Evidence Tables

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Randomized Clinical Trials

Study	Enrolled	Inclusion/Exclusion Criteria	Results	Note
Kowark 2024	616	Include: Patients age 65-80; elective inpatient surgery (excluding cardiac and intracranial surgeries) with planned duration ≥30 min using general anesthesia with or without regional anesthesia; planned extubation after surgery. Exclude: Not fluent in German; alcohol or drug use disorder; severe neurological or psychiatric disorders; undergoing chronic benzodiazepine treatment; undergoing repeated operations for same reason; contraindication to study drugs.	In patients undergoing various surgeries, a difference in patient satisfaction was not detected in patients receiving oral preoperative midazolam compared with patients receiving placebo, treatment effect -0.2 (95% CI: -1.9 to 1.6). A difference in postoperative delirium and neurocognitive recovery at postop day 1 was not detected between the groups.
Dieleman 2012	4,494	Include: Age > 18 yrs. Exclude: Emergent or off-pump procedure; life expectancy < 6 mo.	Postoperative delirium was seen in 9.2% dexamethasone group and 11.7% in the placebo group (RR 0.79, 95% CI: 0.66-0.94, p=0.006).	Large multicenter clinical trial on dexamethasone. There were two substudies from this trial (Sauer 2014 and Ottens 2014) that focused on delirium and cognitive decline.
Subramaniam 2019	140	Include: Patients >60 years having coronary artery bypass graft surgery with or without aortic and/or mitral value replacement. Exclude: Preoperative left ventricular ejection fraction of less than 30%; preexisting cognitive impairment; alzheimer disease; parkinson disease; medications for cognitive decline; history of recent seizures; serum creatine levels above 2ml/dL; liver dysfunction; recent history of alcohol misuse; hypersensitivity to study medications.	Delirium was seen in 21% (13/61) of patients receiving propofol for sedation and in 17% (10/59) in patients given dexmedetomidine.	4 arms: dex-placebo, propofol-placebo, dex-acetaminophen, propofol-acetaminophen only extracted placebo arms as of now.
Li 2022	950	Include: Patients ≥65 years with a fragility hip fracture; ASA I-IV; scheduled for surgical repair. Exclude: Patients with multiple trauma or fractures; contraindications for regional or general anesthesia; malignant hyperthermia; enrolled in another RCT.	Postoperative delirium occurred in 29 (6.2%) in the regional anesthesia group vs 24 (5.1%) in the general anesthesia group (unadjusted risk difference, -1.1) Regional anesthesia without sedation did not significantly reduce the incidence of postoperative delirium compared with general anesthesia.
Lu 2021	808	Include: ≥60; elective abdominal surgery; expected surgical duration of 1-6 hours. Exclude: Gastrointestinal motility disorders; previous abdominal surgery; severe hepatic or kidney dysfunction; second or third-degree heart blockage; bradyarrhythmia with a baseline rate lower than 50 beats/minute; mental disorders; history of difficult airway or delayed extubation; opioid medication misuse; allergy to dexmedetomidine or other anesthetics; preop gastrointestinal hemorrhage; emergency reoperations; ASA class IV or V.	The dexmedetomidine group had a significantly shorter time to first flatus. The incidence of delirium was comparable between the dexmedetomidine and control groups in the first 3 postoperative days.
Deiner 2017	429	Include: >68; major elective noncardiac surgery. Exclude: MMSE <20; dementia; emergency surgery; intracardiac or intracranial surgery; planned postop intubation; severe visual or auditory handicap; illiteracy; parkinsons disease; life expectancy <6months; renal failure requiring dialysis; sick sinus syndrome; second or third-degree heart block or clinically significant sinus bradycardia; contraindication for use of an a2-adrenic agonist; ASA class IV or V; hepatic dysfunction.	No difference in postop delirium delirium between the dexmedetomidine and placebo groups. After adjusting for age and education, there was no difference in postop cognitive performance between treatment groups at 3 and 6 months. Adverse events were comparably distributed between the two groups.	The study was stopped for futility in accord with the DSMB in January 2014 based on a planned interim analysis in the spring of 2013. The conditional power for concluding efficacy under the original assumption of treatment effect was 3% and under the observed trend and a null trend was less than 1% for both. The conditional power for concluding harm was less than 25% under the 3 different assumptions.
O'Brien 2023	1,600	Include: Adults age 50 or older scheduled to undergo surgical repair of femoral neck, intertrochanteric, or subtrochanteric hip fracture. Exclude: Planned concurrent surgery not amenable to spinal anesthesia; absolute contraindications to spinal anesthesia; periprosthetic fracture; patient at risk for malignant hyperthermia; previous participation in the trial; unable to walk approximately 10 ft or across a room without the assistance of another person before the fracture (as reported by the patient or by a proxy), and if considered to be unsuitable for randomization by the surgeon or anesthesiologists on the basis of the physician’s clinical assessment.	Rate of new onset of delirium did not differ between spinal and general anesthesia in patients with Alzheimer’s (31.6% vs 30.3%, OR; 1.08, 95% CI: 0.72-1.62) and without Alzheimer’s (14.5% vs 14.4%, OR; 1.01, 95% CI: 0.69-1.50).
Partridge 2017	201	Include: Age ≥ 65 years scheduled for elective endovascular/open aortic aneurysm repair or lower-limb arterial bypass surgery. Exclude: Admitted directly to the ward from surgical clinic or emergency department.	There was a lower incidence of postoperative delirium (11% vs 24%, p=0.018), cardiac complications (8% vs 27%, p=0.001), and length of stay (3.32 vs 5.53 days, p<0.001) in patients receiving a CGA compared to standard preoperative care.
Li 2020b	620	Include: Patients aged 60 years or older; scheduled to undergo elective major non-cardiac surgery under general anaesthesia with an expected duration of 2 hours or more. Exclude: History of schizophrenia; history of epilepsy; history of Parkinson’s disease; visual barrier; hearing barrier; language barrier; history of traumatic brain injury; history of neurosurgery; severe bradycardia (heart rate less than 40 beats per minute); sick sinus syndrome; atrioventricular block of degree 2 or above without pacemaker; severe hepatic dysfunction (Child-Pugh grade C); and renal failure (requirement for renal replacement therapy).	The incidence of delirium within 5 days of surgery was lower with dexmedetomidine treatment (5.5%; 17 of 309) versus 10.3% (32 of 310) in the control group (RR=0.53; 95% CI=0.30 to 0.94; P=0.026). The overall incidence of complications at 30 days was also lower after dexmedetomidine (19.4%; 60 of 309) versus 26.1% (81 of 310) for controls (RR=0.74; 95% CI= 0.55 to 0.99; P= 0.047).
Xin 2021	60	Include: >65; laparoscopic cholecystectomy; patients with mild cognitive impairment (MoCA 15-24, MMSE <27, CDR 0.5, daily living score <26). Exclude: Preoperative delirium; preop neurological diseases affecting cognitive function; severe liver and renal insufficiency; autoimmune diseases; recent use of sedatives; antidepressants or immunosuppressive drugs; traumatic brain injury; history of alcoholism.	POD occurred in 10/30 patients in the control group, and 3/30 patients in the dexmedetomidine group. Dex can alleviate POD in elderly patients with MCI.
Qiao 2023	69	Include: Patients age ≥65; ASA I-II; undergoing elective laser laryngeal surgery under general anesthesia. Exclude: Uncontrolled hypertension or diabetes; untreated cardiac or pulmonary disease; hepatic or renal failure; epilepsy; using drugs affecting central nervous system; preexisting mental status alterations; MMSE ≤23.	In patients undergoing laser laryngeal surgery, a difference in cognitive impairment was not detected in patients receiving propofol compared with patients receiving desflurane, 1/32 (3%) vs 3/31 (10%), p=0.583.
Rohan 2005	45	Include: Age above 65; presenting for urological and gynecological surgery; requiring general anesthesia; anticipated hospital stay of on night postoperatively;. Exclude: Diseases of the central nervous system including pre-existing cognitive dysfunction; consumption of phenothiazines or antidepressants; cardiac or neurosurgery; previous neuropsychological testing; poor comprehension of the language used in processing the study tests; patients with alcoholism or addictive drug dependence.	Incidence of post-operative cognitive dysfunction (POCD) in elderly patients on the first day after minor surgery was similar in patients given sevoflurane than TIVA with propofol 47% (7/15) vs 47% (7/15) p= 0.003.
Ding 2021	180	Include: Scheduled to undergo non-cardiac surgery. Exclude: Severe lung or heart diseases; renal or hepatic dysfunction;.	For older patients, intravenous anesthesia was a better anesthesia method because it has no distinct effect on the cognitive function of people after surgery.
Purwar 2015	60	Include: Patients undergoing vaginal prolapse or incontinence surgical procedures. Exclude: ASA >III; contraindication to spinal anesthesia.	In a feasibility study of patients undergoing vaginal surgery for pelvic floor disorders, differences were not detected in pain, quality of life, or functional outcomes in patients receiving spinal anesthesia (n=31) compared with patients receiving general anesthesia (n=28).	Proportion converting from spinal anesthesia to general anesthesia: 8/31 (26%). Four due to inadequate analgesia, 2 changed their mind after allocation, 1 inability to insert spinal, and 1 undocumented reason.
Alas 2020	61	Include: Women age 40 years or older scheduled for pelvic organ prolapse, ASA I-II, and BMI < 40. Exclude: Neurological diseases that can interfere with spinal anesthesia, anticoagulation therapy within a week of surgery, evidence of voiding dysfunction or urinary retention, and history of back deformity.	Postoperative urinary retention rates between spinal and general anesthesia were 92.9% vs 78.6%, p= 0.2516. There was also no difference in the QoR-15 scores between the two types of anesthesia (p= 0.467).
Jia 2014	240	Include: Patients with age ranging from 70 to 88 years with colorectal carcinoma. Exclude: Patients with a history of dementia, Parkinson’s disease, alcohol intake of ≥250 g/day, long-term use of sleeping pills or anxiolytics, and those who received anesthesia within the past 30 days were excluded.	The incidence of postoperative delirium was significantly lower in patients with epidural anesthesia (4/117, 3.4 %) than with general (15/116, 12.9 %; p =0.008).
Nishikawa 2007a	30	Include: Patients age >65; undergoing laparoscopic cholecystectomy; ASA physical status I-II. Exclude: Contraindications for epidural anesthesia; previous or current neurologic disease; abnormal mental status (Abbreviated Mental Test score <8).	In patients undergoing laparoscopic cholecystectomy, a difference in postoperative delirium and opioid use was not detected in patients receiving inhaled anesthesia compared with patients receiving IV-based anesthesia. Patients receiving inhaled anesthesia reported less satisfaction compared with patients receiving IV-based anesthesia (p=0.024).	Patients receiving inhaled anesthesia received epidural-based analgesia and cited anxiety or discomfort with epidural analgesia, resulting in lower satisfaction ratings. IV patients received analgesia through the IV.
Deng 2023	108	Include: Patients age ≥65; elective joint arthroplasty under neuraxial anesthesia. Exclude: Remimazolam or dexmedetomidine allergy; sleep disorder requiring medical interventions within 1 month; severe arrythmia including sick sinus syndrome, severe bradycardia (heart rate <50 beats/min), or atrioventricular block of ≥second degree without pacemaker; severe renal dysfunction; Child-Pugh class C; ASA physical status ≥IV.	Among patients undergoing TKA or THA, a difference was not detected in complications or length of stay in patients receiving remimazolam compared with patients receiving dexmedetomidine.
Fukata 2014	121	Include: Patients age ≥75 years; elective abdominal surgery under general anesthesia; elective orthopedic surgery under general/spinal anesthesia. Exclude: Emergency surgery; preop NEECHAM <20; periodic dosing with new or switched antipsychotics, antidepressants, hypnotics, or anti-Parkinson agents within 2 wks of surgery; previous treatment with haloperidol for delirium after surgery.	Among patients undergoing abdominal or orthopedic surgery, 25/59 (42%) patients receiving 2.5 mg haloperidol on days 1-3 postoperatively experienced delirium compared with 20/60 (33%) patients receiving no treatment, [adjusted OR (95% CI): 1.30 (0.54-3.17), p=0.558].
Fukata 2017	201	Include: Patients age ≥75 years; elective abdominal surgery under general anesthesia or elective orthopedic surgery under general/spinal anesthesia. Exclude: Emergency surgery; preop NEECHAM <20; use of new antipsychotics, antidepressants, hypnotics, or anti-Parkinson agents 2 wks before surgery.	Among patients undergoing abdominal or orthopedic surgery, patients receiving 5 mg haloperidol (n=99) postoperatively, experienced less delirium on postoperative day 1 compared with patients receiving no treatment (n=100), 3% vs 13%, respectively, p=0.017. Adjusting for age, sex, preoperative cognition, and type of surgery, the risk (OR, 95% CI) of developing severe postoperative delirium in patients receiving haloperidol compared with no treatment was 0.31, 0.13-0.66.
Aizawa 2002	42	Include: Age 70-86 yrs. Exclude: Liver cirrhosis; liver dysfunction; respiratory disturbance; metal disorder; visual impairment; emergency surgery.	The incidence of postoperative delirium, measured using DSM-IV criteria, was (35.0%) in the non delirium prevention protocol group and (5.0%) in the delirium prevention protocol group (p = 0.023).
Egawa 2016	148	Include: Patients scheduled for elective lung surgery; age 20-85l ASA physical status I-III; fluency in Japanese; ability to read; absence of serious hearing or visual impairments that would preclude neuropsychological testing. Exclude: Patients with interstitial lung disease or lung fibrosis; pregnancy or possibility of pregnancy; history of neurological or mental illness; baseline MMSE score below 24; renal insufficiency (serum creatine in excess of 1.5 mg.dL-1); active liver disease (aspartate aminotransferase in excess of 40 U.dL-1); documented coagulopathy.	Rates of POCD did not differ statistically between groups five days postoperatively or three months postoperatively. Multivariable regression analysis revealed older age as an independent predictor of POCD.
Liu 2016	200	Include: Age 65-80; ASA II-III; total hip arthroplasty or total knee arthroplasty. Exclude: Neurological diseases that may affect cognitive function (subdural hematoma, vascular dementia, B12 deficiency, encephalitis); hypoxic pulmonary disease; perioperative serious cardiopulmonary complications.	In patients with amnestic mild cognitive impairment (aMCI) undergoing THA or TKA, patients administered dexmedetomidine experienced less postoperative delirium compared with patients receiving placebo, 10/39 (26%) vs 25/40 (63%), p<0.01. In patients without aMCI, patients administered dexmedetomidine experienced less postoperative delirium compared with patients receiving placebo, 5/60 (8%) vs 18/58 (31%), p<0.01.	A subgroup analysis on age showed increased risk in patients aged >=75 with aMCI who were not treated with dexmedetomidine.
Xie 2023	240	Include: Patients aged 60 years or older and undergoing elective surgery for gastrointestinal or lung tumors. Exclude: Patients with a clear preoperative history of nervous system and mental system disease or long term use of sedatives or antidepressants; history of alcoholism, drug abuse or drug dependence; have a history of brain surgery or injury; serious visual or hearing impairment; patients who failed to compete the cognitive function test or refused to participate in the study; diagnosis of sick sinus syndrome; diagnosis of second-degree or greater atrioventricular block or other contraindications for use of alpha-2-adrenergic agonist; and renal failure requiring dialysis or hepatic dysfunction.	The incidence of postoperative delirium in all patients was 7%. The incidence of postoperative delirium in the control arm was significantly higher than that in the dexmedetomidine (10.1% vs 3.4%, P = 0.042). There was no difference detected in length of hospital stay after operation, non-delirium complications, and 30-day all-cause deaths between the two groups. the incidence of hypertension in group D was lower than that in group C (P=0.003), and there were no differences detected in other adverse events.
Whitlock 2015	7,507	Include: Patients age ≥18 years; EuroSCORE ≥6 (Jul 2011, China and India included EuroSCORE≥4); cardiac surgery requiring cardiopulmonary bypass. Exclude: Taking or expected to receive systemic steroids immediately postoperation; history of bacterial or fungal infection in past 30 days; allergy or intolerance to steroids; expected to receive aprotinin.	Differences were not detected in 30-day mortality between patients receiving methylprednisolone (154/3755, 4%) compared with patients receiving placebo (177/3752, 5%), RR, 95% CI: 0.87, 0.70-1.07. Differences were not detected in delirium by day 3 between patients receiving methylprednisolone (295/3755, 8%) compared with patients receiving placebo (289/3752, 8%), RR, 95% CI: 1.02, 0.87-1.19.
Turan 2020	798	Include: Age 18-85 yrs. Exclude: Sick-sinus or Wolff-Parkinson-White syndrome; allergy to dexmedetomidine; hepatic disease; atrial fibrillation; permanent pacemaker; MI within 7 days; severe heart failure; BMI >+ 40 kg/m2; clonidine within 48 hours.	The incidence of delirium was higher in patients given dexmedetomidine compared with placebo (12% vs 17%; RR 1.48, 97.8% CI: 0·99–2·23). Atrial arrhythmia was also higher in patients given a placebo (30% vs 34%; RR 0.91, 97.8% CI: 0.72-1.15).	DECADE is a multi-center randomized controlled trial across 6 academic medical centers in the USA and funded by Hospira Pharmaceuticals.
Tanifuji 2022	112	Include: Patients age >65; elective liver, biliary system, or pancreas open abdominal surgery under general anesthesia, with exception of laparoscopic surgery and exploratory surgery. Exclude: Study drug allergy; severe hepatic dysfunction (Child-Pugh 10-15); use of ≥3 hypnotics; use of antidepressants or antipsychotics; history of delirium; <2 wks administration time before surgery; sedation after surgery.	In patients undergoing hepatic, biliary, or pancreatic surgery, a difference was not detected in delirium among patients receiving ramelteon compared with patients receiving placebo, 1/23 (4%) vs 4/19 (21%), RR=0.21 (95% CI, 0.03-1.70).
Zhang 2018a	392	Include: Age ≥65 and <90 years; primary cancer without any radio- or chemotherapy before surgery; scheduled to undergo surgery for cancer with an expected duration ≥2hrs under general anesthesia. Exclude: History of schizophrenia, epilepsy, Parkinsonism, or myasthenia gravis; inability to communicate in the preoperative period because of coma, profound dementia, language barrier, or incapacity from severe disease; critical illness (ASA status >III), severe hepatic dysfunction (Child-Pugh class C), or severe renal dysfunction (undergoing dialysis before surgery); or neurosurgery.	The incidence of delayed neurocognitive recovery at 1 week was lower in the propofol group [14.8%(28/189)] than in the sevoflurane group [23.2%(44/190)]; OR=0.58 (95% CI: 0.34-0.98).	“[P]respecified analysis of one center” from 17 participating centers
Soh 2020	108	Include: Patients age 20 or older; scheduled for aortic surgery under CPB using either moderate hypothermic circulatory arrest with antegrade cerebral perfusion via the right axillar artery or ACC interrupting renal blood flow. Exclude: Congestive heart failure with a left ventricular ejection fraction <30%; uncontrolled arrhythmia combined with unstable hemodynamics; acute coronary syndrome; estimated glomerular filtration rate <15 ml/min; and use of ventricular assist devices.	Acute kidney injury occurred in 7/54 (13%) subjects randomized to dexmedetomidine, compared with 17/54 (31%) subjects randomized to saline infusion (OR=0.32; 95% CI=0.12 to 0.86; P=0.026). Secondary outcomes, including stroke, mortality, and delirium, were similar between subjects randomized to dexmedetomidine (16/54 [30%]) or saline control (22/54 [41%]; OR=0.61; 95% CI=0.28 to 1.36). The incidence of bradycardia and hypotension was similar between groups (14/54 [26%] vs 17/54 [32%]; OR=0.76; 95% CI=0.33 to 1.76) and 29/54 (54%) vs 36/54 (67%) (OR=0.58; 95% CI=0.27 to 1.26, respectively). The length of hospital stay was shorter in the dexmedetomidine group (12 [10-17] days) vs saline control (15 [11-21] days; P=0.039).
Momeni 2021	420	Include: Patients age ≥60; cardiac surgery with cardiopulmonary bypass. Exclude: Hepatic dysfunction (liver enzyme 3x upper normal limit with serum albumin below normal limit); preop delirium; surgery without cardiopulmonary bypass; emergency surgery; chronic renal replacement therapy.	In patients undergoing cardiac surgery with cardiopulmonary bypass, a difference was not detected in postoperative delirium during the hospital stay, among patients receiving postoperative dexmedetomidine vs saline, 31/177 (18%) and 33/172 (19%), OR (95% CI): 0.89 (0.52-1.54). Patients receiving dexmedetomidine experienced shorter duration of delirium compared with patients receiving saline, p=0.026.
Villalobos 2023	140	Include: Patients age ≥60; scheduled non-neurological, non-cardiac surgery under general anesthesia planned to last ≥2 h. Exclude: Inmate at a correctional facility; pregnancy; documented or suspected family or personal history of malignant hyperthermia; contradictions to receiving isoflurane or propofol.	A difference in 6-week overall cognition was not detected in patients receiving isoflurane maintenance anesthesia compared with patients receiving propofol maintenance anesthesia, mean difference (95% CI): 0.01 (-0.12 to 0.13).
Cao 2023	1,228	Include: Patients aged ≥ 65 years old and < 90; who were thought to have primary solid organ non-neurological cancer; had not been previously treated with either radiation or chemotherapy; were undergoing primary cancer surgery that was expected to last ≥ 2 hours. Exclude: Patients with ASA physical status ≥ 4; history of schizophrenia; history of epilepsy; history of Parkinson’s disease; history of myasthenia gravis; inability to communicate in the preoperative period due to coma, profound dementia, language barrier, or incapacity from severe disease; severe hepatic dysfunction (Child-Pugh Class C); required preoperative dialysis.	Delirium occured in 8.4% (50/597) of subjects given propofol-based anesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anesthesia (RR 0.68[95% CI: 0.48–0.95]; P=0.023; adjusted RR 0.59 [95% CI: 0.39–0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anesthesia vs 10.7% (64/597) with sevoflurane anesthesia (RR 0.50 [95% CI: 0.33–0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalization, major complications within 30 days, cognitive function at 30 days and 3 year, and safety outcomes, did not differ between groups.	Note that the Chinese Clinical Trial Registry was done 4/7/2015 but the study was not registered into the ClinicalTrials.gov until 4/18/22
Qu 2023	469	Include: Age > 60 years undergoing cardiac surgical procedure with scheduled ICU admission. Exclude: Allergy to dexmedetomidine, renal or liver failure, were on chronic benzodiazepine or antipsychotic therapy, had severe deficit(s) due to structural or anoxic brain damage, or were SARS-CoV-2 positive or symptomatic.	Postoperative delirium occurred in 5 of 175 patients (2.9%) in the dexmedetomidine group and 16 of 189 patients (8.5%) in the placebo group (OR 0.32, 95% CI: 0.10–0.83; p = 0.029) on the first postoperative day. A higher proportion of participants experienced delirium within three days postoperatively in the placebo group (25/177; 14.1%) compared to the dexmedetomidine group (14/160; 8.8%; OR 0.58; 95% CI, 0.28–1.15).	MINDSS is a single-center placebo-controlled superiority trial studying the effect of nighttime administration of dexmedetomidine on the incidence of delirium in elderly patients undergoing cardiac surgery.
Mohamed 2014	58	Include: >60; ASA class I to III; elective abdominal surgery expected to be longer than 2 hours; hospital stay >48hrs; educable. Exclude: High vagal tone (heart rate <60); arrhythmic disorders; severe ventricular dysfunction (EF <35%); hypovolemic patients; any psychological disorders; preexisting cognitive impairment; alcohol or drug abuse; preexisting CNS deficit; neurological symptomatic disorder confirmed by MRI.	The use of Dexmedetomidine as an adjuvant during Sevoflurane anesthesia did not have significant effect on protection against POCD in one day and one week postoperatively. The anesthetic and analgesic sparing effect of Dexmedetomidine was significantly proved by lower Sevoflurane need and significant lesser amount of total 24 hours postoperative Fentanyl requirements, but with significant prolonged extubation and orientation times in Dexmedetomidine group than placebo group.
Brondum 2022	39	Include: Patients age ≥18; ventral incisional hernia with horizontal fascial defect ≥10 cm described at either clinical exam or CT; planned elective open hernia repair. Exclude: Daily systemic glucorticoid medication; BMI ≥35 kg/m2; tobacco smoking within 6 wks of surgery; heart disease (NYHA class 3-4); chronic renal failure (glomerular filtration rate <60 mL/min/1.73 m2); insulin dependent diabetes; excessive alcohol use; methylprednisolone allergy; planned pregnancy within 3 mons postop; pregnant; breastfeeding; peptic ulcer disease treatment within 1 mon preop; significant vision, hearing, motor skills impairment; mental illness leading to inability to complete neuropsychological test.	In patients undergoing open hernia repair, a difference in neurocognitive recovery was not detected in patients receiving methylprednisolone at anesthesia (n=17) induction compared with patients receiving saline (n=16).
Parker 2015	322	Include: Patients over 49 years of age with an acute hip fracture. Exclude: Patients who expressed a preference to a particular method of anesthesia were excluded at their request. In addition those patients in whom either the attending anesthetist or surgeon felt either technique was more appropriate were also excluded.	30-day mortality was marginally reduced for spinal anesthesia 7/164(4.3%) compared to general 5/158(3.2%) (p = 0.57). Postoperative delirium was seen in 3/164 (1.8%) in the spinal anesthesia group compared to 0 with general (p=0.25).
Tzimas 2018	72	Include: Patients over 65 years of age with hip fracture, spoke Greek, and have at least elementary level of education. Exclude: Patients with central nervous system disease, dementia, alcoholism, on anti-depressants, previous neurophysiological testing, severe visual or auditory disorder, or debilitating previous cerebral vascular event.	The results of neuropsychological testing showed that there were no significant differences between general and spinal anesthesia groups in eight out of ten neurocognitive tests at baseline and 30 days after surgery. There was a significant decline of the Instrumental Activities of Daily Living Scale score in spinal group compared with general anesthesia on the 30th postoperative day (p = 0.043).
Oh 2021	80	Include: Planned orthopedic surgery (elective primary or revision join, hip or knee, replacement) and inpatient stay following surgery; age >65 years; MMSE >15 before surgery; ability to understand, speak, read, and write English. Exclude: Diagnosis of delirium by CAM prior to surgery; inability to give informed consent due to cognitive impairment and a suitable Legally Authorized Representative cannot be identified; declines participation; currently taking ramelteon, melatonin, and medications that will alter systemic ramelteon levels including fluvoxamine, rifampin, ketoconazole, or fluconazole; history of ramelteon or riboflavin intolerance; heavy daily alcohol intake by medical record or history; current moderate to severe liver failure (as defined by Charlson criteria); evidence of Systemic Inflammatory Response Syndrome (SIRS) as measured by >2 criteria; or presence of a condition that in the opinion of the Principle Investigator might compromise patient safety if enrolled in the study.	Delirium incidence during the two days following surgery was 7% (5/71), with no difference detected between the ramelteon versus placebo: 9% (3/33) and 5% (2/38), respectively. The adjusted odds ratio for postoperative delirium as a function of assignment to the ramelteon treatment arm was 1.28 (95% CI 0.21-7.93; p = 0.79). Adverse events were similar between the two groups.
Kinouchi 2023	108	Include: Age ≥ 65 years and ASA I-III. Exclude: Delirious at admission, currently taking Ramelteon, lactose intolerance, NPO postop, length of stay < 6 days, severe hepatic impairment, and Lewy-body dementia.	The Cox proportional hazard ratio for ramelteon compared to placebo was 1.40 (95% CI: 0.40−4.85, p=0.60).
Nishikawa 2007b	80	Include: Patients age 65-80; ASA physical status I-II; elective outpatient prostate biopsy. Exclude: Clinically significant cardiovascular, respiratory, renal/hepatic, or metabolic disease; mental dysfunction or inability to give accurate responses.	Among patients undergoing prostate biopsy, differences were not detected in complications or satisfaction in patients receiving spinal anesthesia compared with patients receiving general anesthesia.
Ishii 2016	59	Include: All patients scheduled to undergo elective gastrectomy, colectomy, or rectectomy under general anesthesia combined with epidural anesthesia. Exclude: Patients with a history of dementia, depression, alcoholism, and liver cirrhosis; a history of using benzodiazepine, major tranquilizers, or steroids; an ineffective postoperative analgesia via epidural anesthesia; and allergic reactions to local anesthetics.	The incidence of POD in the propofol anesthesia group (6.9%) was significantly less than that observed in the sevoflurane anesthesia group (26.7%).
Geng 2017	150	Include: Patients age≥65; with ASA score II-III; sufficient level of education to be capable of completing neuropsychological tests. Exclude: Mini Mental State Examination score ≤26; preexisting diagnosis of schizophrenia; preexisting diagnosis of dementia; known disorder affecting cognition; mental dysfunction; history of cerebral surgery; severe anxiety; recent history of alcohol abuse; history of chronic opioid or other psychotropic drug use; history of allergy to anesthetics; dialysis-dependent renal failure; liver transaminase level <1.5 times the normal value; recent stroke.	The incidence of POCD was lower in the propofol group compared to the isoflurane and sevoflurange group at postoperative day 1 (D1) and postoperative day 3 (D3) (propofol vs isoflurane: D1 and D3, P <0.001; propofol vs sevoflurane: D1, P = 0.012; D3, P = 0.013). The incidence of POCD was lower in the sevoflurane group compared to the isoflurane group at D1 (P = 0.041), but not at D3.
Tanaka 2017	100	Include: Age >65 years old; BMI >30kg/m2; undergoing primary knee arthroplasty surgery; ASA class II-III. Exclude: Failure of regional block; preexisting neurocognitive disorders.	Found a low incidence of delirium, but significant cognitive decline in the first 48 hours after surgery. There was no difference in the incidence of postoperative delirium between the two groups.
Fan 2017	148	Include: Age > 65 yrs; ASA I-III. Exclude: MMSE < 23; allergy to melatonin; chronic sleep disorder; alcoholism; drug abuse; psychiatric or neurological diseases.	MMSE score in the melatonin group remained unchanged during the 7 days of postoperative monitoring compared to control group (p <0.05).
Lu 2017	152	Include: Patients age ≥60 years; ASA status II-III; elective shoulder arthroscopy. Exclude: History of neurological or psychiatric disorders; psychotropic drugs; alcohol or drug dependence; use of pain medications; use of opioid or dexmedetomidine for allergies; MMSE <23; COPD; history of heart block or sinus bradycardia.	In patients undergoing shoulder arthroscopy, patients receiving dexmedetomidine pre- and post-operatively experienced higher MMSE scores on day 1 (p=0.003), day 2 (p=0.002), and day 7 (p=0.001) following surgery compared with patients receiving dexmedetomidine only pre-operatively.
Lee 2018a	354	Include: Age >65 years; ASA I-III; scheduled for laparoscopic major non-cardiac surgery under general anesthesia. Exclude: History of kidney or liver disease; allergy to the drug; cognitive impairment; use of antipsychotic alpha-2 agonists or antagonist meds; use of anti-inflammatory drugs.	Dexmedetomidine group 1 (1 ug/kg bolus followed by 0.2-0.7 ug/kg infusion) reduced incidence and duration of delirium compared to control (9.5% vs 24.8%, p=0.017). Dexmedetomidine group 2 (1 ug/kg bolus only) decreased its duration in patients with delirium compared to control (18.4% vs 24.8%). Dose and timing of dexmedetomidine appeared to be important in preventing delirium.
Hollinger 2021	143	Include: Aged ≥65 years and scheduled for visceral, orthopaedic, vascular, gynaecological, cardiac, or thoracic surgery. Exclude: Delirium at admission; MMSE score < 24; DOS ≥ 3; dementia; known ICU admission; haloperidol or ketamine intolerance; communication issues; QT interval prolongation; Parkinson’s disease; epilepsy; body weight > 100 kg; intake of dopaminergic drugs.	Delirium was seen in 6.4% of patients in the ketamine group, 11.1% with haloperidol, and 9.1 % with placebo (p=0.16).	Baden PRIDe Trial was an investigator-initiated, phase IV, two-centre, randomised, placebo-controlled, double-blind clinical trial. The purpose of this study was to identify within a cohort of ICU patients admitted for severe illness those who are at risk of death in the year following the discharge from ICU. Eleven other articles have indexed this trial.
Hongyu 2019	90	Include: Age 65-80 years; tumor grade I-III; BMI 18.5-23.9; lung cancer. Exclude: Patients with glaucoma, cataract and other eye diseases; patients with central nervous system and psychiatric disorders, linguistically ineffective communication with psychologists; mini-mental state examination (MMSE) scores ≤23 points.	Mean MMSE score in elderly patients given penehyclidine hydrochloride was higher on POD 1 (24.7 vs 23.8; p<0.05) and lower POD 4 compared to controls (16.7 vs 23.5; p<0.001). Postoperative delirium was seen in 10% of PHH patients on POD 1 and 26.7% on POD 4 compared to 13.3% in controls.
Salonia 2004	72	Include: Patients undergoing radical retropubic prostatectomy with pelvic lymphadenectomy. Exclude: None described.	In patients undergoing radical retropubic prostatectomy, patients receiving spinal anesthesia experienced more mobilization on postoperative day 1 compared with patients receiving general anesthesia, 17/36 (47%) vs 6/34 (18%), p=0.02. Differences were not detected in pain or in willingness to receive the same anesthesia in subsequent surgeries between the two groups.
