Holmes GL, Riviello JJ. Midazolam and pentobarbital for refractory status epilepticus. Pediatr Neurol 1999 20 259-264. 

Labar DR, Ah A, Root J. High-dose intravenous lorazepam for the treatment of refractory status epilepticus. Neurology 1994 44 1400-1403. 

Mirski MA,Wilhams MA, Hanlet DF. Prolonged pentobarbital and phenobarbital coma for refractory generalized status epilepticus. Crit Care Med 1995 23 400-404. 

---