Lorazepam 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. 

Alldredge BK, Gelb AM, Isaacs SM, et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med 2001 345 631-637. 

All benzodiazepines are indicated in obsessive compulsive disorders. Diazepam and lorazepam are effective in status epilepticus, whereas chlordiazepoxide is indicated in alcohol withdrawal. 

Lorazepam is a short-acting benzodiazepine indicated for use in relieving anxiety and insomnia. Lorazepam may also be administered perioperatively to alleviate pain and in status epilepticus. Imipramine is a tricyclic antidepressant, paroxetine is a selective serotonin re-uptake inhibitor, venlafaxine is a serotonin and adrenaline re-uptake inhibitor and moclobemide is a reversible monoamine oxidase inhibitor. Imipramine, paroxetine, venlafaxine and moclobemide are all classified as antidepressants. 

Status epilepticus For the treatment of status epilepticus (lorazepam). 

Seizures. Simple isolated seizures may require only observation and supportive care. Repetitive seizures or status epilepticus require therapy. Give IV diazepam or lorazepam followed by fosphenytoin and/or phenobarbital. Pancuronium may also be considered. 

Cock HR, Schapira AH. A comparison of lorazepam and diazepam as initial therapy in convulsive status epilepticus. QJM 2002 95(4) 225-31. 

One recent report also detailed three cases of convulsive status epilepticus after abrupt discontinuation of long-term use of 25 mg lorazepam in one patient and more than 20 mg flunitrazeparr, in two patients. These patients were nonepileptics and free of other high-risk factors for seizure ( 271). 

Several members of the benzodiazepine group are effective in treating epilepsy, but most are limited because of problems with sedation and tolerance. Some agents such as diazepam (Valium) and lorazepam (Ativan) are used in the acute treatment of status epilepti-cus (see Treatment of Status Epilepticus ), but only a few are used in the long-term treatment of epilepsy. Clonazepam (Klonopin) is recommended in specific forms of absence seizures (e.g., the Lennox-Gastaut variant) and may also be useful in minor generalized seizures such as akinetic spells and myoclonic jerks. Clorazepate (Tranxene) is another benzodiazepine that is occasionally used as an adjunct in certain partial seizures. 

Benzodiazepines used to treat epilepsy include diazepam, clonazepam, clobazam and lorazepam. Of these, diazepam and lorazepam have been most widely used to control status epilepticus, while use of clonazepam is usually restricted to the chronic treatment of severe mixed types of seizures (e.g. Lennox-Gastaut syndrome and infantile spasm). The major problem with most of the benzodiazepines, with the possible exception of clobazam, is sedation. 

Lorazepam is less lipophilic than diazepam and there is evidence that it has a longer duration of anticonvulsant action than diazepam after intravenous administration. This could be due to the fact that diazepam is more rapidly removed from the brain compartment than lorazepam, which limits its duration of antiepileptic activity. In practice, when diazepam is used to control status epilepticus it is often necessary to continue treatment with diphenylhydantoin, which has a longer duration of action in the brain. The principal hazards of benzodiazepines when given intravenously include respiratory depression and hypotension. Diazepam may be administered rectally, its ease of absorption leading to peak plasma levels within about 10 minutes. 

The use of intravenous benzodiazepines administered by paramedics for the treatment of out-of-hospital status epilepticus has been evaluated in a double-blind, randomized trial in 205 adults (54). The patients presented either with seizures lasting 5 minutes or more or with repetitive generalized convulsive seizures, and were randomized to receive intravenous diazepam 5 mg, loraze-pam 2 mg, or placebo. Status epilepticus was controlled on arrival at the hospital in significantly more patients taking benzodiazepines than placebo (lorazepam 59%, diazepam 43%, placebo 21%). The rates of respiratory or circulatory complications related to drug treatment were 11% with lorazepam, 10% with diazepam, and 23% with placebo, but these differences were not significant. 

In a multicenter, randomized, double-blind comparison of diazepam (0.15 mg/kg followed by phenytoin 18 mg/kg), lorazepam (0.1 mg/kg), phenobarbital (15 mg/kg), and phenytoin (18 mg/kg) in 518 patients with generalized convulsive status epilepticus, lorazepam was more effective than phenytoin and at least as effective as phenobarbital or diazepam plus phenytoin (1). Drug-related adverse effects did not differ significantly among the treatments and included hypoventilation (up to 17%), hypotension (up to 59%), and cardiac rhythm disturbances (up to 9%). 

Leppik IE, Derivan AT, Homan RW, et al. Double-blind study of lorazepam and diazepam in status epilepticus. JAMA 1983 249 1452-1454. 

TreimanDM, De Giorgio CM, Ben-Menachem E, etal. Lorazepam versus phenytoin in the treatment of generalized convulsive status epilepticus Report of an ongoing study. Neurology 1985 35 284. 

Appleton R, Sweeney A, Choonaral, etal. Lorazepam versus diazepam in the acute treatment of epileptic seizures and status epilepticus. Dev Med Child Neurol 1995 37 682-688. 

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

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