Anesthesiologists and surgeons should rethink the widespread practice of giving subanesthetic doses of ketamine during surgery to prevent postoperative delirium and reduce pain and opioid administration in older patients, results from an international randomized controlled trial suggest.
The study, published online May 30 in The Lancet, shows that a single dose of intraoperative ketamine did not decrease delirium or reduce pain levels and opioid analgesics use after major surgery in older adults. In fact, patients given ketamine suffered more hallucinations in the 3 days after surgery.
“If these results were to be confirmed in subsequent research, present pain guidelines, clinical practice, and the search for effective alternatives to opioids would need to be modified accordingly,” write Michael S. Avidan, MBBCh, professor of anesthesiology and surgery at Washington University School of Medicine in St. Louis, Missouri, and colleagues.
“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,” Dr Avidan said in an university news release. “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.”
The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study enrolled adults aged 60 years or older undergoing major surgery under general anesthesia between 2014 and 2016 in Canada, India, South Korea, and the United States. The double-blind trial included 672 patients with a mean age of 70. Patients were randomly assigned to receive one of three treatments after induction of anesthesia and before surgical incision: placebo (normal saline, n = 222), low-dose ketamine (0.5 mg/kg, n = 227), or high-dose ketamine (1.0 mg/kg, n = 223). Approximately one third of patients (31%) were undergoing cardiac procedures.
Assessing delirium twice daily, the researchers found no difference in incidence between patients in the combined ketamine groups and the placebo arm: 19.45% vs 19.82%, respectively (absolute difference 0.36%, 95% CI –6.07 – 7.38, P = .92). The incidence was 17.65% in the low-dose ketamine arm vs 21.30% in the higher-dose arm.
The authors also found more hallucinations (P = .01) and nightmares (P = .03) with increasing doses of ketamine compared with placebo.
By visual analog scale (0 – 100 mm) measurements, no differences in pain emerged between the three groups on days 1 to 3 after surgery. On day 1, for example, the morning pain at rest score averaged about 22 for all groups, ranging from 20 for high-dose ketamine to 24 for placebo.
Similarly, there was no difference between groups in postsurgery opioid use, calculated as morphine equivalents, at any point. On day 1, for example, the amounts ranged from 30 for the high-dose group to 33 for the placebo group.
The trial results run counter to the study’s hypothesis that ketamine can reduce postoperative pain and delirium and also run counter to earlier delirium research as well as current pain management guidelines.
Adverse events, including bleeding and cardiovascular, renal, infectious, and gastrointestinal events were similar across groups (P > .40 for each type of complication analyzed individually). The overall rates were 36.9% in the placebo arm, 39.6% in the low-dose ketamine arm, and 40.8% in the high-dose arm (P = .69).
“This international pragmatic study does not support the evidence that a single intraoperative bolus administration of subanaesthetic ketamine decreases the incidence of postoperative delirium, the severity of pain, or the requirement for postoperative opioids in older adults,” the authors write. “On the other hand, this study suggests that intraoperative ketamine might increase the incidence of postoperative nightmares and hallucinations across groups.”
As Dr Avidan explained in the news release, delirious patients spend more time in intensive care, have longer hospital stays, and are at greater risk of dying. “So it’s really important to try to prevent it if we can,” he said.
If further research replicates the study’s findings, “present pain guidelines, clinical practice, and the search for effective alternatives to opioids would need to be modified accordingly,” Dr Avidan and coauthors write.
They suggest that future investigations should explore drug regimens backed by more compelling data such as postoperative dexmedetomidine infusion.
This study was supported by the National Institutes of Health and Cancer Center Support.
The authors have disclosed no relevant financial relationships.
Lancet. Published online May 30, 2017. Full text
For more news, join us on Facebook and Twitter
Tidak ada komentar:
Posting Komentar