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Postoperative delirium is common in older adult patients and associated with a poor prognosis. The use of benzodiazepine was identified as an independent risk factor for delirium, but there is no randomized controlled trial regarding the relationship between remimazolam, a new ultra-short acting benzodiazepine, and postoperative delirium. We designed a randomized controlled trial to evaluate if remimazolam increases the incidence of postoperative delirium compared with propofol in older adult patients undergoing orthopedic surgery with general anesthesia. We enrolled 320 patients aged more than 60 with American Society of Anesthesiologists physical status I-III who underwent orthopedic surgery. Patients were randomized to two groups to receive intraoperative remimazolam or propofol, respectively. Our primary outcome was the incidence of delirium within 3 days after surgery. Secondary outcome was emergence quality including the incidence of emergence agitation, extubation time, and length of post-anesthesia care unit (PACU) stay. Adverse events were also recorded. The incidence of postoperative delirium was 15.6% in the remimazolam group and 12.4% in the propofol group (Risk ratio, 1.26; 95% CI, 0.72 to 2.21; Risk difference, 3.2%; 95% CI, -4.7% to 11.2%; P = 0.42). No significant differences were observed for time of delirium onset, duration of delirium, and delirium subtype between the two groups. Patients in remimazolam group had a lower incidence of hypotension after induction and consumed less vasoactive drugs intraoperatively, but had a longer postoperative extubation time and PACU stay. General anesthesia with remimazolam was not associated with an increased incidence of postoperative delirium compared with propofol in older adult patients undergoing orthopedic surgery.

Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. HIP ATTACK was an international, randomised, controlled trial done at 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were aged 45 years or older were eligible. Research personnel randomly assigned patients (1:1) through a central computerised randomisation system using randomly varying block sizes to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. The coprimary outcomes were mortality and a composite of major complications (ie, mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Patients, health-care providers, and study staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation. Patients were analysed according to the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT02027896). Between March 14, 2014, and May 24, 2019, 27 701 patients were screened, of whom 7780 were eligible. 2970 of these were enrolled and randomly assigned to receive accelerated surgery (n=1487) or standard care (n=1483). The median time from hip fracture diagnosis to surgery was 6 h (IQR 4–9) in the accelerated-surgery group and 24 h (10–42) in the standard-care group (p<0·0001). 140 (9%) patients assigned to accelerated surgery and 154 (10%) assigned to standard care died, with a hazard ratio (HR) of 0·91 (95% CI 0·72 to 1·14) and absolute risk reduction (ARR) of 1% (−1 to 3; p=0·40). Major complications occurred in 321 (22%) patients assigned to accelerated surgery and 331 (22%) assigned to standard care, with an HR of 0·97 (0·83 to 1·13) and an ARR of 1% (−2 to 4; p=0·71). Among patients with a hip fracture, accelerated surgery did not significantly lower the risk of mortality or a composite of major complications compared with standard care. Canadian Institutes of Health Research.

Delirium is a postoperative complication that occurs frequently in patients older than 65 years, and presages adverse outcomes. We investigated whether prophylactic low-dose dexmedetomidine, a highly selective α2 adrenoceptor agonist, could safely decrease the incidence of delirium in elderly patients after non-cardiac surgery. We did this randomised, double-blind, placebo-controlled trial in two tertiary-care hospitals in Beijing, China. We enrolled patients aged 65 years or older, who were admitted to intensive care units after non-cardiac surgery, with informed consent. We used a computer-generated randomisation sequence (in a 1:1 ratio) to randomly assign patients to receive either intravenous dexmedetomidine (0·1 μg/kg per h, from intensive care unit admission on the day of surgery until 0800 h on postoperative day 1), or placebo (intravenous normal saline). Participants, care providers, and investigators were all masked to group assignment. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method for intensive care units during the first 7 postoperative days. Analyses were done by intention-to-treat and safety populations. This study is registered with Chinese Clinical Trial Registry, www.chictr.org.cn, number ChiCTR-TRC-10000802. Between Aug 17, 2011, and Nov 20, 2013, of 2016 patients assessed, 700 were randomly assigned to receive either placebo (n=350) or dexmedetomidine (n=350). The incidence of postoperative delirium was significantly lower in the dexmedetomidine group (32 [9%] of 350 patients) than in the placebo group (79 [23%] of 350 patients; odds ratio [OR] 0·35, 95% CI 0·22–0·54; p<0·0001). Regarding safety, the incidence of hypertension was higher with placebo (62 [18%] of 350 patients) than with dexmedetomidine (34 [10%] of 350 patients; 0·50, 0·32–0·78; p=0·002). Tachycardia was also higher in patients given placebo (48 [14%] of 350 patients) than in patients given dexmedetomidine (23 [7%] of 350 patients; 0·44, 0·26–0·75; p=0·002). Occurrence of hypotension and bradycardia did not differ between groups. For patients aged over 65 years who are admitted to the intensive care unit after non-cardiac surgery, prophylactic low-dose dexmedetomidine significantly decreases the occurrence of delirium during the first 7 days after surgery. The therapy is safe. Braun Anaesthesia Scientific Research Fund and Wu Jieping Medical Foundation, Beijing, China. Study drugs were manufactured and supplied by Jiangsu Hengrui Medicine Co, Ltd, Jiangsu, China.