Chen 2020	88	Include: Patients age ≥60; ASA physical status I-II; MMSE ≥25; normal kidney and liver function. Exclude: Hypertension, heart disease, diabetes history; cerebral hemorrhage, brain trauma, or cerrebral infarction history; mental illness or mental abnormality; alcohol or drug abusedeath during the study; significant abnormalities in study measures; serious adverse reactions during operation (difficult intubation, major bleeding, anaphylactic shock).	In patients undergoing radical resection for colorectal cancer, patients receiving dexmedetomidine (n=43) experienced higher MMSE scores compared with patients in the control group (n=45) on postoperative days 1 and 3, p<0.05 on both days. MMSE scores for the dexmedetomidine group were 27.3 +/- 0.8 and 28.8 +/- 0.9 on days 1 and 3 respectively, and the control group’s scores were 21.1 +/- 0.5 and 22.5 +/- 0.8.
Prestmo 2015	397	Include: Home-dwelling people aged 70 years or older who had been able to walk 10 m before the fracture were eligible. Exclude: Pathological fractures, multiple traumas, short life expectancy, or nursing home resident.	Mobility measured by SPPB index at 4 months postoperative was better in the CGA group compared to usual care with mean difference of 0.74 (95% CI: 0.18, 1.30; p=0.10).
Avidan 2017	672	Include: Age >60; undergoing major open cardiac; undergoing non-cardiac surgeries; under general anaesthesia. Exclude: Dx of delirium prior to surgery; allergy to ketamine; those for whom a significant elevation of blood pressure would constitute a serious hazard; hx of drug misuse; pts currently taking anti-psychotic medications; pts with a weight outside the range of 50 kg - 200 kg.	There was no difference in postoperative delirium incidence between those in the combined ketamine groups and those who received the placebo (19.45% vs 19.82%, respectively; absolute difference, 0.36%; 95% CI, -6.07% to 7.38%, p=0.92).
Casati 2003	30	Include: Elderly patients ASA II-III; undergoing hemiarthroplasty of the hip for repair of fractured femur. Exclude: Patients with contraindications to spinal anesthesia or laryngeal mask placement; those with severe and uncompensated cardiovascular or pulmonary disease; and psychiatric pathology.	Cognitive decline (MMSE test decreased >=2 points from baseline) was seen in 8 patients in the spinal group (53%) and 9 patients in the general group (60%; P = n.s.). 24h post surgery. Seven days postop confusion was still present in 1 patient in the regional group (6%) and in 3 patients in the general group (20%; P = n.s.).
Luntz 2004	96	Include: Patients age ≥65; ASA physical status I-III; elective unilateral ophthalmic surgery. Exclude: Cardiovascular complaints (New York Heart Association III-IV); adverse reaction to study drug; general anesthesia in past 3 months; <60% vision in contralateral eye.	In patients undergoing opthalmic surgery, patients receiving sevoflurane alone reported less satisfaction with anesthesia induction compared with patients receiving propofol or propofol with sevoflurane (p<0.05). Differences in satisfaction with awakening and with anesthesia in general were not detected between the groups.
Papaiannou 2005	50	Include: Patients aged greater than or equal to 60 years. Exclude: Illiteracy, severe auditory or visual disturbances, central nervous system disorders, alcoholism or drug dependence, treatment with tranquillizers or antidepressants, Parkinson’s disease and a preoperative MMSE score <23 points.	Postoperative delirium was diagnosed in 21% (6/28) of patients in the general anesthesia group and 16% (3/19) in the spinal anesthesia group.
Wang 2022b	100	Include: Patients age 65-80 years; ASA I-III; normal preoperative coagulation; no analgesia or sedatives 1 day before surgery; no study drug allergy; education junior high or above; MoCA ≥23; MMSE ≥23. Exclude: Neurological or psychiatric disease; using drugs affecting nervous or mental systems; severe vision, hearing, speech dysfunction; severe heart, lung, brain, liver, kidney diseases.	In patients undergoing various surgeries under general anesthesia, patients receiving dexmedetomidine experienced higher MMSE and MoCA scores at 24 and 72 h postsurgery compared with patients receiving placebo.
Rasmussen 2003	428	Include: Patients aged 60 years or older. Exclude: Disease of the central nervous system.	At 7 days, POCD was found in 37/188 patients (19.7%, [14.3—26.1%]) after general anesthesia and in 22/176 (12.5%, [8.0—18.3%]) after regional anesthesia, p=0.06. After 3 months, POCD was present in 25/175 patients (14.3%, [9.5—20.4%]) after general anesthesia vs. 23/165 (13.9%, [9.0—20.2%]) after regional anesthesia, p=0.93.
Epple 2001	124	Include: Patients age >65; ASA physical status I, II, III; scheduled for elective cataract surgery under general anesthesia. Exclude: Patients with a history of allergic reaction to one of the drugs used in the study.	In the propofol and remifentanil group, more patients were satisfied and would accept the same anesthetic again.
Marcantonio 2001	126	Include: Patients age ≥65; surgical repair of hip fracture. Exclude: Metastatic cancer or other comorbid illness reducing life expectancy <6 months.	In patients undergoing emergency hip fracture repair, a difference was not detected in postoperative delirium in patients receiving daily proactive geriatrics consultation compared with patients receiving usual care, when adjusting for prefracture dementia and ADL impairment, OR=0.6 (95% CI: 0.3-1.3). A difference in severe postoperative delirium was also not detected when adjusting for prefracture dementia and ADL impairment, OR=0.4 (95% CI: 0.1-1.2).
Hudetz 2009b	58	Include: Patients age ≥55; elective coronary artery bypass graft surgery and/or valve replacement/repair procedures with a cardiopulmonary bypass. Exclude: Cerebrovascular accident within 3 y; permanent ventricular pacing; previously documented cognifive deficits; hepatic impairment (aspartate aminotransferase or alanine aminotransferase greater than twice upper normal limit); chronic renal insufficiency (creatinine >2 mg/dL); increased risk of perioperative complications; use of psychoactive drugs for psychosis.	In patients undergoing surgeries requiring cardiopulmonary bypass, patients receiving ketamine experienced less postoperative delirium compared with patients receiving a placebo, 1/29 (3%) vs 9/29 (31%) within 5 days postsurgery, p=0.01.	Delirium defined as ICDSC >=4.
Zangrillo 2011	153	Include: Over age of 18; signed written informed consent; planned for general anesthesia;. Exclude: Previous unusual response to anesthetic use of sulfonylurea, theophylline, or allopurinol;.	There were no cardiac events 30 days post operation in either the sevoflurane or TIVA groups.
Kalimeris 2013	50	Include: Not reported. Exclude: MMSE < 20 and use of psychiatric drugs.	Compared with sevoflurane group, patients in the TIVA group exhibited a greater increase in their MMSE values 24 hours postoperatively. Patients who had their MMSE performance reduced at 24 hours also were significantly fewer in the TIVA group (13% v 43%, p< 0.05) compared to sevoflurane.
Chitnis 2022	70	Include: Age > 75; undergoing CABG or aortic valve replacement (AVR) surgery on cardiopulmonary bypass. Exclude: Dx of moderate dementia MMSE score < 20; hx of hypersensitivity to any medication in the study protocol.	There was no significant difference in QoR-40 scores (95% CI, -7.6 to 11.0; P= 1.0), the incidence of delirium (group Propofol, 42.4% vs group Dexmedetomidine, 24.2%, P=0.19) or mean duration of delirium (95% CI, -5.5 to 1.5; P=0.30).
Racman 2023	78	Include: Patients aged 18 years or older admitted for TAVR. Exclude: Patients with a history of: alcohol abuse, dementia of any origin, psychiatric illness, cerebrovascular insult or neurologic disease of nonvascular origin, decompensated liver disease, chronic kidney failure on hemodialysis, severe pulmonary disease (COPD, asthma), surgical aortic valve replacement, severe coronary artery disease, presentation of acute myocardial infarction that would require simultaneous percutaneous coronary intervention or patients within 4 weeks after acute myocardial infarction.	The incidence of delayed neurocognitive recovery measured 3 days post surgery was lower in the dexmedetomidine group compared to propofol (24.3% (9/37) vs 58.8% (20/34), p=0.005). Postoperative delirium was also lower the in dexmedetomidine group (2.7% (1/37) vs 11.8% (4/34), p=0.126).
Kuang 2023	88	Include: Patients age ≥65; ASA I-III; BMI 18-28 kg/m2; scheduled thorascopic lobectomy and undergoing one-lung ventilation; MMSE ≥21. Exclude: Moderate to severe reduction of pulmonary function (pulmonary ventilation dysfunction, inability to tolerate one lung ventilation, severe COPD, pulmonary encepahalopathy, severe cor pulmonale); anemia (hemoglobin <90 g/L); renal or hepatic insufficiency; SBP <90 mmHg; sinus bradycardia or atrioventricular block; severe arrhythmia; diabetes; allergy to benzodiazepines or other narcotic drugs; CNS or psychiatric disease; illiteracy; hearing or visual disturbances that affect neuropsychological tests; preoperative memory or cognitive impairment; underwent previous cognitive function tests; surgery <1.5 h; intraop blood transfusion; inability to accomplish cognitive assessment; reoperation; serious adverse reactions.	Among patients undergoing lobectomy, patients receiving remimazolam experienced improvements in 2 of 4 neurocognitive test scores at postop day 7, while patients receiving propofol experienced lower scores in 2 of 4 neurcognitive test scores.
Neuman 2021	1,600	Include: Patients aged > 50 years; undergoing surgery for hip fracture; ability to walk 10 feet or across a room without human assistance before fracture. Exclude: Planned concurrent surgery not amenable to spinal anesthesia; absolute contraindications to spinal anesthesia; periprosthetic fracture; patient at risk for malignant hyperthermia; previous participation in the trial; unable to walk approximately 10 ft or across a room without the assistance of another person before the fracture (as reported by the patient or by a proxy), and if considered to be unsuitable for randomization by the surgeon or anesthesiologists on the basis of the physician’s clinical assessment.	Primary outcome (composite of death or an inability to walk approximately 10ft independently or with a walker/cane at 60 days) occured in 132 of 712 patients (18.5%) in the spinal anesthesia group and 132 of 733 (18.0%) in the general anesthesia group (RR = 1.03, 95% CI = 0.84 to 1.27; P=0.83). Delirium occured in 130 of 633 patients (20.5%) in the spinal anesthesia group and in 124 of 629 (19.7%) in the general anesthesia group (RR=1.04; 95% CI=0.84 to 1.30).
Farrer 2023	200	Include: Adult patients aged 65 years or older who were undergoing elective total joint replacement (total knee or hip arthroplasty) or spine surgery. Exclude: MMSE < 18 or exhibited confusion at admission.	The incidence of post-operative delirium was 14% in the inhaled group and 13% in the TIVA group (p = 0.84).
Harsten 2013	124	Include: ASA I-III; able to understand given information; age > 45 years and < 85 years; signed informed consent;. Exclude: Previous major knee surgery to the same knee; obesity (BMI > 35); rheumatoid arthritis; immunological depression; allergy to any of the drugs used in this study; taking opioids or steroids; history of stroke or psychiatric disease that could affect perception of pain.	The median (IQR) 24 h postoperative consumption of morphine was 19 mg (11–28) in the general anesthesia group and 54 mg (37–78) in the regional anesthesia group (p< 0.001).
Silbert 2014	98	Include: Patients aged ≥ 55 years. Exclude: Pre-existing neurological disease, MMSE score ≤ 25, anticipated difficulty with neuropsychological assessment, contraindications to general or spinal anesthesia.	At 7 days after operation, the incidence of POCD was 4.1% (95% CI: 0.5–14%) in the general anaesthesia group and 11.9% (95% CI: 4.0–26.6%) in the spinal group (p=0.16). At 3 months, POCD was detected in 6.8% (95% CI: 1.4–18.7%) of patients in the general anaesthesia group and 19.6% (95% CI: 9.4–33.9%) in the spinal group (p=0.07).
Shyu 2008	162	Include: Patients ≥60 years; accidental single-side hip fracture; undergoing hip arthroplasty or internal fixation; able to perform full range of motion against gravity and against some or full resistance; prefracture Chinese Barthel Index >70. Exclude: Severe cognitive impairment; Chinese MMSE <10; terminally ill.	Patients receiving expanded preoperative evaluations and postoperative gerontological visits experienced improved self-care ability and less depression compared to patients receiving standard care.
Xiang 2022	174	Include: Age 65-80 years; ASA II-III. Exclude: Dementia; unstable mental status or illness; hx of stroke; hx of gastric ulcer.	Compared with placebo, methylprednisolone greatly reduced the incidence of delirium at 72 hours following surgery (9 [10.7%] vs 20 [23.8%], p = .03, OR = 2.22 [95% CI 1.05–4.59]).
Jellish 2003	60	Include: Isolated unilateral endarterectomies by the same surgeon. Exclude: Patients undergoing emergency procedures; atrial fibrillation; significant renal or hepatic disease.	Postoperative variables were similar except that patients who received iso/fen had lower Stewart recovery scores during the first 15 minutes after post anesthesia care unit admission and a higher incidence of nausea and vomiting the day after surgery, whereas patients receiving remi/prop had discharge delays secondary to hypertension. ICU admittance, time to first void, oral intake, and time to hospital discharge were similar between the groups.	No COI, funding, or registration number reported. No age criteria
Zeng 2022	60	Include: Patients age 18-80; elective primary unilateral TKA; BMI 20-35 kg/m2; ASA physical status I-III. Exclude: Knee stiffness; allergies to study drugs; long-term use of opioids (≥3 months); history of knee surgery; neuropathy of lower extremity on target side; local skin infection; puncture site bleeding.	Among patients undergoing total knee arthroplasty, patients receiving dexamethasone and ropivacaine experienced higher QoR-15 scores compared with patients receiving ropivacaine alone.
Ottens 2014	291	Include: Age > 18 yrs;. Exclude: Vision impairments; hearing or motor impairment; mental illness.	At 1-month follow-up, 13.6% in the dexamethasone group 7.2% in the placebo group were diagnosed with POCD (relative risk, 1.87; 95% CI, 0.90 to 3.88; P = 0.09). At 12-month follow-up, 7.0% in the dexamethasone group and 3.5% in the placebo group had POCD (relative risk, 1.98; 95% CI, 0.61 to 6.40; P = 0.24).
Brown 2021	219	Include: Patients age ≥65; undergoing lumbar spine fusion; expected surgery duration <3 h. Exclude: Contraindiations to spina anesthesia (eg, severe aortic stenosis, anticoagulant therapy); BMI >40 kg/m2; previous L2-L5 full lumbar fusion; baseline dementia or MMSE <24; psychiatric disease precluding cooperation with seation; surgeon or anesthesiologist preference for either anesthetic approach.	In patients undergoing lumbar spine fusion, a difference was not detected in postoperative delirium in patients receiving spinal anesthesia with targeted sedation compared with patients receiving general anesthesia with masked BIS values, 28/111 (25%) vs 20/106 (19%), RR (95% CI): 1.22 (0.85-1.76), p=0.259.
Cai 2012	2,216	Include: Patients undergoing surgery in the Second Affiliated Hospital. Exclude: Requiring post-operative intensive care; post-operative sedation; did not consent to the study; severe lung disease or hepatic or renal dysfunction;.	MMSE score in inhalation group was lower at day 3 after surgery compared with the intravenous anesthesia group (mean score 20.8 vs 26.9, p<0.01).
Hakim 2012	101	Include: Age > 65 yrs. Exclude: Hx of neuropsychiatric disorders, alcoholism; intake of psychotropic mediations.	Incidence of postoperative delirium was lower in the risperidone group compared to placebo (13.7% vs 34%, p=0.031) when given post-operatively.
Lindholm 2013	231	Include: Patients who were scheduled for open, elective abdominal aortic aneurysm surgery; ASA class I-IV. Exclude: Patients <18 years old; included in other pharmaceutical studies; history of opioids, bensodiazepins, antiepileptic drugs, alcohol, and a2-agonist abuse; pregnant and breastfeeding women; family history of malignant hyperthermia; hypersensitivity to opioids, propofol or volatile anesthetics; considerable arrhythmia; uncontrolled hypertension, or serious psychiatric disease; unstable angina pectoris or myocardial infarction last month before inclusion; acute abdominal aortic surgery; acute dissection or rupture; planned laparoscopic abdominal aortic aneurysm surgery.	Although underpowered, the authors found no differences in postoperative complications, nonfatal coronary events, or mortality between groups.
Mazul-Sunko 2010	57	Include: Patients undergoing elective carotid endarterectomy. Exclude: None described.	In patients undergoing carotid endarterectomy, differences were not detected in cognitive outcomes (perceptual speed, attention, working memory, spatial working memory, or verbal fluency) in patients receiving general anesthesia compared with patients receiving regional anesthesia.
Wang 2012	457	Include: Patients age ≥65 years; noncardiac surgery admitted to ICU. Exclude: Schizophrenia; epilepsy; parkinsonism; cholinesterase inhibitor use; levodopa treatment; inability to communicate (coma, profound dementia, language barrier); haloperidol or other neuroleptic use during or after anesthesia; neurosurgery; unlikely survival >24 hrs; prolonged corrected QT ≥460 for men or ≥470 for women at baseline.	Among patients undergoing non-cardiac surgery, 35/229 (15%) patients receiving 5 mg haloperidol IV over 12 h postoperatively experienced delirium during the first 7 days post-surgery compared with 53/228 (23%) patients receiving no treatment, OR (95% CI): 0.57 (0.35-0.94), p=0.026. A difference was not detected in 28-day mortality between the haloperidol group (0.9%) and the control group (2.6%), p=0.175.
Mei 2018	336	Include: Age >65 yrs; ASA I-IV. Exclude: Contradictions to lumbosacral plexus and T12 paravertebral block (ie coagulopathy, infection at puncture site, and refusal); patients with mental or language barriers; patients anesthetized within the past 30 days; severe congestive heart failure/severe chronic obstructive pulmonary disease; sinus sick syndrome; severe sinus bradycardia; second or greater atrioventricular block without pacemaker; cognitive impairment (MMSE <24)/preop delirium(CAM).	The patients sedated with dexmedetomidine had lower incidences of POD and POCD and were out of bed and discharged sooner than the patients sedated with propofol. There was no difference in complications between the two groups.
Mei 2020a	415	Include: Age ≥65; undergoing total knee arthroplasty; ASA I to IV. Exclude: Contraindications to spinal anesthesia (i.e., coagulopathy, infection at puncture site, and refusal of spinal anesthesia); having a mental or language barrier; patients with infections; patients who had been anesthetized within the past 30 days; history of congestive heart failure (New York Heart Association, class IV); and/or severe chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease Guidelines, stages III to IV); diagnosis of sick sinus syndrome; severe sinus bradycardia (<50 beats/min); and second or greater atrioventricular block without pacemaker; patients exhibiting cognitive impairment (i.e., a MMSE score <24) and/or perioperative delirium (i.e., CAM result).	Pts who received dexmedetomidine sedation had lower incidences of POD (odds ratio: 0.54; 95%CI: 0.31-0.92; P=0.032). In addition they had better postoperative cognitive function than patients sedated with Propofol on the third (24.3 ± 3.9 vs 22.1 ± 4.3; P<0.001, respectively) and seventh (25.6 ± 4.8 vs23.3 ± 3.3; P<0.001, respectively) day postoperatively.	Figure 1 shows the flowchart for the patient enrollment and randomization, but does not specify which groups is the control and which is the intervention.
Djainai 2016	185	Include: Age >60 undergoing elective complex cardiac surgery; AND age >70 undergoing either isolated coronary revascularization or single-valve repair/replacement surgery with the use of cardiopulmonary bypass (CPB). Exclude: Hx of serious mental illness; hx of delirium; hx of severe dementia; currently undergoing emergency procedures.	POD was present in 16 of 91 (17.5%) and 29 of 92 (31.5%) of patients in dexmedetomidine and propofol groups, respectively (odds ratio, 0.46; 95% CI, 0.23 to 0.92; P= 0.028). Duration of POD 2 days (1 to 4 days) versus 3 days (1 to 5 days), P=0.04, in dexmedetomidine and propofol groups, respectively. The absolute risk reduction for POD was 14% with a number needed to treat of 7.1.
Royse 2017	555	Include: Enrolled in SIRS (Whitlock 2015): age ≥18 years; EuroSCORE ≥6; cardiac surgery requiring cardiopulmonary bypass. Exclude: Known cognitive impairment or psychiatric illness; (from Whitlock 2015: taking or expected to take steroids immediately postop; bacterial or fungal infection preceding 30 days; steroid intolerance or allergy; expected to receive aprotonin).	In a substudy of patients undergoing cardiac surgery requiring cardiopulmonary bypass, a difference was not detected in overall quality of recovery at 6 months in patients receiving methylprednisolone compared with patients receiving placebo, odds ratios over time 0.39 to 1.45 (95% CI, 0.08-2.04 to 0.40-5.27). Differences were not detected in the subcategories of the recovery scale (cognitive, anxiety and depression, activities of daily living) between the study groups.
Leung 2017	750	Include: Patients ≥65; undergoing spine surgery, TKA, or THA; anticipated length of stay ≥3 days. Exclude: Sensitivity to gabapentin; preoperative gabapentin, pregabalin, or anti-epilectic use; spinal surgery involving more than 1 procedure to be performed within same hospitalization; emergency surgery; preop renal dialysis; opioid tolerance (total daily dose ≥30 mg morphine equivalent for more than 1 month in past year).	In patients undergoing spinal surgery, TKA, or THA, a difference in postoperative delirium incidence within 3 days postsurgery was not detected in patients receiving gabapentin compared with patients receiving placebo, difference (95% CI): 3.2% (-3.22 to 9.72%).
Li 2021a	544	Include: Major elective gastrointestinal, gynecological, prostate, or bladder surgery patients who are ≥ 60 years old; laparoscopic surgery that is expected to last for ≥ 2hours under general anesthesia and the patient will be hospitalized for at least 7 days after surgery; lack of serious hearing and vision impairment. Exclude: Life expectancy less than 3 months; MMSE score ≤23; history of dementia, psychiatric illness or any diseases of the central nervous system; current use of sedatives or antidepressants; alcoholism or drug dependence; patients previously included in this study; uncontrolled hypertension (>180/100mmHg).	46 patients in the sevoflurane group and 38 patients in the propofol met the criteria for delayed neurocognitive recovery (OR:0.77, 95%CI: 0.48, 1.24). Anesthetic choice did not appear to affect the incidence of delayed neurocognitive recovery.
Shin 2023	748	Include: Patients ASA I-II and age 65 years or older undergoing orthopedic surgery under spinal anesthesia. Exclude: Patients who refused intraoperative sedation, and those with visual, cognitive, language, or speech impairment, neuropsychiatric diseases including dementia, Parkinson’s disease, or cerebrovascular accidents were excluded.	The delirium incidence was lower in the dexmedetomidine group than in the propofol group (11 [3.0%] vs. 24 [6.6%]; OR, 0.42; 95% CI, 0.201 to 0.86; p = 0.036).
Jaiswal 2019	120	Include: Patients age ≥18; elective pulmonary thromboendarterectomy. Exclude: Pregnancy; cirrhosis; use of fluvoxamine.	In patients undergoing pulmonary thromboendarterectomy, a difference in postop delirium was not detected between patients receiving ramelteon 8 mg the night before surgery through maximum 6 nights compared with patients receiving placebo, 19/59 (32%) vs 22/58 (38%), RR 0.8, 95% CI (0.5-1.4). Differences in delirium duration and in-hospital mortality were also not detected.
Li 2019	164	Include: Patients age ≥65; ASA physical status I-III; elective unilateral total hip replacement or total knee replacement. Exclude: Contraindications to spinal surgery (eg, aortic stenosis, coagulopathy, anticoagulant use, spinal cord disease, refusal of spinal anesthesia); severe hepatic or renal insufficiency; stroke or transient ischemic attack in 1 month; difficulty with neuropsychological assessment (<9 yr education or existing mental disorder).	Among patients undergoing THA or TKA with spinal anesthesia, patients receiving midazolam experienced more postoperative cognitive dysfunction at day 7 compared with patients receiving propofol, 28/54 (52%) v 10/55 (18%), p<0.001. A difference in cognitive dysfunction was not detected between patients receiving midazolam compared with dexmedetomidine, 28/54 (52%) vs 22/55 (40%), p=0.214. Differences were not detected in cognitive function among any of the groups at 1 year followup.
Xu 2020	240	Include: Patients >65 years old and undergoing primary hip replacement. Exclude: Patients with severe hypertension (systolic pressure ≥ 180 mmHg or diastolic pressure ≥ mmHg); long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs); coagulation disorders, such as abnormal prothrombin time, activated partial prothrombin time, and thrombin time; low platelet count (<100x10^9/L); history of deep vein thrombosis or pulmonary embolism; hematological disorder; peripheral vascular disease, such as Klippel-Trenaunay syndrome and anemia; and ankylosing spondylitis.	Single subarachnoid anesthesia combines with propofol TCI seems to perform better than CSEA and GA for posterior THA in elderly patients, with less blood loss and peri-operative transfusion, higher patients satisfaction degree and fewer complications.
Glumac 2017	169	Include: Patients age 41-84 years; elective coronary artery bypass graft, heart valve, or combined surgery with or without cardiopulmonary bypass. Exclude: Cerebrovascular incident past 3 yrs; mental illness; visual, hearing, or motor impairment interfering with cognitive assessment; left ventricular ejection fraction <35%; adrenal gland disease requiring steroids >7 days in past yr; alcohol (>50 g/day or >500 g/wk) or substance abuse; MMSE <26; BDI-II >19; preop CRP >5 mg/L; preop WBC <4 or >10 x10(ninth)/L; stroke; additional corticosteroid during study period.	Patients undergoing cardiac surgery who received dexamethasone (n=80) experienced less postoperative cognitive decline compared with patients who received placebo (n=81), RR (95% CI): 0.43 (0.21-0.89). Subgroup analysis by age shows patients >=65 experience less cognitive decline when receiving dexamethasone (RR, 95% CI: 0.22, 0.05-0.94), while no difference is detected among patients <65 (RR, 95% CI: 0.59, 0.26-1.36).
Hu 2021	177	Include: Patients age 60-80 years; ASA status I-III; open transthoracic oesophagectomy under general endotracheal anesthesia. Exclude: BMI >30 kg/m2; severe pulmonary, cardiac, renal, hepatic, cerebrovascular comorbidities; chronic pain or substance abuse; dementia or treatment with antipsychotic drugs; dexmedetomidine allergy; life expectancy <6 months.	In patients undergoing open transthoracic oesophagectomy under general endotracheal anesthesia, patients receiving dexmedetomidine experienced less postoperative delirium compared with patients receiving saline, 15/90 (16.7%) vs 32/87 (36.8%), RR (95% CI): 0.45 (0.26-0.78).
Harsten 2015	120	Include: Patients age 46-84; ASA I-III; elective total hip arthroplasty. Exclude: Previous surgery to same hip; BMI >35; rheumatoid arthritis; immunological depression; allergy to study drugs; taking opioids or steroids; history of stroke or psychiatric disease that could affect pain perception.	In patients undergoing total hip arthroplasty, patients receiving regional anesthesia had longer length of stay (p=0.004), less pain at 2 h (p<0.001), more pain at >6 h (p<0.05) and requested a change in anesthesia method more often (0.022) compared with patients receiving general anesthesia.
van Norden 2021	63	Include: Age >60 yrs; major elective cardiac or major abdominal surgery. Exclude: Known drug intolerance or allergy to dexmedetomidine; unable to provide written consent; history of major neurocognitive disorder (MMSE< 24); severe audiovisual impairment; traumatic brain injury; intracranial bleeding < 1 y before the inclusion date; psychiatric illness; history of alcohol or drug abuse; pregnancy; haemodynamic dysfunction (severe hypotension, defined as a mean arterial pressure < 55 mmHg despite optimal preload and vasopressor therapy); second- or third-degree atrioventricular heart block; severe sinus bradycardia (< 50 bpm at rest); spinal injury with autonomic dysfunction; pre-operative cerebrovascular accident with residual neurological deficit; Child C liver cirrhosis; intra-operative use of remifentanil or clonidine; additional administration of dexmedetomidine within 3 months after inclusion; and planned postoperative deep sedation Richmond Agitation Sedation Scale (RASS) < 4.	Dexmedetomidine was associated with a reduced incidence of postop delirium within the first 5 preop days compared to placebo, 43.8% vs. 17.9%, p = 0.038.
Forsmo 2016	653	Include: Patients >18 years; scheduled for elective open or laparoscopic colorectal surgery for malignant or benign diseases, with or without stoma; rectal cancer who had pelvic radiation. Exclude: Patients with a planned multivisceral resection; ASA class IV; pregnancy; emergency operations; impaired mental capacity.	Total hospital stay was significantly shorter among patients randomized to ERAS than among the standard group. The two treatment groups exhibited similar outcomes regarding overall major and minor morbidity, reoperation date, readmission rate, and 30-day mortality.
Ommundsen 2018	122	Include: Patients age >65; meeting one or more frailty criteria - 1) Vulnerable Elders Survey score >2, 2) severe comorbidity (eg, heart failure, COPD, renal failure), 3) cognitive impairment (eg, dementia), 4) malnutrition (BMI <20 kg/m2 or weight loss >5% last 6 months), and 5) polypharmacy (>5 daily medications); elective resection of adenocarcinoma in colon and/or rectum. Exclude: Emergency surgery.	In frail patients undergoing resection of adenocarcinoma in colon or rectum, differences were not detected in patients receiving tailored interventions based on preoperative geriatric assessments compared with patients receiving usual care in Grade II-V complications (68% vs 75%, p=0.43), reoperation (19% vs 11%, p=0.24), length of stay (8 days both groups), readmission (16% vs 6%, p-0.12), or 30 day survival (4% vs 5%, p=0.79).	A model including study group, Vulnerable Elders Survey score, and TNM stage showed patients receiving tailored interventions experienced fewer Grade I-V complications compared with the control patients, OR=0.33 (95% CI, 0.11-0.95).
Nishikawa 2004	50	Include: Patients in ASA class I or II; age >65; scheduled for elective laparoscope-assisted surgical procedures which would last more than 3 hours under combined general and epidural anesthesia. Exclude: Patients with anticoagulation; symptomatic coronary artery disease; cardiac valvular regurgitation or stenosis; central nervous system or neuromuscular disorders; major or minor tranquilizer medication; psychotic symptoms; and neurocognitive impairment as judged by a psychiatrist were excluded.	There was no significant difference between the incidences of POD in the two groups during the first 3 days after surgery. The scored for DRS on day 2 and 3 after surgery, however, were significantly higher in group propofol than in group servoflurane (p<0.01).	No registration, dates, funding, or COI info included. Searched all 3 databases by title but could not find the study on any registration site.
Hudetz 2009a	78	Include: Patients age ≥55; elective coronary artery bypass graft surgery and/or valve replacement/repair procedures with a cardiopulmonary bypass. Exclude: Cerebrovascular accident within 3 y; permanent ventricular pacing; previously documented cognifive deficits; hepatic impairment (aspartate aminotransferase or alanine aminotransferase greater than twice upper normal limit); chronic renal insufficiency (creatinine >2 mg/dL).	In patients undergoing surgeries requiring cardiopulmonary bypass, patients receiving ketamine experienced less of a decrease in cognitive performance (at least 2 standard deviations) compared with patients receiving a placebo, 7/26 (27%) vs 21/26 (81%), p<0.001 at 1 week postsurgery.	Tests used: Repeatable Battery for the Assessment of Neuropsychological Status subtests; Brief Visual Memory Test Revised; Backward Digit Span; Semantic Fluency; Phonemic Fluency
Salonia 2006	121	Include: Patients undergoing radical retropubic prostatectomy. Exclude: None described.	In patients undergoing radical retropubic prostatectomy, patients receiving general anesthesia experienced more postoperative holding area pain compared with patients receiving spinal anesthesia combined with diazepam, propofol, or midazolam (p<0.0004). Patients receiving spinal anesthesia combined with midazolam reported the lowest pain scores in the holding area. Patients receiving spinal anesthesia combined with either diazepam or propofol reported the lowest pain scores on postoperative day 1 (p=0.007).
Vidan 2005	321	Include: Patients aged 65 years or older admitted for acute hip fracture surgery. Exclude: Inability to walk before fracture and dependency in all basic ADLs, pathological hip fracture, and know terminal illness.	Median length of stay was 16 days in the geriatric intervention group and 18 days in the usual care group (p=0.06). There was a lower mortality rate in the intervention group (0.6% vs 5.8%, p=0.03) and major medical complications (45.2% vs 61.7%, p=0.003).
Kalisvaart 2005	430	Include: Patients age ≥70 years; acute or elective hip surgery; at intermediate (1-2 risk factors) or high risk (3-4 risk factors) for postop delirium out of following: 1) visual impairment (worse than 20/70 after correction), 2) APACHE II ≥16, 3) MMSE ≤24, and 4) index of dehydration (blood urea nitrogen/creatinine ratio ≥18). Exclude: Delirium at admission; no risk factors for postop delirium; haloperidol allergy history; cholinesterase inhibitor use; parkinsonism; epilepsy; levodopa treatment; inability to participate in interviews (profound dementia, language barrier, intubation, respiratory isolation, aphasia, coma, terminal illness); surgery delay >72 h after admission; prolonged QTc interval >460 ms (males) or >470 ms (females).	In patients undergoing hip arthroplasty or hip fracture surgery, delirium incidence was 15.1% (32/212) among patients receiving haloperidol (1.5 mg daily from admission to 3 days postop) and 16.5% (36/218) among patients receiving placebo, (RR, 95% CI: 0.91, 0.59-1.44). Delirium severity (Delirium Rating Scale mean difference, 4.0 [95% CI: 2.0-5.8]) and delirium duration (mean difference in days, 6.4 [95% CI: 4.0-8.0]) were lower in the haloperidol group compared with the placebo group.
