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Three Part Question

[In children undergoing ketamine sedation in the emergency department] is [benzodiazepines plus ketamine better than ketamine alone] at [reducing emergence phenomena and minimising complications and time of sedation]?

Clinical Scenario

A 4 year old boy presents to the emergency department with a 4cm laceration to the thigh. This requires cleaning and layered suture closure. You decide to sedate him using Ketamine IM. You are successful and close the wound. However, while he is recovering he appears to be experiencing unpleasant hallucinations. You wonder whether a small dose of midazolam given with the ketamine would have prevented this.

Search Strategy

Medline 1966-02/01 using the OVID interface.
[(exp ketamine OR ketamine.mp) AND (exp benzodiazepines OR benzodiazepines.mp OR exp midazolam OR midazolam.mp OR exp diazepam OR diazepam.mp OR VERSED.mp OR exp lorazepam OR lorazepam.mp OR hyponotics and sedatives.mp OR hypnovel.mp) AND (child.mp OR children.mp)] LIMIT human, english and abstracts

Search Outcome

71 papers found of which only one was relevant. An additional paper has recently been published and was not indexed on Medline at the time of searching. These 2 papers are shown in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Wathen JE et al, 2000, USA	266 patients aged 4 months to 18 years. 65% had fractures and 25% had lacerations. Ketamine 1 mg/kg plus glycopyrrolate 5 microgram/kg (137) vs Ketamine 1 mg/kg plus glycopyrrolate 5 microgram/kg plus midazolam 0.1 mg/kg	PRCT	Distress (Observational score of behavioural distress)	No difference	Large age range No data on IM ketamine use Low power for low incidence complications
			Total sedation time	78 min vs 70 min (not significant)
			Adverse events	Less vomiting (19.4% vs 9.6%) and nightmares (0% vs 3.1%) with midazolam
			Physician satisfaction	No difference
			Parental satisfaction	No difference
Sherwin TS et al, 2000, USA	104 children aged 1 - 15 years. 68% had orthopaedic injuries and 30% had wounds. Ketamine 1.5mg/kg vs ketamine 1.5 mg/kg plus midazolam 0.05 mg/kg 2 min later	PRCT	Time to discharge	96 min vs 105 min (not significant)	Large age range No data on IM ketamine use Low power for low incidence complications
			Adequatacy of sedation	64% vs 61% (not significant)
			Emergence phenomena	No difference

Comment(s)

These two well designed studies address the question directly. There appears to be no advantage to the addition of midazolam for IV ketamine sedation. Its use in IM ketamine sedation may be different as the pharmacokinetics of both drugs may be different via the IM route. Midazolam is commonly used when adults are sedated with ketamine. Further work is required in this group.

Clinical Bottom Line

Midazolam is not needed as an adjunct to ketamine sedation in children.

References

1. Wathen JE, Roback MG, Mackenzie T et al. Does midazolam alter the clinical effects of intravenous ketamine sedation in children? A double blind randomized controlled emergency department trial. Ann Emerge Med 2000;36:579-588.
2. Sherwin TS, Green SM, Khan A et al. Does adjunctive midazolam reduce recovery agitation after ketamine sedation for pediatric procedures? A randomized double blind placebo controlled trial. Ann Emerge Med 2000;35:229-238.