Ketamine doesn't reduce delirium or pain after surgery, researchers claim

US anaesthesiologists have questioned the efficacy of ketamine use during surgery, stating the drug does not reduce pain during recovery or alleviate delirium as previously claimed. The results of their study have been published in The Lancet.

Ketamine was first introduced into clinical practice in the mid-1960s as a general anaesthetic that could offer advantages, such as preserving breathing, not afforded by other anaesthetic drugs at the time. With ketamine administration during surgery now increasing in an effort to reduce reliance on opioid drugs, researchers sought to determine the effect the drug has on delirium and pain — two serious postoperative complications.

“When patients become delirious after surgery, they tend to spend more time in the intensive care unit, have longer hospital stays and have a greater chance of dying,” said Michael Avidan from the Washington University School of Medicine in St. Louis, first author on the new paper. “Overall, patients who develop delirium have worse outcomes and are at higher risk for long-term cognitive decline. It’s really important to try to prevent it if we can.”

“Previous studies found evidence that ketamine could prevent delirium and reduce pain after surgery,” added George A Mashour, a professor at the University of Michigan Medical School and senior author on the paper. “However, these studies were often in small cohorts.

“We wanted to test this in a larger cohort along with the outcome of delirium in patients at high risk. The two adverse outcomes are linked — pain can cause delirium, but opioids, the usual treatment for pain, can also cause delirium. We reasoned that if ketamine could reduce pain and delirium, it would be an important advance.”

The researchers subsequently undertook a multicentre, international study of patients aged 60 or over who were undergoing major surgery. Located in the United States, Canada, India and South Korea, all patients were undergoing major cardiac or non-cardiac surgery under general anaesthesia between February 2014 and June 2016.

Of the 1360 total patients assessed, 672 were eligible and randomised to three different arms — with 222 in a placebo group, 227 in a low-dose ketamine group and 223 in a high-dose ketamine group. “The drug was administered to the patients following the onset of general anaesthesia, but prior to any surgical incision,” said Mashour.

Participants were assessed twice a day for the three days following surgery for delirium and pain. The researchers also recorded each patient’s postoperative opioid use, hallucinations and nightmares. Their results were surprising, to say the least.

“We found no difference in delirium incidence between the combined ketamine groups and the group that received the placebo,” said Mashour. “Ketamine doesn’t reduce delirium, which was not all that unexpected, but it also doesn’t increase it.

“We then assessed the pain data, fully expecting ketamine would reduce pain and use of opioids. Lo and behold, it didn’t have any effect on pain or opioid consumption.”

The research group noted that there were no significant differences among any of the three groups in terms of maximum pain scores or median opioid consumption over time. In addition, they found that giving higher doses of ketamine appeared to increase negative consequences of the drug.

“Unfortunately, we also found that some of the known negative effects of ketamine, such as hallucinations and nightmares, were increased in dose-dependent ways,” Mashour said. Patients were more likely to experience such hallucinations and nightmares in the recovery room and for several days following surgery.

“This was a big surprise for our team,” said co-investigator Phillip Vlisides, an assistant professor at Michigan Medicine. “However, our study was fourfold larger than any studies that had come before it with respect to pain, and was rigorous in its methodology.”

Mashour said the contradictory findings on ketamine use underscore the need for more research on the drug, “to ensure we are not administering something that isn’t working to benefit our patients”.

“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,” he said.

Image credit: ©stock.adobe.com/au/Melpomene