Tan 2022	99	Include: Age >60; undergoing upper GI endoscopy; ASA I-II. Exclude: Clinically significant cardiorespiratory instability; clinically significant renal or hepatic dysfunction; history of drug/alcohol abuse, neurological disease, auditory, or visual disturbances; pre-existing memory or cognitive impairment; and allergy to anesthetics.	The addition of 0.1 mg/kg of Remimazolam tosilate as an adjunct to opiate sedation not only achieves more stable perioperative hemodynamics, but also achieves acceptable neuropsychiatric function in elderly patients.
Ford 2020	210	Include: Patients age ≥50; elective cardiac surgery (coronary artery bypass graft or valve replacement). Exclude: Emergency surgery; contraindication to melatonin or already taking melatonin; dementia; Modified Telephone Interview for Cognitive Status score ≤19; Alcohol Use Disorders Identification Test score ≥15.	In patients undergoing cardiac surgery, a difference in postoperative delirium was not detected in patients receiving melatonin for 7 days (starting 2 days before surgery) compared with patients receiving placebo, 21/98 (21%) vs 21/104 (20%), adjusted OR (95% CI): 0.78 (0.35-1.75). Differences in delirium duration, delirium severity, cognitive function, anxiety and depression were also not detected between the groups.
Wang 2020a	44	Include: Currently using a nasal tracheal duct in ICU postop; required sedative treatment; age ≥ 18; ASA I or II. Exclude: Dx liver dysfunction; dx of kidney dysfunction; ALT exceeding 3x the upper limit of normal as indicator of liver damage; Serum creatinine and urea nitrogen exceeding the upper limit of normal as indicator of impaired renal function; acute myocardial infarction or severe heart failure; drug dependence; alcoholism’ hx of psychological illness; severe cognitive dysfunction; currently pregnant or lactating; allergic to midazolam; allergic to dexmedetomidine.	The incidence of delirium in the dexmedetomidine group was significantly lower than in the midazolam group (1 (1.5%) vs 9 (45%), respectively; P=0.003).	Authors were emailed to inquire what scale was used to measure delirium.
Zhang 2021	174	Include: Age 18-79 yrs; ASA I-III. Exclude: Dementia; psychosis; cerebrovascular disease; acid-base imbalance, electrolyte imbalance; diabetes.	Incidence of POCD was calculated in both dexmedetomidine and control groups as 9.20% and 21.31% (p=0.038), respectively.
Zhu 2022	155	Include: Age greater than 65 years with hip, neck, femur, or lesser trochanter fractures. Exclude: Pathological fracture, old fracture, or multiple fractures.	Incidence of postoperative delirium was higher in the standard care group when compared to the CGA group (21.4% vs 31.8%, p<= 0.001). The ADL score was similar in both groups (m=50.5 vs 51.7, p=0.522) respectively.
Guo 2022	90	Include: ASA II-III patients undergoing radical gastrectomy. Exclude: History of other GI surgery, severe cardiovascular, cerebrovascular, respiratory, endocrine, or metabolic disease, mental illness, allergic to anesthetics, or renal or liver dysfunction.	The incidence of delirium was lower in the dexmedetomidine group when compared to control (8.8% (4/45) vs 13.3 (6/45), p> 0.05).
Wang 2020b	25	Include: Patients were (1) a diagnosis with malignant bone tumor around the knee by preoperative biopsy; (2) no distant metastasis upon clinical examination; (3) Enneking staging IA, IB, IIA and IIB with good response to chemotherapy; and (4) tumors with no main blood vessel invasion, no nerve invasion, and no pathological fractures and diffuse skin infiltration. Exclude: Patients had (1) coagulopathy, (2) local skin infection, (3) peripheral neuropathy, (4) mental retardation, (5) mental illness, and (6) rheumatoid knee arthritis.	There were no statistical differences in pre- and postoperative WOMAC indexes (49.89 ± 7.9, 25.12 ± 6.2 vs. 51.3 ± 8.3, 23.15 ± 5.3) between the general and spinal anesthesia groups (p > 0.05).
Larsen 2010	495	Include: Age <65 with with a history of post op delirium; age≥65, elective TKR or THR. Exclude: Diagnosis of dementia; active alcohol use; history of alcohol abuse; allergy olanzapine; current use of antipsychotic.	The incidence of delirium was significantly lower in the olanzapine group than in the placebo group (14.3% vs 40.2%, Adjusted OR:0.2, CI: 0.1-0.4, p<0.001). However, delirium lasted longer in the olanzapine group (2.2 [SD1.3] versus 1.6 [SD0.7] days; p=0.02). The severity of delirium was also greater in the olanzapine-treated group than in the placebo group (16.44 [SD: 3.7] vs 14.5 [SD: 2.7]; p=0.02).	High dropout rate, patients stratified by complexity of surgery
Tang 2014	220	Include: Memory complaints documented by the patient and a collateral informant; Montreal Cognitive Assessment test score 15-24; MMSE< 27; Activities of Daily Living score <22; no evidence of dementia. Exclude: Current diagnosis of dementia (preoperative MMSE score <23); current or past psychiatric illness; current use of antidepressant or antianxiety medication; history of drug dependence or alcohol abuse; history of coronary artery, peripheral arterial or cerebrovascular disease; severe visual, auditory, or motor handicap; acute infection; preoperative hemoglobin < 85 g/L.	At 7 days after surgery, the incidence of POCD was 29.7% in the propofol group and 33.3% in the sevoflurane group. Sevoflurane anesthesia had a more severe impact on cognitive function than propofol anesthesia.
Wu 2020	80	Include: Age 40-75 yrs; ASA II-III; carotid stenosis. Exclude: Cognitive dysfunction; mental disorders; cerebral infarction or intracranial hemorrhage.	The MMSE scores in both groups increased at 1 and 7 days postoperatively; although the increase in the dexmedetomidine group was sharper, there was no significant difference.
Liu 2022a	60	Include: Patients age 45-70; ASA I-II; elective video-assisted thoracoscopic lobectomy. Exclude: Cardiovascular or cerebrovascular disease; arrhythmia; sinus bradycardia; ischemic heart disease; obstructive sleep apnea; dexmedetomidine allergy; education below junior high school; on medication for mental disorders; previous neurological disease; memory impairment; abnormal coagulation function, puncture site infection, or perioperative blood transfusion; spinal surgery; chronic pain or oral analgesics prior to surgery; complications leading to secondary surgery; converted to pneumonectomy; catheter prolapse; use of 2-adenoceptor agonist in past week.	In patients undergoing video-assisted thoracoscopic lobectomy, patients receiving dexmedetomidine experienced higher MoCA scores compared with patients receiving placebo on days 1 and 3 postsurgery, mean (SD): 26.4 (0.7) vs 25.5 (1.0), p<0.001 on day 1, and 27.1 (0.8) vs 26.6 (0.8), p=0.032 on day 3. Differences in MoCA were not detected on postoperative day 7.
Prakanrattana 2007	126	Include: Patients age >40; elective cardiac surgery with cardiopulmonary bypass. Exclude: Emergency surgery; patients admitted to ICU; tracheal intubation prior to operating room arrival; preoperative delirium; history of psychiatric problems.	In patients undergoing cardiac surgery requiring cardiopulmonary bypass, patients receiving sublingual risperidone postoperatively experienced less postoperative delirium compared with patients receiving placebo, 7/63 (11%) vs 20/63 (32%), RR (95% CI): 0.35 (0.16-0.77).
Watne 2014	329	Include: All patients admitted with a hip fracture. Exclude: Moribund on admission or patients with high energy trauma.	There was no difference in cognitive function four months after surgery between patients in the comprehensive geriatrics assessment group and standard care group (Clinical Dementia Rating Scale 54.7 versus 52.9, 95% CI: −5.9 to 9.5; p=0.65). Postoperative delirium was seen in 49% in the intervention group and 53% in the standard care group (p=0.51).
Qiao 2015	90	Include: Patients in ASA status I, II, or III; preoperative MMSE score ≥23; no evidence of cardiovascular, respiratory or central nervous system disease; normal renal and hepatic function; no serious hearing or visual impairment; absence of a history of benzodiazepine or antidepressant use, alcohol or cigarette misuse or drug dependence. Exclude: Alzheimer’s disease; a family history of mental illness or mental illness; a cognitive impairment of the disease; a history of alcohol and drug dependence.	The MMSE and MoCA scored were significantly lower in the sevoflurane group than in the propofol control group on the first, third, and seventh postoperative days (p<0.05).	Only abstracted propofol vs sevoflurane, the article provided a separate p-value
Hong 2021	712	Include: Age 65-90 yrs; ASA I-III. Exclude: Hx of schizophrenia, epilepsy, parkinsons, or myasthenia gravis; dementia; sick sinus syndrome, severe bradycardia; sleep apnea; hepatic dysfuncion; renal failure;.	The incidence of postoperative delirium was 7.3% with placebo and 4.8% with dexmedetomidine (RR 0.65, 95% CI 0.36 to 1.18; p=0.151).
Bielka 2021	90	Include: Patients age >18; planned osteosynthesis of the proximal femur. Exclude: Pregnancy and lactation; opiate addiction history; traumatic brain injury; acute stroke; dementia; acute cerebrovascular accident; chronic heart failure (NYHA class III-IV); respiratory failure; renal failure (creatinine clearance <30 ml/min/1.73 m2); hepatic insufficiency (Child-Pugh class C).	In patients undergoing osteosynthesis of the proximal femur, patients receiving psoas compartment block had less opioid use 24 h postsurgery compared with patients receiving spinal anesthesia and patients receiving general anesthesia, median (IQR): 0 (0-5) vs 15 (10-20) and 20 (15-25)mg, respectively, p<0.001. Patients receiving psoas compartment block also reported less severe pain within 48 h postsurgery compared with the other 2 groups, p<0.05.
Huang 2023a	160	Include: Patients age >60; intertrochanteric fracture within 3 wks. Exclude: Systemic or fracture site infection; multiple traumas or open fracture; stroke within 3 months; acute MI within 6 months; active peptic ulcer; pathological fracture or pending fracture diagnosed by radiographic data; chronic organic failure without effective replacement therapy; advanced malignant tumor; severe cognitive disorder (MMSE ≤9); severe malnutrition or overnutrition (BMI <16 or BMI ≥35); corticosteroid use over 2 wks.	Among patients undergoing hip fracture repair, patients receiving dexamethasone experienced less postopertive delirium compared to patients receiving placebo, RR (95% CI): 0.83 (0.71-0.97).
Wang 2022a	125	Include: Age 60-75 yrs; ASA I-II. Exclude: Cognitive dysfunction; adverse response to propofol, remifentanil, dexmedetomidine; cardiovascular disease; endocrine disease; liver or kidney dysfunction; alcohol, sedatives, or opioid use.	The mean MMSE score was similar between the dexmedetomidine and placebo groups on postoperative days 2 and 3 (25.2 vs 25.1, p=0.66; 25.4 vs 25.3, p=0.76).
Carron 2007	40	Include: Patients ASA status ≤3; age ≥18 and ≤85 years old, life expectancy ≥3months; S-creatine <220 umol/L; S-bilirubin total <68 umol/L; WBCc ≥3109/L; PLTc >75109/L; Hemoglobin >85g/L; PT ≥60%; aPTT ≥22s; no chemotherapy in the last month. Exclude: Not specified.	GA and SA did not differ in times to achieve home readiness or patient satisfaction. Compared with GA, SA significantly (P<0.05) reduced anesthesia times, postoperative VAS scored for pain and nausea, and the number of admissions ti the postanesthesia care unit.	Inclusion criteria from other article (Subarachnoid anesthesia for loco-regional antiblastic perfusion with circulatory block (stop-flow perfusion))
Sauer 2014	737	Include: Age >18 yrs; undergoing cardiopulmonary bypass. Exclude: Emergency surgery; scheduled for an off-pump technique; patients with a life expectancy of <6months.	The intraoperative admin of dexamethasone did not reduce the incidence or duration of delirium in the first 4 days after cardiac surgery.	A substudy of DECS trial
Remerand 2009	160	Include: All adult patients undergoing total hip arthroplasty. Exclude: Patient refusal, inability to use PCA device or NRS, chronic treatment with gabapentin and clonazepam, chronic morphine or fentanyl intake, contraindication to NSAIDs, paracetamol, or ketamine, history of gastric ulcers, allergy, porphyries, hepatic, renal, or coagulation disorders.	Patients given Ketamine used post-operatively had less morphine consumption at 24 h compared with placebo (19+-12 mg to 14+-13 mg, p=0.004). Lower incidence of hallucinations was observed with Ketamine compared to placebo (10.1% (8/79) vs 14.7 (11/75), p=0.51). Length of stay was similar in both groups (8.8 vs 8.3 days, p=0.20).
Rascon-Martinez 2016	80	Include: Patients age ≥60; ASA I-III; vitrectomy or cataract surgery involving retrobulbar block. Exclude: History of psychosis, schizophrenia, nephropathy; difficult to control arterial blood pressure; uncontrolled hepatic disorders; ketamine allergy; moderate to severe depression; postop depression; required medications other than study drugs.	In patients undergoing opthalmic surgeries, more patients receiving ketamine during surgery experienced improved cognitive scores 2 h postsurgery compared with patients receiving a placebo, mean change in error score of -1.0 (1.1) vs -0.2 (0.9), p=0.001.	Short Portable Mental Status Questionnaire used, scoring is 0-2 errors=intact cognition; 3-4 errors=mild cognitive deterioration; 5-7 errors=moderate deterioration; and 8-10 errors=severe deterioration.
Dai 2021	164	Include: Patients had a known diagnosis of CAD confirmed by prior AMI or coronary angiography, or the occurrence of representative angina pectoris, and at least 2 of the following risk factors: age >65, active smoking, hypertension, hyperlipidemia, and diabetes mellitus; patient was scheduled for major noncardiac surgery; percutaneous coronary intervention within 2 months. Exclude: Signs of acute cardiac failure; unstable angina; recent onset (< 6 months) myocardial infarction; percutaneous coronary intervention within 2 months; emergency surgery; combined or repeated procedures; participation in other research that might interfere with the current study endpoint.	Occurrence of delirium did not differ between the sevoflurane and propofol groups.
Liang 2017	198	Include: Patients with ASA I-III. Exclude: Patients with history of nervous system or cardiac surgery, mental disorder, defective vision, and neurological disorders.	Patients in the general anesthesia group higher rates of pulmonary embolism 3% (2/66) when compared to epidural alone 0% and combined spinal epidural 1.5% (1/66). MMSE score was higher in patients given epidural anesthesia than general or combined spinal epidural (m=24.46 vs 22.45 vs 22.48, p< 0.05).
Wang 2016	206	Include: Patients over 66 years old undergoing non-cardiac surgery below the abdomen. Exclude: Patients who had heart associated disease; were allergic to the anesthetic and analgesic drugs or had allergic constitution; had other surgical contraindication or were unwilling to participate in the research.	On the 7th dat after surgery, incidence of cognition impairment in observation group and control group was 48.5% and 44.7%, but there was no statistical significance between the two groups. VAS score in the regional group was much lower than in the general group (p<0.05).
Yang 2022	80	Include: Patients age greater than 65 years; preoperative ASA grade I-II; undergoing elective laparoscopic surgery; without risk factors for thrombosis (included obesity, hypertension, coronary heart disease, and diabetes); without severe uncontrollable cardiovascular disease; and without severe uncontrollable cerebrovascular disease. Exclude: Patients with preoperative ASA grade III or above; severe anemia (Hb<100g/L); medical history of opioid allergy; anticoagulant use during perioperative period; diagnosis of acute and chronic respiratory disease history; history of drug or alcohol abuse.	A difference was not detected at postoperative 1 day between the two groups for postoperative cognitive function in elderly patients undergoing laparoscopic surgery (Propofol: Mean28.79; SD: 1.44; Sevoflurane: Mean: 27.16; SD: 1.31; p>0.05).
Li 2023	98	Include: Age ≥ 60 years; those who met the surgical indications of hip replacement; traumatic fracture admission; complete clinical data; informed consent of this study. Exclude: Preoperative severe malnutrition; patients with severe infectious diseases; patients with severe organ dysfunction and malignant tumors.	There was a higher incidence of hypotension in the control group compared with dexmedetomidine (6.1% vs 2.0%).
Hempenius 2013	297	Include: Patients age >65; elective surgery for solid tumor; frail (defined as Groningen Frailty Indicator [screening instrument with 4 domains - physical, cognitive, social, psychological] score >3). Exclude: Non-frail; unable to complete questionnaires.	In frail patients undergoing elective surgery for solid tumors, a difference in delirium was not detected in patients receiving geriatric liaison interventions compared with patients receiving standard care, 12/127 (9.4%) vs 19/133 (14.3%), OR (95% CI): 0.63 (0.29-1.35). Differences in complications, and physical and mental scores, were also not detected between the groups.	Ten day results (SF-36, MMSE) and 30-day results (mortality, readmission) reported in Hempenius 2016.
Hempenius 2016	297	Include: Age > 65 yrs with Groningen Frailty Indicator > 3 (frail). Exclude: Unable to fill out questionnaires or comply with follow-up visits.	Overall incidence of postoperative delirium in this clinical trial was 11.5% (26/227). There was no difference in the MMSE score at discharge between the standard care group and multicomponent preoperative assessment group (26.5 vs 26.9, p=0.97). The Short Form-36 physical component measure were similar in both groups, respectively (49.3 vs 48.4, p=0.17).	Liaison Intervention in Frail Elderly (LIFE), was a multicenter, randomized clinical trial in the Netherlands. Primary outcome of postoperative delirium is not reported by study groups but by mortality.
Valentin 2016	140	Include: Patients over 60 years of age undergoing non-cardiac and non-neurologic surgeries under general anesthesia. Exclude: MMSE < 18 or 23 based on education level, history of brain disease, dementia or other psychiatric disorders, on continuous use corticosteroids, antidepressants, or opioids preoperatively.	Postoperative cognitive disorder measured by TICS (Telephone Interview for Cognitive Status)was lower in the dexamethasone group compared to controls at 21 days postop (2.3% vs 44.2%) and 3 months postop (2.25 vs 21.6%).
Li 2017	285	Include: Age ≥60; scheduled to undergo elective coronary artery bypass graft and/or valve replacement surgery. Exclude: History of schizophrenia; history of epilepsy; diagnosis of Parkinson disease; diagnosis of severe dementia; inability to communicate because of severe visual/auditory dysfunction or language barrier; history of functional neurosurgery or brain injury; diagnosis of preoperative sick sinus syndrome; diagnosis of severe bradycardia (heart rate <50); diagnosis of second-degree or above atrioventricular block without pacemaker; diagnosis of severe hepatic insufficiency (Child-Pugh grades C); diagnosis of severe renal insufficiency (requirement of renal replacement therapy); patient refused to participate in the study.	Dexmedetomidine administered during anesthesia and early postoperative period did not decrease the incidence of delirium (4.9% [7/142] in the DEX group vs 7.7% [11/143] in the CTRL group; OR 0.62, 95% CI 0.23 to 1.65, p = 0.341) in elderly patients undergoing elective cardiac surgery.
Wongyingsinn 2020	54	Include: Patients age > 18 years and ASA I-III scheduled for elective unilateral inguinal hernia repair. Exclude: Patients were excluded due to allergy to any study medications, femoral hernia, recurrent hernia, bilateral hernia, bleeding abnormalities, severe hepatic/renal/cardiovascular disease, chronic use of opioids, or history of NSAID use.	There were no significant differences between regional and general anesthesia for postoperative pain at rest or on mobilization at 8 and 24 hours after surgery.
de Jonghe 2014	452	Include: Patients aged ≥ 65; acute admission for surgical repair of hip-fracture; enrolment within 24 hours of admission. Exclude: Transferred for surgical repair from another hospital; concomitant use of melatonin and prior participation in this study.	Did not observe an effect of melatonin on the incidence of delirium, 55/186 (29.5%) in the melatonin group vs 49/192 (25.5%) in the placebo group; difference 4.1 (95% CI -0.05 to 13.1) percentage points. There were no between-group differences in mortality or in cognitive functional outcomes at 3-months follow-up.
Shi 2021	297	Include: Age > 60 yrs; ICU admission. Exclude: Mental illness and epilepsy; neurologic disease; brain injury or neurosurgery; high cholesterol with diabetes.	The incidence of postoperative delirium was significantly lower in the melatonin group than in the placebo group (27.0% vs. 39.6%, respectively, p = 0.02). No difference was detected in 30-day all-cause mortality (12.2% vs. 14.1%, p = 0.62).
Gao 2021	40	Include: Age 65-77 yrs; ASA II-III; weight 56-75 kg; HYHA II-III;. Exclude: Dementia and mental history; cerebrovascular disease; acid-base imbalance; electrolyte disturbance; abnormal liver and kidney function; MI; brain trauma; diabetes.	The incidence of postoperative cognitive dysfunction (POCD) in the Dexmedetomidine group was significantly lower than that in the control group at postoperative 7 days and postoperative 30 days (10% vs 40%; 0% vs 20%, p < .05).
Lv 2022	327	Include: Patients >60; undergoing surgery with general anesthesia and admitted to ICU postsurgery. Exclude: Unsalvageable at admission; diabetes combined with high cholesterol; history of brain injury, neurosurgery, severe sinus bradycardia, neurological disease, rhabdomyolysis, myopathy, mental illness, epilepsy, severe lung disease, multiple organ dysfunction.	In patients undergoing various surgeries under general anesthesia, patients receiving dexmedetomidine experienced less delirium compared to patients receiving placebo, 21/152 (14% vs 46/152 (29%), p<0.01. Differences were not detected between the groups in 30-day mortality.
Du 2019	87	Include: Age ≥ 65; ASA I-II;. Exclude: Dxof cognitive dysfunction; dxof psychosis; dxof severe cardiac disease; dx of lung disease; dx of liver disease; dx of renal disease; dx of any other system disease; surgery time >1h; surgery could not be accomplished successfully and turned into laparotomy operation.	Postoperative cognitive dysfunction was greater in the control group compared to the dexmedetomidine group. MMSE scores were lower in the control group compared to the dexmedetomidine group at 12h (19.4±1.8 vs 22.4±1.9), 24h (22.3±1.4 vs 23.7±1.3), and 48h (24.1±1.1 vs 25.0±1.5) postop (P<0.05).
Ornek 2010	60	Include: Patients ages 65 yrs or older and ASA II-III were enrolled. Exclude: Patients with BMI > 32 and having allergy to study medications.	PACU length of stay was shorter in patients given general anesthesia compared to spinal (m=21.7 vs 23.3, p=0.970). Patient satisfaction was higher in the general anesthesia group (85.2% vs 75%).
Yang 2023	320	Include: Patients were age at least 60 years; ASA class I-III; and planned general anesthesia for the proposed orthopedic surgery. Exclude: Patients with preoperative delirium or dementia; other conditions including intolerance or allergy to benzodiazepines, history of myasthenia gravis; history of schizophrenia; history of severe depressive states; having emergency surgery; and inability to communicate verbally due to deafness and muteness.	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.
Liu 2023c	304	Include: Patients aged ≥65 years and scheduled for a laryngectomy. Exclude: Patients with a diagnosis of delirium or pre-existing cognitive impairment; unable to complete baseline cognitive assessments; factors that might affect cognitive assessment, such as language, visual, and auditory dysfunction; an unstable mental health or mental illness; sick sinus syndrome; second-degree or third-degree heart block or clinically significant sinus bradycardia; contraindication for use of an alpha-2-adrenergic agonist and female sex.	There was no difference in the incidence of postoperative delirium between the dexmedetomidine and control groups (21.3% [32 of 150] vs 24.2% [36 of 149], P=0.560). However, dexmedetomidine reduced postoperative delirium in patients with laryngeal cancer and a higher tumor stage (21.6% vs 38.5%; OR=0.441; 95% CI=0.209-0.979; P=0.039).
Lai 2023	90	Include: Patients aged 65-75 years, ASA II-III, and NYHA I or II. Exclude: (1) sinus bradycardia or atrioventricular block; (2) local allergy to anesthetics; (3) previous use of immunosuppressants and recent chemoradiotherapy; (4) current use of nonsteroidal anti-inflammatory drugs or steroids, angiotensin converting enzyme inhibitors, or bronchodilators; (5) liver and kidney insufficiency; (7) epilepsy and associated mental and cognitive dysfunction, long-term stress stimulation, or psychological disorders; and (8) history of alcoholism, analgesic drug dependence, and long-term use of sedatives.	The incidence of postoperative delirium was higher in control group compared to dexmedetomidine on day 2 and day 7 (30% vs 17.2% and 17.2% vs 6.8% respectively).
Han 2023	84	Include: Patients aged 65 and above; receiving gastrointestinal surgery under general anesthesia; MMSE score >24; ASA I-III; and right handed. Exclude: History of neurodegenerative diseases (Alzheimer’s disease or Parkinson’s disease); intracranial hypertension; severe uncontrolled hypertension; communication disorders; glaucoma; serious postoperative complications and admitted to the ICU; reoperation; and loss of follow up.	The incidence of delayed neurocognitive recovery in group esketamine was lower than that of the control (18.15% vs 38.24%; P=0.033). contrarily there was no difference in both groups regarding postoperative cognitive delay 3 months postoperatively (6.06% vs 14.37%; P=0.247).
Ma 2023	68	Include: Patients age ≥65; ASA status I-III; BMI 18-30 kg/m2; elective major abdominal surgery under general anesthesia for gastrointestinal tumors; operation time ≥2 h. Exclude: Preoperative cognitive dysfunction (MMSE: <17 for illiteracy, <20 for primary school education, <24 for high school education and above); inability to communicate; use of psychotropic drugs; alcohol abuse history; use of sevoflurane, dexmedetomidine, scopolamine, penehyclidine hydrochloride during study; severe circulatory disease and history of cardiac surgery; severe respiratory disease; history of cerebral hemorrhage; coagulation abnormalities; contraindication to esketamine; severe subcutaneous emphysema or serious adverse events; emergency surgery; postoperative ICU; second operation within 3 days.	Among patients undergoing gastrointestinal tumor surgery, patients receiving eskatamine experienced less postoperative neurocognitive recovery (5/31, 16%) compared with patients receiving placebo (12/31, 39%), p=0.046. Differences in postoperative delirium were not detected between the groups in days 1-3 postsurgery.
Liu 2022b	120	Include: Age greater than and equal to 65 years, ASA I-II, preop MMSE > 24. Exclude: Dementia, combined neuropsychiatric system diseases, emergency surgery, bradycardia (HR <50 beats/min), pathological sinus syndrome, heart block, serious cardiovascular and cerebrovascular diseases (Heart failure, myocardial infarction, cerebral infarction, cerebral hemorrhage), liver and kidney insufficiency, coagulation dysfunction and other systemic diseases, preoperative lesions with infection, and drug allergy.	Postoperative delirium developed in 13.3% (8/60) of patients in the control group and 8.3% (5/60) in the dexmedetomidine group (p=0.378).
El-Naggar 2018	50	Include: Patients age ≥60 years; ASA III-IV; elective coronary artery bypass graft, 2 or 3 vessel grafts. Exclude: Emergency surgery; ejection fraction <40%; MMSE ≤24; history of neuropsychiatric disorders; liver cirrhosis; renal failure; chronic pulmonary disease; uncontrolled systemic disease such as diabetes or hypertension; serious perioperative or postoperative complications causing unexpected morbidity; prolonged ventilation >8 h; history of choni sedative hypnotic use >3/week in month prior to surgery; study drug allergy.	In patients undergoing coronary artery bypass graft, patients receiving melatonin experienced less delirium compared with patients receiving placebo, 2/25 (8%) vs 7/25 (28%), p=0.046.
Li 2021b	120	Include: Age 65-90 yrs undergoing laparoscopic abdominal surgery likely > 2 h. Exclude: MMSE < 24; mental and neurological disease; hepatic or renal disease; bradycardia or hypotension.	Incidence of POCD was 40% in the control group and 6.7% in patients given highest dose of dexmedetomidine.	Three doses of dexmedetomidine compared to placebo to determine occurrence of POCD.
Haghighi 2017	100	Include: Patients aged >60 years; ASA class I-III; undergoing hip fracture fixation. Exclude: Dementia; cognitive disorders; history of opioid use; hepatorenal diseases; pulmonary diseases; sensitivity to anesthetic agents; coagulopathies; neurologic disease; inability to give accurate responses to questions; high intra-cerebral pressure; infection at site of injection; massive hemorrhage during surgery; low blood pressure during surgery.	Pain and opioid consumption were lower in the spinal anesthesia group compared to the general anesthesia group (M=2.36, SD=1.85 vs M=4.86, SD=1.75; P=0.001 and M=0.86, SD=1.52 vs M=2.66, SD=1.63; P=0.001, respectively).
Sciberras 2022	210	Include: Patients ages 18-75 years undergoing TKA. Exclude: Age > 75 years, rheumatoid arthritis, contraindication to spinal anesthesia, chronic pain syndrome.	Spinal anesthesia group had better function (WOMAC: 14.4 vs 16.9, p = 0.015) at 3 months, but not at 6 months compared to general anesthesia.
Huyan 2019	360	Include: Age ≥ 65 yrs; ASA II-III; BMI 18-25 kg/m3; forced vital capacity > 80%; 1st second forced expiration > 70%;. Exclude: Hx of metabolic disorder (diabetes); discharge to ICU after surgery; preop delirium; new atrial fibrillation; cardiac arrest; stock blood infusion; hypoxemia (SpO2 < 90%, > 1 min).	Postoperative delirium was seen 15.6% of patients receiving dexmedetomidine compared to 27.2% in the control group on postoperative day 1 and 0% on postoperative day 7 in both groups.
Tian 2021	62	Include: Patients ASA I-II; scheduled pulmonary lobectomy. Exclude: MMSE <24.	In patients undergoing pulmonary lobectomy, patients administered propofol experienced higher MMSE scores at postop day 1 compared with patients administered sevoflurane, p<<0.05.
Qin 2019	104	Include: Patients who met lung cancer diagnostic criteria; age ≥ 60; no contraindications to surgery and anesthesia; gave informed consent; >9 years of education in China;. Exclude: Patients with cardio-cerebrovascular diseases; abnormal lung function; cognitive disorders; history of drug dependence;.	At postoperative day 1, MMSE scores were higher in the sevoflurane group than in the propofol group (m=28.87 +- 0.54 vs 27.54 +- 0.89, p=0.002).
Zhang 2019a	80	Include: Patients with normal consciousness before surgery, age >60 years, and >9 years of education in China. Exclude: Patients with neurological diseases, cognitive disorders, history of long-term administration of sedatives and those with malignant tumors.	At 24h after surgery, the number of cases suffering postoperative cognitive dysfunction (POCD) after spinal anesthesia was lower than that of the general anesthesia (15% vs 35%, p=0.039).
Javaherforoosh 2021	60	Include: ≥30 years; elective on-pump CABG; ASA class II-III; minimum ejection fraction of 30%;. Exclude: Presence of melatonin contraindications; allergy to the drug; chronic or recent use of melatonin or hypnotic drugs; receiving barbiturates or or antipsychotics; a history of kidney or liver disease or chronic pulmonary disease; history of neurological or psychological diseases; alcohol consumption; inability to communicate verbally; occurrence of serious and like threatening events during or after.	Melatonin may be effective in reducing the severity of delirium after cardiac surgery. The effect of melatonin asa delirium prevention agent should be considered in patients admitted in the cardiovascular intensive care.
Sun 2023b	120	Include: Patients ≥60 years old at the time of admission; undergone elective hip arthroplasty; ASA class I-III; evaluated preoperatively using the Montreal Cognitive Assessment with scores ≥23; evaluated preoperatively using Mini-Mental State Examination with scores ≥23; no history of previous hip surgery; no analgesic or sedative medication on 1 day before surgery; no allergy to the anesthetic drug used in the study; and able to cooperate in completing the scale. Exclude: Diagnosis of psychiatric disorder; diagnosis of central nervous system disorders; long-term medications affecting the nervous and psychiatric systems; severe visual, hearing, and speech impairment; allergy to the anesthetic drugs in this study; history of severe brain tumor or brain surgery; severe liver and kidney function and metabolic abnormalities.	Patients in the remimazolam group had less cognitive and mental impairment compared to the control group at 24hr and 72 hrs postop (MoCA: Mean=22.34; SD=4.24 vs Mean=19.65; SD=3.79; P<0.001; MMSE: Mean=24.21; SD=3.57; vs Mean= 19.71; SD=3.23; P<0.001 at 24 hours respectively; MoCA: Mean=24.72; SD=3.25 vs Mean=22.35; SD=3.52; P<0.01; MMSE: Mean=25.31; SD=2.62; vs Mean=23.39; SD=3.28; P<0.01 at 72 hours, respectively).
Hu 2022	60	Include: Age at least 60 years undergoing hip fracture surgery. Exclude: Patients with hematological diseases, malignant tumors, or other serious organic diseases; patients with severe liver and kidney dysfunction; patients with long term use of sedation drugs and mental diseases.	The total delirium rates in the placebo and dexmedetomidine groups were 15.0% and 5.0% respectively.
Mei 2020b	240	Include: Age at least 60 years, ASA I-III, normal cognitive function a MMSE ≤ 24, and have verbal and written communication skills. Exclude: History or existing delirium, neurologic diseases, mental disorders, impaired vision, and unwillingness to participate.	The incidence of postoperative delirium was higher in the propofol group compared to sevoflurane (33% vs 23.3%, p=0.119).
Gao 2020	60	Include: Age 65-75; ASA II-III; NYHA grade II-III; Body Weight 55-85 kg;. Exclude: Mental illness; Previous acute myocardial infarction; previous diagnosis of heart failure; diabetes; brain trauma; cerebrovascular accident; left ventricular ejection fraction >40%; abnormal liver and kidney function; sedatives or antidepressants intake; history of drug abuse; sick sinus syndrome;.	At 72 h and 7d after operation, incidence of cognitive dysfunction in the dexmedetomidine group was lower compared with the placebo group (P <0.05).
Liang 2022	224	Include: Patients aged 65–80 years and scheduled for spinal surgery. Exclude: Preoperative neurological diseases (such as vascular dementia), severe liver and renal insufficiency, autoimmune diseases, recent use of sedatives, antidepressants, or immunosuppressive drugs, traumatic brain injury or history of alcoholism.	The incidence of neurocognitive dysfunction was higher in the sevoflurane group compared to TIVA with propofol 33% (23/70) vs 14% (10/70) p< 0.05.
