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Randomised controlled trial
Intravenous analgesia for out-of-hospital traumatic pain in adults: ketamine gives a greater reduction in pain than morphine but causes more adverse effects
  1. William Paul McKay
  1. Department of Anesthesia, University of Saskatchewan, Saskatoon SK, Saskatchewan Canada
  1. Correspondence to: Dr William Paul McKay
    Department of Anesthesia, University of Saskatchewan, 103 Hospital Drive, Saskatoon SK, Saskatchewan, Canada S7N 0W8; bill.mckay{at}

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Implications for practice and research

  • Intravenous ketamine has been shown to be useful for acute pain in a variety of settings.1

  • The present study shows that it provides a greater reduction in pain than morphine but causes more adverse effects in out-of-hospital care.


Conscious trauma patients often suffer severe pain. In general, once a head injury has been ruled out, it is safe to give analgesics as promptly as possible.2 Analgesics are often given in the initial out-of-hospital setting, but are often not as effective as they might be. Thus, it is important to investigate methods of improving out-of-hospital analgesia for trauma patients. Too much opioid can result in respiratory depression. Thus, it is of interest to study adjunctive therapies that do not cause respiratory depression, such as ketamine.


This study is an open label randomised controlled trial of intravenous ketamine versus morphine given after an initial dose of morphine was ineffective. Attending paramedics were not blinded because frequent side effects, such as nystagmus, feeling peculiar or frank hallucinations, are more common with ketamine then with morphine. It was felt that the attending paramedics would know which patients had which treatment. The open-label design, which is unavoidable for studies such as this, nevertheless can introduce the possibility of bias and is thus a limitation.

Pain severity was determined using a validated 0–10 verbal numeric rating scale. Pain was then reassessed after 5 mg of intravenous morphine was given, and if the score was 5 or greater, the patient was randomised to the study. The morphine group got 1–5 mg of morphine every 5 min, depending on the patient's condition, and the ketamine group 10–20 mg of ketamine intravenously every 3 min. The endpoint of drug administration was a pain-free patient, serious adverse event or arrival at the emergency department.


Ketamine performed significantly better and faster, with a mean pain score change of −5.6 compared with a mean pain score change of −3.2 in the morphine group; ketamine lowered the pain score by 2.5 points per min faster than morphine. Changes in vital signs were not significantly different. Individually, none of the minor adverse effects were different between the two groups, but the sum of adverse effects was significantly greater in the ketamine group. The common adverse effects in this group were disorientation and emergence phenomena.


The trial is well done. Of the 37 items listed in the ‘CONSORT 2010 checklist of information to include when reporting a randomised trial’,3 only the trial registration number is missing.

Although trauma victims often experience excruciating pain, research into pain relief in the out-of-hospital setting is limited.2 ,4–6 This study provides evidence for the use of ketamine, which is inexpensive and effective. Ketamine has been available since 1970, so its safety profile is well-documented. Although long-term users/misusers of ketamine suffer long-term brain7 and bladder dysfunction,8 the short-term use is considered safe.2

A few caveats are not dealt with in the paper. Ketamine is contraindicated in patients with increased intracranial pressure (which is well dealt with in their paper). However, it is also relatively contraindicated in patients with an open eye injury or a history of psychosis. These are all easily incorporated in a clinical protocol for trauma analgesia.

The pharmacokinetics of ketamine allow patients to pass through a stage of altered consciousness or confusion in 10 or 15 min, so that they are able to give informed consent for surgery soon after arrival at hospital.

It is a hallowed tradition to always require more research than one randomised controlled trial before adopting a new therapy. In this case, and considering the enormous literature on the use of ketamine in acute postoperative pain, it is probably time to incorporate the findings of this study into clinical practice.

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  • Competing interests None.

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