A randomized trial evaluating spinal as compared with general anesthesia for hip-fracture surgery in adults 50 years of age or older did not show superiority of spinal anesthesia with respect to a composite of death or an inability to walk unassisted at 60 days. Postoperative delirium occurred in similar percentages of patients in the two groups.

This study aims to evaluate the effects of preoperative low-dose dexmedetomidine administration for one night on the incidence of postoperative delirium in elderly patients with hip fracture. This was a randomized, double blind, placebo-controlled clinical trial. Lu'an Hospital of Anhui Medical University, Anhui, China. Patients aged ≥65 years with hip fracture (femoral neck, intertrochanteric, or subtrochanteric fracture) and scheduled for surgical repair(total hip arthroplasty, hemiarthroplasty, internal fixation with cannulated screw or intramedullary nail) under spinal anesthesia were eligible. Patients were randomized 1:1 to receive low-dose dexmedetomidine or placebo from 8:00 pm before surgery to 8:00 am the day of surgery. The primary outcome was the incidence of POD between postoperative days 1 and 7 or at hospital discharge. The secondary outcome measures included preoperative sleep quality, days of delirium, visual analog scale scores in quiet and active states on postoperative days 1–3, C-reactive protein level, number of analgesic pump presses, activities of daily living score at discharge and postoperative hospital stay. Perioperative adverse events were recorded. Of the 248 patients randomized to the placebo (n = 124) or dexmedetomidine (n = 124) group, 233 participants (117 in the placebo group and 116 in the dexmedetomidine group) were included in the modified intention-to-treat analysis. The incidence of POD was lower in the dexmedetomidine group (10.3 %) than placebo group (22.2 %, P = 0.014). Compared to the placebo group, the dexmedetomidine group had higher preoperative Leeds Sleep Evaluation Questionnaire (LSEQ) scores (P < 0.001), lower preoperative Insomnia Severity Index (ISI) scores (P < 0.001), and lower postoperative C-reactive protein (CRP) levels (P < 0.001). No differences in other secondary outcomes and perioperative adverse events were observed between the two groups. In patients aged ≥65 years undergoing elective hip fracture surgery under spinal anesthesia, continuous overnight administration of low-dose dexmedetomidine improved sleep quality on the night before surgery and reduced the incidence of POD. •There are currently no interventions to effectively reduce postoperative delirium in old patients with hip fracture.•The incidence of preoperative sleep disorders is high in elderly patients with hip fractures.•Low-dose dexmedetomidine given the night before surgery reduced postoperative delirium and improved sleep quality in patients.•The results offer a new perspective for future delirium prevention.

