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Three Part Question

[In ED patients with acute pain who do not respond to conventional therapies], is the [low-dose ketamine better than morphine] at [safely and effectively reducing pain scores]?

Clinical Scenario

A man aged 25 years presents to the ED with a closed fracture of the right humeral head. He has severe pain around the shoulder and is allergic to opioids. He is given intravenous ketorolac and midazolam. Unfortunately, the patient's pain does not improve. A colleague recommends the use of subdissociative dose of ketamine for intractable pain and you wonder whether this is supported by the evidence.

Search Strategy

Ovid MEDLINE(R) 1946 to October Week 2 2016: [(exp ketamine/) AND (exp emergency medical services/ OR emergency medicine.mp.) AND (exp morphine/].

OVID Embase via OVIDSP.com 1974 to 2016 Week 43: [(exp ketamine/) AND (exp emergency medicine/ OR exp emergency health service/) AND (exp morphine/].

The Cochrane Library date of searching 26/10/16: MeSH descriptor: [Ketamine] explode all trees AND MeSH descriptor: [Morphine] explode all trees.

Search Outcome

One hundred and thirty-two papers were identified, of which 17 addressed the question. One systematic review and two subsequent randomised controlled trials offered the best evidence and are summarised in the table

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Motov et al, 2015 USA	90 ED patients aged 18–55 years with moderate-to-severe abdominal, flank, back or musculoskeletal pain	RCT	Reduction in pain score at 15 and 30 Side effects	No difference in average pain scores Higher incidence of dizziness, disorientation, mood changes in ketamine group	Single-centre trial, convenience sample, minimum sample size
Sin et al 2015 USA	Patients of any age who presented to the ER for acute pain and received intravenous ketamine for pain control at a dose of <1 mg/kg	Systematic Review	Difference in pain score Adverse events	Decrease in pain scores and/or morphine dose with ketamine Emergence phenomenon was noted in one trial	Only English literature evaluated Low level of evidence of original articles Small sample sizes with varying doses of the study medication
Miller et al 2015 USA	Convenience sample of 69 patients aged 18–59 years complaining of abdominal, flank, low back or extremity pain who required intravenous opioid treatment	RCT	Difference in pain score, secondary outcomes of agitation or sedation	Low-dose ketamine was not superior to morphine	Performed at a single military medical centre, small sample size

Comment(s)

Studies are not of the best quality. More rigorous prospective studies with larger numbers are required to make definite recommendations. Although some of these smaller studies showed some improvement in pain scores with subdissociate doses of ketamine, the differences seemed to be transient. Overall, there were minimal significant side effects from the ketamine administration. Also, many noted that the typical dose was 0.3 mg/kg but stated that there is no defined standardised dose for subdissociative ketamine.

Editor Comment

RCT, randomised controlled trial.

Clinical Bottom Line

Ketamine can be an effective alternative or adjunct to intravenous opioid pain medications and in some instances may provide more effective pain relief when compared with opioids. However, further trials need to be performed to establish more robust data.

References

1. Motov S, Rockoff B, Cohen V et al. Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med 2015;66:222–229
2. Sin B, Ternas T, Motov SM. The use of subdissociative-dose ketamine for acute pain in the ED. Acad Emerg Med 2015;22:251–7.
3. Miller JP , Schauer SG , Ganem VJ , et al . Low dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial Am J Emerg Med 2015;33:402–8.