Review question

This review aimed to assess whether the use of different anticonvulsant drugs, given by different routes of administration, have an impact on how quickly an acute tonic-clonic-convulsion (fit) can be stopped. The review also investigated whether different anticonvulsant drugs were accompanied by less frequent or different serious side effects.

Background

Tonic-clonic convulsions and convulsive status epilepticus are medical emergencies. In children, the first anticonvulsant drug is usually given in the Accident and Emergency (A&E) Department of a hospital. This drug may be administered in a number of ways, including into a vein (intravenously), into the mouth and between the cheeks (buccally), into the nostrils (intranasally) or into the rectum (rectally). The first-choice drug should be effective, work rapidly and not be associated with any serious adverse effects. Research is important to try and find the most effective and the safest anticonvulsant drug in this clinical situation.

Study characteristics

We carried out a review of all available and relevant evidence on the effectiveness and safety of anticonvulsant drugs used in the first-line treatment of tonic-clonic convulsions in children who attended hospital A&E departments. This review examined data from 18 randomised controlled trials (RCTs); RCTs provide the most reliable evidence. They investigated the use of different anticonvulsant drugs and given by different routes.

Key Results

The review included 18 RCTs involving 2199 children, and investigated many different anticonvulsant drugs, doses of the drugs and routes of administration of the drugs. The studies also had some differences in their designs, their settings and the populations of children included, in terms of their ages and their clinical situation (such as how long their convulsion had been going on when they were recruited into the trial).

Analysis of two trials found no clear evidence of a different effect between intravenous lorazepam and intravenous diazepam in stopping a tonic-clonic convulsion taken to an Emergency Department. There is uncertainty about whether buccal midazolam is more effective than rectal diazepam as the first management of a tonic-clonic convulsion or convulsive status epilepticus when intravenous access is unavailable. There is no good evidence that the intranasal route is as effective as the intravenous route. Consequently there is no evidence that it can be used as an alternative route of administration.

Although medications such as midazolam, lorazepam and paraldehyde can reduce breathing rates, this is not a common complication and was not seen very often in the included studies. Rates of serious side effects of these medications are generally very low.

Quality of the evidence

Many of the trials used different drugs, different dosages and different routes of administration. This has to be taken into account when looking at the overall conclusion of this review. Most of the trials took place in large children’s hospitals or in large children’s departments in a general hospital. This means that the results found in this review are probably relevant for similar clinical situations throughout the world.

The quality of the evidence provided in this review ranged from very low to high. The quality of the evidence provided for some outcomes is low to very low, due to imprecise results where limited information was available for analysis. There were also variability and problems within the designs of some studies, which may have influenced the findings. The quality of evidence was lower in some study settings which were specific to the country in which they were conducted, so the results may not reflect clinical practice worldwide.

The evidence is current to May 2017.