Liao 2023	104	Include: Patients between 65-80 years of age, ASA II-III, and BMI 18-24 kg/m3. Exclude: MMSE ≤ 23, history of cardiac surgery, cerebrovascular accident, alcoholism, liver and kidney dysfunction, coagulation disorders, visual and hearing impairment, psychiatric disorders, long-term depression medication.	The incidence rate for post operative cognitive dysfunction was lower in both the remimazolam and dexmedetomidine groups compared to controls 3 days post surgery (8.8% vs 8.6% vs 28.6%, p=0.029).
Zhu 2018	178	Include: Patients age 65-75 years; elective total knee arthroplasty under general anesthesia. Exclude: MMSE <23; peptic ulcer disease; cardiac-cerebral vascular disease; chronic obstructive pulmonary disease; neurological or psychiatric disorders; NSAIDS allergy; drug or alcohol abuse; hepatic and/or kidney dysfunction; BMI >35; inability to communicate.	In patients undergoing total knee arthroplasty, at 7 days follow-up, 10/81 (12.3%) patients receiving celecoxib (200 mg, twice daily, 7 days preop) experienced postoperative cognitive dysfunction compared with 28/82 (34.1%) patients receiving placebo, p<0.05. A difference in cognitive function was not detected at the 3-month followup (9% vs 10%).
Zhou 2019b	156	Include: Patients age 60-80 years; ASA status I-III; heart valve replacement surgery. Exclude: MMSE ≤23; acute or chronic infectious disease; use of infammatory drugs or immunosuppressants; stroke in past 6 months or other central nervou system disease; ICU ≥3 days; BMI >35; severe deafness or vision problems; communication difficulties; postoperative delirium.	In patients undergoing heart valve replacement surgery, patients receiving ulinastatin alone (n=39), dexmedetomidine alone (n=38), and ulinastatin plus dexmedetomidine (n=39 ), experienced less postoperative cognitive dysfunction after 7 days of followup compared with patients receiving saline (n=38), incidences of 18%, 16%, and 10% vs 32%, respectively, p<0.05.
Zhao 2020	432	Include: Age > 65; ASA I-III; scheduled to undergo non-cardiac major surgery. Exclude: MMSE scores of less than 17 in illiterate (uneducated) patients; MMSE score less than 20 for pts with elementary education (education of ≤6 years); MMSE scores less than 24 for patients with secondary education or higher (education > 6 years); inability to communicate during the preoperative period (owing to coma, profound dementia, or a language barrier); regular use of opioids; use of sedatives; use of antidepressants; use of anxiolytic drugs; hx of drug addiction; severe visual or hearing disorders; preoperative hx of schizophrenia; hx of epilepsy; hx of Parkinsons; Hx of myathenia gravis; brain injury; hx of neurosurgery; serious hepatic dysfunction (Child-Pugh class C); serious renal dysfunction (undergoing dialysis before surgery); a preoperative left ventricular ejection fraction less than 50%; sick sinus syndrome; severe sinus bradycardia (<50/min); second degree or greater atrioventricular block without a pacemaker; allergy to sufentanil; allergy to dexmedetomidine.	The overall incidence rates of POD and early POCD 7 days after surgery were lower in the dexmedetomidine 200 mcg and 400 mcg groups than in the dexmedetomidine 0 mcg and 100 mcg groups (p <0.05). Compared with dexmedetomidine 200 mcg, dexmedetomidine 400 mcg reduced early POCD in patients who underwent open surgery (P >0.05).
Zhang 2020a	240	Include: Age 65-90 yrs; ASA I-III. Exclude: Hx psychosis, long-term use of psychotropic medication; alcohol abuse; MMSE ≤23; illiterate; stroke; TIA; communication barriers.	Dexmedetomidine decreased POD incidence on first day after surgery compared to placebo (18.2 vs. 30.6%, P = 0.033).
Shen 2022	120	Include: Patients age 65-75; ASA status II-III; elective pulmonary lobectomy by video-assisted thoracoscopic surgery; anticipated duration of one-lung ventilation >60 min. Exclude: Severe impairment of respiratory function (FEV in 1 s of <50% predicted value); contraindications for flurbiprofen or intralipid; NSAIDs within 1 month surgery; MMSE <24; smoking, alcohol, or drug abuse; difficulty maintaining oxygenation with 1 lung ventilation intraoperatively; duration of one-lung ventilation <1 h; cerebral oximeter machine malfunction; conversion to open thoracotomy.	Among patients undergoing lobectomy by VATS, patients receiving flurbiprofen experienced less postoperative delirium compared with patients receiving placebo, p<0.05.
Tang 2021	100	Include: Patients age 60-85 years; ASA status I-II; laparoscopic radical resection of rectal cancer. Exclude: History of neurological or mental illness; drug allergy; alcoholism; use of anticoagulants, NSAIDS, or hormones 3 months prior; blood loss during operation >20% basal blood volume; intractable hypotension; anaphylactic shock.	In patients undergoing laparoscopic radical resection of rectal cancer, patients recevieving dexmedetomidine experienced higher cognitive scores through 48 h postsurgery compared with patients receiving placebo (p<0.05).
Gao 2022	95	Include: Patients (range: 60–80 years) and ASA I-III scheduled to undergo unilateral TKA. Exclude: Patients with POCD preoperatively, allergic to anesthetics, with history of narcotic abuse; infection around puncture sites, ipsilateral neuromuscular diseases, knee revision, and education level higher than junior high school.	MoCA-B scores in the dexmedetomidine group was higher at discharge when compared to placebo group (mean=25.37 +- 1.03 vs 24.60 +- 1.63, p=0.034).
Kowalczyk 2022	49	Include: All adult (age > 18 years) patients with ASA II-III qualified for elective coronary artery bypass grafts (CABG), (with CPB) with good ejection fraction - above 40%. Exclude: ASA ≥ IV, an ejection fraction < 40%, internal carotid or vertebral artery obstruction, severe myocardial infarction, chronic obstructive pulmonary disease, diabetes, and neurological and immunological diseases.	No differences in ACE-III scores were observed between dexmedetomidine and control groups at discharge; however, the values were increased when compared with initial values after 3 months (p = 0.000).
Kang 2023	102	Include: Patients aged 20–79 years, with ASAPS I–IV, and who were undergoing off-pump coronary artery bypass graft surgery (OPCAB). Exclude: Patients who were taking any sedatives, opioids, or sleep aids and those with a history of allergic reactions to any of the study drugs, with physical disabilities, illiterate, severe left ventricular dysfunction, major organ failure, needed continuous mechanical ventilation were excluded.	No difference was detected between TIVA and inhaled anesthetics groups with respect to any of the five dimensions of QoR-40K at 24 and 48 h after extubation.
Yoo 2023	128	Include: Patients age ≥65; elective orthopedic surgery lasting >2 h under general anesthesia; surgery requiring >3 days hospital stay. Exclude: Dementia; features of delirium; dexmedetomidine allergy; hearing or speaking difficulty; illiteracy; alcohol-related disorders; ASA physical status IV-V; ICU admission.	Among orthopedic patients, patients receiving dexmedetomidine experienced improved neurocognitive scores compared with patients receiving saline at postoperative day 3, p=0.001. A difference was not detected in delirium between the groups, p=0.089.
Shin 2020	186	Include: Patients over the age of 65 years that received daytime hip fracture surgery. Exclude: Patients with absolute contraindications to spinal anesthesia, known allergies to propofol, and altered mental status due to intracranial lesions were excluded.	Postoperative delirium rates were similar between regional, TIVA, and general groups (13.8% vs 13.8% vs 15.0%, p= 0.977). There was no in-hospital mortality in the TIVA group, 3.4% in the regional, and 1.7% in the general group.
Chen 2013	126	Include: Age 60-75 yrs. Exclude: Hx of mental illness; hypotension; bradycardia; CNS disease.	Severe cognitive impairment was not seen in either dexmedetomidine or control groups 24 hour after surgery. Moderate cognitive impairment was seen in 1.7% of patients in the dexmedetomidine group and 3.2% in the control (p=0.598). In patients older than 65 years, mean MMSE was 27.9+-1.3 in the dexmedetomidine group and 28.2+-0.9 in the control group one month after surgery.
Li 2015	100	Include: ASA I-III; age >60 yrs;. Exclude: Age > 75 yrs; stroke; stupor; dementia; hepatic or renal dysfunction; bradycardia; hypotension.	Moderate cognitive impairment (MMSE 9-21) 24 hour after surgery was seen in 2% patients in dexmedetomidine group and 4% in the control group. No patients developed severe cognitive impairment (MMSE <9) 24 hour surgery.
Ge 2016	50	Include: Diagnosis of carotid stenosis of ≥70% with or without symptoms; no prior hx of undergoing carotid surgery. Exclude: MMSE score <20; pt undergoing emergency surgery; pt refusal to general anesthetic; pt undergoing treatment with psychiatric drugs;.	MMSE scores were lower POD1 compared to 1 day prior to surgery for both groups (Control 25.80 vs 26.88; Dexmedetomidine 26.09 vs 27.18; p<=0.001. MMSE scores were higher in the dexmedetomidine group at 48 hours and 72 hours post-op compared to the control group (26.72 vs 25.87; p=0.025 and 27.10 vs 26.39; p=0.03, respectively).
Zhou 2019a	180	Include: Patients age >70 years; ASA status I-II; hip arthroplasty surgery. Exclude: History of gastric ulcer or duodenal ulcer; flurbiprofen allergy; severe hepatic or renal disorders; ischemic heart disease; general or local infections.	Among patients undergoing hip arthroplasty surgery, patients receiving 50 mg flurbiprofen preoperatively (n=60) experienced higher MMSE scores compared with patients receiving nothing (n=60, p<0.01) and patients receiving 50 mg flurbiprofen intraoperatively (n=60, p<0.05) at 3, 12, and 24 h postsurgery. Patients receiving flurbiprofen intraoperatively experienced higher MMSE scores compared to patients receiving nothing, p<0.05.
Shi 2020	106	Include: MMSE >24; ≥65; male; scheduled for thoracoscopic lobectomy with OLV; expected surgery time between 2 and 4 hr; general anesthesia. Exclude: Not allowed to smoke for at least 14 days prior; systolic bp ≥ 180 or <90 mmHg; diastolic bp ≥110 or <60 mmHg; serious heart, liver, kidney, lung, endocrine, nervous system, or severe infection; administration of sedatives or antidepressants; abnormal results of preop MMSE, MoCA, or CAM; contradictions regarding epidural anesthesia, epidural puncture failure; severe vision disorder; allergies to study drugs; sleep disorders; history of: perioperative severe cardiovascular disease, respiratory complications, inability to complete thoracoscopic lobectomy incompatibility with the neurologic scale assessments and other unpredictable adverse events.	At 6 h and on the first day postoperatively, the MoCA score in the DEX group was significantly higher than that in the saline group. The incidence of POCD and POD in the DEX group was 13.2 and 7.5%, respectively, while that in the saline group was 35.8 and 11.3%, respectively. There was a significant difference in the incidence of POCD between the two groups (P<0.01). In the DEX group, mean sleep quality was increased, whereas the mean VAS was decreased compared with the corresponding values in the saline group. In conclusion, elderly male patients who underwent thoracoscopic lobectomy under continuous infusion of DEX exhibited a reduced incidence of POCD during the first 7 postoperative days as compared with the placebo group.	only male ??
Apan 2016	52	Include: Patients aged between 18 to 85 years; scheduled for elective single-level percutaneous kyphoplasty. Exclude: Cognitive disorders preventing cooperation; ASA IV; pathology in cervical vertebra; history of allergy to the study drugs; contraindication to epidural anesthesia; pregnancy; severe systemic disease such as myelomatous disease; requiring surgical intervention at more than one level.	VAS scores were lower in the epidural group compared to the general group at the first 4 hours postoperative (P < 0.05). Postoperative analgesic requirement was higher for those in the general group (16%) compared to the epidural group (8%); P < 0.667.
Lee 2018b	132	Include: Patients age 18-75 years; ASA physical class I-II; elective TKA or THA under spinal anesthesia. Exclude: Allergy and/or contraindication to study drugs; clinically significant medical or psychiatric conditions; pregnancy; alcohol or drug abuse; use of opioids and/or study drugs for chronic pain; significant cardiac, hepatic, or renal disease.	In patients undergoing TKA or THA, patients receiving dexmedetomidine experienced less postoperative delirium compared with patients receiving placebo or pregabalin, 3/31 (9.7%) vs 11/31 (35.5%) or 14/33 (42.4%), p<0.05. A difference was not detected in postoperative delirium in patients receiving dexmedetomidine compared with patients receiving pregabalin plus dexmedetomidine.	Dexmedetomidine was more effective than pregablin for clinically relevant pain. Differences were not detected in pain or morphine use in patients receiving dexmedetomidine compared with patients receiving pregabalin plus dexmedetomidine.
Mandal 2011	60	Include: Adult patients with ASA I-II scheduled for hip and knee surgery. Exclude: MMSE score ≤ 23, patients with diseases of the central nervous system, patients with history of consumption of tranquilizers or antidepressants, patients with severe visual or auditory handicap, patients currently diagnosed with alcoholism or drug dependence, history of previous neuropsychological testing, and those having a geriatric depression score ≥21.	Postoperative MMSE score between the general and regional anesthesia groups were 25.16 vs 26.83 p= 0.0051.
Sultan 2010	152	Include: Age > 65 yrs; ASA I-III. Exclude: Dementia; alcohol abuse; blind/deaf; severe infection; severe anemia; stroke; fluid or electrolyte imbalance; acute cardiac event; acute pulmonary events; on anticonvulsants, antidepressants, antihistamines, antiparkinsonians, antipsychotics, benzodiazepines.	Postoperative delirium was seen in 9.4% of patients given melatonin compared to 32.6% in the control group. This study also compared patients given midazolam (44%) and clonidine (37.2%) preoperatively.
Mansouri 2019	150	Include: > 65 years of age; ASA I and II characteristics; No history of sensitivity to anesthetics; No history of moderate to severe mental disorders;. Exclude: Occurrence of severe hemodynamic disorder during the surgery leading to a change in anesthesia; extended surgery duration for >1 hour; Sensitivity to the anesthetics.	No statistically significant difference between the midazolam and dexmedetomidine groups in the MMSE score 24 hours after surgery (14% vs 12%, respectively) and 1 week postop (8% vs 12%, respectively; P > 0.05). However, there was a significant difference between these two groups and the control (8% for Midazolam, 12% for Dexmedetomidine vs 20% Control; P < 0.05).
Siripoonyothai 2021	75	Include: Age >65 yrs; Euroscore <4. Exclude: Dementia; cognitive impairment; psychiatric or mental disorder; positive on CAM; cerebrovascular disease; carotid disease;.	Postoperative delirium was detected in 31% of patients in the ketamine group and 56% in the Propofol group.
Chawdhary 2020	87	Include: Age ≥55 yrs; ASA I-III. Exclude: MMSE ≤23; any cognitive impairment; substance abuse; cardiac co-morbidity; stroke or seizures.	POCD on postoperative day 3 in the dexmedetomidine group was 32.5% compared to the propofol group 22.5% (p=0.31).
Oriby 2023	90	Include: Patients aged between 65-85 years; physical status ASA II to III; scheduled for cataract extraction. Exclude: Patients with a MMSE score less than 24; history of psychological disorders; receiving treatment with antipsychotic or antidepressant medications; history of uncontrolled medical conditions; known allergies to the medications used; inadequate vision in the non-operated eye.	In comparison with the control group, ketamine and dexmedetomidine groups exhibited a greater decline in number of patients who developed POCD (P<0.0001).
Zhang 2018b	120	Include: 65-75; underwent esophageal carcinoma; level of education that is capable of completing the neuropsychological teats; preop MMSE score ≥23; no central nervous system lesions; no tranquilizers or antidepressants; no history of cardiovascular or respiratory disease; no history of alcohol or cigarette abuse or drug dependence; no obvious or abnormal renal or hepatic functions; no serious hearing or vision impairments; no anaphylactic reactions to anesthetics. Exclude: <65, >75; see inclusion.	Compared with Group M+S, the MMSE and MoCA scores were significantly higher in group D+S at the 1st, 3rd, and 7th postoperative days.
Azeem 2018	70	Include: Age ≥60; ASA I-II; 70-100kg body weight; height 160-180 cm; undergoing elective cardiac surgery under general anesthesia. Exclude: Allergy to any drugs of the study; hx of drug abuse; hx of alcohol abuse; hx of uncontrolled diabetes; hx of hypertension; hx of chronic pain; daily intake of analgesics within 24 h before surgery; impaired kidney function; impaired liver function.	Differences were not detected in delirium following cardiac surgery between the Dexmedetomidine group and the midazolam with morphine group (3.33%, n=1 vs 6.67%, n=2, respectively; p=1).	Note that what is written in the abstract box is opposite to what the results section notes (i.e., abstract box notes significance where results notes no difference being detected).
Ren 2021	281	Include: Patients aged 65-79 years; undergoing proximal femoral fracture surgery. Exclude: Current diagnosis of CNS diseases (i.e., dementia and Parkinson’s disease) and currently undergoing antidepressant therapy.	No difference detected between both groups for the development of postoperative delirium (P>0.05). Cognitive impairment, as measured with the trail making test, showed an increase in both groups. However, overall there was no difference between the groups ( P >0.05).	Study notes there was no significant difference in the number of patients who developed postoperative delirium with a p value of >0.05, but don’t provide any data. Also, no valid scale was used to detect delirium. Study noted that it was an assessment for confusion in which there was dichotomous outcomes (absence or presence based on definition they provided).
Meuret 2018	40	Include: Patients > 75 years of age undergoing emergent hip fracture repair with ASA I-III. Exclude: Contraindication to spinal anesthesia and consent refusal.	Excellent patient satisfaction was reported by 53% (10/19) in the regional groups and 23% (5/21) in the general anesthesia group.
Mohamed 2022	80	Include: Patients ≥65 years old; ASA physical status I-III; operations done in the morning; upper limb (accompanied or not with lower limb) orthopedic trauma; receiving perioperative opioids to alleviate trauma pain; surgeries under general anesthesia;. Exclude: ASA physical status ≥IV; allergy to the study medications; patients with Abbreviated Mental Test score of <8; preoperative sedation score >3; alcohol abuse; lost vision or hearing; hematocrit <27%; cerebral insults (stroke, hemorrhage, infection); fluids and electrolyte abnormalities; acute cardiac problems (infarction, heart failure, dysrhythmias); acute respiratory events (asthma or chronic obstructive lung disease exacerbation, pulmonary embolism, hypoxemia, hypercarbia); drugs (anticonvulsants, antidepressants, antihistamines, anti-parkinsonism agents, antipsychotics, melatonin); history of chronic sedative-hypnotic use >3 times per week during a month before the surgery.	The incidence of delirium was lower postoperatively in those who received melatonin (25%) compared to those who did not receive melatonin (52.5%; p<0.001; OR=2.3; 95%CI=-0.44 to 1.23).
Ozer 2017	88	Include: Age >64; elective OPCAB surgery. Exclude: More than 50% carotid artery stenosis; severe chronic obstructive pulmonary disease (COPD) requiring daily therapy with steroids or bronchodilators; renal insufficiency (creatine concentration >150 mmol liter 1); severe liver disease (alanine aminotransferase or aspartate aminotransferase >75 IU liter-1); a history of allergy to propofol; a history of seizure or stroke; preoperative MMSE score of >23.	We believe that well-performed hemodynamic stability with either intravenous or general anesthesia may offer a well-controlled mental function in elderly patients undergoing off-pump CABG surgery.	No registration or dates provided.
Lee 2015	56	Include: Age >60; ASA I-III; undergoing orthopedic surgery (duration of anesthesia > 2 hours). Exclude: Dementia; Hx of CNS-related diseases; medication with tranquilizers; medication with antidepressants; inability to perform neurocognitive function tests; severe visual or auditory dysfunction; hx of alcohol abuse; hx of drug dependence; hx of a cerebrovascular accident within the previous 3 years.	There was a difference between the trail-making test scores in which the saline group had increased scores than the ketamine group at POD 1 (52.5 vs 13 points, respectively; p=0.047). There was no difference detected in the mini-mental status examination at either POD 1 (p=0.98) or POD 6 (p=0.33) and the digit substitution test at either POD 1 (p=0.39) or POD 6 (p=0.81). There was no difference in the MMSE (p=0.19), trail making test (p=0.08) and digit substitution test socres (p=0.28) between the two groups throughut the time.
Esmaeii 2022	150	Include: Age over 65 years. Exclude: History of depression, dementia, cerebral trauma, cerebral tumor, cerebral infarction, suffering from common endocrine disorders such as hyperthyroidism and hypothyroidism, chronic metabolic disorders, head and neck radiation therapy, heavy metal and carbon monoxide poisoning, chronic liver diseases, chronic kidney diseases, infectious diseases, fluid and electrolyte disturbance. In addition, alcohol use for more than a year, regular use of psychiatric drugs and hypnotics, the Abbreviated Mental Test (AMT) score < 8 and systolic blood pressure less than 100 mmHg were other exclusion criteria.	There was a higher incidence of delirium on postoperative day 3 in the melatonin group compared to controls (4.1% (2/49) vs 2.1% (1/48), p=0.355) when assessed using MMSE.
Xing 2021	110	Include: Age ≥ 60 yrs; ASA I-II. Exclude: Cognitive dysfunction; cardiopulmonary abnormalities; coagulation disorders; concomitant immune system and endocrine system disease.	The incidence of delirium 24 hours post operation was lower in the dexmedetomidine group compared to controls (3.6% vs 14.5%, p<0.05).
Neuman 2022	1,600	Include: Adults aged 50 years or older who were scheduled to undergo surgical repair of a clinically or radiographically diagnosed femoral neck, intertrochanteric, or subtrochanteric hip fracture. Exclude: Inability to walk approximately 10 feet or across a room without human assistance before fracture, need for a concurrent procedure not amenable to spinal anesthesia, periprosthetic fracture, and contraindications to spinal anesthesia (coagulopathy, anticoagulant medications, critical or severe aortic stenosis, infection at the injection site, and elevated intracranial pressure).	NA	There was no difference detected in patient satisfaction between general and regional anesthesia methods (85.3% vs. 86.9%, RR: 0.89 (0.68-1.17).
Gupta 2019	100	Include: Age ≥ 65 yrs; ASA I-II. Exclude: Dementia; severe infection; intracranial bleed; acute cardia event.	The incidence of delirium in Ramelteon group was lower in comparison with placebo group (4% vs 12%).
Yan 2021	100	Include: Age 60-85 yrs; ASA I-II. Exclude: Dementia, schizophrenia, or depression; use of psychotropic drugs; stroke; alcohol abuse; smoking.	The incidence of postoperative delirium in the dexmedetomidine group was lower than that in control group (10% vs 26%; p=0.037). The duration of delirium (1.3 6 0.6 days) was shorter in the dexmedetomidine group compared to controls (1.3 vs 3.0 days; p=0.000).
Bornemann-Cimenti 2016	60	Include: Patients age >18 years; ASA status I-III; weight between 40-120 kg; elective major open abdominal (colorectal and hepatic) surgery. Exclude: Acute or chronic pain treated with opioid therapy; severe kidney or liver dysfunction; alcohol or opioid addiction; present or past psychotic disorders.	In patients undergoing open abdominal surgery, patients receiving low-dose S-ketamine experienced higher delirium compared with patients receiving minimal-dose S-ketamine or placebo (p=0.007). Patients receiving low-dose and minimal-dose S-ketamine used less opioid compared with patients receiving placebo (p<0.05). Opioid use did not differ between the low-dose and minimal-dose S-ketamine groups (p=0.59).
Celik 2011	100	Include: Patients age 65-80; ASA physical status I-III; elective urological surgery lasting >1.5 hrs. Exclude: Routine use of sedative drugs; dialysis; emergency surgery; cardiac or repiratory failure.	In patients undergoing urologic surgery, patients receiving propofol had improved cognitive scores compared with patients receiving sevoflurane (p<0.05) at 30 minutes postoperation. Differences in cognition were not detected between the groups at 60 and 90 minutes postoperation.
Chu 2006	60	Include: Patients having primary total knee replacement. Exclude: Bilateral knee arthroplasty; revision knee arthroplasty; patient refusal; abnormal coagulation profile; systemic or local infection; allergy to study drugs; abnormal mental status; and physical disability to operate the PCA device.	Postoperative median pain scores were lower at 1 (P<0.0001), 6 (P=0.08), 12 (P=0.003), 24 (P=0.14), and 48 hours (P=0.007) in those given regional anesthesia. Complications were also lower in this group (P=0.503). Patients with regional aesthesia also showed a trend towards earlier hospital discharge (P=0.32).
Dianatkhah 2015	145	Include: Patients undergoing elective coronary artery bypass graft. Exclude: Use of psychiatric medications, central nervous system depressants, or hypnotic drugs; history of sleep disorder.	In patients undergoing coronary artery bypass graft, patients receiving melatonin experienced less delirium compared with patients receiving a benzodiazepine, 4/66 (6%) vs 9/71 (13%), p=0.187.
Ding 2015	40	Include: Age 45-80 yrs; ASA I-III; BMI 18-25 kg/m2;. Exclude: Cardiovascular disease; hepatic or renal dysfunction; COPD; endocrine and metabolic disease; CNS disease; acute upepr respiratory infection.	POCD was seen in 15% of patients in the dexmedetomidine group compared to 35% in the control group 1 day after surgery, and 5% vs 20% 5 days after surgery respectively.
Edipoglu 2019	80	Include: Patients age < 90 years, BMI < 40, and MMSE > 15. Exclude: Emergent trauma cases, patients with prior psychiatric or neurologic disorders, patients using steroids or NSAID, and patients with uncontrolled diabetes were excluded.	Patients who received regional anesthesia showed higher Mini-Mental State Examination (MMSE) scored compared with the general anesthesia at POD 7 (22.58 vs 20.27 p = 0.037).
Fazel 2017	60	Include: Patients >65 years; ASA class I, II, III. Exclude: Patients with MMSE <23; inadequate education to complete the neuropsychological test; severe visual and hearing impairment; a history of known psychological disorders; consumption of antipsychotic, anti-anxiety, and anti-depression medications; consumption of alcohol; a history of mental illness, addictions, sensitivity to anesthetic medications or unwillingness to cooperate.	Postoperative cognitive function in the sevoflurane group was significantly better than the propofol group in the 6-12 and 12-24 hours after surgery, but the assessment of the two groups in 24-48 hours after surgery showed similar conditions.	The registration says the age range is 55-65, but the article says 65+
Fazel 2022	80	Include: Patients ≥60 years of age; Abbreviated Mental Test (AMT) >8; undergoing hip, femur, or knee surgery. Exclude: Patient diagnosed with dementia; history of substance abuse; history of psychotropic medications; sensory disorders including blindness and hearing loss; cognitive disorders; severe underlying diseases including severe infection, severe anemia, seizures, stroke, and cerebral hemorrhage; heart disease including acute myocardial infarction, congestive heart failure, and arrhythmia, and currently taking medications including anticonvulsants, antihistamines, and psychotropic drugs.	On the first day after the surgery, the incidence of delirium was significantly lower in the melatonin group compared to the placebo group (22.2% vs 44.4%, p = 0.046). On the second and third days after the surgery, the levels of delirium in the melatonin group was also significantly lower than that in the placebo group. The generalized estimating equations model (GEE) showed a significant interaction between time and treatment groups.
Guo 2015	184	Include: Age 65-80 yrs; ASA I-III;. Exclude: Dementia or MMSE < 24; hx of CNS injury; hypotension; endocrine/metabolic disorders; inflammatory diseases; alcohol or drug dependence;.	Mean MMSE on postoperative day 3 was higher in the dexmedetomidine group compared to placebo (27.1 +- 2.0 vs 25.8 +- 2.7, p=0.001). Quality of recovery score was higher in the dexmedetomidine group compared to placebo in all three postoperative days compared to placebo (Day 1: 146.8 +- 24.2 vs 129.5 +- 22.5; Day 2: 155.3 +- 26.4 vs 136.9 +- 21.1; Day 3: 163.1 +- 25.3 vs 145.6 +- 28.6, p<0.001).
He 2018	90	Include: Age 75-90; ASA grade I-III; receiving selective operation; dx of thoracic or lumbar vertebral fractures. Exclude: Pts gaining ≤23 points in the MMSE; taking sedatives; taking antipsychotics; dx of mental illness; dx of central nervous system illness; unable to effectively communicate; dx of severe heart disease; dx of severe lung disease; dx of severe brain disease; dx of severe liver disease; dx of severe kidney disease; dx of severe disease to any other important organ; dx of severe vision impairment; dx of severe hearing impairment; allergies to the drugs used in the study; those not suitable for this study.	The incidence rate of POD in the dexmedetomidine group was apparently lower than those in both the midazolam and control groups (F=38.731; p<0.001); the incidence rate of POD at 1-2 days after operation in the midazolam group was higher than the control group (F=26.759; p=0.003 vs F=17.685; p=0.031); there was no significant difference in the incidence rate of POD at 3-5 days after operation between the midazolam and control group (F=4.716; p=0.528 vs F=3.681; p=0.815; vs F=6.257; p=0.482).
Mardani 2013	110	Include: Did not specify. Exclude: Illiteracy; prolonged intubation; >3hrs of CPB; >80 yrs; EF lower than 20% hemodynamic instability; hx of delirium; Emergency Operation; >24hr intubation postoperatively.	Delirium and hospital length of stay significantly decreased in the dexamethasone group compared to the placebo in the first postoperative day (4 [9.3%] vs. 13 [26%], p=0.03; 12.93 ± 1.03 vs 13.64 ± 1.75 days, p=0.02, respectively).
Nesek-Adam 2012	40	Include: Patients scheduled for peripheral vascular surgery; ASA physical status II-III. Exclude: Allergy to local anesthetics; severe spinal deformity; coagulopathy; failed or inadequate spinal anesthesia; alcohol or narcotic substance abuse; psychiatric history.	In patients undergoing peripheral vascular surgery, patients receiving spinal anesthesia report less pain in the first 4 hours postsurgery (p<0.05) and more overall satisfaction (p=0.028) compared with patients receiving general anesthesia.
Tu 2021	80	Include: Patients age ≥60 years; ASA status I-III. Exclude: Hepatic and renal dysfunction; coagulation dysfunction; infectious disease; blood system diseases; increased blood lactic acid or metabolic diseases; end-stage chronic diseases; active bleeding; severe pulmonary hypertension, heart failure and acute myocardial infarction; surgical contraindications; anesthesia contraindications; severe infections; functional abnormality of important organs; mental disorders or psychological illness.	In patients undergoing spinal surgery, patients induced with propofol and esketamine experienced higher neurocognitive scores (Montreal Cognitive Assessment) at 24 h postop compared with patients induced with propofol and sufentanil, mean (SD) of 21.8 (1.5) vs 17.4 (0.9), p<0.05.	This study administered esketamine (not ketamine).
Wang 2019	198	Include: ≥ 65 years of age; ASA status of I, II, or III; operative time of about 2-4 hours, with the ability to complete MMSE; preoperative MMSE score >15; no significant evidence of serious central nervous, cardiovascular, respiratory, etc; no contraindications to dexmedetomidine or midazolam; no history of antidepressant usage, benzodiazepine, alcohol, cigarette misuse, drug dependence;. Exclude: Preoperative bradyarrhythmia (HR < 50 bpm); central nervous system or mental disease; use of sedatives or analgesics recently; renal and/or hepatic dysfunction; chronic alcohol or drug abuse; life expectancy of less than three months; massive blood loss (>1500 mL); MMSE score <15 before surgery; refusal to participate in study;.	Incidence of POCD 5-7 days postoperative was higher in the midazolam group compared to dexmedetomidine 28% (28/100) vs 24.5% (24/98) p= 0.575.
Yu 2017	92	Include: Age >60 yrs; ASA I-II. Exclude: Senile dementia; coronary heart disease; hypertension; severe hepatic and renal dysfunction; other disease.	Postoperative delirium occurrence rate of 6.52% in dexmedetomidine group was significantly lower than that in the control group, and the difference between the two groups had statistical significance (p <0.05).
Zhao 2023	88	Include: Elderly patients aged ≥ 60 years with ASA scale I-III and were scheduled for lower extremity joint replacement surgery. Exclude: History of spinal trauma, MMSE < 21, on tranquillizers or antidepressants, severe hearing and vision impairment, contraindication to anesthesia, participated in other clinical trials, no consent given, withdrawl from surgery.	Compared to the control group, the MMSE scores in the DEX group were higher at 72 h after the surgery (mean 23.01 vs. 25.08, p< 0.05), and the incidence of POCD was lower in the DEX group (17.5% (7/40) vs. 38.1% (16/42), p=0.038).
Zhu 2021	187	Include: Age ≥ 65 yrs; ASA II-III; no anesthesia contraindications. Exclude: Mental illness; MoCA score ≤ 26; coronary heart disease; diabetes; hypertension; liver malfunction; renal failure; coagulation dysfunction; use of antidepressants or beta blockers.	Mean MMSE score 48 hours post operation in the dexmedetomidine group was higher (27.15±1.17) compared to control group (23.11±0.83, p<0.05).
Shyu 2005	159	Include: Patients ≥60 years; accidental single-side hip fracture; undergoing hip arthroplasty or internal fixation; able to perform full range of motion against gravity and against some or full resistance; prefracture Chinese Barthel Index >70. Exclude: Severe cognitive impairment; Chinese MMSE <10; terminally ill.	Patients receiving expanded preoperative evaluations and postoperative gerontological visits experienced improved activities of daily living at 1 and 3 months, and mental and physical function at 3 months compared to patients receiving standard care. No difference was detected in Geriatric Depression Scale scores at 1 month; however, at 3 months, the patients receiving expanded care experienced less depression.
Spence 2020	800	Include: All adult patients who underwent cardiac surgery at each site when the study was being conducted were included. Exclude: None.	In patients with restricted benzodiazepine administration, delirium was assessed in 17.5% (72/411) compared to 14.1% (55/389) in patients with liberal benzodiazepines.

