• 
• 

Three Part Question

[In children undergoing ketamine sedation]is(intravenous ketamine) better than (Intramuscular Ketamine)] at[being more effective and reducing the complications of sedation and recovery time]?

Clinical Scenario

A 3yr old girl is brought to emergency department by mother with a wound on the left knee.Child was playing and fell on glass peice.There is a visible laceration of 3cm length and moderate depth.xray didn't show foreign body.You decide to go forward and suture the laceration under Ketamine Sedation.In the previuos hospital you worked sedation was always given IV route but in the current hospital you are working ketamine sedation is done IM route .You go through the hospital protocol for ketamine sedation and finish the procedure.Next while discussing this case with one your seniors they suggest the reason for using ketamine IM is that it is assocaiated with less complications and longer duartion of sedation.You wonder what is the evidence.

Search Strategy

Medline(OVID interface 1950 to February Week 2 2009[(exp ketamine OR ketamine.mp)AND(exp Infusions Intravenous OR INTRAVENOUS.mp OR exp Injections Intravenous OR exp Injections Intramuscular or INTRAMUSCULAR.mp)AND(exp Deep Sedation/ or exp Conscious Sedation/ or SEDATION.mp AND Paediatric filter
EMBase 1980 to Present

Search Outcome

Medline-Of 151 papers found of which only 4 were relevant
EMBase-34 papers found and none were relevant to the question
Cochrane Database of Systematic Reviews-No relevant papers found

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Mark G. Roback etal 2006 USA	225 patients children aged 4 months to 18yr presenting with orthopaedic injury, ASA1 and 2 receiving procedural sedation for orthopaedic reduction are randomised to receive either IV(1mg/kg) or IM(4mg/kg) ketamine	PRCT Level of Evidence 1b	Respiratory adverse events	12/109 8.3% in IV group and 4 of 99 i;e 4% in IM group Odds Ratio 0.45 CI 95%	No blinding done in the study Difference in the adverse events is secondary to the dose or route of administration? Sample not large enough to show significant difference in the adverse events Study on only Orthopaedic procedures
			Vomiting	20/109 (18.3%) in IV 35/99 (35.4%) in IM
			Distress during the procedure(Mean pain score)	IM -0.34, IV-0.81, difference of 0.47 95% CI
			Parental satisfaction	93.6% IV group 89.9% IM group
			Physician Satisfaction	91.7% IV group 93.9% IM group
			Length of sedation	Median IM 129min(55-365) Median IV 80min(27-210) P<0.01
McCarty etal 2000 USA	114 children(12 months to 12 yr) undergoing closed reduction of isolated fracture or dislocation 99 received 2mg/kg IV Ketamine and 4mg/kg in 15 patients	Prospective Case Series Level of Evidence 4	Mean Duration of procedure	IV -7 min 48 sec(5-46 min) IM 19 min 42 sec(10-50min)	Small sample Randomisation not clear Study subjects having only one treatment module Adverse events not reported or compared between the groups
			Discharge time	IV-84 min(22-115) IM-90min(60-130)
			Pain Score	IV-6.3 IM-6.5
K C Ng etal Singapore 1999	500 paediatric patients given ketamine for conscious sedation either IM (3-4 mg/kg) or IV (1-2 mg/kg) together with atropine(0.02 mg/kg), with or without intravenous midazolam (0.05 mg/kg)	Retrospective case series review Level of Evidence-4	Discharge from hospital	480/500 (96% ) discharged safely , 11/500(2.2%) admitted because of Failure of manipulation and reduction,7/500 (1.4%) admitted because of other clinical indications,1/500(0.2%) admitted because of conscious sedation	Didn’t study the difference in the IV and IM group and any other adverse events during or after the procedure. This article was mainly to prove that ketamine was safe to be used in ED
Stephen J Priestley etal 2001 Australia	Twenty-eight children aged 1.5–12 years were administered ketamine sedation prior to undergoing a painful procedure. Ketamine was administered either i.m. (dose 3–4 mg/kg) or i.v. (dose 1.00 –2.75 mg/kg) depending on physician preference.Midazolam (dose 0.02 mg/kg) and atropine (dose 0.02 mg/kg) were given as adjuncts in the majority of cases.	Case Control Study Level of Evidence 3b	Mean time to onset (min)	IV 2 min(1–4), IM 3.7 min(2–7)	Small sample Adverse events not documented.
			Mean length of procedure (min)	IV 12.4 min(2–26) IM 15.5 min(6–60)
			Mean time to discharge (min)	IV 93.9 min(67–145) IM 112.3 min(78–180)
Steven M. Green, MD etal 2009 Feb USA	Pooled individual-patient data from 32 ED studies(24 prospective) where ketamine was used as procedural sedation in children and determine which clinical variables would predict airway and respiratory adverse events. ketamine technique variables chosen were route (IM/IV), initial dose (in mg/kg), total dose (in mg/kg), the presence or absence of coadministered anticholinergics (eg, atropine, glycopyrrolate), and the presence or absence of coadministered benzodiazepines (eg, midazolam, diazepam). patient variables chosen were age, ASA physical status and oropharyngeal procedural indication Route Intramuscular 2,604 Intravenous 5,678	Metanalysis/Systematic review of different type of studies Level of Evidence 3a	airway/respiratory adverse events.	IV Realtive to IM Odds Ratio in Total Sample 1.38 (0.99–1.90) Prospective subset 1.12 (0.79–1.59) 95%CI	Heterogenicity of the studies and observational nature of the data. Under reporting of adverse events in the studies very less number of studies comparing IV to IM
			Apnea	IV Realtive to IM Odds Ratio in Total Sample 2.26 (0.85–5.99) Prospective Subset 1.48 (0.50–4.40) 95% CI
			laryngospasm	IV route 10 of 22 patients(45.5%)

