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Anticonvulsant therapy for status epilepticus

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Abstract

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Background

Status epilepticus is a medical emergency associated with significant mortality and morbidity, which 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

We searched the following electronic databases using the highly sensitive search strategy for identifying published randomised controlled trials: (1) Cochrane Epilepsy Group Specialized Register (July 2005); (2) Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2,2005); (3) MEDLINE (1966 ‐ August 2004); (4) EMBASE (1966 ‐ January 2003).

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

Eleven studies with 2017 participants were included. Few studies used the same interventions. Diazepam was better than placebo in reducing the risk of non‐cessation of seizures (RR 0.73, 95% 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). 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). Lorazepam was better than diazepam for reducing 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). Lorazepam was better than phenytoin for risk of non‐cessation of seizures (RR 0.62, 95% CI 0.45 to 0.86). Diazepam (30 mg intrarectal gel) was better than a lower dose (20 mg intrarectal gel) in premonitory status epilepticus for the risk of seizure continuation (RR 0.39, 95% CI 0.18 to 0.86).

Authors' conclusions

Lorazepam is better than diazepam or phenytoin alone for cessation of seizures and carries a lower risk of continuation of status epilepticus requiring a different drug or general anaesthesia. Both lorazepam and diazepam are better than placebo for the same outcomes. In the treatment of premonitory seizures, diazepam 30 mg in an intrarectal gel is better than 20 mg for cessation of seizures without a statistically significant increase in adverse effects. Universally accepted definitions of premonitory, early, established and refractory status epilepticus are required.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

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Anticonvulsant therapy for status epilepticus

Lorazepam is better than diazepam or phenytoin for immediate control of status epilepticus.

Status epilepticus is a medical emergency in which there is either more than 30 minutes of continuous seizure activity; or there are two or more sequential seizures without recovery of full consciousness between two seizures. Many drugs have been studied in the management of this condition. The review found that 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. There is a need to conduct more studies on other drugs routinely used for this condition.