Lorazepam, Diazepam Similar in Pediatric Status Epilepticus

Megan Brooks

April 30, 2014

Lorazepam does not have better efficacy and safety than diazepam for pediatric status epilepticus, according to results of a head-to-head comparison.

On the basis of the findings, "hospitals should feel comfortable in treating children with either medication," James Chamberlain, MD, chief of emergency medicine, Children's National Health System, Washington, DC, told Medscape Medical News.

"This is important because we often face medication shortages and may have to substitute one medication for another. In this case, it won't make a difference," he said.

The study is published in the April 23/30 issue of JAMA, a neurology theme issue.

Equal Efficacy, Safety

Diazepam but not lorazepam is approved by the US Food and Drug Administration for status epilepticus in children, although both drugs are widely used for this purpose.

"Several retrospective studies in children and prospective studies in adults seemed to suggest that lorazepam was more effective or safer (depending on the study) than diazepam," Dr. Chamberlain said. "We performed a phone survey of approximately 100 emergency departments and found that 80% were using lorazepam."

To test the hypothesis that lorazepam has better efficacy and safety for pediatric status epilepticus, the Pediatric Emergency Care Applied Research Network (PECARN) conducted a double-blind randomized clinical trial at 11 pediatric emergency departments.

The investigators randomly assigned 273 patients aged 3 months to younger than 18 years presenting with convulsive status epilepticus to diazepam (0.2 mg/kg) or lorazepam (0.1 mg/kg) given intravenously, with half the dose repeated at 5 minutes if needed. If status epilepticus continued at 12 minutes, fosphenytoin was administered.

There was no difference in the primary efficacy outcome of cessation of status epilepticus for 10 minutes without recurrence within 30 minutes, which occurred in 101 of 140 (72.1%) patients in the diazepam group and 97 of 133 (72.9%) patients in the lorazepam group. The absolute efficacy difference was 0.8 percentage point (95% confidence interval [CI], –11.4 to 9.8 percentage points).

Twenty-six patients in each group required assisted ventilation (16.0% given diazepam and 17.6% given lorazepam; absolute risk difference, 1.6 percentage points; 95% CI, –9.9 to 6.8 percentage points).

There were also no statistically significant differences in other outcomes, such as rates of seizure recurrence and time to cessation of convulsions, with 1 exception: Sedation was more common with lorazepam than diazepam (67% vs 50%, respectively; absolute risk difference, 16.9 percentage points; 95% CI, 6.1 to 27.7 percentage points).

These findings do not support the superiority of lorazepam over diazepam as a first-line agent for pediatric status epilepticus, the investigators say.

Three "Reasonable" First-Line Options

"Essentially they found no difference between the 2. This is important to know as diazepam does not need to be kept in the fridge," John Duncan, MA, DM, FRCP, FMedSci, professor of neurology, University College London, United Kingdom, who was not involved in the study, told Medscape Medical News.

"Hearsay in adults is that lorazepam has a longer action, and so recurrence of seizures hours later is less likely to occur. This aspect of what occurs hours later does not seem to be addressed in this paper," Dr. Duncan noted.

Dr. Chamberlain said ambulance personnel "should now feel comfortable using diazepam. They are giving effective therapy. Parents should feel reassured that they are also giving effective antiseizure therapy when they use rectal diazepam (trade name Diastat) at home," he said.

As reported previously by Medscape Medical News, the RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial) study of adults and children found that, overall, intramuscular midazolam initiated in the prehospital setting stopped more seizures at arrival to the emergency department than intravenous lorazepam (73% vs 63%). However, a subgroup analysis of the 149 children enrolled showed similar results for the 2 medications (70% vs 68%, respectively).

"When taken together with the results of the RAMPART study (intramuscular midazolam vs intravenous lorazepam in the ambulance), any of the 3 benzodiazepines is a reasonable first-line treatment for children," Dr. Chamberlain said. "Logistic considerations, such as ease of storage and route of administration, are important considerations because the effectiveness and safety are so nearly equal," he concludes.

The investigators say their results point to future research opportunities. They note that failure of efficacy was observed in roughly 1 in 4 children and severe respiratory depression rate in about 1 in 6. "Future trials should consider newer medications and novel interventions targeting those at highest risk for medication failure or respiratory depression," they conclude.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors and Dr. Duncan have disclosed no relevant financial relationships.

JAMA. 2014;311:1652-1660. Abstract

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