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Ketamine Not Effective Against Postoperative Delirium, Pain in Older Adults

June 20, 2017
New research suggests anesthetic may do more harm than good for older adults undergoing cardiac surgery.

Commentary by Lee Kral, PharmD

Surgeons and anesthesiologists have used intraoperative ketamine to prevent 2 serious postoperative complications in older adults: delirium and pain. However, a new study found ketamine ineffective at preventing delirium, decreasing pain levels, and reducing opioid use after surgery in older adults. In fact, ketamine was associated with more postoperative hallucinations and nightmares.

The results of the international randomized controlled trial, led by anesthesiologists at Washington University School of Medicine in St. Louis and the University of Michigan Medical School, were published May 30 online in The Lancet.1

"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 first author Michael S. Avidan, MBBCh, professor of anesthesiology and surgery at Washington University School of Medicine in St. Louis, Missouri, in a news release.

“We found that the current practice of giving low doses of ketamine to patients during surgery is not having the desired effect,” Dr. Avidan said.

The use of intraoperative ketamine has recently become popular as a means to lessen postoperative pain and the use of opioids. A new study calls into question this practice.

Study Suggests It’s Time to Rethink Ketamine

Between February 2014 and June 2016, the research team assessed 1,360 patients in Canada, India, South Korea, and the United States age 60 and older who underwent major surgery with general anesthesia (31% of cases were cardiovascular surgery). Of the 1,360, 672 patients were eligible and randomly assigned to receive 1 of 3 treatments after anesthesia and before surgical incision: 227 received low-dose ketamine (0.5 mg/kg), 223 received high-dose ketamine (1.0 mg/kg), and 222 received a placebo (normal saline).

For the 3 days following surgery, researchers assessed patients for delirium and pain twice daily.

They found no difference in delirium incidence between the patients in the combined ketamine groups and those in the placebo group (19.45% and 19.82%, respectively). The incidence was 17.65% in the low-dose ketamine group vs 21.30% in the higher-dose ketamine group.

Moreover, the researchers reported more hallucinations (P = 0.01) and nightmares (P = 0.03) with larger doses of ketamine compared to the placebo group. 

From a pain standpoint, the results were more surprising. While the authors hypothesized that ketamine would reduce postoperative pain—and past evidence suggested the same—no significant differences in pain scores and opioid use emerged among the 3 groups.

What Factors Influence the Rate of Delirium and Pain?

This current research evaluated the effects of pain and delirium on older adults, an age group at particular risk for delirium, said Lee Kral, PharmD, BCPS, CPE, clinical pharmacy specialist and adjunct assistant professor in the Department of Anesthesia at the University of Iowa Carver College of Medicine.

“It is well-known that older patients are more susceptible to post-operative delirium, and this is multifactorial,” Dr. Kral said. “And, patients at highest risk are those with pre-existing cognitive impairment.” The lack of apparent acknowledgement to potential cognitive disability and dysfunction is a potential limitation of this study, Dr. Kral said.

“The study design excluded patients with known delirium prior to surgery but did not assess, nor stratify patients, based on any pre-existing cognitive dysfunction like dementia,” she said. “This makes it difficult to evaluate the results.”

In addition to age over 60 years being a significant risk factor for delirium, Dr. Kral also said depression was a well-known risk factor that was confirmed as such in this study (OR 2.176).     

Another question is whether type of surgery would influence delirium and pain rates. The study considered patients who underwent many types of major surgery, though cardiac was the most common and showed an odds ratio of 2.768 compared to all other surgeries, Dr. Kral noted.

Could cardiac surgery increase delirium and pain? That alone is likely not a risk factor, though those surgical cases can be quite complex, she said.

“Cardiac surgery cases are often very long cases, which means more time under general anesthesia and more total opioid/benzodiazepine throughout the case,” Dr. Kral said. 

“Given the sample size of 746, this may indicate a clinical difference,” she continued. “However, other studies have not shown a difference between cardiac and non-cardiac surgeries.”

Unanswered Questions Signal a Need for More Research

Data on ketamine for perioperative pain management is still being studied and published with mixed outcomes, Dr. Kral said. 

“The populations and specific protocols used are still quite variable,” Dr. Kral noted. “Since most of the positive studies include an intraoperative infusion, and this study didn’t show benefit with single doses, it might indicate that an infusion is needed.”

Dr. Kral also noted that the research doesn’t indicate if any of these patients were opioid tolerant, which she speculates might be one of the factors that portend positive outcomes with ketamine. 

While more research is needed to gain a definitive understanding of ketamine’s postoperative effects, the results of this particular study may be reason enough for surgeons and anesthesiologists to question the use of low-dose ketamine during surgery (particularly cardiac) in this patient population.

Last updated on: June 20, 2017
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