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Three Part Question

In [children presenting to the ED with seizures] is [intranasal Lorazepam an acceptable intervention] for achieving [termination of seizures]?

Clinical Scenario

A 4 year old child is brought to the Emergency Department by her parents. She presents with protracted seizures. It proves difficult to gain intravenous access for administration of IV Lorazepam, which is the standard of care. You wonder whether intranasal administration of Lorazepam may be an acceptable alternative.

Search Strategy

PubMed using MeSH database
Search terms “Seizures” [Mesh] AND “Lorazepam” [Mesh] AND (intranasal OR intravenous)

Search Outcome

• 18 papers found, two of which were relevant.
• Cochrane: No review found.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Arya et al 2011 India	141 consecutive children aged 6-14 years who presented convulsing to the Emergency Department	Randomised open-label non-inferiority trial	Cessation of clinically visible seizures within 10 minutes of either intravenous Lorazepam or intranasal Lorazepam.	Clinical seizure remission in 80% of intravenous group compared to 83.1% of intranasal group.	EEG was not available to monitor response to Lorazepam. Atomiser device was not used to administer the intranasal Lorazepam, which may have resulted in inadvertent oral absorption and thus artificially prolonged efficacy. The study only included children over the age of 6 years.
			Persistent seizure cessation for 1 hour.	Persistent seizure remission for 1 hour in 58.57% of intravenous group compared to 61.97% of intranasal group.
			Development of hypotension or respiratory depression.	None of the patients in either group developed significant hypotension. 2 patients in the intravenous group and 1 patient in the intranasal group required assisted ventilation.
Ahmad et al 2006 Malawi	160 consecutive children aged over 2 months who presented to the Emergency Department with seizures persisting for over 5 minutes	Randomised open-label trial	Cessation of clinically visible seizures within 10 minutes of 1 dose of either intranasal Lorazepam or intramuscular Paraldehyde.	Clinical seizure remission in 75% of intranasal Lorazepam group compared to 61.3% of intramuscular Paraldehyde group.	EEG was not available to monitor response to the drug intervention resulting in inability to exclude sub-clinical persisting seizure activity. Different patient group and underlying seizure aetiology compared to patient group in the UK.
			Development of hypotension or hypoxia during the 30 minutes after drug administration.	None of the patients in either group developed significant hypotension. 2 patients in the intranasal Lorazepam group and 1 patient in the Paraldehyde group required supplemental oxygen to maintain oxygen saturations above 92%.
			Seizure recurrence within 24 hours of termination of the presenting convulsion.	10% seizure recurrence within 24 hours in intranasal Lorazepam group compared to 14% of intramuscular Paraldehyde group.

Comment(s)

These studies were not blinded, but were randomised. The methods used for randomisation were appropriate and adequately described. There was no loss to follow-up and protocol violations were accounted for. The study by Ahmad and colleagues demonstrated that intranasal lorazepam was as effective as intramuscular paraldehyde in achieving seizure cessation. Intramuscular paraldehyde is not used in the developed world much. The study by Arya and colleagues showed that intranasal lorazepam was not inferior to intravenous lorazepam in the control of acute seizures in children. Both studies assessed intranasal lorazepam as a safe and effective intervention.

Clinical Bottom Line

In children presenting to the ED with seizures, intranasal lorazepam appears to be an acceptable intervention for the termination of seizures, demonstrating both efficacy and safety.

References

1. Arya R, Gulati s, Kabra M et al. Intranasal versus intravenous Lorazepam for control of acute seizures in children: A randomised open-label study. Epilepsia 2011; 52:788-793.
2. Ahmad S, Ellis JC, Kamwendo H et al. Efficacy and safety of intranasal Lorazepam versus intramuscular Paraldehyde for protracted convulsions in children: an open randomised trial. Lancet 2006; 367:1591-97.