Abstract
Background
Status epilepticus is a medical emergency associated with significant mortality and morbidity that requires immediate and effective treatment.
Objectives
(1) To determine whether a particular anticonvulsant is more effective or safer to use in status epilepticus compared to another and compared to placebo.
(2) To delineate reasons for disagreement in the literature regarding recommended treatment regimens and to highlight areas for future research.
Search methods
For the latest update of this review, the following electronic databases were searched on 15/08/2013: the Cochrane Epilepsy Group’s Specialized Register, CENTRAL The Cochrane Library July 2013, Issue 7, and MEDLINE (Ovid) 1946 to 15/08/2013.
Selection criteria
Randomised controlled trials of participants with premonitory, early, established or refractory status epilepticus using a truly random or quasi-random allocation of treatments were included.
Data collection and analysis
Two review authors independently selected trials for inclusion, assessed trial quality and extracted data.
Main results
Eighteen studies with 2755 participants were included. Few studies used the same interventions. Intravenous diazepam was better than placebo in reducing the risk of non-cessation of seizures (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.57 to 0.92), requirement for ventilatory support (RR 0.39, 95% CI 0.16 to 0.94), or continuation of status epilepticus requiring use of a different drug or general anaesthesia (RR 0.73, 95% CI 0.57 to 0.92). Intravenous lorazepam was better than placebo for risk of non-cessation of seizures (RR 0.52, 95% CI 0.38 to 0.71) and for risk of continuation of status epilepticus requiring a different drug or general anaesthesia (RR 0.52, 95% CI 0.38 to 0.71). Intravenous lorazepam was better than intravenous diazepam for reducing the risk of non-cessation of seizures (RR 0.64, 95% CI 0.45 to 0.90) and had a lower risk for continuation of status epilepticus requiring a different drug or general anaesthesia (RR 0.63, 95% CI 0.45 to 0.88). Intravenous lorazepam was better than intravenous phenytoin for risk of non-cessation of seizures (RR 0.62, 95% CI 0.45 to 0.86). Diazepam gel was better than placebo gel in reducing the risk of non-cessation of seizures (RR 0.43 95% CI 0.30 to 0.62)
For pre-hospital treatment, intramuscular midazolam is at least as effective as (probably more effective than) intravenous lorazepam in control of seizures (RR1.16, 95% CI 1.06 to 1.27) and frequency of hospitalisation (RR 0.88, 95% CI 0.79 to 0.97) or intensive care admissions (RR 0.79, 95% CI 0.65 to 0.96). It was uncertain whether Intravenous valproate was better than intravenous phenytoin in reducing risk of non-cessation of seizures (RR 0.75, 95% CI 0.28 to 2.00). Both levetiracetam and lorazepam were equally effective in aborting seizures (RR 0.97, 95% CI 0.44 to 2.13). Results for other comparisons of anticonvulsant therapies were uncertain due to single studies with few participants.
The body of randomised evidence to guide clinical decisions is small. It was uncertain whether any anticonvulsant therapy was better than another in terms of adverse effects, due to few studies and participants identified. The quality of the evidence from the included studies is not strong but appears acceptable. We were unable to make judgements for risk of bias domains incomplete outcome reporting (attrition bias) and selective outcome reporting (selection bias) due to unclear reporting by the study authors.
Authors’ conclusions
Intravenous lorazepam is better than intravenous diazepam or intravenous phenytoin alone for cessation of seizures. Intravenous lorazepam also carries a lower risk of continuation of status epilepticus requiring a different drug or general anaesthesia compared with intravenous diazepam. Both intravenous lorazepam and diazepam are better than placebo for the same outcomes. For pre hospital management, midazolam IM seemed more effective than lorazepam IV for cessation of seizures, frequency of hospitalisation and ICU admissions however,it was unclear whether the risk of recurrence of seizures differed between treatments. The results of other comparisons of anticonvulsant therapies versus each other were also uncertain. Universally accepted definitions of premonitory, early, established and refractory status epilepticus are required. Diazepam gel was better than placebo gel in reducing the risk of non-cessation of seizures. Results for other comparisons of anticonvulsant therapies were uncertain due to single studies with few participants.
Plain language summary
Anticonvulsant therapy for status epilepticus
Some patients develop abnormal excessive electrical activity of brain nerve cells. This is called seizure activity and may involve a small area of the brain or the whole brain, resulting in sudden dysfunction of the structures involved, such as shaking of the limbs. The seizure activity often results in jerky movements (convulsions) and usually lasts a few minutes. When there is either more than 30 minutes of continuous seizure activity; or there are two or more seizures in a row without recovery of full consciousness between two seizures, the condition is called status epilepticus, which is a medical emergency. Many drugs have been studied in the management of this condition. This review found that intravenous (injected into a vein) lorazepam is better than diazepam or phenytoin for immediate control of status epilepticus. In the treatment of serially occurring seizures, diazepam gel administered rectally is effective in controlling seizures. Intravenous lorazepam is better than intravenous diazepam or phenytoin for immediate control of status epilepticus. For pre-hospital treatment, intramuscular midazolam is as effective as (probably more effective than) intravenous lorazepam in control of seizures and frequency of hospitalisation or intensive care admissions. There is a need to conduct more studies on other drugs routinely used for this condition.
