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Delirium is a common and serious postoperative complication. Subanaesthetic ketamine is often administered intraoperatively for postoperative analgesia, and some evidence suggests that ketamine prevents delirium. The primary purpose of this trial was to assess the effectiveness of ketamine for prevention of postoperative delirium in older adults. The Prevention of Delirium and Complications Associated with Surgical Treatments [PODCAST] study is a multicentre, international randomised trial that enrolled adults older than 60 years undergoing major cardiac and non-cardiac surgery under general anaesthesia. Using a computer-generated randomisation sequence we randomly assigned patients to one of three groups in blocks of 15 to receive placebo (normal saline), low-dose ketamine (0·5 mg/kg), or high dose ketamine (1·0 mg/kg) after induction of anaesthesia, before surgical incision. Participants, clinicians, and investigators were blinded to group assignment. Delirium was assessed twice daily in the first 3 postoperative days using the Confusion Assessment Method. We did analyses by intention-to-treat and assessed adverse events. This trial is registered with clinicaltrials.gov, number NCT01690988. Between Feb 6, 2014, and June 26, 2016, 1360 patients were assessed, and 672 were randomly assigned, with 222 in the placebo group, 227 in the 0·5 mg/kg ketamine group, and 223 in the 1·0 mg/kg ketamine group. There was no difference in delirium incidence between patients in the combined ketamine groups and the placebo group (19·45% vs 19·82%, respectively; absolute difference 0·36%, 95% CI −6·07 to 7·38, p=0·92). There were more postoperative hallucinations (p=0·01) and nightmares (p=0·03) with increasing ketamine doses compared with placebo. Adverse events (cardiovascular, renal, infectious, gastrointestinal, and bleeding), whether viewed individually (p value for each >0·40) or collectively (36·9% in placebo, 39·6% in 0·5 mg/kg ketamine, and 40·8% in 1·0 mg/kg ketamine groups, p=0·69), did not differ significantly across groups. A single subanaesthetic dose of ketamine did not decrease delirium in older adults after major surgery, and might cause harm by inducing negative experiences. National Institutes of Health and Cancer Center Support.

ObjectivePostoperative neurologic symptoms (PONS) in the operative arm are important complications of shoulder surgery and interscalene blockade (ISB). This systematic review aimed to compare the risk of PONS between ISB and other techniques, and the relative safety of different agents used in ISB.MethodsOur systematic review followed Cochrane review methodology and was registered in PROSPERO. A search of MEDLINE (Ovid), EMBASE (Ovid), and CENTRAL (Wiley) from inception to June 2020 was completed. We included randomized or quasi-randomized trials of patients (> five years old) undergoing shoulder surgery with any ISB technique as an intervention, compared with any other nonregional or regional technique, or ISB of alternate composition or technique. The primary outcome was PONS (study author defined) assessed a minimum of one week after surgery.ResultsFifty-five studies totalling 6,236 participants (median, 69; range, 30–910) were included. Another 422 otherwise eligible trials were excluded because PONS was not reported. Heterogeneity in when PONS was assessed (from one week to one year) and the diagnostic criteria used precluded quantitative meta-analysis. The most common PONS definition, consisting of one or more of paresthesia, sensory deficit, or motor deficit, was only used in 16/55 (29%) trials. Risk of bias was low in 5/55 (9%) trials and high in 36/55 (65%) trials, further limiting any inferences.ConclusionThese findings highlight the need for a standardized PONS outcome definition and follow-up time, along with routine, rigorous measurement of PONS in trials of ISB.Study registrationPROSPERO (CRD42020148496); registered 10 February 2020.