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Three Part Question

Is [intranasal ketamine] as a sole agent a safe and effective form of [sedation] in [children] for short procedures within the emergency department?

Clinical Scenario

A 5 year old boy is brought to the emergency department following riding his bike into a lamp-post. On examination he is noted to have a large laceration across his forehead that unfortunately needs suturing. The young boy is petrified by needles and will not allow you to place a cannula or give an IM injection. The question is asked whether intranasal ketamine is a safe and effective alternative for sedation in this patient.

Search Strategy

Using medline via OVID interface the following search strategy: 1950 - June Week 5 2010
[Sedation .mp. or Anesthetics, Dissociative or Conscious Sedation] and [Intransal Ketamine.mp. or (Intranasal and ketamine)] and [children.mp. Pediatrics/ or Child/ or Child, Preschool/ or paediatrics.mp. or Infant]

Search Outcome

18 articles were found using the above search. 14 were irrelevant (6 Articles did not answer the question, 4 articles did not refer to intranasal ketamine and 4 did not use intranasal ketamine as a sole agent).
4 Articles were found to be relevant to the topic.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Weksler, N et al 1993 Israel	Ketamine at a dose of 6 mg / kg was nasally administered to 86 healthy children (ASA I and II), aged from two to five years undergoing elective general, urological or plastic surgery. Results were compared to 62 patients aged from two to five years who received IM promethazine and meperidine, 1 mg/ kg. Premedication was prepared and administered by an anaesthetist not involved in the study and an IM injection or a nasal instillation of saline was administrated along side each premedication to make it a double-blind study.	Randomised control trial – Level 1b	Level of sedation	In the ketamine group sedation was excellent in 48 patients, adequate in 19 patients and sedation failed in 19 patients. In the promethazine group 9 patients had excellent sedation, 12 had adequate sedation and sedation failed in 41 patients.	Small groups. Unequal number in each group. Study stopped due to ethical consideration of subjecting children to unnecessary injections. There was no saline-only control group, since in that case, no premedication would have been administered and no sedation obtained.
			Salivation	Salivation was graded as 1 in 35 children in the ketamine group and 28 children in the promethazine group. Graded as 2 in 39 of the children in the ketamine group and 26 in the promethazine. The remaining patients in each group were graded as 3.
			Emergence reaction	No children had an emergence reaction
			Recovery Time	The recovery time was 22.5 ± 7.5 min in ketamine group and 20.8 ± 6.5 min in control group.
Abrams, R et al 1993 USA	Thirty children between the age of 17 and 62 months of age who presented to a paediatric hospital requiring brief but urgent dental care, and who could not be satisfactorily examined or treated, were administered one of three mediations-ketamine (Ketalar), 3 mg/kg; midazolam (Versed), 0.4 mg/kg; or sufentanil (Sufenta), 1.5 or 1.0 ,ug/kg intranasally in a randomized, double-blinded protocol.	Randomised Control trial – Level 1b	Sedation scores	Patients administered ketamine and midazolam had mean sedation scores of 4. The group given high- dose sufentanil (1.5 ,ug/kg) had a mean score of 7, while the group receiving the low dose (1.0 ug/kg) had a mean score of 4.	Small number in study. Uneven patients numbers in each group.
			Recovery time	Mean recovery times (± standard deviation) prior to discharge were ketamine, 7 ± 7 min; midazolam, 3 ± 2 min; and sufentanil, 58 + 40 min and 7 ± 13 min for the high and low dose, respectively.
			Desaturation	Two patient receiving ketamine had brief desaturations. The first spontanaeously resolved and second patient responded with minimal stimulation. High incidence of significant desaturation in the high dose sufentanil group.
Diaz JH 1997 USA	A double-blinded, placebo-controlled study compared the outcomes of intranasal ketamine premedication with placebo in outpatients. Forty paediatric outpatients were assigned randomly in a prospective fashion to one of two separate study groups of equal size. A placebo group received 2 ml of intranasal saline, 1 ml per naris. The study group received intranasal ketamine, 3 mg/kg, diluted to 2 ml with saline, 1 ml per naris.	Randomised Control trial - level 1b	Cooperation index	Intranasal ketamine, 3 mg.kg-1, was associated with a significantly better (P = 0.013) cooperation index than intranasal placebo.	Small numbers in study
			Recovery and discharge times	There was no significant difference in recovery and discharge times among the two groups.
			Side effects	There was no significant difference in vomiting between the two groups.
Malinovsky JM 1997 France	During halothane anaesthesia 32 children aged 2 – 9 yr, weight 10-30kg were allocated randomly to receive either ketamine 3mg/kg nasally, ketamine 9mg/kg rectally or ketamine 3mg/kg IV. Venous blood supply were obtained before and up to after 360 min after administration of ketamine. Plasma concentrations or ketamine and norketamine were measured by gas liquid chromatography.	Case series Level 2 -3	Plasma concentration	Administration of ketamine via nasal route produced more rapid and greater plasma concentrations than after rectal administration. Rectal route was associated with high dose of nor-ketamine because of first pass metabolism.	Small numbers of patients. Problems with pharmocokinetic interpretation of the data obtained after different models of administration of ketamine as children were not their own controls. Instead patients of similar age and weight were compared in the IV and Non IV ketamine. Relationships with clinical effects may not be established as sampling occurred during general anaesthesia. Ketamine metabolism is dependent on hepatic blood flow and could be influenced by other drugs e,g. halothane that increases hepatic blood flow.
			Dosage	Nasal administration of low dose ketamine produces plasma concentration associated with analgesia, but using high doses via the nasal route produced high plasma concentrations of ketamine similar to those that induce anaesthesia.
			Variability of effect	Large volumes were required for anaesthesia due the amount of ketamine swallowed. Unacceptable variability of effect that preludes the route for induction of anaesthesia.

Comment(s)

There is no research currently available to support the use of intranasal ketamine for short procedures within the emergency department. However articles 1 and 3 have shown that intranasal ketamine can be used safely and effectively with good sedation scores and minimal side effects as an anaesthetic premedication. Article 3 demonstrates that intranasal ketamine can be used safely and effectively during short dental procedures and is preferable to other agents. Article 4 shows us that plasma concentration via the intranasal route are both adequate for sedation and equivalent to both rectal and IV routes but warns of the possibility of variability of effects secondary to ketamine being swallowed.

Clinical Bottom Line

Intranasal ketamine is a safe and effective form of sedation however further research is needed to determine the use of intranasal ketamine for short procedures in the emergency department.

References

1. Weksler, N, Ovadia L, Muati G, Stav A Nasal Ketamine for paediatric premedication Canadian Journal of Anaesthesia 1993; 119 -121
2. Abrams. R, Morrison JE, Villasenor A, Hencmann D, Da Fonseca.M, Mueller.W. Safety and Effectiveness of Intranasal Administration of Sedative Medications (Ketamine, Midaolam, or Sufentanil) for Urgent Brief Pediatric Dental Procedures Anesthesia Progress 1993; 63-66
3. Diaz JH Intranasal ketamine preinduction of paediatric outpatients. Paediatric Anaesthesia 1997; 273-278
4. Malinovsky,JM, Servin.F, Cozian A, Lepage JY, Pinaud M. Ketamine and Norketamine plasma cocentrations after i.v., nasal and rectal administration in children British Journal of Anaesthesia 1993; 203-207