Lorazepam is better than diazepam for generalised convulsions in adults
Date First Published:
March 1, 2000
Last Updated:
October 8, 2001
Report by:
John Butler, Specialist Registrar (Manchester Royal Infirmary)
Search checked by:
Mark Lewis, Manchester Royal Infirmary
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.
Search Details:
[(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
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):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Double-blind study of lorazepam and diazepam in status epilepticus. Leppik IE, Derivan AT, Homan RW 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 |
| A comparison of four treatments for generalized convulsive status epilepticus. Treiman DM, Meyers PD, Walton NY 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 |
Author Commentary:
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.
Bottom Line:
Intravenous lorazepam is effective and safe in the treatment of status epilepticus. It should be the first line of treatment.
References:
- Leppik IE, Derivan AT, Homan RW et al.. Double-blind study of lorazepam and diazepam in status epilepticus.
- Treiman DM, Meyers PD, Walton NY et al.. A comparison of four treatments for generalized convulsive status epilepticus.