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Q In patients with status epilepticus (SE), which anticonvulsant drugs are most effective?
Cochrane Epilepsy Group Specialised Register, Cochrane Central Database of Controlled Trials, Medline, EMBASE/Excerpta Medica, and bibliographies of relevant studies.
Study selection and assessment:
randomised or quasi-randomised controlled trials (RCTs) that compared any anticonvulsant drug with placebo or another anticonvulsant drug in patients with premonitory, early stage, established, or refractory SE. Quality assessment of individual studies was based on randomisation method, baseline comparability of groups, blinding, and intention to treat analysis. 11 RCTs (n = 2017) met the selection criteria. Patients had premonitory (5 RCTs), established (1 RCT), refractory (1 RCT), and mixed SE (2 RCTs); 2 RCTs did not define the status.
depending on SE stage, outcomes included development of SE, death, continuation of seizures, continuation of SE requiring use of a different drug or general anaesthesia for control, long term disabling sequelae, and need for ventilatory support.
Superior results were seen with intravenous (IV) lorazepam for reducing continuation of seizures and continuation of SE requiring a different drug (table). IV diazepam was better than placebo for reducing death, continuation of seizures, continuation of SE, and ventilatory support (table). Diazepam gel was better than placebo, and 30 mg of diazepam gel was superior to 20 mg for reducing continuation of seizures (table). No differences were seen for comparisons of lorazepam with diazepam plus phenytoin, phenobarbital, or midazolam; diazepam with midazolam (IV or intramuscular); diazepam plus phenytoin with phenobarbital or phenytoin alone; or phenobarbital with phenytoin.
In patients with status epilepticus, lorazepam is better than diazepam, phenytoin, or placebo for cessation of seizures, and diazepam is better than placebo.
A modified version of this abstract appears in ACP Journal Club.
SE may be defined as a single clinical seizure lasting >30 minutes or repeated seizures for >30 minutes without intervening recovery of consciousness. Although SE constitutes a medical emergency with significant morbidity and mortality, few randomised, blinded trials are available to inform pharmacological treatment decisions. Rosenow et al attribute the lack of good quality evidence to problems in obtaining informed consent, low potential gain for the pharmaceutical industry in developing drugs for SE, the emergency nature of SE with little time to establish the diagnosis and underlying aetiology, and the effectiveness of current accepted treatment for controlling generalised tonic-clonic SE in 64% of patients.1
Prasad et al found only 11 RCTs with analysable data, but their review provides a good evidence base for the immediate pharmacological control of SE. The authors also delineated reasons for disagreement in the literature regarding recommended treatment regimens.
Although this review focused on anticonvulsant use, important pre-treatment assessment includes investigation for chronic alcoholism or hypoglycaemia, the possibility of psychogenic presentation, and the underlying aetiology and prognosis.1 Because treatment becomes more difficult and less effective over time, nurses would benefit from an evidence-based algorithm that indicated initial treatment with lorazepam, as supported by Prasad et al, treatment of refractory SE, and avoidance and management of complications. Furthermore, although lorazepam was superior in several comparisons in this review, availability and licensing will play a part in determining choice of drug.
For correspondence: Dr K Prasad, All India Institute of Medical Sciences, New Delhi, India.
Source of funding: no external funding.
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