From the Journals

Intraoperative ketamine makes no dent in postop delirium or pain



A single subanesthetic, intraoperative dose of ketamine does little or nothing to reduce postoperative delirium, according to data from the PODCAST trial.

Postoperative delirium remains a problem without an effective solution, wrote Michael S. Avidan, MBBCh, FCASA, of Washington University, Saint Louis, and his colleagues (Lancet 2017;390[10091]:267-75).

Recent guidelines published by the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council include ketamine as a recommended component of multimodal pain therapy for several commonly performed surgeries. “Before recommending widespread administration of an intraoperative bolus of subanaesthetic ketamine, demonstrating that ketamine decreases either delirium or pain, or both, without incurring adverse effects in a large, pragmatic trial was warranted,” the researchers said.

In the PODCAST (Prevention of Delirium and Complications Associated With Surgical Treatments) trial, the researchers randomized 672 patients over the age of 60 undergoing major open surgery under general anesthesia (such as open cardiac or noncardiac surgery, urological surgery, gynecologic surgery, or intra-abdominal surgery) to 0.5 mg/kg ketamine (227), 1.0 mg/kg ketamine (223), or placebo (222). The ketamine or placebo was given after anesthesia and before surgical incision.

Overall, no difference in the incidence of delirium occurred between patients in the combined ketamine groups (19.5%) and the placebo group (19.8%), and there was no significant difference in delirium across all three treatment groups.

No differences in pain based on visual analog scale scores were observed across the three groups, and overall adverse event rates were similar as well: approximately 40.8% in the 1.0-mg ketamine group, 39.6% in the 0.5-mg ketamine group, and 36.9% in the placebo group.

Surgeons work on a patient in the operating room Dmitrii Kotin/Thinkstock
In addition, ketamine was associated with significantly more reports of postoperative hallucinations and nightmares, compared with placebo, over a period of 3 postoperative days. The reports of both hallucinations and nightmares increased with the higher ketamine dose. Hallucinations were reported by 18% of placebo patients, 20% of 0.5-mg ketamine patients, and 28% of 1.0-mg ketamine patients; nightmares were reported by 8%, 12%, and 15% of patients in the three groups, respectively.

The study findings were limited by several factors, including a study population potentially too small to show an effect of ketamine on delirium, and a lack of data on other variables that might contribute to delirium and pain, the researchers noted. However, the results suggest that “despite present evidence and guidelines, the administration of a subanaesthetic ketamine dose during surgery is not useful for preventing postoperative delirium (primary outcome) or reducing postoperative pain and minimising opioid consumption (related secondary outcomes),” and appears to increase postoperative hallucinations and nightmares to an extent that might be prohibitive, they said.

The National Institutes of Health and Cancer Center Support funded the study. The researchers had no financial conflicts to disclose.

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