Comment(s)

The route of administration ok ketamine in cildren for procedural sedation has always been controversial.Different hospitals have their own protocols.The CEM guideline published in 2004 advocate IM Ketamine 2mg/kg. From the limited evidence we got from above studies especially RCT and meta analysis suggest that Adverse events like airway or respiratory events are higher in IV route compared to IM route in the and it is more related to high IV dose as well.(1)(5) Which route is less painful during the procedure is less conclusive as distress during the procedure was higher in IV group in the RCT study(1) and no significant difference in the McCarty study(2).The remaining two studies did not consider that variable. Duration of sedation is longer in IM group compared to IV group and this might help decreased chance of additional doses of Ketamine which could lead to more likelihood of having adverse events. Recovery time is longer in IM group which means longer hospital stay and associated with high incidence of vomiting. Even though the IM Ketamine is more painful and needed more dose of Ketamine and has got more recovery time it is safer than IV ketmaine.The evidence is limited and a large scale Multi center RCT could be able to give more concrete conclusions.

Clinical Bottom Line

IV Ketamine IM Ketamine has got the same safety index and efficacy provided the dose of IV ketamine is low and no need of repeated dose.

References

1. Mark G. Roback, MD A Randomized, Controlled Trial of IV Versus IM Ketamine for Sedation of Pediatric Patients Receiving Emergency Department Orthopedic Procedures Annals of Emergency Medicine 2006;48:605-612
2. ERIC C. MCCARTY Ketamine Sedation for the Reduction of Children’s Fractures in the Emergency Department* The Journal of Bone and Joint Surgery America 2000;82:912
3. K C Ng, S Y Ang Sedation with Ketamine for Paediatric Procedures in the Emergency Department – A Review of 500 Cases Singapore Med J 2002 Vol 43(6) : 300-304
4. Stephen J Priestley,James Taylor,Catherine M McAdam and Peter Francis Ketamine sedation for children in the emergency department Emergency Medicine (2001) 13, 82-90
5. Steven M. Green, MD Mark G. Roback, MD Predictors of Airway and Respiratory Adverse Events With Ketamine Sedation in the Emergency Department: An Individual-Patient Data Meta-analysis of 8,282 Children Annals of Emergency medicine 2008.12.011