Nonrandomized Trials

Study	Enrolled	Inclusion/Exclusion Criteria	Results	Note
Xu 2017	96	Include: Patients < 60 years old; indications of laparoscopic ovarian cystectomy; no primary mental disorder or dementia. Exclude: Primary diseases in heart, lung, liver, kidney or urinary system; allergy to dexmedetomidine; alcoholism; deaf or mute.	At 2 d after operation, we found that the scores of MoCA in the control were remarkably decreased in comparison with the scores in the dexmedetomidine group with a statistically significant difference (p < .05). The incidence rate of postoperative cognitive dysfunction (POCD) in the dexmedetomidine group was significantly lower than that in the control group, and the difference had statistical significance (p < .05).
Van Grootven 2016	86	Include: Patients age >65 yrs; non-pathological hip fracture. Exclude: Polytrauma; life expectency <6 months; not admitted on traumatology wards for postop care; missed premorbid assessment.	A univariate logistic regression of predictors of postoperative delirium reported an OR (95% CI) for benzodiazepine use: 1.44 (0.52-3.99). The purpose of this analysis was to investigate preoperative anxiety and postoperative delirium.
Zhang 2019b	140	Include: Patients age 60-85; ASA II-III; colorectal cancer diagnosis; no serious immune system disease; MMSE >27. Exclude: Central nervous system conditions and mental illness; taking sedatives or anti-depressants; high blood pressure; diabetes; coronary heart disease; cerbral infarction; liver or kidney dysfunction; other prognostic diseases; radiotherapy or chemotherapy before surgery.	In patients undergoing laparoscopic colorectal cancer surgery, patients receiving dexmedetomidine experienced less POCD at day 3 post-surgery compared with patients receiving placebo, p=0.0008.
Wang 2020c	110	Include: Diagnosed with gastric cancer and consented to surgical resections; no radiotherapy, chemotherapy, or comorbidity with other malignant tumors. Exclude: Liver and renal disfunction; communication and cognitive dysfunction.	The number of postoperative cognitive dysfunction of patients in the experimental group was lower than that of patients in the control group (P<0.05). The total number of adverse reactions in the control group was higher than that of patients in the experimental group (P<0.05). The MMSE scores of the two groups were decreased at 1 day after operation and were significantly lower in the control group than in the experimental group (P<0.05).	Text says a total of 100 patients, but there are 60 in the experimental group and 50 in the control?
Li 2020a	87	Include: Patients with lung cancer diagnosis willing to receive surgical resection. Exclude: Received prior radiotherapy or chemotherapy; other malignant tumors; liver or kidney dysfunction; communicative or cognitive impairment.	In patients undergoing lung resection, a difference was not detected in neurocognitive scores among patients receiving dexmedetomidine with conventional anesthesia intraoperatively (n=41) compared with patients receiving conventional anesthesia alone (n=46) (MMSE scores: 27.3 +/- 2.5 vs 27.2 +/- 3.1, p=0.8).
Zhou 2021	265	Include: Patients diagnosed with lung cancer; undergoing thoracoscopy surgery; and had ASA scores I or II. Exclude: Patients with MMSE score <24 before induction of anesthesia.	Results obtained in the study showed that intravenous Propofol improved cognitive function compared to patients receiving sevoflurane (p <0.05).
Artemiou 2015	500	Include: Cardiac surgery patients. Exclude: Emergency surgeries.	The incidence of postoperative hyperactive delirium was lower in the melatonin group compared to controls (8.4% vs 20.8%, p=0.001).
Bily 2015	500	Include: Patients undergoing cardiac surgeries. Exclude: Not reported.	The incidence of delirium was lower in the melatonin group compared to controls (8.4% vs 20.8%, p=0.001). The patients developed a hyperactive and mixed type of delirium.
Deschodt 2011	171	Include: Verbally competent individuals aged 65 and older consecutively admitted to the emergency department with a traumatic hip fracture. Exclude: Multiple trauma or metastatic cancer or other known comorbidity expected to reduce the individuals’ life expectancy to less than 6 months.	There was no difference in the mean length of stay between the expanded evaluation and standard care group (11.1 vs 12.4 days, p=0.24).
Xie 2018	140	Include: ASA I-III patients aged 62-85 years. Exclude: MMSE < 24, respiratory system disease, cardio cerebral vascular disease, severe impairment of liver and kidney function, history of sedative drug use, mental or neurologic diseases.	There were 3 cases (4.28%) of postoperative delirium in the dexmedetomidine group, which were less than 12 cases (17.14%) in the control group.
Zhang 2020b	165	Include: Patients age >60; spinal fracture diagnosis requiring surgery. Exclude: Allergy to study drugs; preoperative cognitive impairment or delirium; co-infection; other tumors; severe inflammation; severe immunodeficiency; congenital functional defects of liver, kidney, or heart.	In patients undergoing spinal surgery, patients receiving dexmedetomidine intraoperatively experienced higher MMSE scores 7 days postoperatively compared with patients receiving placebo, p<0.05.

