Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial

Abstract

Background Delirium and pain are common and serious postoperative complications. Subanaesthetic ketamine is often administered intraoperatively for postoperative analgesia and to spare postoperative opioids. Some evidence also suggests that ketamine prevents delirium. The primary purpose of this trial was to evaluate the effectiveness of ketamine in preventing postoperative delirium in older adults after major surgery. Secondary outcomes, viewed as strongly related to delirium, were postoperative pain and opioid consumption. Methods This was a multicentre, international, randomised trial that enrolled adults older than 60 undergoing major cardiac and noncardiac surgery under general anaesthesia. Participants were enrolled prior to surgery and gave written informed consent. We used a computer-generated randomisation sequence. Patients at study sites were randomised to one of three study groups in blocks of 15 to receive intraoperative administration of (i) placebo (intravenous normal saline), (ii) low dose ketamine (0.5 mg/kg) or (iii) high dose ketamine (1 mg/kg). Study drug was administered following induction of anaesthesia, prior to surgical incision. Participants, clinicians, and investigators were all masked to group assignment. Delirium and pain were assessed twice daily in the first three postoperative days using the Confusion Assessment Method and Visual Analog Scale, respectively. Postoperative opioid use was recorded, and hallucinations and nightmares were assessed. Analyses were performed by intention-to-treat and adverse events were evaluated. The Prevention of Delirium and Complications Associated with Surgical Treatments [PODCAST] trial is registered in clinicaltrials.gov; NCT01690988 Findings Between February 6, 2014 and June 26, 2016, 1360 patients assessed and 672 were randomised, with 222 in the placebo group, 227 in the low dose ketamine group, and 223 in the high dose ketamine group. There was no difference in postoperative delirium incidence between those in the combined ketamine groups and those who received placebo (19.45% vs. 19.82%, respectively; absolute difference, 0.36%; 95% CI, −6.07% to 7.38%; p=0.92). There were no significant differences among the three groups in maximum pain scores (p=0.88) or median opioid consumption (p=0.47) over time. There were more postoperative hallucinations (p=0.01) and nightmares (p=0.03) with escalating doses of ketamine. Adverse events (cardiovascular, renal, infectious, gastrointestinal, bleeding), whether viewed individually (P value for each >0.40) or collectively (82/222 [36.9%] in placebo group, 90/227 [39.6%] in low dose ketamine group, 91/223 in high dose ketamine group [40.8%]; P=0.69), did not differ significantly across the three groups. Interpretation The administration of a single subanaesthetic dose of ketamine to older adults during major surgery did not show evidence of reducing postoperative delirium, pain, or opioid consumption, and might cause harm by inducing negative experiences. Given current evidence and guidelines related...

A nurse‐driven enhanced recovery after surgery (ERAS) nursing program for geriatric patients following lung surgery

“…On the first day following surgery, the patient should get out of bed and stand for 1–2 hours, and walk at least 60 m, with the assistance of a caregiver (oxygen supplied when necessary). The activity level is raised gradually within the tolerance range, and upon discharge, the patient should be able to engage in off‐bed activities for 4–6 hours every day. The urinary catheter is removed within 48 hours. Delirium prevention: Delirium patients are monitored routinely following the Confusion Assessment Method (CAM) to confirm if there is delirium. Each day at 08:00 and 18:00 hours it is necessary to communicate with the doctor during a shift change, mainly about possible causes and symptomatic treatment for delirium, so that symptomatic treatment can be provided.…”

“…• The urinary catheter is removed within 48 hours. • Delirium prevention: Delirium patients are monitored routinely 22 following the Confusion Assessment Method (CAM) 23 to confirm if there is delirium. Each day at 08:00 and 18:00 hours it is necessary to communicate with the doctor during a shift change, mainly about possible causes and symptomatic treatment for delirium, so that symptomatic treatment can be provided.…”

Low-Dose Ketamine for Acute Pain Management

“…1 The dose and mode of ketamine use suggested in the present guidelines differ from those used in the recent high-profile PODCAST trial, which used a single large bolus of ketamine before incision in older patients and found a higher incidence of postoperative delirium with no benefit in terms of pain. 23 In contrast, studies with a much smaller sample size where low-dose ketamine was added to opioids postoperatively show only a small decrease in pain intensity but substantial reduction in opioids and opioid-related adverse effects such as postoperative nausea and vomiting. 26,27 Use of low-dose ketamine may well be a valuable strategy to help with both aspects of the current opioid crisis.…”

Physical Activity and Risk of Postoperative Delirium

“…5 Several intraoperative strategies to reduce delirium, such as opiate-sparing analgesia, avoidance of general anesthesia using regional and neuraxial techniques, better hemodynamic control, and pharmacologic interventions, have had limited benefit. [6][7][8] This suggests that the best strategies for prevention of POD may rest in the preoperative setting.…”