Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial

@painfreeED. 2015;Annals of Emergency Medicine;66(3)222-229

Clinical Question

• In patient with acute, moderate to severe pain in the ED, does ketamine compared with morphine, reduce pain scores by an equivalent amount?

Design

• Randomised controlled trial
  • Use of ‘randomisation list’
  • Block randomisation
• Double-blinded
• Convenience sample (required both study investigator and ED pharmacist to be available)
• Sample size of 90 provided at least a 83% power to detect a difference of at least 1.3 in pain score (Standard deviation assumed = 3) at 30 minutes, with false positive rate of 5%

Setting

• Single centre
• Community teaching ED in the USA
• June 2013 – May 2014

Population

• Inclusion criteria:
  • Age 18-55
  • Presented with acute (<7 days) abdominal, flank, back or musculoskeletal pain
  • Pain score of ≥ 5
  • Required opioid analgesia as determined by treating physician
• Exclusion criteria:
  • Pregnancy, altered mental status, allergy, weight <46kg or >115kg, unstable vital signs, acute head or eye injury, seizure, chronic pain, renal or hepatic insufficiency, alcohol or drug use, psychiatric illness, opioid use within previous 4 hours
• 90 patients randomised

Intervention

• 0.3mg/kg ketamine

Control

• 0.1mg/kg morphine

For both intervention and control groups

• Medication prepared by pharmacist in 10ml of normal saline, and administered as an IV push over 3-5 minutes.
• Fentanyl 1mcg/kg given as rescue analgesic if pain score of ≥5 and requested analgesia

Outcome

• Primary outcome:
  • Reduction of pain score at 30 minutes – no significant difference
    • Ketamine vs. morphine mean difference 0.2 (95% C.I. -1.19 to 1.46, p=0.97)
• Secondary outcomes:
  • Need for rescue analgesia at 30 or 60 minutes – no significant difference
  • Vital signs
    • No significant difference in pulse rate at 15 or 30 minutes
    • Systolic and diastolic BP, and respiratory rate significantly higher at 15 minutes in ketamine vs. morphine group; but no significant difference at 30 minutes
  • Adverse events
    • Significantly greater number of patients reported adverse effects immediately after medication injection and at 15 minutes, predominately dizziness and disorientation
    • Equivalent at 30 minutes
    • No serious adverse effects in either group
• Post-hoc analysis
  • Complete resolution of pain at 15 minutes – significantly greater in ketamine group
  • Complete resolution of pain at 30 minutes – no significant difference
  • Need for rescue analgesia at 120 minutes – significantly greater in ketamine group

Authors’ Conclusions

• Subdissociative ketamine is effective and safe as morphine for the treatment of acute pain

Strengths

• Randomised controlled trial
• Double blinded
• Allocation concealment maintained

Weaknesses

• Single centre
• Convenience sample
• Potential for unblinding due to effects of ketamine e.g. nystagmus
• It would have been useful for the presence/absence of delirium to be reported at > 30 minutes. With equivalent pain reductions, if one of these drugs decreased the rate of delirium in patients admitted to hospital, this may be a reason to preferentially use that drug
• It would have also been useful to know if the introduction of ketamine as a standard medication for treating pain had any affects on patients with drug seeking behaviour who present to the ED. This was not reported.

The Bottom Line

• In patients with acute moderate to severe pain, the use of subdissociative ketamine achieved a similar reduction in pain scores compared with morphine. It resulted in an increased number of minor side effects post-injection, that had resolved by 30 minutes. Further evidence will be required for me to change from my current standard of morphine.

External Links

• [article abstract] Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial
• [Further reading] EM Literature of note
• [Further reading] St Emlyns K is Good For You – Subdissociative Ketamine vs Morphine in the ED

Metadata

Summary author: @davidslessor
Summary date: 17th September 2015
Peer-review editor: @duncanchambler