Before-after & Time Series

Study	Enrolled	Inclusion/Exclusion Criteria	Results	Note
Ernst 2014	310	Include: Patients undergoing elective surgery; surgical palliative care consultations. Exclude: None described.	In a large Veterans Affairs hospital, overall 30-day mortality in patients receiving palliative care consultations decreased from 32% (51/160) to 21% (32/150) after the Frailty Screening Initiative was implemented, p<0.05. Six month and 1 year mortality rates also decreased following the screening initiative, both p<0.05. After initiation of the screening program, palliative care consultations were more often ordered prior to surgery (52% vs 26.%, p<0.05) and mortality rates were reduced when palliative care was ordered prior to surgery (adjusted OR [95% CI]: 0.5 [0.3-0.9], p=0.02).	All intervention patients were assessed for frailty with Risk Analysis Index, and approximately 10% were identified as frail. Those who were deemed frail received additional review by chief of surgery and were strongly encouraged to undergo preoperative palliative care consultation.
Hall 2017	9,153	Include: Patients presenting for major elective surgical procedures. Exclude: Cardiac surgery.	In a large Veterans Affairs hospital, overall 30-day mortality decreased from 1.6% (84/5275) to 0.7% (26/3878) after the Frailty Screening Initiative was implemented, adjusted OR (95% CI): 3.5 (1.8-7.0). Six month and 1 year mortality rates also decreased following the screening initiative, OR (95% CI): 2.9 (2.0-4.2) and 3.0 (2.1-4.2), respectively. The multivariate models controlled for age, frailty, and predicted mortality.	Improvement in mortality rates was greatest among frail patients (12.2% [24/197] to 3.8% [16/424]), though mortality rates also decreased among robust patients (1.2% [60/5078] to 0.3% [10/3454]). All intervention patients were assessed for frailty with Risk Analysis Index, and 6.8% were identified as frail. Those who were deemed frail received additional review by chief of surgery in regards to surgical decision making.
McDonald 2018	326	Include: Patients age 65-84 years; elective abdominal surgery; having one of the following conditions: prior diagnosis of cognitive disorder, weight loss >4.54 kg in past year, multimorbidity (2 or more chronic medical conditions), polypharmacy (>5 prescription medications), visual or hearing impairment, or surgeon perceives increased risk. Exclude: None listed.	In patients undergoing abdominal surgery, patients receiving care under the Perioperative Optimization of Senior Health (POSH) initiative had higher rates of documented delirium compared with patients prior to POSH, 52/183 (28%) vs 8/143 (6%), p<0.001. Patients in the POSH group experienced lower 30-day readmission rates, 14/180 (3%) vs 26/142 (18%), p=0.004, and were more likely to be discharged to home with self-care, 114/183 (62%) vs 73/143 (51%), p=0.04.	A proportion of patients in each study arm had qualified to be part of the ERAS program simultaneously (control - 47% and POSH - 57%). Regression modeling including age, comorbidities, surgical approach, and ERAS enrollment did not change comparison results of POSH vs pre-POSH in length of stay or readmission (regression results not reported).
Staiger 2023	83	Include: Patients with age >65 years and multiple comorbidities (≥3) with a clinical frailty scale score of >4 that underwent major colorectal surgery. Exclude: Not specified.	The length of stay was shorter in the enhanced preanesthsia group compared to usual care (median=4 vs , p=0.08). Hospital mortality was higher in the usual care group (3.7% vs 0%, p>0.9).
Bakker 2014	241	Include: Patients age ≥70; expected length of stay >48 h. Exclude: Contagious disease; terminally ill; treatment by medical specialist from department outside of study.	Differences were not detected in delirium, neurocognitive delay, or 30-day readmission in patients receiving care after CareWell in Hospital program implementation compared with patients receiving care before implementation of the program.
Indrakusuma 2015	443	Include: Patients age ≥70; colorectal carcinoma undergoing elective resection. Exclude: Acute operation; transanal endoscopic microsurgery.	In patients undergoing colorectal carcinoma resection, differences were not detected in 30-day mortality or postoperative delirium in patients screened with the Identification of Seniors at Risk questionnaire compared with patients receiving standard preoperative care (mortality: 14/221 [6%] vs 17/222 [8%], p=0.71; delirium: 22/221 [10%] vs 27/222 [12%], p=0.55).	Of the 221 patients screened preoperatively, 50 (23%) were referred for a Geriatric Daycare Examination by an in-house geriatrician. The assessment included a full medical history, full physical exam, lab tests, MMSE, Geriatric Depression Scale, and Mini Nutritional Assessment. Geriatricians may then advise interventions (eg, haloperidol prophylaxis, blood transfusions, supplements). A case-control analysis compared the 50 patients referred for the additional assessment with patients who did not need the additional assessment. Differences in mortality and delirium were not detected.
Souwer 2018	149	Include: Patients age ≥75; surgical resection for colorectal cancer. Exclude: None described.	In patients undergoing resection for colorectal cancer, patients receiving a multidisciplinary preoperative assessment experienced fewer cardiac complications (p=0.01) and shorter length of stay (p=0.047) compared with patients receiving usual care. Differences were not detected between the groups in 30-day mortality, 1-year mortality, readmission, or surgical complications.
Lester 2022	492	Include: Patients age ≥75; elective general, gynecologic-oncology, or orthopedic surgery. Exclude: None described.	In patients undergoing general, gynecologic-oncology, or orthopedic surgeries, differences were not detected in postoperative delirium, discharge location, 30-day readmission, or 30-day mortality in patients receiving expanded comprehensive interdisciplinary preoperative assessments compared with patients receiving usual care.	Results are from 1 center of 11 sites involved in the American College of Surgeons’ Geriatric Surgery Quality Program during the Alpha pilot.
Giannotti 2022	207	Include: Patients aged 70 or older admitted for elective GI cancer surgery or palliative treatments and required a hospital stay of at least 1 day. Exclude: Any clinical instability needing acute surgery, or if they were admitted for secondary surgeries.	In the geriatric co-management group, a reduction in complications (adjusted OR 0.29; 95% CI: 0.21-0.40); p< .001) and in 1-year readmissions (adjusted HR 0.53; 95% CI: 0.28-0.98; p< .044) was observed.
Smoor 2023	281	Include: Patients age ≥70; routine elective cardiac surgery; considered frail by surgeon or trained nurse. Exclude: Not provided.	Among frail patients undergoing cardiac surgery, a difference in health-related quality of life was not detected in patients receiving preoperative multidisciplinary team care compared to patients receiving standard care.	All patients from intervention and historical controls were considered frail.
Harari 2007	108	Include: Patients greater than 65 years undergoing elective orthopedic procedures. Exclude: Not specified.	NA	The incidence of delirium was lower in the CGA group compared to historical cohort (5.6% vs 18.5%, p=0.036) as well as medical complications (13.0% vs 37.0, p<0.0001).
Miyata 2017	82	Include: Age > 70 yrs; undergoing lung resection. Exclude: Not specified.	There were no incidence of postoperative delirium in patients taking ramelteon compared to 9% of controls.
Richter 2005	62	Include: Patients age >60; undergoing pelvic floor surgery. Exclude: None described.	In women undergoing pelvic floor surgery, differences in SF-36 physical and mental scores were not detected at 6-week followup in patients receiving enhanced preoperative assessment compared with patients receiving usual care (6-week physical: 39.0 +/- 8.3 vs 37.6 +/- 7.5; 6-week mental: 55.5 +/- 9.5 vs 53.7 +/- 8.6). Differences in SF-36 scores were not detected in 6-month followup between the groups (6-month physical: 45.3 +/- 10.9 vs 49.2 +/- 10.4; 6-month mental: 56.3 +/- 7.3 vs 53.9 +/- 10.8).
Ushida 2009	122	Include: Patients age >50 years; cervical decompression surgery. Exclude: Pre-existence of dementia or other psychological disorder.	Patients undergoing cervical decompression surgery following a change in protocol (reduction in methylprednisolone dose and encouragement of free body movement) experienced lower incidence of postoperative delirium compared with patients prior to protocol changes [3/41 (7%) vs 23/81 (28%), p=0.009]. During the first period found increased incidence of delirium with high-dose (≥1000mg cumulative, anything >500mg administered postoperative days 1 or 23). Noted that under the modified protocol (second period) methylprednisolone use was “reduced or avoided”, but did not report by how much. modified protocol, we reduced or avoided using methyl-.
Braude 2017	242	Include: Patients age ≥65; elective or emergency urological surgery. Exclude: None described.	In patients undergoing urologic surgery, patients receiving geriatric liaison services experienced fewer medical and surgical complications compared with patients receiving usual care, medical OR (95% CI): 0.26 (0.10-0.54) and surgical OR (95% CI): 0.16 (0.05-0.49). Differences were not detected in unplanned readmissions between the groups.	Study included patients undergoing non-surgical procedures (15 in each arm) and emergency admissions (32 in control group and 41 in intervention group).
Bjorkelund 2010	276	Include: Patients age ≥65 years; hip fracture; cognitively intact based on Short Portable Mental Status Questionnaire (≥8 correct answers). Exclude: History of cognitive impairment; multi-trauma.	In patients undergoing hip fracture surgery, patients receiving care within a multi-factorial intervention program experienced lower postoperative delirium rates compared with patients receiving care prior to the program implementation, 29/131 (22%) vs 45/132 (34%), p=0.031. Difference in 30-day mortality was not detected between the groups.
Vochteloo 2011	1,056	Include: Patients age ≥65; hip fracture due to low energy trauma, non-pathologic origin. Exclude: None mentioned.	In patients undergoing hip fracture surgery, a difference in delirium incidence was not detected in patients assessed by the Risk Model for Delirium compared with patients receiving usual care. Delirium incidence in intervention group was 27% compared with 3 pre-intervention years of 29%, 24%, and 28%.
Olsson 2014	266	Include: Patients undergoing total hip arthroplasty; ability to complete study instruments. Exclude: Cognitive impairment.	In patients undergoing total hip arthroplasty, differences were not detected in physical functioning and health-related quality of life in patients receiving comprehensive patient-centered care compared with patients receiving standard care. Length of stay was shorter in patients receiving the patient-centered care compared with patients receiving standard care, mean (SD) 5.3 (2.2) vs 7 (5.0), p<0.0005.
Yamasaki 2019	21	Include: Patients age ≥65 years; hepatectomy. Exclude: Laparoscopic hepatectomy; ICU admission following hepatectomy.	In patients undergoing hepatectomy, patients receiving omeprazole experienced less postoperative delirium compared with patients receiving famotidine, 3/11 ((27%) vs 9/10 (90%), p<0.01.
Hokuto 2020	309	Include: Patients who underwent liver resection at Nara Medical University (Nara, Japan) from January 2014 to August 2018 were retrieved (from registration). Exclude: Patients who underwent biliary reconstruction; patients who could not take water or medicine on POD 1 were excluded (from registration).	The incidence of postoperative delirium was significantly lower in the ramelteon group compared to controls (5.8% vs. 15.1%, p = 0.035).
Adogwa 2017	125	Include: Patients age ≥65; elective lumbar decompression and fusion surgery; back pain and/or radiculopathy; radiographic evidence of thoracolumbar deformity; prior failed nonsurgical treatment; underwent multilevel lumbar decompression and fusion. Exclude: Severe coexisting pathology that would confound outcomes; nonambulatory.	In patients undergoing lumbar decompression and fusion surgery, differences were not detected in complications or postoperative delirium in patients receiving additional care from a geriatrician compared with patients receiving standard care. More patients in the intervention group were discharged to home compared with the standard care group, 54% vs 24%, p=0.01.
Romano 2021	181	Include: Patients undergoing elective hip or knee arthroplasty replacement. Exclude: None described.	In patients undergoing total hip or knee arthroplasty, patients receiving care under a fast-track recovery system experienced higher rates of home discharge compared with patients prior to the fast-track system, adjusted OR (95% CI): 41.9 (12.1-144.9) and shorter length of stay, p<0.01.	Complications also reported, but all of the following combined: pain, range of motion, infections, surgical wound, hypotonus, tendonitis, hematoma, joint effusion, periprosthetic joint infection, and thromboembolioc events. No differences in complications detected at 1 month; intervention group experiencing lower rate of complications at 6-, 12-, 24-, and 36-months followup compared with control group.