Background We aimed to evaluate whether a single dose of ketamine or dexmedetomidine before induction of general anesthesia could reduce the incidence of postoperative delirium (primary outcome) or cognitive dysfunction (secondary outcome) in elderly patients undergoing emergency surgery. Patients and methods This randomized, double-blinded, placebo-controlled trial included 60 elderly patients who were scheduled for emergency surgery. The patients were randomly assigned into one of three groups (n = 20): group I received 0.9% normal saline, group II received 1 µg/kg dexmedetomidine, and group III received 1 mg/kg ketamine right before anesthesia induction. Patients were observed for three days after surgery and tested for postoperative delirium and cognitive dysfunction using the delirium observation screening scale and the mini-mental state examination score, respectively. Results The dexmedetomidine group had the lowest incidence of delirium (p = 0.001) and cognitive dysfunction (p = 0.006) compared to the ketamine and placebo groups. The multivariate logistic regression model revealed that dexmedetomidine reduced the incidence of postoperative delirium by 32% compared to placebo (reference) (OR = 0.684, 95% CI: 0.240–0.971, p = 0.025), whereas ketamine increased the risk by threefold (OR = 3.012, 95% CI: 1.185–9.681, p = 0.013). Furthermore, dexmedetomidine reduced the incidence of postoperative cognitive dysfunction by 62% (OR = 0.375, 95% CI: 0.091–0.543, p = 0.012), whereas ketamine increased the risk by 4.5 times (OR = 4.501, 95% CI: 1.161–8.817, p = 0.006). Conclusion A single pre-anesthetic bolus of dexmedetomidine is a practical choice for preventing postoperative delirium in elderly patients undergoing emergency surgery. Trial registration This study was approved by the Ethics Committee of Aswan University Hospital (approval number: aswu/548/7/2021; registration date: 06/07/2021) and registered on ClinicalTrials.gov (NCT05341154) (22/04/2022).

IntroductionPostoperative delirium (POD) is a common cognitive disturbance in elderly individuals that is characterised by acute and fluctuating impairments in attention and awareness. Remimazolam tosylate is a novel, ultrashort-acting benzodiazepine, and there is limited evidence of its correlation with the incidence of early POD. The aim of this study is to evaluate the incidence of POD after anaesthesia induction and maintenance with remimazolam tosylate or propofol in elderly patients undergoing major non-cardiac surgery.Methods and analysisThis is a single-centre, randomised controlled trial. 636 elderly patients undergoing major non-cardiac surgery will be enrolled and randomised at a 1:1 ratio to receive total intravenous anaesthesia with either remimazolam tosylate or propofol. The primary outcome is the incidence of POD within 5 days after surgery. Delirium will be assessed twice daily by the 3 min Diagnostic Interview for the Confusion Assessment Method or the Confusion Assessment Method for the intensive care unit (ICU) for ICU patients. Secondary outcomes are the onset and duration of delirium, cognitive function at discharge and within 1-year postoperatively, postoperative analgesia within 5 days, chronic pain at 3 months, quality of recovery and postoperative inflammatory biomarker levels.Ethics and disseminationThe study was approved by the institutional ethics committee of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (approval No. 22/520–3722). Written informed consent will be obtained from each patient before enrolment. The results of this trial will be presented at scientific conferences and in peer-reviewed scientific journals.Trial registration numberChiCTR2300067368.

Importance Postoperative delirium (POD) is a common and serious complication after surgery. Various predisposing factors are associated with POD, but their magnitude and importance using an individual patient data (IPD) meta-analysis have not been assessed. Objective To identify perioperative factors associated with POD and assess their relative prognostic value among adults undergoing noncardiac surgery. Data Sources MEDLINE, EMBASE, and CINAHL from inception to May 2020. Study Selection Studies were included that (1) enrolled adult patients undergoing noncardiac surgery, (2) assessed perioperative risk factors for POD, and (3) measured the incidence of delirium (measured using a validated approach). Data were analyzed in 2020. Data Extraction and Synthesis Individual patient data were pooled from 21 studies and 1-stage meta-analysis was performed using multilevel mixed-effects logistic regression after a multivariable imputation via chained equations model to impute missing data. Main Outcomes and Measures The end point of interest was POD diagnosed up to 10 days after a procedure. A wide range of perioperative risk factors was considered as potentially associated with POD. Results A total of 192 studies met the eligibility criteria, and IPD were acquired from 21 studies that enrolled 8382 patients. Almost 1 in 5 patients developed POD (18%), and an increased risk of POD was associated with American Society of Anesthesiologists (ASA) status 4 (odds ratio [OR], 2.43; 95% CI, 1.42-4.14), older age (OR for 65-85 years, 2.67; 95% CI, 2.16-3.29; OR for >85 years, 6.24; 95% CI, 4.65-8.37), low body mass index (OR for body mass index <18.5, 2.25; 95% CI, 1.64-3.09), history of delirium (OR, 3.9; 95% CI, 2.69-5.66), preoperative cognitive impairment (OR, 3.99; 95% CI, 2.94-5.43), and preoperative C-reactive protein levels (OR for 5-10 mg/dL, 2.35; 95% CI, 1.59-3.50; OR for >10 mg/dL, 3.56; 95% CI, 2.46-5.17). Completing a college degree or higher was associated with a decreased likelihood of developing POD (OR 0.45; 95% CI, 0.28-0.72). Conclusions and Relevance In this systematic review and meta-analysis of individual patient data, several important factors associated with POD were found that may help identify patients at high risk and may have utility in clinical practice to inform patients and caregivers about the expected risk of developing delirium after surgery. Future studies should explore strategies to reduce delirium after surgery.

