August 07, 2018
By Will Boggs MD
NEW YORK (Reuters Health) - Low-dose ketamine appears to be as effective as opioids for treating acute pain in the emergency department (ED), according to a systematic review and meta-analysis.
"If physicians believe that opioids are not the best analgesic for a particular patient, there is an alternative option that has similar analgesic effects without significantly more adverse effects which can be safely administered," Dr. Evan S. Schwarz from Washington University School of Medicine in St. Louis, Missouri, told Reuters Health by email.
As many as 78% of ED visits include pain as a presenting complaint, and opioids are commonly used to treat that pain. In response to the ongoing epidemic of opioid misuse, several research groups are studying alternative analgesics in this setting.
Dr. Schwarz and colleagues compared the analgesic effect of intravenous low-dose ketamine (LDK; 0.5 mg/kg or less per dose) versus intravenous opioids in patients with acute pain in their systematic review and meta-analysis of three randomized controlled trials that enrolled 261 patients.
None of the trials found a clinically significant difference between pain score reduction between ketamine and morphine, the team reports in Academic Emergency Medicine, online July 17.
The pooled estimate of the mean change in pain scores between the ketamine and morphine arms was 0.42 point in favor of ketamine. None of the studies demonstrated a difference between ketamine and morphine greater than 1.4 points, the margin of clinical significance.
Based on the statistical criteria used for this meta-analysis, ketamine was noninferior to morphine as an analgesic in this setting.
Quantitative analysis of adverse events and rescue medication was not possible because of the different manner and degree of reporting among the included trials. Ketamine appeared to have a lower risk of severe adverse reactions than morphine, but a greater risk of emergence phenomenon and dizziness.
"I think one of the most interesting findings was the similarity in the number of adverse effects," Dr. Schwarz said. "One barrier to the administration (of ketamine) seems to be concern for severe adverse effects, particularly emergence reactions, while discounting the number of adverse events from opioids."
"If patients are already on other sedatives or have risk factors for respiratory depression, that could make me favor ketamine," he said. "Additionally, even though ketamine can be abused, I might prefer it for patients with opioid use disorders that need a strong analgesic and don't want opioids."
"While not part of this research, other trials indicate that a short infusion, as opposed to a fast bolus, of ketamine significantly minimizes the chances of psychiatric adverse events (such as an emergence reaction) to ketamine," Dr. Schwarz explained. "Once again, this is one reason people are scared to use this medication."
He added that "the point of this paper is not to say no one should ever receive opioids; it's just to make physicians feel comfortable about using an alternative if they don't want to administer opioids."
Dr. Sergey Motov from Maimonides Medical Center and SUNY Downstate Medical Center, in Brooklyn, New York, who worked on one of the trials included in this review and meta-analysis, told Reuters Health by email, "Large-scale, prospective, randomized clinical trials including more diverse patients population (elderly and pediatric) are needed for better and more robust evaluation of the role of ketamine analgesia in the ED."
A "patient-specific, pain-syndromes-targeted approach would drive my choice of analgesia in the ED," he said. "Patients with severe opioid-tolerant pain, opioid-induced hyperalgesic state, (or) breakthrough neuropathic and malignant pain would benefit to a greater extent from ketamine given in sub-dissociative (analgesic) doses."
"In the setting of acute pain, if patients' comorbidities, co- medications, and hemodynamic status preclude them from receiving opioids, ketamine might be considered," Dr. Motov added.
Dr. Steven P. Cohen, director of pain research at Walter Reed National Military Medical Center, in Bethesda, Maryland, who also was not involved in the new work, told Reuters Health by email, "In the age of precision medicine, a shotgun approach (one size fits all) is not the best approach to acute or chronic pain medicine, as the NIH task force evaluating top pain research priorities determined."
Dr. Cohen, who is also at Johns Hopkins School of Medicine, in Baltimore, said that his choice of analgesia is driven by "the type of pain (although 2 studies included patients with acute abdominal pain, opioids can worsen abdominal pain by decreasing peristalsis); tolerance to opioids and history of opioid abuse (those on opioids are less likely to respond); contraindications to one of the medications (e.g., poorly controlled psychiatric condition for ketamine, severe respiratory disease with opioids); and whether a procedure is being done in the ED (ketamine is ideal for procedure-related pain)."
Academic Emerg Med 2018.
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