Observational

Study	Enrolled	Inclusion/Exclusion Criteria	Results	Note
Aoki 2023	222	Include: ≥ 65 years; underwent elective cardiovascular surgery; admitted to the ICU postoperatively. Exclude: No written informed consent; undergoing second elective surgery during the same hospitalization; come and seizures after surgery; alcohol withdrawal patients; patients with an MMSE of ≤23 preoperative; surgery was cancelled after inclusion; could not be admitted to the ICU postoperatively; refused to continue after surgery; had to be reoperated within 5 days postoperatively.	30.3% of the remimazolam group patients and 26.6% of the control group patients developed delirium within 5 days (risk diference, 3.8%; 95% confdence interval−11.5% to 19.1%; p=0.63). Remimazolam was not signifcantly associated with postoperative delirium when compared with other anesthetic agents.
Deiner 2015	105	Include: Patients older than 68 years. Exclude: Intracranial surgery, cardiac surgery, pre-existing neuropsychiatric disease, history of cerebrovascular accident with residual deficits, baseline Mini Mental State Examination (MMSE) score <20, unable to consent for study participation, or unable to speak English.	Postoperative cognitive dysfunction was detected in 26.4% (9/34) in the sevoflurane group compared to 27.9% (12/43) in the TIVA group.
Juliebo 2009	187	Include: Age greater than 65 years, spoke Norwegian, no severe aphasia, head injury, or terminal illness undergoing hip fracture surgery. Exclude: Patients with delirium.	There was a higher incidence of delirium in patients given ketamine intraoperatively compared to no ketamine (44% (30/68) vs 32% (38/119), p=0.10).
Jones 2021	466	Include: Patients age ≥75 years; inpatient operations (elective, urgent, emergent) across all subspecialties. Exclude: Outpatient surgery; <24 h admission.	Differences in complication occurrence and 30-day mortality were not detected in patients receiving care under the Geriatric Surgery Verification Program (GSV) compared with matched controls from the Veterans Affairs Surgical Quality Improvement Program. Length of stay was reduced in patients in the GSV program (median 4 days, range 1-31) compared with the controls (median 5 days, range 1-86).
Pipanmekaporn 2021	429	Include: Patients aged 60 years or older; undergoing noncardiac surgery. Exclude: Patients with severe visual and auditory impairment; preoperative delirium; death upon the first 24 hours after surgery.	No difference in the incidence of delirium was detected in those not receiving preoperative benzodiazepine (6.9%) compared to those receiving preoperative benzodiazepine (4.3%; p=0.390).
Deiner 2014	76	Include: Age 68 years or older scheduled for major noncardiac surgery. Exclude: Intracranial surgery, cardiac surgery, preexisting neuropsychiatric disease, history of cerebrovascular accident (CVA, stroke) with residual deficits, baseline Mini-Mental State Exam (MMSE) score <20 or unable to consent to study participation, and/or unable to speak English.	The incidence of postoperative delirium seen in the PACU was 3.2% (1/36) in the volatile group and 7.5% (3/36) in the TIVA group with p=0.622.
Konishi 2018	300	Include: Age 60 or older, elective first-time total hip replacement for osteoarthritis; living within reasonable proximity to the hospital to allow investigators to travel to participant’s homes for cognitive testing. Exclude: Pre-existing neurological or clinically evident neurovascular disease; MMSE score less than 26; Clinical Dementia Rating Scale more than 1; anticipated difficulty with neuropsychological assessment; poor English; ability to perform neuropsychological testing; blindness; deafness; critical medical problems such as ASA physical status IV or higher;.	There was no difference between the incidence of POCD (MMSE score) at postoperative day 7 with sevoflurane compared to propofol (20.2% vs 15.0%, p=0.26).
Barreto Chang 2022	98	Include: Age ≥ 65 yrs. Exclude: Inability to read, understand, or speak English.	Incidence of postoperative delirium occurred in 32% of patients in the ketamine group and 18% of patients in the control group.
Duprey 2022	566	Include: Age 70 years or older English speaking (English need not be first language) Scheduled for eligible high-risk surgery: Orthopedic (total hip or knee replacement; lumbar, cervical, or sacral laminectomy) Vascular (lower extremity arterial bypass surgery; open abdominal aortic aneurysm repair; lower extremity amputation) General (open or laparoscopic colectomy) Planned general or regional anesthesia Scheduled at least 6 days before surgery to allow adequate time for the baseline assessment Planned admission to the hospital for at least 2 days Living within 40 miles from study hospitals Exclusion criteria Active delirium. Exclude: Active delirium Dementia (dementia diagnosis or score <69 or education-adjusted equivalent on baseline 3MS cognitive test) Hospitalization within 3 months before enrollment to minimize risk of recent delirium Terminal condition with life expectancy < 6 months (eg, metastatic cancer, pancreatic cancer, or receiving palliative care) Inability to perform cognitive tests because of legal blindness or severe deafness.	134 (24%) developed delirium during hospitalization. Preoperative medication associations with delirium: benzodiazepines (RR, 1.44; 95% CI, 0.85–2.44) beta-blocker (RR, 1.38; 95% CI, 0.94–2.05) NSAID (RR, 1.12; 95% CI, 0.77–1.62) opioid (RR, 1.22; 95% CI, 0.82–1.82) statin (RR, 1.34; 95% CI, 0.92–1.95) Postoperative medication associations with delirium (before delirium): benzodiazepine (aHR, 3.23; 95% CI, 2.10–4.99) antipsychotic (aHR, 1.48; 95% CI, 0.74–2.94) opioid (aHR, 0.82; 95% CI, 0.62–1.11) Antipsychotic use (either presurgery or postsurgery) was associated with a 0.34 point (standard error, 0.16) decrease in general cognitive performance at 1 month through its effect on delirium (P = .03), despite no total effect being observed.
Wang 2021	1,266	Include: Age 65-85 years, English fluency. Exclude: Brain or cardiac surgery, no written consent.	From a secondary analysis of three studies (1 prospective cohort and 2 RCTs ), results were inconclusive concerning midazolam premedication and delirium incidence — 23% on the first postoperative day in older patients undergoing major noncardiac surgery compared with 25% for those not receiving midazolam (OR = 0.91; 95% CI, 0.65-1.29; p=0.67).
Sun 2023a	676	Include: Patients ≥ 60 years and ASA I-III. Exclude: History of cognitive impairment, delirium, dementia, on anti-psychotic drugs, stroke of Alzheimer’s disease, autoimmune disease, or MI.	The incidence of delirium was 17.8% in patients with dexmedetomidine and 16.9% in patients without dexmedetomidine (OR; 1.06, 95% CI (0.70-1.59), p=0.78).
Leigheb 2022	83	Include: Patients age ≥65; undergoing femur fracture osteosynthesis or total hip arthroplasty. Exclude: Delirium at admission.	In patients undergoing hip fracture or THA, patients receiving preoperative midazolam experienced more postoperative delirium (12/47, 36%) compared with patients not receiving midazolam (5/36, 14%), p=0.000.
Ke 2022a	98	Include: Patients aged 65 years and above presenting for noncardiac surgery that was expected to last longer than 2 hours. Exclude: Neurosurgical procedures and those undergoing surgery performed under local anesthesia.	There was a higher incidence of delirium in patients receiving midazolam intraoperatively compared to no midazolam (14% (¼) vs 10% (10/91), p=0.790).
Ke 2022b	98	Include: Patients aged 65 years and above presenting for noncardiac surgery that was expected to last longer than 2 hours. Exclude: Neurosurgical procedures and those undergoing surgery performed under local anesthesia.	A higher incidence of delirium was reported in patients receiving ketamine intraoperatively compared to no ketamine (16.7% (⅙) vs 10.9% (10/92), p=0.671).
Park 2022	237,872	Include: Patients aged 65 years or older undergoing major surgical procedures. Exclude: Discharged within 2 days, in-hospital mortality, patients diagnosed with psychosis, received antipsychotics, critical care admission, mechanical ventilation or a feeding tube.	There was a higher incidence in delirium between gabapentin and no gabapentin use (3.4% vs 2.6%, RR 1.28 CI: 1.23-1.34).
Huang 2023b	46	Include: Patients aged>65 years with severe systemic disease (ASA IV) undergoing low-energy hip fracture surgery. Exclude: We excluded patients with pathologic fractures, polytrauma, prior surgery at the affected hip, bilateral hip fracture, or missing information about the anesthesia type.	There was no difference in the 30-day mortality (5.0 vs. 3.8%, p=0.85) and 1-year mortality (15 vs. 12%, p=0.73) between TIVA and inhaled anesthetic groups.
Kadoi 2007	109	Include: Patients undergoing elective CABG. Exclude: Patients with cerebrovascular disease as determined by a history of ischemic cerebrovascular disease with symptomatic neurological disorders and confirmed by preoperative brain computed tomography and magnetic resonance imaging (MRI) were excluded.	Cognitive dysfunction rates measured 6 months after surgery was similar in both TIVA and inhaled anesthetics group (23% vs 22%, p=0.94).
Yoshimura 2022	738,600	Include: Patients older than 65 years. Exclude: Those who underwent surgical procedures under regional anesthesia alone underwent multiple surgical procedures per admission or had preoperative delirium.	The incidence of postoperative delirium occurred in 8.6% (50827/589060) of patients in the inhalation group and 7.0% (10425/149540) in the TIVA group (OR 0.79; CI 0.78-0.81, p< 0.001).
Kaneko 2023	98	Include: Adult patients; undergoing transcatheter aortic valve implantation under general anesthesia. Exclude: Anesthesia maintenance with inhalation anesthetics; admission to ICU under sedation; tracheal intubation due to intraoperative complications.	Among patients undergoing transfemoral transcatheter aortic valve implantation, patients receiving remimazolam experienced less postoperative delirium compared with patients receiving propofol, OR (95% CI): 0.17 (0.04-0.80).
Kishimoto 2018	21,899	Include: Patients who underwent TKA with general anesthesia. Exclude: A history of prior THA within 30 days of surgery; a history of prior contralateral TKA within 30 days of surgery; age <40 years; surgical site infection treatment during the hospitalization with antibiotics other than anti-methicillin- resistant Staphylococcus aureus (MRSA) drugs and aminoglycosides; missing data on hospital characteristics; missing data on duration of anesthesia; missing data on type of intraoperative analgesia; use of ketamine for anesthesia induction; and diagnosis of gout or pseudogout.	Propensity score analysis suggested no significant association between the choice of anesthetic maintenance agent and the occurrence of suspected early-onset periprosthetic joint infection in patients undergoing total knee arthroplasty (1.3% propofol vs 1.7% sevoflurane [relative risk = 0.76; 95% CI = 0.55 to 1.04; P = 0.10]). The mean (SD) length of stay in the propofol group was significantly longer than in the sevoflurane group (32.5 (18.4) days vs 31.4 (14.4) days, respectively [mean difference = 1.1; 95% CI = 0.5 to 1.8; P < 0.001]).
Fuchita 2019a	84	Include: Patients aged 18 years or older undergoing esophagectomy. Exclude: A history of severe dementia, alcohol abuse, schizophrenia, Parkinson disease, or neuroleptic malignant syndrome. Patients were also excluded if they were pregnant or nursing, on cholinesterase inhibitors or levodopa, or if they had a corrected QT interval exceeding 500 milliseconds.	Postoperative delirium occurred in 32% (26/81) of patients given benzodiazepine intraoperatively and in 33% (⅓) without benzodiazepine (p=1.00).	This is a secondary analysis for the PEPOD placebo-controlled single-center clinical trial comparing scheduled low-dose haloperidol versus placebo for delirium prevention in postoperative noncardiac thoracic surgery patients.
Fuchita 2019b	84	Include: Patients aged 18 years or older undergoing esophagectomy. Exclude: A history of severe dementia, alcohol abuse, schizophrenia, Parkinson disease, or neuroleptic malignant syndrome. Patients were also excluded if they were pregnant or nursing, on cholinesterase inhibitors or levodopa, or if they had a corrected QT interval exceeding 500 milliseconds.	No incidence of postoperative delirium was reported in patients given dexamethasone intraoperatively compared to 35% (27/57) without dexamethasone (p=0.091).	This is a secondary analysis for the PEPOD placebo-controlled single-center clinical trial comparing scheduled low-dose haloperidol versus placebo for delirium prevention in postoperative noncardiac thoracic surgery patients. This study was not included in our analysis due to younger age in the overall study cohort.
Fuchita 2019c	84	Include: Patients aged 18 years or older undergoing esophagectomy. Exclude: A history of severe dementia, alcohol abuse, schizophrenia, Parkinson disease, or neuroleptic malignant syndrome. Patients were also excluded if they were pregnant or nursing, on cholinesterase inhibitors or levodopa, or if they had a corrected QT interval exceeding 500 milliseconds.	Postoperative delirium occurred in 30% (3/10) of patients given ketamine intraoperatively and in 32% (24/74) without ketamine (p=1.00).	This is a secondary analysis for the PEPOD placebo-controlled single-center clinical trial comparing scheduled low-dose haloperidol versus placebo for delirium prevention in postoperative noncardiac thoracic surgery patients.
Paille 2021	228	Include: Age 75 years or greater having more than one cardiac surgery. Exclude: AVR for aortic insufficiency without stenosis and salvage surgery.	There was a lower incidence of delirium in the CGA group compared to no CGA (11.4% vs. 15.8%, p=0.44). Lower rates of pulmonary complications, acute renal failure, infectious complications, and congestive heart failure was observed in the CGA group.
Weinstein 2018a	41,766	Include: Patients age >18 who had THA or TKA. Exclude: Patients with missing record data.	The incidence of delirium was higher in those not receiving intraoperative benzodiazepine (6.1%) compared to those receiving intraoperative benzodiazepine (1.9%; p<0.001).	Delirium was based on ICD-9 codes.
Weinstein 2018b	41,766	Include: Patients age >18 who had THA or TKA. Exclude: Patients with missing record data.	The incidence of delirium was lower in those not receiving postoperative benzodiazepine (1.9%) compared to those receiving postoperative benzodiazepine (4.8%; p<0.001).	Delirium was based on ICD-9 codes.
Weinstein 2018c	41,766	Include: Patients age >18 who had THA or TKA. Exclude: Patients with missing record data.	The incidence of delirium did not differ in those not receiving intraoperative ketamine (2.2%) compared to those receiving intraoperative ketamine (2.1%; p=0.676).	Delirium was based on ICD-9 codes.
Weinstein 2018d	41,766	Include: Patients age >18 who had THA or TKA. Exclude: Patients with missing record data.	The incidence of delirium was higher in those receiving postoperative ketamine (13.1%) compared to those not receiving postoperative ketamine (2.1%; p<0.001).	Delirium was based on ICD-9 codes.
Hasselager 2022	22,179	Include: Patients undergoing surgery for colorectal cancer under general anesthesia from 2004-2018; having available data on anesthesia type. Exclude: Patients with local endoscopic polyp resections to include only procedures with a substantial level of surgical stress.	In this propensity score-matched registry study, use of inhalation anesthesia was associated with fewer postoperative complications after colorectal cancer surgery than use of TIVA (n=1933; 22.2% vs n=2199; 25.2%, respectively; OR=0.84; 95% CI 0.79-0.91).
Ishibashi-Kanno 2020a	69	Include: Patients undergoing major head and neck surgery. Exclude: Not reported.	There was no difference in the incidence of delirium between the ramelteon and no ramelteon groups (31.4% vs 35.3, p=0.73).
Ishibashi-Kanno 2020b	69	Include: Patients undergoing major head and neck surgery. Exclude: Not reported.	There was a higher incidence of delirium between in the benzodiazepine group compared to no benzodiazepine (36.1% vs 30.3, p=0.61).
Ishibashi-Kanno 2020c	69	Include: Patients undergoing major head and neck surgery. Exclude: Not reported.	There was a lower incidence of delirium with H2blocker compared to no H2blockers (21.9% vs 43.2, p=0.06).
Mueller 2020a	651	Include: Patients age ≥65; gastrointestinal, genitourinary, gynecological, or thoracic cancer surgery. Exclude: MMSE <24; ≥2 concurrent carcinomas; emergency surgery; life expectancy <2 months.	In patients undergoing cancer surgery, a difference was not detected in postoperative delirium incidence in patients receiving preoperative benzodiazepines (51/529, 10%) compared with patients not receiving the drug (11/82, 13%), p=0.32.	This is a retrospective study of an RCT with goal of empowering patients to be active in postop rehabilitation.
Mueller 2020b	651	Include: Patients age ≥65; gastrointestinal, genitourinary, gynecological, or thoracic cancer surgery. Exclude: MMSE <24; ≥2 concurrent carcinomas; emergency surgery; life expectancy <2 months.	In patients undergoing cancer surgery, a difference was not detected in postoperative delirium in patients receiving prophylactic haloperidol (delirium in 14/92, 15%) compared with patients not receiving the drug (delirium in 51/558, 9%), p=0.09.	This is a retrospective study of an RCT with goal of empowering patients to be active in postop rehabilitation.
Zarour 2023	1,973	Include: Patients 70 years and older having elective non-cardiac surgery under general anesthesia with postoperative delirium assessment. Exclude: Ambulatory surgery, craniotomy, planned ICU admission, surgery < 30 minutes, missing pre-operative cognitive screening, dementia.	No difference was detected in postoperative delirium between the patients with and without midazolam (14.7% (115/783) vs 15.7% (187/1191).p=0.54).
Tarazona-Santabalbina 2019	310	Include: Patients age ≥70 years; elective colorectal cancer surgery. For intervention group: ASA III-IV, previous diagnosis of dementia, history of heart failure, ischemic cardiomyopathy, chronic obstructive pulmonary disease, peripheral artery disease, diabetes, or Barthel score <60. Exclude: Secondary surgeries; life expectancy <6 months.	In patients undergoing colorectal cancer surgery, patients receiving expanded care from a multidisciplinary team experienced less postoperative delirium compared with patients receiving usual care, 23/203 (11%) vs 31/107 (29%), p<0.001. Differences were not detected in readmissions, or in-hospital and 1-year mortality between the groups.
Shimizu 2010	265	Include: All adult patients undergoing gastrointestinal surgery. Exclude: Patients aged <20; ASA physical status IV-VI; laparoscopic surgeries.	After matching, standardized infection ratio after sevoflurane anesthesia was 1.89, which was significantly lower than after propofol anesthesia.
Jakobsen 2007	10,535	Include: All procedures performed since January 1999. Exclude: Reoperations during the same hospitalization; heart transplants where cardioprotection was not relevant; procedures primarily involving surgery on the ascending or descending aorta.	The 30-day mortality was lower after sevoflurane (2.84%) versus propofol (3.30%) although not significantly. No difference was found in the incidence of postoperative myocardial infarction.
Cheng 2016	505	Include: Patients undergoing CABG, valve surgery, or CABG/valve combined. Exclude: Emergency surgery; off-pump or robotic surgery; deep hypothermic circulatory arrest; surgery involving thoracic aorta.	In patients undergoing cardiac surgery, patients receiving dexmedetomidine experienced less postoperative delirium compared with patients administered saline, adjusted OR (95% CI): 0.35 (0.212-0.578).
Goins 2018	116	Include: Patients undergoing transcatheter aortic valve replacement; general anesthesia. Exclude: Not specified.	The odds of delirium were lower in patients with TIVA compared to volatile anesthesia after adjusting. No significant difference in hospital or intensive care unit length of stay was seen after adjusting for procedural characteristics.
Yoshimura 2023	16,185	Include: Patients aged ≥65 years who underwent cardiovascular surgery. Exclude: Patients who underwent transcatheter surgery, multiple surgeries per admission, and those with preoperative delirium.	No differences were observed in the incidences of postoperative delirium (OR 0.95; 95% CI 0.87-1.03; p = 0.21) and hospital mortality (OR 0.92; 95% CI 0.76-1.11; p = 0.39) between patients given midazolam or no midazolam.
Poeran 2020a	527,254	Include: ICD–9 diagnosis codes for a femoral neck, intertrochanteric, or subtrochanteric fracture together with ICD-9 procedure codes for hemi-arthroplasty, total hip arthroplasty or an appropriate fixation procedure. Exclude: Age < 18 years, multi-trauma or missing information on admission status, unknown sex, unknown discharge status, procedures classified as outpatient, procedures performed at hospitals with fewer than 30 procedures during the study period.	NA
Poeran 2020b	527,254	Include: ICD–9 diagnosis codes for a femoral neck, intertrochanteric, or subtrochanteric fracture together with ICD-9 procedure codes for hemi-arthroplasty, total hip arthroplasty or an appropriate fixation procedure. Exclude: Age < 18 years, multi-trauma or missing information on admission status, unknown sex, unknown discharge status, procedures classified as outpatient, procedures performed at hospitals with fewer than 30 procedures during the study period.	NA
Poeran 2020c	527,254	Include: ICD–9 diagnosis codes for a femoral neck, intertrochanteric, or subtrochanteric fracture together with ICD-9 procedure codes for hemi-arthroplasty, total hip arthroplasty or an appropriate fixation procedure. Exclude: Age < 18 years, multi-trauma or missing information on admission status, unknown sex, unknown discharge status, procedures classified as outpatient, procedures performed at hospitals with fewer than 30 procedures during the study period.	NA
Poeran 2020d	527,254	Include: ICD–9 diagnosis codes for a femoral neck, intertrochanteric, or subtrochanteric fracture together with ICD-9 procedure codes for hemi-arthroplasty, total hip arthroplasty or an appropriate fixation procedure. Exclude: Age < 18 years, multi-trauma or missing information on admission status, unknown sex, unknown discharge status, procedures classified as outpatient, procedures performed at hospitals with fewer than 30 procedures during the study period.	NA
Poeran 2020e	527,254	Include: ICD–9 diagnosis codes for a femoral neck, intertrochanteric, or subtrochanteric fracture together with ICD-9 procedure codes for hemi-arthroplasty, total hip arthroplasty or an appropriate fixation procedure. Exclude: Age < 18 years, multi-trauma or missing information on admission status, unknown sex, unknown discharge status, procedures classified as outpatient, procedures performed at hospitals with fewer than 30 procedures during the study period.	NA
Poeran 2020f	527,254	Include: ICD–9 diagnosis codes for a femoral neck, intertrochanteric, or subtrochanteric fracture together with ICD-9 procedure codes for hemi-arthroplasty, total hip arthroplasty or an appropriate fixation procedure. Exclude: Age < 18 years, multi-trauma or missing information on admission status, unknown sex, unknown discharge status, procedures classified as outpatient, procedures performed at hospitals with fewer than 30 procedures during the study period.	NA
Poeran 2020g	527,254	Include: ICD–9 diagnosis codes for a femoral neck, intertrochanteric, or subtrochanteric fracture together with ICD-9 procedure codes for hemi-arthroplasty, total hip arthroplasty or an appropriate fixation procedure. Exclude: Age < 18 years, multi-trauma or missing information on admission status, unknown sex, unknown discharge status, procedures classified as outpatient, procedures performed at hospitals with fewer than 30 procedures during the study period.	NA
Poeran 2020h	527,254	Include: ICD–9 diagnosis codes for a femoral neck, intertrochanteric, or subtrochanteric fracture together with ICD-9 procedure codes for hemi-arthroplasty, total hip arthroplasty or an appropriate fixation procedure. Exclude: Age < 18 years, multi-trauma or missing information on admission status, unknown sex, unknown discharge status, procedures classified as outpatient, procedures performed at hospitals with fewer than 30 procedures during the study period.	NA
Oh 2019	3,084	Include: Patients ages >19; underwent curative lung resection surgery for primary nonsmall cell lunch cancer (NSCLC). Exclude: Patients with end stage rental disease; defined as requiring renal replacement therapy or having pre-operative estimated glomerular filtration rate less than 15 ml min -1 1.73 m-2; those with incomplete or missing medical records; those who required repeat lung cancer after surgery during the study period.	No significant difference was found in the incidence of postoperative AKI after lung resection surgery between patients who received TIVA and sevoflurane.
Slor 2011a	526	Include: Patients age ≥70; acute or elective hip surgery. Exclude: Delirium at admission; inability to participate in interviews (profound dementia, language barrier, intubation, respiratory isolation, aphasia, coma, terminal illness); surgery delay >72 h after admission; cholinesterase inhibitor use; parkinsonism; levodopa treatment; epilepsy; prolonged QTc interval >460 ms (males) or >470 ms (females) on ECG.	In this secondary analysis of RCT data, 36/430 (8%) patients receiving benzodiazepines and 24/96 (25%) patients receiving no benzodiazepines developed postoperative delirium (OR, 95% CI: 0.73, 0.35-1.51).
Slor 2011b	526	Include: Patients age ≥70; acute or elective hip surgery. Exclude: Delirium at admission; inability to participate in interviews (profound dementia, language barrier, intubation, respiratory isolation, aphasia, coma, terminal illness); surgery delay >72 h after admission; cholinesterase inhibitor use; parkinsonism; levodopa treatment; epilepsy; prolonged QTc interval >460 ms (males) or >470 ms (females) on ECG.	In this secondary analysis of RCT data, 8/46 (17%) patients receiving any anticholinergic and 52/480 (11%) patients receiving no anticholinergics developed postoperative delirium, p=0.18.
Memtsoudis 2019a	564,226	Include: Patients undergoing primary hip or knee arthroplasty. Exclude: Patients undergoing both hip and knee arthroplasty; non-elective procedures; outpatient procedures; surgery at hospital performing <30 procedures/yr.	In patients undergoing total hip arthroplasty, the OR (95% CI) of delirium after benzodiazepine use on day of surgery and/or postop day 1: short-acting vs none, 0.79 (0.72-0.87); long-acting vs none, 2.10 (1.82-2.42); both short- and long-acting vs none, 1.74 (1.56-1.94).	Delirium identified by ICD-9 codes and/or billing for antipsychotics (haloperidol, olanzapine, and quetiapine).
Memtsoudis 2019b	564,226	Include: Patients undergoing primary hip arthroplasty. Exclude: Patients undergoing both hip and knee arthroplasty; non-elective procedures; outpatient procedures; surgery at hospital performing <30 procedures/yr.	In patients undergoing total hip arthroplasty, the OR (95% CI) of delirium after ketamine on day of surgery and/or postop day 1: 1.06 (0.92-1.24).	Delirium identified by ICD-9 codes and/or billing for antipsychotics (haloperidol, olanzapine, and quetiapine).
Memtsoudis 2019c	564,226	Include: Patients undergoing primary total hip arthroplasty. Exclude: Patients undergoing both hip and knee arthroplasty; non-elective procedures; outpatient procedures; surgery at hospital performing <30 procedures/yr.	In patients undergoing total hip arthroplasty, the OR (95% CI) of delirium after corticosteroids on day of surgery and/or postop day 1: 0.95 (0.81-1.11).	Delirium identified by ICD-9 codes and/or billing for antipsychotics (haloperidol, olanzapine, and quetiapine).
Memtsoudis 2019d	564,226	Include: Patients undergoing primary total hip arthroplasty. Exclude: Patients undergoing both hip and knee arthroplasty; non-elective procedures; outpatient procedures; surgery at hospital performing <30 procedures/yr.	In patients undergoing total hip arthroplasty, the OR (95% CI) of delirium after NSAIDs on day of surgery and/or postop day 1: 0.85 (0.79-0.91).	Delirium identified by ICD-9 codes and/or billing for antipsychotics (haloperidol, olanzapine, and quetiapine).
Memtsoudis 2019e	564,226	Include: Patients undergoing primary total hip arthroplasty. Exclude: Patients undergoing both hip and knee arthroplasty; non-elective procedures; outpatient procedures; surgery at hospital performing <30 procedures/yr.	In patients undergoing total hip arthroplasty, the OR (95% CI) of delirium after cyclooxygenase-2 inhibitors on day of surgery and/or postop day 1: 0.82 (0.77-0.89).	Delirium identified by ICD-9 codes and/or billing for antipsychotics (haloperidol, olanzapine, and quetiapine).
Memtsoudis 2019f	1,130,569	Include: Patients undergoing primary total knee arthroplasty. Exclude: Patients undergoing total knee arthroplasty; non-elective procedures; outpatient procedures; surgery at hospital performing <30 procedures/yr.	In patients undergoing total knee arthroplasty, the OR (95% CI) of delirium after benzodiazepines on day of surgery and/or postop day 1: short-acting vs none, 0.82 (0.77-0.88); long-acting vs none, 2.24 (2.01-2.49); short- and long-acting vs none, 1.78 (1.64-1.92).	Delirium identified by ICD-9 codes and/or billing for antipsychotics (haloperidol, olanzapine, and quetiapine).
Memtsoudis 2019g	1,130,569	Include: Patients undergoing primary total knee arthroplasty. Exclude: Patients undergoing both hip and knee arthroplasty; non-elective procedures; outpatient procedures; surgery at hospital performing <30 procedures/yr.	In patients undergoing total knee arthroplasty, the OR (95% CI) of delirium after ketamine on day of surgery and/or postop day 1: 0.99 (0.89-1.11).	Delirium identified by ICD-9 codes and/or billing for antipsychotics (haloperidol, olanzapine, and quetiapine).
Memtsoudis 2019h	1,130,569	Include: Patients undergoing primary total knee arthroplasty. Exclude: Patients undergoing both hip and knee arthroplasty; non-elective procedures; outpatient procedures; surgery at hospital performing <30 procedures/yr.	In patients undergoing total knee arthroplasty, the OR (95% CI) of delirium after corticosteroids on day of surgery and/or postop day 1: 0.96 (0.86-1.06).	Delirium identified by ICD-9 codes and/or billing for antipsychotics (haloperidol, olanzapine, and quetiapine).
Memtsoudis 2019i	1,130,569	Include: Patients undergoing primary total knee arthroplasty. Exclude: Patients undergoing both hip and knee arthroplasty; non-elective procedures; outpatient procedures; surgery at hospital performing <30 procedures/yr.	In patients undergoing total knee arthroplasty, the OR (95% CI) of delirium after NSAIDs on day of surgery and/or postop day 1: 0.84 (0.80-0.88).	Delirium identified by ICD-9 codes and/or billing for antipsychotics (haloperidol, olanzapine, and quetiapine).
Memtsoudis 2019j	1,130,569	Include: Patients undergoing primary total knee arthroplasty. Exclude: Patients undergoing both hip and knee arthroplasty; non-elective procedures; outpatient procedures; surgery at hospital performing <30 procedures/yr.	In patients undergoing total knee arthroplasty, the OR (95% CI) of delirium after COX-2 inhibitors on day of surgery and/or postop day 1: 0.83 (0.79-0.88).	Delirium identified by ICD-9 codes and/or billing for antipsychotics (haloperidol, olanzapine, and quetiapine).
Memtsoudis 2019k	564,226	Include: Patients undergoing primary hip or knee arthroplasty. Exclude: Patients undergoing both hip and knee arthroplasty; non-elective procedures; outpatient procedures; surgery at hospital performing <30 procedures/yr.	In patients undergoing total hip arthroplasty, the OR (95% CI) of delirium after gabapentinoid use on day of surgery and/or postop day 1: 1.26 (1.16-1.36).	Delirium identified by ICD-9 codes and/or billing for antipsychotics (haloperidol, olanzapine, and quetiapine).
Memtsoudis 2019l	1,130,569	Include: Patients undergoing primary knee arthroplasty. Exclude: Patients undergoing both hip and knee arthroplasty; non-elective procedures; outpatient procedures; surgery at hospital performing <30 procedures/yr.	In patients undergoing total knee arthroplasty, the OR (95% CI) of delirium after gabapentinoid use on day of surgery and/or postop day 1: 1.29 (1.22-1.36).	Delirium identified by ICD-9 codes and/or billing for antipsychotics (haloperidol, olanzapine, and quetiapine).
Chuich 2019	278	Include: Patients age ≥18; cardiovascular ICU who received either dexmedetomidine or propofol infusion intraoperatively or postoperatively in addition to general anesthesia medications; underwent valve repair or replacement, CABG, or CABG plus valve repair or replacement. Exclude: Pregnant; lactating; incarcerated; received both dexmedetomidine and propofol concurrently intraoperatively or postoperatively.	In patients undergoing CABG or valve repair or replacement, a difference in postoperative delirium was not detected between patients receiving dexmedetomidine or propofol, p=0.27.
Chang 2024	281	Include: Elderly patients ≥ 65 years of age who underwent spine surgery under total intravenous anesthesia with propofol or inhalational anesthesia with sevoflurane. Exclude: Patients with preoperative delirium, a history of dementia, psychiatric disease, alcoholism, hepatic or renal dysfunction, requirement for postoperative mechanical ventilation, a history of surgery within the recent six months, or maintenance of anesthesia with combined anesthetics (propofol and sevoflurane) were excluded.	POD occurred more frequently in the sevoflurane group than in the propofol group (15.7% vs. 5.0%, respectively; p=.003). The multivariable logistic regression analysis showed that sevoflurane-based anesthesia was associated with an increased risk of POD compared with propofol-based anesthesia (OR, 4.120; 95% CI, 1.549-10.954; p= .005).
Burfeind 2022	1,627	Include: Patients age ≥65; undergoing inpatient elective non-cardiac surgery; documentation of preoperative Mini-Cog and Edmonton Frail Scale scores (study period began after implementation of cognitive and frailty screening program). Exclude: Cardiac surgery.	In a retrospective study of elective surgeries, the authors suggested that potentially inappropriate medication (PIM) was associated with longer lengths of stay among cognitively impaired and frail patients. Almost all PIMs were dexamethasone, midazolam, or promethazine; few patients received diphenhydramine, scopolamine, metoclopramide, prochlorperazine, meperidine, and famotidine). Differences in discharge location were not detected.	The study results are limited. The length of stay result was not adjusted for the type of procedure, and justification for the selection of confounders was not provided. No distinction between the type/class of PIM was examined. The investigators were unable to examine delirium owing to a lack of ascertainment. The authors included 3-way interactions in the multivariable model (PIM, cognitive status, and frailty) yet reported results for frailty and cognition independently. Important outcomes including surgical success, complications, and mortality were not examined.
Park 2020	1,254	Include: Adult patients who underwent non-cardiac surgery under general anesthesia with troponin measurement before surgery and repeated measurement within 7 postoperative days. Exclude: Not specified.	In-hospital mortality was higher in the TIVA group than the volatile group (22% vs 13.5%) adjusted HR 1.78, 95% CI: 1.08–2.92 p=0.02. 30 day mortality was higher in the TIVA group than the volatile group (17% vs 9.1%) adjusted HR 2.60, 95% CI: 1.14–5.93 p=0.02.
Cho 2021	3,045	Include: End-stage renal disease (ESRD) patients on hemodialysis in the institutional database; age 20-80; underwent general anesthesia. Exclude: Patients who had undergone cardiac surgery, cancer surgery, organ transplantation, or emergency surgery; patients who received both forms of anesthesia within the study period, either during the same surgical procedure or for additional procedures.	After the multivariate analysis, factors associated with a significantly lower MACE risk included preoperative chloride concentration, baseline SBP, and propofol TIVA.
Liu 2023a	195	Include: Patients age ≥65; elective urinary calculi surgery. Exclude: Delirium; coma; gout; severe renal insufficiency or renal failure; hospitalization <1 day postop; drugs affecting uric acid level.	Among patients undergoing urologic procedures, a difference was not detected in postoperative delirium incidence in patients receiving intraoperative midazolam (14/145, 9.7%) compared with patients not receiving the drug (5/50, 10%).	This was a risk factor study for delirium.
Liu 2023b	195	Include: Patients age ≥65; elective urinary calculi surgery. Exclude: Delirium; coma; gout; severe renal insufficiency or renal failure; hospitalization <1 day postop; drugs affecting uric acid level.	Among patients undergoing urologic procedures, patients receiving intraoperative dexmedetomidine experienced less postoperative delirium (12/160, 7.5%) compared with patients not receiving the drug (7/35, 20%), p=0.024.	This was a risk factor study for delirium.
Koch 2023	1,058	Include: Patients age ≥60; surgery lasting ≥60 minutes; general anesthesia. Exclude: History of neurologic deficits; current MMSE <24.	Among patients undergoing various surgical procedures, a difference was not detected in postoperative delirium incidence in patients receiving preoperative midazolam (14/57, 25%) compared with patients not receiving the drug (184/1001, 18%).	This is a retrospective secondary analysis of an RCT evaluating surgical depth of anesthesia and cognitive outcomes.
Park 2021	714	Include: Patients ≥ 65 years undergoing orthopedic surgery under spinal anesthesia. Exclude: Having either general or epidural anesthesia, dementia, requiring ICU admission, on anti-emetics/steroids/anti-histamines, incomplete medical record.	The rate of postoperative delirium was lower in the dexmedetomidine group compared to propofol (2.0% vs 5.6%, p=0.011, OR; 0.19, CI: 0.07-0.56).
Mangusan 2015a	656	Include: Not specified. Exclude: Not specified.	There was a higher incidence of postoperative delirium occurred in patients who took oral benzodiazepines compared to no benzodiazepines (31% vs 21%) after cardiac surgery.
Mangusan 2015b	656	Include: Not specified. Exclude: Not specified.	There was a lower incidence of postoperative delirium occurred patients who took Ketorolac compared to no Ketorolac (19.8% vs 28.2%).
Mangusan 2015c	656	Include: Not specified. Exclude: Not specified.	There was a higher incidence of postoperative delirium occurred patients who took zolpidem compared to no zolpidem (41.7% vs 23.5%).
Koo 2016	1,934	Include: Adult inpatients who underwent elective colorectal surgery under general anesthesia; ICD-9-CM procedure codes: 45.7, 45.8, 46.1, 46.52, 48.5, 48.63, and 17.3. Exclude: Not specified.	Study results suggest that intravenous anesthesia may have beneficial effects for reducing surgical site infection in colorectal surgery compared to volatile anesthesia (2 [0.5%] vs 10 [2.6%], OR = 5.0 [95% CI = 1.1-22.8], respectively).	Notes it was registered at ClinicaTrials but no record number provided.
Xu 2022	60	Include: Patients age over 60 years with complete medical records undergoing total hip arthroplasty. Exclude: Patients with preoperative hemodynamic abnormality; other cardiovascular diseases, cerebrovascular diseases, chronic diseases or autoimmune defects; organ dysfunction or abnormality;.	No difference was detected in MMSE scores between dexmedetomidine group 36 hours postop and control group (mean=18.47 vs 18.13, p=0.821).
Yin 2020	120	Include: >24 on preoperative MMSE scale; did not use any drugs affecting delirium before surgery; classified as ASA I-II; was free of cardiovascular and cerebrovascular or respiratory diseases; signed informed consent. Exclude: Allergic to drugs; has existing mental and cognitive dysfunction; has history of recovery from abnormal anesthesia; has been using long-term sedative medication; has severe hepatic and renal dysfunction.	Dexmedetomidine reduces postoperative delirium; Dexmedetomidine decreases Ramsay score for sedation; Dexmedetomidine increases the Price-Henry pain score.
Nandi 2014	463	Include: Patients undergoing primary or revision total hip or knee arthroplasty under general anesthesia. Exclude: Spinal anesthesia; antipsychotic drug use.	A case-control study of patients undergoing THA or TKA, reported an increased risk of postoperative delirium among patients administered benzodiazepines during hospital stay compared with patients not receiving benzodiazepines [adjusted OR (95% CI): 9.68 (4.30-21.79)].	OR adjusted for sex, preop alcohol use, and preop depression.
Choi 2019	58	Include: Patients with postoperative acute lung injury after lung resection surgery for lung cancer. Exclude: Respiratory distress due to respiratory/systemic infection.	In a case-control study of patients developing acute lung injury after lung resection surgery, patients administered corticosteroids early (within 72 h) experienced less postoperative delirium compared with patients receiving corticosteroids later (after 72 h), 10/42 (24%) vs 10/16 (63%), p=0.012. Differences were not detected between the groups in complications or length of stay.	Patients receiving early treatment with corticosteroids had greater improvements in lung injury score (primary outcome) compared with patients receiving later treatment; however, no difference was detected in mechanical ventilation weaning within 7 days (primary outcome).

References

1.

Adogwa O, Elsamadicy AA, Vuong VD, Moreno J, Cheng J, Karikari IO, Bagley CA: Geriatric comanagement reduces perioperative complications and shortens duration of hospital stay after lumbar spine surgery: A prospective single-institution experience. J Neurosurg Spine 2017; 27:670–5

2.

Aizawa K, Kanai T, Saikawa Y, Takabayashi T, Kawano Y, Miyazawa N, Yamamoto T: A novel approach to the prevention of postoperative delirium in the elderly after gastrointestinal surgery. Surg Today 2022; 32:310–4

3.

Aksoy MS, Bozkurt M, Sayıt E, Ünlü S, Karadağ H: Does spinal anesthesia increase the pain and anxiety after total knee arthroplasty? A randomized prospective study. Eklem Hastalik Cerrahisi 2013; 24:30–2

4.

Alas A, Martin L, Devakumar H, Frank L, Vaish S, Chandrasekaran N, Davila GW, Hurtado E: Anesthetics’ role in postoperative urinary retention after pelvic organ prolapse surgery with concomitant midurethral slings: A randomized clinical trial. Int Urogynecol J 2020; 31:205–13

5.

Aoki Y, Kurita T, Nakajima M, Imai R, Suzuki Y, Makino H, Kinoshita H, Doi M, Nakajima Y: Association between remimazolam and postoperative delirium in older adults undergoing elective cardiovascular surgery: A prospective cohort study. J Anesth 2023; 37:13–22

6.

Apan A, Cuvas Apan O, Kose EA: Segmental epidural anesthesia for percutaneous kyphoplasty:comparison with general anesthesia. Turk J Med Sci 2016; 46:1801–7

7.

Artemiou P, Bily B, Bilecova-Rabajdova M, Sabol F, Torok P, Kolarcik P, Kolesar A: Melatonin treatment in the prevention of postoperative delirium in cardiac surgery patients. Kardiochir Torakochirurgia Pol 2015; 12:126–33

8.

Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, Veselis RA, Grocott HP, Emmert DA, Rogers EM, Downey RJ, Yulico H, Noh GJ, Lee YH, Waszynski CM, Arya VK, Pagel PS, Hudetz JA, Muench MR, Fritz BA, Waberski W, Inouye SK, Mashour GA: Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: An international, multicentre, double-blind, randomised clinical trial. Lancet 2017; 390:267–75

9.

Azeem TMA, Yosif NE, Alansary AM, Esmat IM, Mohamed AK: Dexmedetomidine vs morphine and midazolam in the prevention and treatment of delirium after adult cardiac surgery; a randomized, double-blinded clinical trial. Saudi Journal of Anaesthesia 2018; 12:190–7

10.

Bakker FC, Persoon A, Bredie SJH, Haren-Willems J van, Leferink VJ, Noyez L, Schoon Y, Olde Rikkert MGM: The CareWell in hospital program to improve the quality of care for frail elderly inpatients: Results of a before-after study with focus on surgical patients. Am J Surg 2014; 208:735–46

11.

Bao L, Tian X, Zhang J, Chen L, Gao K: Effects of ulinastatin combined with dexmedetomidine on postoperative cognitive function and central nerve specific protein level in elderly colorectal cancer patients after laparoscopic. Oncologie 2020; 22:167–78

12.

Barreto Chang OL, Kreuzer M, Morgen DF, Possin KL, Garcia PS: Ketamine associated intraoperative electroencephalographic signatures of elderly patients with and without preoperative cognitive impairment. Anesth Analg 2022 doi:10.1213/ANE.0000000000005875

13.

Bielka K, Kuchyn I, Tokar I, Artemenko V, Kashchii U: Psoas compartment block efficacy and safety for perioperative analgesia in the elderly with proximal femur fractures: A randomized controlled study. BMC Anesthesiol 2022; 21:252

14.

Bily B, Sabol F, Török P, Artemiou P, Bilecova-Rabajdova M, Kolarcik P: Influence of prophylactic melatonin administration on the incidence of early postoperative delirium in cardiac surgery patients. Anesteziologie a Intenzivni Medicina 2015; 26:319–27

15.

Bjorkelund KB, Hommel A, Thorngren KG, Gustafson L, Larsson S, Lundberg D: Reducing delirium in elderly patients with hip fracture: A multi-factorial intervention study. Acta Anaesthesiol Scand 2010; 54:678–88

16.

Bornemann-Cimenti H, Wejbora M, Michaeli K, Edler A, Sandner-Kiesling A: The effects of minimal-dose versus low-dose s-ketamine on opioid consumption, hyperalgesia, and postoperative delirium: A triple-blinded, randomized, active- and placebo-controlled clinical trial. Minerva Anestesiol 2016; 82:1069–76

17.