IntroductionPerioperative cognitive disorders include three essential elements: the progression of a pre-existing neurocognitive lesion, the occurrence of postoperative delirium (POD) and, finally, a mild or severe postoperative neurocognitive disorder. These perioperative disorders are associated with increased morbidity and mortality. Numerous risk factors are associated with perioperative cognitive disorders, the most salient being advanced age and the type of surgery. Specifically, major surgeries and cardiac surgery with associated tissue injuries and inflammation are significant causes of these cognitive impairments. The depth of anaesthesia has recently emerged as an important risk factor for perioperative cognitive disorders, particularly in older patients. The aim of our study is to evaluate whether a reduction in anaesthesia depth is associated with perioperative cognitive disorders in patients aged over 75 years who undergo planned cardiac surgery.Methods and analysisThis is a multicentric randomised controlled trial with the aim to investigate whether a lower level of anaesthesia evaluated with a Bispectral Index (35 vs 55) reduces the prevalence of POD in patients aged 75 years and over who undergo planned cardiac surgery (heart valve surgery, coronary artery bypass graft surgery, aortic surgery or combined surgery). 200 patients are planned for enrolment. The analysis evaluates the prevalence of delirium during the first 3 days after surgery with the Confusion Assessment Method for the Intensive Care Unit Scale.Ethics and disseminationThe study protocol has been approved by the relevant French medical review board: the French Committee for Protection of Persons (ID: 2022-A02200-43, Comité de protection des personnes Est III). We plan to present the results at (inter)national conferences after the completion of the study and to publish them in peer-reviewed journals.Trial registration numberFrench Ethic Committee (ID: 2022-A02200-43) and ClinicalTrials.gov Registry (NCT05877326).

IntroductionThe effect of different anaesthetics on the incidence of postoperative delirium is still not entirely clear. Therefore, we will evaluate the effect of desflurane versus sevoflurane versus propofol for the maintenance of anaesthesia on the incidence of postoperative delirium in older adults undergoing moderate- to high-risk major non-cardiac surgery. We will further compare the incidences of delayed neurocognitive recovery, long-term postoperative neurocognitive disorder, postoperative nausea and vomiting between the groups.Methods and analysisIn this multicentre, prospective, observer-blinded, randomised controlled clinical trial, we will include 1332 patients ≥65 years of age undergoing moderate- to high-risk major non-cardiac surgery lasting at least 2 hours. Patients will be randomly 1:1:1 assigned to receive desflurane, sevoflurane or propofol for anaesthesia. Maintenance of anaesthesia will be performed in a goal-directed manner using processed electroencephalography with an intraoperative goal of bispectral index 40–60. Our primary outcome will be the incidence of postoperative delirium within the first five postoperative days. Postoperative delirium will be assessed using the three-dimensional-confusion assessment method (3D-CAM) or CAM-intensive care unit (ICU) in the morning and evening of the first five postoperative days by blinded study personnel. The primary outcome, the incidence of postoperative delirium, will be compared between the three study groups using a χ2 test. Furthermore, a logistic regression model for the incidence of postoperative delirium will be performed, accounting for randomised groups as well as other predefined confounding factors.Ethics and disseminationThis clinical trial has been approved by the ethics committee and the Federal Office for Safety in Healthcare as the competent authority for clinical trials in Austria. The results of this trial will be published in a peer-reviewed journal.Trial registration numberClinicalTrials.gov NCT05990790.