Cochrane review: Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children

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. Benzodiazepines (midazolam, diazepam, lorazepam), phenobarbitone, phenytoin and paraldehyde may all be regarded as drugs of first choice. This is an update of a Cochrane review first published in 2002 and previously updated in 2005. Objectives To review the evidence comparing the efficacy and safety of midazolam, diazepam, lorazepam, phenobarbitone, phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status epilepticus in children treated in hospital. Search strategy We searched the Cochrane Epilepsy Group's Specialized Register (1st July 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007), and MEDLINE (1966 to July 2007). Selection criteria Randomized and quasi-randomized controlled trials comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children. Data collection and analysis Two review authors independently assessed trials for inclusion and extracted data. We contacted study authors for additional information. Main results Four trials involving 383 participants were included. (1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions, 19/27 (70%) versus 22/34 (65%), RR 1.09 (95% CI 0.77 to 1.54), has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam, 6/6 versus 6/19 (31%), RR 3.17 (95% CI 1.63 to 6.14) (2) Buccal midazolam controlled seizures in 61/109 (56%) compared with 30/110 (27%) of rectal diazepam treated episodes with acute tonic-clonic convulsions, RR 2.05 ( 95% CI 1.45 to 2.91) (3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile convulsions, 23/26 (88%) versus 24/26 (92%), RR 0.96 (95% CI 0.8 to 1.14) (4) There is moderate evidence that intranasal lorazepam is more effective than intramuscular paraldehyde for acute tonic-clonic convulsions and patients treated with intranasal lorazepam are significantly less likely to require further anticonvulsants to control continuing seizures, 8/80 (10%) versus 21/80 (26%), RR 0.58 (95% CI 0.42 to 0.79). Authors' conclusions The conclusions of this update have changed to suggest that intravenous lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions. Where intravenous access is unavailable there is evidence from one trial that buccal midazolam is the treatment of choice. Plain Language Summary Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children Tonic-clonic convulsions and convulsive status epilepticus are medical emergencies. In children, initial treatment is usually given in the Accident and Emergency (A&E) department of a hospital. Initial treatment may be administered in a number of ways including into a vein (intravenously), into the nasal or oral cavities (buccally) or into the rectum (rectally). The first choice anticonvulsant should be effective, work rapidly and not be associated with any serious adverse effects. Four trials involving 383 participants were included. A review of two trials in children found evidence to inform a choice of intravenous lorazepam over intravenous diazepam as first line treatment for children presenting to an A&E department in an acute tonic-clonic convulsion. There is evidence from one trial to suggest that buccal midazolam is more effective than rectal diazepam in the initial management of convulsive status epilepticus in childhood where intravenous access is unavailable/unobtainable.