COMMENTARY Benzodiazepines for Acute Management of Seizures Satinder Aneja Received: 20 January 2012 / Accepted: 25 January 2012 / Published online: 16 February 2012 # Dr. K C Chaudhuri Foundation 2012 Status Epilepticus (SE) is a common neurological emergency in children and is associated with significant morbidity and mortality. SE is conventionally defined as seizure activity lasting more than 30 min or 2 or more seizures without regaining consciousness in between. For operational purpo- ses, any child brought convulsing to the hospital is considered as SE. The goals of treatment of a convulsing child are initial stabilization, prompt seizure termination and treatment of the underlying cause. The drug used to terminate seizures should be rapid acting, efficacious, safe, and easy to administer. A systematic population-based study which analysed factors associated with seizure termination showed that for each minute delay from the onset of convulsive SE to arrival at the accident and emergency department, there was a 5% cumulative increase in the risk of the episode lasting more than 60 min [1]. Rapid termination of seizure is therefore a priority. Immediate administration of benzodiazapines given intravenously is cur- rently the standard first line treatment. Benzodiazepines have a potent anticonvulsant action and the 3 commonly used benzodiazepines—Diazepam, Midazolam and Lorazepam have a fairly rapid action. The peak effect is seen within 3–5 min of administration. Despite the fact these drugs have been in use for a long time, there is a paucity of high quality randomized controlled trials comparing these drugs. This is perhaps due to the inher- ent difficulty in conducting RCTs in emergency situations. Exemption from informed consent prior to treatment is often used in such situation and consent taken from guardians after initiating treatment. In the article by Gathwala et al in this issue, lorazepam was observed to be as efficacious as diazepam and midazo- lam in terminating seizures and associated with lower risk of adverse effects and seizure recurrence [2]. The authors have done a head to head trial of the 3 drugs, all given by intravenous route. The trial has some major limitations. The sample size was not calculated for the primary outcome variable and a convenience sample was used. The trial was not powered to detect the difference in safety either. The assessment of outcome was done by residents posted in the casualty and the assessors were not blinded to the study drug. Besides, the authors did not use any objective methods to monitor respiratory depression to compare the safety of the drugs used. Nevertheless the conclusions are consistent with the published reports [3]. The lower recurrence rate of seizures with lorazepam as compared to diazepam is due to the difference in pharma- cokinetics. The duration of action for IV diazepam, mida- zolam and lorazepam is 30 min, 1–3 h and 12–24 h, respectively. Diazepam rapidly crosses the blood brain bar- rier. Within minutes, however the brain concentration of the diazepam declines as it is redistributed to other fatty tissues resulting in a short distribution half life. Thus, after a single bolus the concentration of free active diazepam in the brain may fall below therapeutic range within half an hour. After repeated dosing, diazepam accumulates, resulting in higher peak levels, which persist. This can result in sudden and unexpected CNS depression and cardiorespiratory collapse. Midazolam has the advantage over other benzodiazepines in that it is water soluble and at physiological pH it becomes highly lipophilic permitting rapid transfer across the blood brain barrier. Midazolam has very short distribution and elimination half life. Its action is thus short-lived, and there is a strong tendency to relapse following a single bolus injection. Phenytoin is often used following diazepam and S. Aneja (*) Department of Pediatrics, Lady Hardinge Medical College, New Delhi 110001, India e-mail: drsaneja@gmail.com Indian J Pediatr (March 2012) 79(3):381–382 DOI 10.1007/s12098-012-0702-3