Intraoperative Ketamine Fails to Reduce Postoperative Pain

A new study concludes that ketamine, often used to reduce postoperative pain and the need for opioids following surgery, is ineffectual.

Researchers at Washington University School of Medicine (WUSTL; St. Louis, MO, USA), Harvard Medical School (HMS; Boston, MA, USA), and other institutions conducted a multicenter, international randomized trial involving 672 surgical patients 60 years of age and older who underwent major cardiac and non-cardiac surgery under general anesthesia. In all, 222 patientswere assigned to the placebo group (normal saline), 227 to the low dose (0·5 mg/kg) ketamine group, and 223 to the high dose (1 mg/kg) ketamine group, which was delivered after induction of anesthesia, but before surgical incision.


The patients were evaluated for several days after surgery, during which they were questioned about their pain, monitored for the amount of opioids needed to control their pain, and evaluated by staff twice daily for delirium, a state that can include confusion, agitation, and inability to recognize friends and family members. The results showed no difference in delirium incidence between patients in the combined ketamine groups and the placebo group, but did show more postoperative hallucinations and nightmares with increasing ketamine doses, compared to placebo. The study was published on May 30, 2017, in The Lancet.

“In recent years there's been a big increase in the amount of ketamine given in the operating room, because clinicians are trying to prevent pain after surgery without relying on opioid drugs,” said lead author professor of anesthesiology and of surgery Michael Avidan, MD, MBBCh, of WUSTL. “We found that the current practice of giving low doses of ketamine to patients during surgery is not having the desired effect. So we need to determine whether higher doses might be more effective, or we need to find other alternatives to opioids.”

“In animal studies, ketamine could speed recovery from anesthesia in rodents, suggesting that the drug might help protect the brain; the new findings present a less encouraging picture. We were particularly surprised by the lack of an effect on postoperative pain,” said senior author Professor George Mashour, MD, PhD, of the University of Michigan Medical School. “Giving single doses of ketamine during surgery to prevent postoperative pain is increasingly common, but our data challenge that practice and suggest that even after decades of use, more research is required if we hope to understand ketamine.”

Ketamine is a rapidly acting dissociative anesthetic agent that can provide analgesia, sedation, and amnesia for rapid sequence intubation in critically ill patients. Short- and long-term effects include increased pulse and blood pressure, nausea, vomiting, numbness, depression, amnesia, hallucinations, and potentially fatal respiratory problems. Sub-anesthetic ketamine is often given intraoperatively for postoperative analgesia due to the detached, dreamlike state it creates.

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Washington University School of Medicine
Harvard Medical School