Ketamine, a noncompetitive N-methyl-D-asparate and glutamate receptor antagonist, is a Phencyclidine-like dissociative agent that possesses potent analgesic, anxiolytic and amnestic properties. In the Emergency Department (ED), ketamine is commonly used for procedural sedation. Outside of the ED, subdissociative doses (0.3 mg/kg), have been successfully used as an adjunct to opiate refractory pain. Recent data has shown that subdissociative doses of ketamine may be comparable to morphine as a first-line agent in out-of-hospital settings. However, there lacks sufficient data to support its use for initial pain management in the ED setting.
Will a subdissociative dose (0.3 mg/kg) of ketamine provide relief similar to that of morphine (0.1 mg/kg) for acute moderate to severe pain in the ED?
Patients aged 18-55 presenting with acute (onset ≤7 days) abdominal, flank, back or musculoskeletal pain with a rating of 5 or more on an 11-point numeric pain scale.
Single dose of ketamine (0.3 mg/kg)
Single dose of morphine (0.1 mg/kg)
Outcome (Primary): Reduction in pain score at 30 minutes.
Outcome (Secondary): Use of rescue analgesia (fentanyl 1 μg/kg) at 30 or 60 minutes, vital sign changes and incidence of adverse events.
Single center, prospective, randomized double-blinded clinical trial
• Pregnancy or currently breast-feeding, altered mentation, allergy to either morphine or ketamine
• Weight <46 kg or >115 kg
• Unstable vital signs (SBP <90 or >180 mm Hg, pulse rate <50 or >150 beats/min, and respiration rate <10 or >30 breaths/min),
• Medical history of: acute head or eye injury, seizure, intracranial hypertension, chronic pain, renal or hepatic insufficiency, alcohol or drug abuse, psychiatric illness or recent (within 4 hours) opioid use
- No significant difference in pain score between ketamine and morphine at 30 minutes: 4.1 vs 3.9, Mean Difference of 0.2 (95% CI 1.19 to 1.46; P = 0.97)
- Both groups demonstrated significant reductions in pain rating at 30 minutes as compared to baseline
- 90 patients (45 patients per group) over 11 months
- No difference between groups in demographic characteristics, or baseline vital signs, pain scores or chief complaint
- More patients reported complete resolution of pain in the ketamine group at 15 minutes (44% vs 31%; percentage difference = 31%), however this difference was no longer present at 30 minutes (27% vs 24%; percentage difference = 3%).
- No significant difference in the use of rescue analgesia for ketamine vs morphine at 30 minutes (9% vs 2%; percentage difference = 7%) or 60 minutes (9% vs 14%; percentage difference = 5%) , however the ketamine group required significantly more rescue analgesia at 120 minutes (29% vs 12%; percentage difference = 17%).
- Adverse Events
- No serious or life threatening adverse events
- No clinically or statistically significant changes in vital signs
- Statistically significant increased incidence of minor adverse events (dizziness, disorientation, mood changes and nausea) in ketamine group at 15 minutes, however this difference was no longer present at 30 minutes
- Well conducted randomization and blinding
- Adequately powered to detect a meaningful difference in pain score
- Validated pain scale used
- Convenience sample
- Small sample size
- Single center
- Potential for unblinding given ketamine specific reactions
- Subjective outcome measure
“Subdissociative intravenous ketamine administered at 0.3 mg/kg provides analgesic effectiveness and apparent safety comparable to that of intravenous morphine for short-term treatment of acute pain in the ED”
In this well designed non-inferiority study, a single subdissociative dose of ketamine was found to have similar effectiveness as morphine for short-term (<30 minute) control of pain in ED patients. Furthermore, this article suggests that ketamine may provide more rapid relief of pain as compared to morphine. Although the authors conclude that ketamine also has the same safety profile, given the small sample size, this study may have been inadequately powered to detect a significant number of adverse events. In addition, although minor adverse effects were not found to be clinically significant, they should not be considered negligible. Patients should be made aware of the potential side effects prior to use, as these may deter use of the medication in the future. Clinicians must be judicious in patient selection as this study excluded many patients (i.e. older age, pregnancy, hepatic insufficiency, psychiatric disease). Further studies are warranted to compare the efficacy of re-dosing ketamine, given most patients presenting to the ED endorsing moderate to severe pain have an average length of stay longer than 30 minutes.
Potential Impact To Current Practice
This study adds to the mounting evidence that ketamine may be a good alternative or, at least, second line agent to opiates for the treatment of pain in ED patients. Although many emergency providers have incorporated ketamine into their pain management algorithm, those less experienced with the drug may be reluctant to change their practice unless evidence shows a clear benefit over opiates.
In the appropriate patient, subdissociative doses of ketamine may be considered as an alternative to opiates for first-line treatment of moderate to severe pain in ED patients.
eMDocs.net: Ketamine for Analgesia in the ED
Emergency Medicine Updates: The Ketamine Brain Continuum
Skeptics Guide to Emergency Medicine: Comfortably Numb- Low dose Ketamine as Adjunct for ED Pain Control
Skeptics Guide to Emergency Medicine: Low Dose Ketamine for Acute Pain Control in the Emergency Department