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Three Part Question

In [an adult epileptic patient suffering a grand mal fit] is [intravenous lorazepam safer and more effective than intravenous diazepam] at [safely terminating the convulsions]?

Clinical Scenario

A 45 year old female epileptic presents after sustaining a grand mal convulsion at home. She starts fitting again on arrival in the emergency department; the fit does not stop spontaneously after 5 minutes. The paramedics have secured intravenous access prior to arrival but have not given any anti-convulsants. You wonder whether lorazepam is more effective than diazepam as a first choice drug to safely terminate this convulsion.

Search Strategy

Medline 1966-09/00 using the OVID interface.
[(exp epilepsy OR exp epilepsy, generalised OR exp epilepsy, tonic-clonic or epilepsy.mp OR fits.mp OR exp convulsions OR convulsion$.mp OR exp seizures OR exp alcohol withdrawal seizures OR seizure$.mp) AND (exp lorazepam OR lorazepam$.mp)] LIMIT to human AND english

Search Outcome

133 papers found of which 131 papers were irrelevant or of insufficient quality. The remaining 2 papers are shown in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Leppik IE et al 1983 USA	78 adult patients with status epilepticus IV Lorazepam (4mg) vs IV Diazepam (10mg)	PRCT	Clinical control of seizure activity:	Lorazepam 89% within 2 doses vs Diazepam 76% within 2 doses	Small numbers Many different types of seizure activity
Treiman DM et al 1998 USA	384 patients with generalised convulsions from 570 patients with status epilepticus IV diazepam (0.15mg/kg) plus phenytoin (0.1mg/kg) vs IV lorazepam (0.1mg/kg) vs IV phenobarbitone (15mg/kg) vs IV phenytoin (18mg/kg)	PRCT	Stopping of all motor seizure activity/EEG activity in <20 minutes	55.8% vs 64.9% vs 58.2% vs 43.6%. In an intention to treat analysis the differences between treatment groups were not significant (p=0.12)	Some patients were treated prior to inclusion in trial No long term follow-up of patients

Comment(s)

The incidence of status epilepticus is given as 15-30 per 100,000 per year. It carries a considerable mortality (approximately 10%). The best first line treatment remains controversial. The use of diazepam is limited by its rapid redistribution out of the CNS. The duration of action of diazepam is approximately 20-30 minutes. Pharmcokinetic studies of lorazepam have shown it has an elimination half-life of 13 hours. Lorazepam has a much longer duration of anti-convulsant action than diazepam and has an equivalent onset of action. Studies in healthy voluteers suggest it has reduced cardio-respiratory side-effects compared to other benzodiazepines. There may be an increased risk of thrombophlebitis when compared to IV Diazemuls.

Clinical Bottom Line

Intravenous lorazepam is effective and safe in the treatment of status epilepticus. It should be the first line of treatment.

References

1. Leppik IE, Derivan AT, Homan RW et al. Double-blind study of lorazepam and diazepam in status epilepticus. JAMA 1983;249:1452-4.
2. Treiman DM, Meyers PD, Walton NY et al. A comparison of four treatments for generalized convulsive status epilepticus. N Eng J Med 1998;339:792-8.