Journal scan 3: Lorazepam vs Diazepam for Pediatric Status Epilepticus: Which is better?

Here is the study of 259 patients was publisheed in JAMA in 2014, by James M. Chamberlain, on efficacy of Lorazepam vs diazepam for pediatric status epilepticus, it was a randomized clinical trial.

Background

Both Diazepam and lorazepam are benzodiazepines used in treatment of status epilepticus. They differ in potency and in the time-course of their action. As a sedative, diazepam 10 mg is equivalent to lorazepam 2–2.5 mg. Diazepam is better absorbed after oral than after i.m. administrations but this does not apply to lorazepam. The clinical effect and amnesia begin more rapidly with diazepam, but last longer following lorazepam.

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.

Importance

Benzodiazepines are considered first-line therapy for pediatric status epilepticus. Some studies suggest that lorazepam may be more effective or safer than diazepam, but lorazepam is not Food and Drug Administration approved for this indication.

Objective

The hypothesis that lorazepam has better efficacy and safety than diazepam for treating pediatric status epilepticus was tested.

The Pediatric Emergency Care Applied Research Network (PECARN) conducted a double-blind randomized clinical trial at 11 pediatric emergency departments. This double-blind, randomized clinical trial was conducted on patients aged 3 months to younger than 18 years with convulsive status epilepticus . There were 273 patients; 140 randomized to diazepam and 133 to lorazepam.
Interventions  Patients received either 0.2 mg/kg of diazepam or 0.1 mg/kg of lorazepam intravenously, with half this dose repeated at 5 minutes if necessary. If status epilepticus continued at 12 minutes, fosphenytoin was administered.

Outcomes

The primary efficacy outcome was cessation of status epilepticus by 10 minutes without recurrence within 30 minutes. Secondary outcomes included rates of seizure recurrence and sedation and times to cessation of status epilepticus and return to baseline mental status. Outcomes were measured 4 hours after study medication administration.

Results

Cessation of status epilepticus for 10 minutes without recurrence within 30 minutes occurred in 72.1% in the diazepam group and 72.9% in the lorazepam group. There were no statistically significant differences in secondary outcomes except that lorazepam patients were more likely to be sedated.

Conclusions

Among pediatric patients with convulsive status epilepticus, treatment with lorazepam did not result in improved efficacy or safety compared with diazepam. These findings do not support the preferential use of lorazepam for pediatric status epilepticus.

Review

The RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial)

Both adults and children studied, 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 no difference results for the 2 medications (70% vs 68%, respectively).

However, following studies supported that lorazepam as a better choice than diazepam for status epilepticus although these were not pediatric specific studies.

This study published in NEJM in 2001 by Brian K. Alldredge for comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus concluded that Lorazepam is likely to be a better therapy than diazepam.

Another study by Kameshwar Prasad in 2007 on Anticonvulsant therapy for status epilepticus published in British Journal of Clinical Pharmacology concluded that 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.

Reference

1. James M. Chamberlain, MD Lorazepam vs diazepam for pediatric status epilepticus: a randomized clinical trial. JAMA. 2014 Apr 23-30;311(16):1652-60. doi: 10.1001/jama.2014.2625.
2. Dundee JW, McGowan WA, Lilburn JK, McKay AC, Hegarty JE. Comparison of the actions of diazepam and lorazepam.
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3211107/
4. N Engl J Med. 2001 Aug 30;345(9):631-7.
5. Kameshwar Prasad Anticonvulsant therapy for status epilepticus. British Journal of Clinical Pharmacology. Volume 63, Issue 6, pages 640–647, June 2007