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Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
R Appleton1, T Martland, B Phillips
1The Roald Dahl EEG Unit, Alder Hey Children's Hospital, Eaton Road, Liverpool, Merseyside, UK, L12 2AP. Richard.Appleton@RLCH-TR.NWEST.NHS.UK
Insights
This review found no evidence that intravenous lorazepam is superior to diazepam for treating pediatric tonic-clonic convulsions or status epilepticus. Rectal lorazepam may be more effective and safer than rectal diazepam, but more data is needed.
Area of Science:
- Pediatric Neurology
- Clinical Pharmacology
- Emergency Medicine
Background:
- Tonic-clonic convulsions and status epilepticus are medical emergencies requiring prompt anticonvulsant treatment.
- Diazepam, lorazepam, phenobarbitone, phenytoin, and paraldehyde are considered first-choice drugs.
Purpose of the Study:
- To review evidence comparing diazepam, lorazepam, phenobarbitone, phenytoin, and paraldehyde for treating acute tonic-clonic convulsions and convulsive status epilepticus in children.
Main Methods:
- Searched specialized registers and databases (Cochrane Epilepsy Group, Cochrane Controlled Trials Register, MEDLINE, EMBASE) up to July 2002.
- Included randomized controlled trials comparing lorazepam with other anticonvulsants for pediatric convulsive status epilepticus.
- Analyzed cessation of seizures, need for additional drugs, respiratory depression, and ICU admission due to respiratory depression.
Main Results:
- Only one trial compared intravenous lorazepam and diazepam; efficacy and recurrence rates were similar.
- Rectal lorazepam showed higher efficacy (RR 3.17) than rectal diazepam in stopping seizures.
- Lorazepam was associated with a lower incidence of respiratory depression (RR 0.21) and less need for additional drugs (RR 0.25) compared to diazepam, though not statistically significant.
Conclusions:
- No evidence supports preferring intravenous lorazepam over diazepam for first-line treatment of pediatric tonic-clonic convulsions and status epilepticus.
- Rectal lorazepam may be more effective and safer than rectal diazepam, but insufficient data exists to recommend it as the first-choice rectal drug.
Background:
Tonic-clonic (grand mal) convulsions and convulsive status epilepticus (currently defined as a grand mal convulsion lasting at least 30 minutes) are medical emergencies and demand urgent and appropriate anticonvulsant treatment. Diazepam, lorazepam, phenobarbitone, phenytoin and paraldehyde may all be regarded as drugs of first choice.
Objectives:
To review the evidence comparing diazepam, lorazepam, phenobarbitone, phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status epilepticus in children.
Search Strategy:
We searched the Cochrane Epilepsy Group's specialized register (4 July 2002); the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2002); MEDLINE (28 May 2002) and EMBASE (January 2002).
Selection Criteria:
Randomized controlled trials comparing lorazepam and other anticonvulsant drugs used for the treatment of convulsive status epilepticus in children.
Data Collection And Analysis:
This was a review of published, aggregate data. The main outcome measures included cessation of the presenting tonic-clonic convulsion/episode of convulsive status epilepticus; the number of additional drugs required to stop the convulsion; people demonstrating respiratory depression and people requiring admission to the intensive care unit because of respiratory depression.
Main Results:
Only one trial was found, in which children were allocated lorazepam or diazepam. The main results are as follows. (1) One or two intravenous doses stopped the convulsion in 19 of 27 (70%) lorazepam and 22 of the 34 (65%) intravenous diazepam-treated children. The relative risk (RR) with 95% confidence intervals (CIs) was 1.09(95% CI 0.77 to 1.54). A single dose of rectal lorazepam stopped the convulsion in six of six, compared to six of 19 children treated with rectal diazepam, RR 3.17(95% CI 1.63 to 6.14). (2) Six of the 27 (22%) intravenous lorazepam and 12 of the 34 (35%) intravenous diazepam-treated children respectively, experienced a further convulsion within 24 hours after presentation RR 0.63(95% CI 0.27 to 1.46). (3) Only one of 27 children (4%) who received intravenous lorazepam compared to five of 34 children (15%) who received intravenous diazepam required additional antiepileptic drugs to terminate the presenting seizure RR 0.25(95% CI 0.03 to 2.03). (4) A lower incidence of respiratory depression occurred in the lorazepam-treated group: one of 27 (4%) children compared to seven of 34 in the diazepam-treated group (21%), RR 0.21(95% CI 0.02 to 1.37).
Reviewer'S Conclusions:
This review provides no evidence to suggest that intravenous lorazepam should be preferred to diazepam as the first-line drug in treating acute tonic-clonic convulsions including convulsive status epilepticus in children. There was some evidence from this review that rectal lorazepam may be more effective and safer than rectal diazepam, but the data were insufficient to indicate that lorazepam should replace diazepam as the first choice rectal drug in treating acute tonic-clonic convulsions and convulsive status epilepticus.
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