Midazolam, status epilepticus

The first-line treatment for status epilepticus is intravenous benzodiazepines. Diazepam, lorazepam, or midazolam may be used to rapidly control clinical signs of seizures. Lorazepam is currently considered the first-line agent by most clinicians. 

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

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. 

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. 

Given intravenously, both diazepam and midazolam are effective first-line treatments for status epilepticus. It is essential to be aware that the large doses that may be necessary to control convulsions are likely to cause respiratory depression and obtund protective reflexes. Oxygen and equipment suitable for its administration should be available. For intractable status epilepticus, clonazepam is a longer-acting alternative which can also be given by intravenous infusion. Overdosage... 

No. Antipyretics may make the child feel more comfortable, but there is no evidence that they reduce the incidence or severity of febrile convulsions. Anticonvulsants certainly have no role to play. If a febrile convulsion does happen they are generally tonic or tonic-clonic and last just a couple of minutes. If they were to continue for longer than 5 minutes then conventional treatment for status epilepticus should be used (rectal diazepam or buccal midazolam). 

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. 

Seizures are present in 30% of patients with star fruit intoxication [17], and most patients have convulsive [6, 8,10,11,13,14,17,18,19] or non-convulsive [16] status epilepticus. The mortality rate of patients with seizures occurring after star fruit intoxication (severe intoxication) is significantly higher than of patients without seizures [13, 17]. Phenytoin, midazolam, diazepam and phenobarbital seem to have little or no effect on the control of persistent seizures provoked by star fruit toxicity. However, significant clinical improvement of seizure was demonstrated in one patient after the use of profofol [20]. 

Galdames-Contreras, D., Carrasco-Poblete, E., Aguilera-Olivares, L., Fabres-Oyarzo, L. and Galdames-Poblete, D. 2006. Intramuscular midazolam in the initial treatment of status epilepticus. Rev. Neurol., 42 332-335. 

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

Koul RL, Aithala GR, Chacko A, et al. Continuous midazolam infusion as treatment of status epilepticus. Arch Dis Child 1997 76 445 48. 

Given the conditions and the requirements for the initial symptomatic treatment of mass casualties, the diazepam derivative avizafone in autoinjectors and/or midazolam for intramuscular injection should be sufficient. In view of lo-razepam s reported efficacy in treatment of status epilepticus, it is recommended that more experimental studies are performed on the efficacy of lorazepam, and also in controlling nerve-agent-induced seizures and convulsions. 

Towne AR, DeLorenzo RJ. Use of intramuscular midazolam for status epilepticus. J Emerg Med 1999 17 323-328. 

B. Convulsions. All three drugs can be used for the treatment of acute seizure activity or status epilepticus resulting from idiopathic epilepsy or convulsant drug overdose. Midazolam and lorazepam have the advantage of rapid absorption after intramuscular injection. Lorazepam also has a longer duration of anticonvulsant action than the other two agents. 

Midazolam. Give 0.05 mg/kg (up to 0.2 mg/kg for refractory status epilepticus) IV over 20-30 seconds, or 0.1-0.2 mg/kg IM this may be repeat if needed after 5-10 minutes or maintained with a continuous infusion (see note above). The dmg is rapidly absorbed after IM injection and can be used when IV access is not readily available. 

A 5-year-old boy with no history of convulsions had a generalized tonic-clonic seizure after taking oral theophylline for 2 days followed by non-convulsive status epilepticus [95 ]. The serum theophylline concentration was 19.7 mg/1. An intravenous bolus dose of midazolam 0.26 mg/kg largely restricted seizure activity to the right hemisphere and another 0.24 mg/kg followed by a continuous infusion of 0.20 mg/kg/hour completely abolished the electrical status. 

Federman MD, Kelly R, Harrison RE. Refractory metabolic acidosis as a complication of high-dose midazolam infusion for pediatric status epilepticus. Clin Neuropharmacol 2009 32(6) 340-1. 

SilbergleiL R-, Lowenstein, D., Durkalski, V, et al., 2011. RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial) a double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics. Epilepsia 52,45-47. 

Status epilepticus is traditionally defined as a situation where there is continuous seizure activity for a period of 30 minutes or where there are a continuous series of seizures during which the sufferer does not regain consciousness. More recently, it has been suggested that any continuous seizure period of longer than 5 minutes should be classified as status epilepticus. In these situations the treatment employed may well consist of one of the previously indicated antiepileptic dmgs such as clonazepam (Fig. 13.15), phenobarbital and phenytoin (Fig. 13.15) or alternatively diazepam, fosphenytoin (a prodrug of phenytoin), loraze-pam, midazolam and paraldehyde (Fig. 13.16) may be employed. For the drugs used in the treatment of status epilepticus, the formulation and dose differ from conventional doses due to the situation and thus many of these will be administered by intravenous injection, intravenous infusion, buccal or rectal administration. 

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