Braude P, Goodman A, Elias T, Babic-Illman G, Challacombe B, Harari D, Dhesi JK: Evaluation and establishment of a ward-based geriatric liaison service for older urological surgical patients: Proactive care of older people undergoing surgery (POPS)-urology. BJU Int 2017; 120:123–9

18.

Brown CH, Edwards C, Lin C, Jones EL, Yanek LR, Esmaili M, Gorashi Y, Skelton R, Kaganov D, Curto R, Lessing NL, Cha S, Colantuoni E, Neufeld K, Sieber F, Dean CL, Hogue CW: Spinal anesthesia with targeted sedation based on bispectral index values compared with general anesthesia with masked bispectral index values to reduce delirium: The SHARP randomized controlled trial. Anesthesiology 2022; 135:992–1003

19.

Brøndum TL, Leerhøy B, Jensen KK: Effect of preoperative, high-dose glucocorticoid on early cognitive function after abdominal wall reconstruction –a randomized controlled trial. International Journal of Surgery Open 2022; 48 C7 - 100567

20.

Burfeind KG, Zarnegarnia Y, Tekkali P, O’Glasser AY, Quinn JF, Schenning KJ: Potentially inappropriate medication administration is associated with adverse postoperative outcomes in older surgical patients: A retrospective cohort study. Anesth Analg 2022; 135:1048–56

21.

Cai Y, Hu H, Liu P, Feng G, Dong W, Yu B, Zhu Y, Song J, Zhao M: Association between the apolipoprotein E4 and postoperative cognitive dysfunction in elderly patients undergoing intravenous anesthesia and inhalation anesthesia. Anesthesiology 2012; 116:84–93

22.

Cao S-J, Zhang Y, Zhang Y-X, Zhao W, Pan L-H, Sun X-D, Jia Z, Ouyang W, Ye Q-S, Zhang F-X, Guo Y-Q, Ai Y-Q, Zhao B-J, Yu J-B, Liu Z-H, Yin N, Li X-Y, Ma J-H, Li H-J, Wang M-R, Sessler DI, Ma D, Wang D-X: Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: A multicentre randomised trial. Br J Anaesth 2023 doi:10.1016/j.bja.2023.04.024

23.

Carron M, Freo U, Innocente F, Veronese S, Pilati P, Jevtovic-Todorovic V, Ori C: Recovery profiles of general anesthesia and spinal anesthesia for chemotherapeutic perfusion with circulatory block (stop-flow perfusion). Anesth Analg 2007; 105:1500–3, table of contents

24.

Casati A, Aldegheri G, Vinciguerra E, Marsan A, Fraschini G, Torri G: Randomized comparison between sevoflurane anaesthesia and unilateral spinal anaesthesia in elderly patients undergoing orthopaedic surgery. Eur J Anaesthesiol 2003; 20:640–6

25.

Celik JB, Topal A, Erol A, Guven S, Kara I: A comparison of recovery characteristics of sevoflurane and propofol remifentanil anesthesia in geriatric patients. Turkish J Geriatr 2011; 14:208–13

26.

Chang J-E, Min S-W, Kim H, Won D, Lee J-M, Kim TK, Kim C, Hwang J-Y: Association between anesthetics and postoperative delirium in elderly patients undergoing spine surgery: Propofol versus sevoflurane. Global Spine Journal 2022:21925682221110828 doi:10.1177/21925682221110828

27.

Chawdhary AA, Kulkarni A, Nozari A: Substitution of propofol for dexmedetomidine in the anaesthetic regimen does not ameliorate the post-operative cognitive decline in elderly patients. Indian J Anaesth 2020; 64:880–6

28.

Chen H, Li F: Effect of dexmedetomidine with different anesthetic dosage on neurocognitive function in elderly patients after operation based on neural network model. World Neurosurg 2020; 138:688–95

29.

Chen J, Yan J, Han X: Dexmedetomidine may benefit cognitive function after laparoscopic cholecystectomy in elderly patients. Exp Ther Med 2013; 5:489–94

30.

Cheng H, Li Z, Young N, Boyd D, Atkins Z, Ji F, Liu H: The effect of dexmedetomidine on outcomes of cardiac surgery in elderly patients. J Cardiothorac Vasc Anesth 2016; 30:1502–8

31.

Chitnis S, Mullane D, Brohan J, Noronha A, Paje H, Grey R, Bhalla RK, Sidhu J, Klein R: Dexmedetomidine use in intensive care unit sedation and postoperative recovery in elderly patients post-cardiac surgery (DIRECT). J Cardiothorac Vasc Anesth 2022; 36:880–92

32.

Cho HB, Kim MG, Park SY, Song S, Jang YS, Park S, Lee HK, Yoo JH, Chung JW, Kim SH: The influence of propofol-based total intravenous anesthesia on postoperative outcomes in end-stage renal disease patients: A retrospective observation study. PLoS One 2022; 16:e0254014

33.

Choi H, Shin B, Yoo H, Suh GY, Cho JH, Kim HK, Choi YS, Kim J, Zo JI, Shim YM, Jeon K: Early corticosteroid treatment for postoperative acute lung injury after lung cancer surgery. Ther Adv Respir Dis 2022; 13:1753466619840256

34.

Chu CPW, Yap JCCM, Chen PP, Hung HH: Postoperative outcome in chinese patients having primary total knee arthroplasty under general anaesthesia/intravenous patient-controlled analgesia compared to spinal-epidural anaesthesia/analgesia. Hong Kong Medical Journal 2006; 12:442–7

35.

Chuich T, Cropsey CL, Shi Y, Johnson D, Shotwell MS, Henson CP: Perioperative sedation in mechanically ventilated cardiac surgery patients with dexmedetomidine-based versus propofol-based regimens. Ann Pharmacother 2019; 53:5–12

36.

Dai Z, Lin M, Li Y, Gao W, Wang P, Lin J, Wan Z, Jiang Y: Sevoflurane-remifentanil versus propofol-remifentanil anesthesia during noncardiac surgery for patients with coronary artery disease - a prospective study between 2016 and 2017 at a single center. Med Sci Monit 2022; 27:e929835

37.

Jonghe A e, Munster BC van, Goslings JC, Kloen P, Rees C van, Wolvius R, Velde R van, Levi M, Haan RJ e, Rooij SE e, Amsterdam Delirium Study G: Effect of melatonin on incidence of delirium among patients with hip fracture: A multicentre, double-blind randomized controlled trial. CMAJ 2014; 186:E547–56

38.

Deiner S, Lin HM, Bodansky D, Silverstein J, Sano M: Do stress markers and anesthetic technique predict delirium in the elderly? Dement Geriatr Cogn Disord 2014; 38:366–74

39.

Deiner S, Luo X, Lin HM, Sessler DI, Saager L, Sieber FE, Lee HB, Sano M, Jankowski C, Bergese SD, Candiotti K, Flaherty JH, Arora H, Shander A, Rock P: Intraoperative infusion of dexmedetomidine for prevention of postoperative delirium and cognitive dysfunction in elderly patients undergoing major elective noncardiac surgery: A randomized clinical trial. JAMA Surg 2017; 152:e171505

40.

Deiner S, Luo X, Silverstein JH, Sano M: Can intraoperative processed EEG predict postoperative cognitive dysfunction in the elderly? Clin Ther 2015; 37:2700–5

41.

Deng CM, Meng ZT, Yang J, Zhang CJ, Lu M, Wang YX, Mu DL: Effect of intraoperative remimazolam on postoperative sleep quality in elderly patients after total joint arthroplasty: A randomized control trial. Journal of Anesthesia 2023; 37:511–21

42.

Deschodt M, Braes T Fau - Broos P, Broos P Fau - Sermon A, Sermon A Fau - Boonen S, Boonen S Fau - Flamaing J, Flamaing J Fau - Milisen K, Milisen K: Effect of an inpatient geriatric consultation team on functional outcome, mortality, institutionalization, and readmission rate in older adults with hip fracture: A controlled trial 2011

43.

Dianatkhah M, Ghaeli P, Hajhossein Talasaz A, Karimi A, Salehiomran A, Bina P, Jalali A, Ghaffary S, Shahmansouri N, Vejdani S: Evaluating the potential effect of melatonin on the post-cardiac surgery sleep disorder. J Tehran Heart Cent 2015; 10:122–8

44.

Dieleman JM, Nierich AP, Rosseel PM, Maaten JM van der, Hofland J, Diephuis JC, Schepp RM, Boer C, Moons KG, Herwerden LA van, Tijssen JG, Numan SC, Kalkman CJ, Dijk D van, Dexamethasone for Cardiac Surgery Study G: Intraoperative high-dose dexamethasone for cardiac surgery: A randomized controlled trial. JAMA 2012; 308:1761–7

45.

Ding DF, Wang P, Jiang YX, Zhang XP, Shi W, Luo YW: Effects of apolipoprotein epsilon epsilon4 allele on early postoperative cognitive dysfunction after anesthesia. Anaesthesist 2022; 70:60–7

46.

Ding L, Zhang H, Mi W, Wang T, He Y, Zhang X, Ma X, Li H: Effects of dexmedetomidine on anesthesia recovery period and postoperative cognitive function of patients after robot-assisted laparoscopic radical cystectomy. Int J Clin Exp Med 2015; 8:11388–95

47.

Djaiani G, Silverton N, Fedorko L, Carroll J, Styra R, Rao V, Katznelson R: Dexmedetomidine versus propofol sedation reduces delirium after cardiac surgery: A randomized controlled trial. Anesthesiology 2016; 124:362–8

48.

Du X, Song F, Zhang X, Ma S: Protective efficacy of combined use of parecoxib and dexmedetomidine on postoperative hyperalgesia and early cognitive dysfunction after laparoscopic cholecystectomy for elderly patients. Acta Cir Bras 2019; 34:e201900905

49.

Duprey MS, Devlin JW, Griffith JL, Travison TG, Briesacher BA, Jones R, Saczynski JS, Schmitt EM, Gou Y, Marcantonio ER, Inouye SK: Association between perioperative medication use and postoperative delirium and cognition in older adults undergoing elective noncardiac surgery. Anesth Analg 2022; 134:1154–63

50.

Edipoglu IS, Celik F: The associations between cognitive dysfunction, stress biomarkers, and administered anesthesia type in total knee arthroplasties: Prospective, randomized trial. Pain Physician 2019; 22:495–507

51.

Egawa J, Inoue S, Nishiwada T, Tojo T, Kimura M, Kawaguchi T, Taniguchi S, Furuya H, Kawaguchi M: Effects of anesthetics on early postoperative cognitive outcome and intraoperative cerebral oxygen balance in patients undergoing lung surgery: A randomized clinical trial. Can J Anaesth 2016; 63:1161–9

52.

El-Naggar DI, Sharaf SI, Nasr El-Din DA, Mahran MG, Nawar DFA: A study of the prophylactic and curative effect of melatonin on postoperative delirium after coronary artery bypass grafting surgery in elderly patients. The Egyptian Journal of Hospital Medicine 2018; 72:4919–26

53.

Epple J, Kubitz J, Schmidt H, Motsch J, Böttiger BW, Martin E, Bach A: Comparative analysis of costs of total intravenous anaesthesia with propofol and remifentanil vs. Balanced anaesthesia with isoflurane and fentanyl. Eur J Anaesthesiol 2001; 18:20–8

54.

Ernst KF, Hall DE, Schmid KK, Seever G, Lavedan P, Lynch TG, Johanning JM: Surgical palliative care consultations over time in relationship to systemwide frailty screening. JAMA Surg 2014; 149:1121–6

55.

Esmaeili A, Fanoodi A, Ebrahimi A, Zangoue M, Khojasteh-Kaffash S: The efficacy of melatonin and clonidine in preventing emergence delirium in the elderly undergoing orthopedic surgery, neurosurgery, and general surgery: A placebo-controlled randomized clinical trial. J Kermanshah Univ Med Sci 2022; 26:e128831

56.

Fan GF, Hu Y, Zhang J, Chen L, He WS: Effect of dexmedetomidine on the postoperative cognitive function of patients undergoing radical resection of esophageal cancer. Biomedical Research (India) 2017; 28:7977–80

57.

Fan Y, Yuan L, Ji M, Yang J, Gao D: The effect of melatonin on early postoperative cognitive decline in elderly patients undergoing hip arthroplasty: A randomized controlled trial. J Clin Anesth 2017; 39:77–81

58.

Farrer TJ, Monk TG, McDonagh DL, Martin G, Pieper CF, Koltai D: A prospective randomized study examining the impact of intravenous versus inhalational anesthesia on postoperative cognitive decline and delirium. Applied neuropsychology Adult 2023:1–7 doi:10.1080/23279095.2023.2246612

59.

Fazel MR, Kheirkhah P, Atoof F: Sevoflurane versus propofol anesthesia on early postoperative cognitive function in older adults: A randomized controlled trial. Middle East Journal of Anesthesiology 2017; 24:237–41

60.

Fazel MR, Mofidian S, Mahdian M, Akbari H, Razavizadeh MR: The effect of melatonin on prevention of postoperative delirium after lower limb fracture surgery in elderly patients: A randomized double blind clinical trial. International journal of burns and trauma 2022; 12 4:161–7

61.

Feng X, Cai Y, Zhao L, Xi J, Qiao Y: Effects of different medication forms of dexmedetomidine on cognitive function in elderly patients undergoing radical operation of stomach neoplasms and ramsay sedation score. Cancer Research and Clinic 2021; 33:339–43

62.

Ford AH, Flicker L, Kelly R, Patel H, Passage J, Wibrow B, Anstey M, Edwards M, Almeida OP: The healthy heart-mind trial: Randomized controlled trial of melatonin for prevention of delirium. J Am Geriatr Soc 2020; 68:112–9

63.

Forsmo HM, Pfeffer F, Rasdal A, Ostgaard G, Mohn AC, Korner H, Erichsen C: Compliance with enhanced recovery after surgery criteria and preoperative and postoperative counselling reduces length of hospital stay in colorectal surgery: Results of a randomized controlled trial. Colorectal Dis 2022; 18:603–11

64.

Fuchita M, Khan SH, Perkins AJ, Gao S, Wang S, Kesler KA, Khan BA: Perioperative risk factors for postoperative delirium in patients undergoing esophagectomy. Ann Thorac Surg 2022; 108:190–5

65.

Fukata S, Kawabata Y, Fujishiro K, Kitagawa Y, Kuroiwa K, Akiyama H, Takemura M, Ando M, Hattori H: Haloperidol prophylaxis for preventing aggravation of postoperative delirium in elderly patients: A randomized, open-label prospective trial. Surg Today 2022; 47:815–26

66.

Fukata S, Kawabata Y, Fujisiro K, Katagawa Y, Kuroiwa K, Akiyama H, Terabe Y, Ando M, Kawamura T, Hattori H: Haloperidol prophylaxis does not prevent postoperative delirium in elderly patients: A randomized, open-label prospective trial. Surg Today 2022; 44:2305–13

67.

Gao C, Huang T, Wu K, Zhang W, Wang S, Chai X, Xie Y, Tang C: Multimodal analgesia for accelerated rehabilitation after total knee arthroplasty: A randomized, double-blind, controlled trial on the effect of the co-application of local infiltration analgesia and femoral nerve block combined with dexmedetomidine. Brain Sciences 2022; 12

68.

Gao Y, Yu H, Wang W, Wang Y, Teng J, Li F: Effect of dexmedetomidine on the neuroglobin expression in elderly patients with minimally invasive coronary artery bypass graft surgery. Heart Surg Forum 2021; 24:E776–e780

69.

Gao Y, Zhu X, Huang L, Teng J, Li F: Effects of dexmedetomidine on cerebral oxygen saturation and postoperative cognitive function in elderly patients undergoing minimally invasive coronary artery bypass surgery. Clin Hemorheol Microcirc 2020; 74:383–9

70.

Ge YL, Li X, Gao J, Zhang X, Fang X, Zhou L, Ji W, Lin S: Beneficial effects of intravenous dexmedetomidine on cognitive function and cerebral injury following a carotid endarterectomy. Experimental and Therapeutic Medicine 2016; 11:1128–34

71.

Geng YJ, Wu QH, Zhang RQ: Effect of propofol, sevoflurane, and isoflurane on postoperative cognitive dysfunction following laparoscopic cholecystectomy in elderly patients: A randomized controlled trial. J Clin Anesth 2017; 38:165–71

72.

Giannotti C, Massobrio A, Carmisciano L, Signori A, Napolitano A, Pertile D, Soriero D, Muzyka M, Tagliafico L, Casabella A, Cea M, Caffa I, Ballestrero A, Murialdo R, Laudisio A, Incalzi RA, Scabini S, Monacelli F, Nencioni A: Effect of geriatric comanagement in older patients undergoing surgery for gastrointestinal cancer: A retrospective, before-and-after study. J Am Med Dir Assoc 2022; 23:1868.e9–16

73.

Glumac S, Kardum G, Sodic L, Supe-Domic D, Karanovic N: Effects of dexamethasone on early cognitive decline after cardiac surgery: A randomised controlled trial. Eur J Anaesthesiol 2017; 34:776–84

74.

Goins AE, Smeltz A, Ramm C, Strassle PD, Teeter EG, Vavalle JP, Kolarczyk L: General anesthesia for transcatheter aortic valve replacement: Total intravenous anesthesia is associated with less delirium as compared to volatile agent technique. J Cardiothorac Vasc Anesth 2018; 32:1570–7

75.

Guo L, Liu Y, Wang M: Effect of perioperative dexmedetomidine anesthesia on prognosis of elderly patients with gastrointestinal tumor surgery. Comput Math Methods Med 2022; 2022:7889372

76.

Guo Y, Sun L, Zhang J, Li Q, Jiang H, Jiang W: Preventive effects of low-dose dexmedetomidine on postoperative cognitive function and recovery quality in elderly oral cancer patients. Int J Clin Exp Med 2015; 8:16183–90

77.

Gupta PK, Verma R, Kohli M, Shukla N, Kannaujia S: The effect of ramelteon on postoperative delirium in elderly patients: A randomised double-blind study. Journal of Clinical and Diagnostic Research 2019; 13:UC15–9

78.

Haghighi M, Sedighinejad A, Nabi BN, Mardani-Kivi M, Tehran SG, Mirfazli SA, Mirbolook A, Saheli NA: Is spinal anesthesia with low dose lidocaine better than sevoflorane anesthesia in patients undergoing hip fracture surgery. Archives of Bone and Joint Surgery 2017; 5:226–30

79.

Hakim SM, Othman AI, Naoum DO: Early treatment with risperidone for subsyndromal delirium after on-pump cardiac surgery in the elderly: A randomized trial. Anesthesiology 2012; 116:987–97

80.

Hall DE, Arya S, Schmid KK, Carlson MA, Lavedan P, Bailey TL, Purviance G, Bockman T, Lynch TG, Johanning JM: Association of a frailty screening initiative with postoperative survival at 30, 180, and 365 days. JAMA Surg 2017; 152:233–40

81.

Han C, Ji H, Guo Y, Fei Y, Wang C, Yuan Y, Ruan Z, Ma T: Effect of subanesthetic dose of esketamine on perioperative neurocognitive disorders in elderly undergoing gastrointestinal surgery: A randomized controlled trial. Drug Des Devel Ther 2023; 17:863–73

82.

Harari D, Hopper A, Dhesi J, Babic-Illman G, Lockwood L, Martin F: Proactive care of older people undergoing surgery (’POPS’): Designing, embedding, evaluating and funding a comprehensive geriatric assessment service for older elective surgical patients. Age and Ageing 2007; 36:190–6

83.

Harsten A, Kehlet H, Ljung P, Toksvig-Larsen S: Total intravenous general anaesthesia vs. Spinal anaesthesia for total hip arthroplasty: A randomised, controlled trial. Acta Anaesthesiol Scand 2015; 59:298–309

84.

Harsten A, Kehlet H, Toksvig-Larsen S: Recovery after total intravenous general anaesthesia or spinal anaesthesia for total knee arthroplasty: A randomized trial. Br J Anaesth 2013; 111:391–9

85.

Hasselager RP, Hallas J, Gögenur I: Inhalation anaesthesia compared with total intravenous anaesthesia and postoperative complications in colorectal cancer surgery: An observational registry-based study†. British Journal of Anaesthesia 2022; 129:416–26

86.

He F, Shen L, Zhong J: A study of dexmedetomidine in the prevention of postoperative delirium in elderly patients after vertebral osteotomy. International Journal of Clinical and Experimental Medicine 2018; 11:4984–90

87.

He Y, Ding Y, Zhu J, He L: Effects of dexmedetomidine combined with sevoflurane on hemodynamics, cognitive function and delirium of elderly patients undergoing laparoscopic gastrointestinal tumor resection. Anti-Tumor Pharmacy 2022; 12:396–9

88.

Hempenius L, Slaets JP, Asselt D van, Bock GH e, Wiggers T, Leeuwen BL van: Outcomes of a geriatric liaison intervention to prevent the development of postoperative delirium in frail elderly cancer patients: Report on a multicentre, randomized, controlled trial. PLoS One 2013; 8:e64834

89.

Hempenius L, Slaets JP, Asselt D van, Bock TH e, Wiggers T, Leeuwen BL van: Long term outcomes of a geriatric liaison intervention in frail elderly cancer patients. PLoS One 2016; 11:e0143364

90.

Hokuto D, Nomi T, Yoshikawa T, Matsuo Y, Kamitani N, Sho M: Preventative effects of ramelteon against postoperative delirium after elective liver resection. PLoS One 2020; 15:e0241673

91.

Hollinger A, Rüst CA, Riegger H, Gysi B, Tran F, Brügger J, Huber J, Toft K, Surbeck M, Schmid HR, Rentsch K, Steiner L, Siegemund M: Ketamine vs. Haloperidol for prevention of cognitive dysfunction and postoperative delirium: A phase IV multicentre randomised placebo-controlled double-blind clinical trial. J Clin Anesth 2021; 68:110099

92.

Hong H, Zhang DZ, Li M, Wang G, Zhu SN, Zhang Y, Wang DX, Sessler DI: Impact of dexmedetomidine supplemented analgesia on delirium in patients recovering from orthopedic surgery: A randomized controlled trial. BMC Anesthesiol 2021; 21:223

93.

Hongyu X, Qingting W, Xiaoling S, Liwu Z, Ailing Y, Xin L: Penehyclidine hydrochloride on postoperatively cognitive function. Med Hypotheses 2019; 129:109246

94.

Hu G, Long A, Wang J, Wang X: Effects of oral atorvastatin on inflammatory markers and postoperative delirium in elderly patients with hip fracture surgery. Farmacia 2022; 70:944–53

95.

Hu J, Zhu M, Gao Z, Zhao S, Feng X, Chen J, Zhang Y, Maze M: Dexmedetomidine for prevention of postoperative delirium in older adults undergoing oesophagectomy with total intravenous anaesthesia: A double-blind, randomised clinical trial. Eur J Anaesthesiol 2021; 38:S9–s17

96.

Huang JW, Yang YF, Gao XS, Xu ZH: A single preoperative low-dose dexamethasone may reduce the incidence and severity of postoperative delirium in the geriatric intertrochanteric fracture patients with internal fixation surgery: An exploratory analysis of a randomized, placebo-controlled trial. J Orthop Surg Res 2023; 18:441

97.

Huang YY, Hui CK, Lau NC, Ng YT, Lin TY, Chen CH, Wang YC, Tang HC, Chen DW, Chang CW: Total intravenous anesthesia for geriatric hip fracture with severe systemic disease. Eur J Trauma Emerg Surg 2023; 49:2139–45

98.

Hudetz JA, Iqbal Z, Gandhi SD, Patterson KM, Byrne AJ, Hudetz AG, Pagel PS, Warltier DC: Ketamine attenuates post-operative cognitive dysfunction after cardiac surgery. Acta Anaesthesiol Scand 2009; 53:864–72

99.

Hudetz JA, Patterson KM, Iqbal Z, Gandhi SD, Byrne AJ, Hudetz AG, Warltier DC, Pagel PS: Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2009; 23:651–7

100.

Huyan T, Hu X, Peng H, Zhu Z, Li Q, Zhang W: Perioperative dexmedetomidine reduces delirium in elderly patients after lung cancer surgery. Psychiatr Danub 2019; 31:95–101

101.

Indrakusuma R, Dunker MS, Peetoom JJ, Schreurs WH: Evaluation of preoperative geriatric assessment of elderly patients with colorectal carcinoma. A retrospective study. Eur J Surg Oncol 2015; 41:21–7

102.

Ishibashi-Kanno N, Takaoka S, Nagai H, Okubo-Sato M, Fukuzawa S, Uchida F, Yamagata K, Yanagawa T, Bukawa H: Postoperative delirium after reconstructive surgery for oral tumor: A retrospective clinical study. International Journal of Oral and Maxillofacial Surgery 2020; 49:1143–8

103.

Ishii K, Makita T, Yamashita H, Matsunaga S, Akiyama D, Toba K, Hara K, Sumikawa K, Hara T: Total intravenous anesthesia with propofol is associated with a lower rate of postoperative delirium in comparison with sevoflurane anesthesia in elderly patients. J Clin Anesth 2016; 33:428–31

104.

Jaiswal SJ, Vyas AD, Heisel AJ, Ackula H, Aggarwal A, Kim NH, Kerr KM, Madani M, Pretorius V, Auger WR, Fernandes TM, Malhotra A, Owens RL: Ramelteon for prevention of postoperative delirium: A randomized controlled trial in patients undergoing elective pulmonary thromboendarterectomy. Crit Care Med 2019; 47:1751–8

105.

Jakobsen CJ, Berg H, Hindsholm KB, Faddy N, Sloth E: The influence of propofol versus sevoflurane anesthesia on outcome in 10,535 cardiac surgical procedures. J Cardiothorac Vasc Anesth 2007; 21:664–71

106.

Javaherforoosh Zadeh F, Janatmakan F, Shafaeebejestan E, Jorairahmadi S: Effect of melatonin on delirium after on-pump coronary artery bypass graft surgery: A randomized clinical trial. Iran J Med Sci 2022; 46:120–7

107.

Javaherforooshzadeh F, Dezfoli AB, Malehi AS, Gholizadeh B: The efficacy of dexmedetomidine alone or with melatonin on delirium after coronary artery bypass graft surgery: A randomized clinical trial. Anesthesiology and Pain Medicine 2023; 13

108.

Jellish WS, Sheikh T, Baker WH, Louie EK, Slogoff S: Hemodynamic stability, myocardial ischemia, and perioperative outcome after carotid surgery with remifentanil/propofol or isoflurane/fentanyl anesthesia. J Neurosurg Anesthesiol 2003; 15:176–84

109.

Jia Y, Jin G, Guo S, Gu B, Jin Z, Gao X, Li Z: Fast-track surgery decreases the incidence of postoperative delirium and other complications in elderly patients with colorectal carcinoma. Langenbecks Arch Surg 2014; 399:77–84

110.

Jones TS, Jones EL, Richardson V, Finley JB, Franklin JL, Gore DL, Horney CP, Kovar A, Morin TL, Robinson TN: Preliminary data demonstrate the geriatric surgery verification program reduces postoperative length of stay. J Am Geriatr Soc 2021; 69:1993–9

111.

Juliebø V, Bjøro K, Krogseth M, Skovlund E, Ranhoff AH, Wyller TB: Risk factors for preoperative and postoperative delirium in elderly patients with hip fracture. J Am Geriatr Soc 2009; 57:1354–61

112.

Kadoi Y, Goto F: Sevoflurane anesthesia did not affect postoperative cognitive dysfunction in patients undergoing coronary artery bypass graft surgery. Journal of Anesthesia 2007; 21:330–5

113.

Kalimeris K, Kouni S, Kostopanagiotou G, Nomikos T, Fragopoulou E, Kakisis J, Vasdekis S, Matsota P, Pandazi A: Cognitive function and oxidative stress after carotid endarterectomy: Comparison of propofol to sevoflurane anesthesia. Journal of Cardiothoracic and Vascular Anesthesia 2013; 27:1246–52

114.

Kalisvaart KJ, Jonghe JF e, Bogaards MJ, Vreeswijk R, Egberts TC, Burger BJ, Eikelenboom P, Gool WA van: Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: A randomized placebo-controlled study. J Am Geriatr Soc 2022; 53:1658–66

115.

Kaneko S, Morimoto T, Ichinomiya T, Murata H, Yoshitomi O, Hara T: Effect of remimazolam on the incidence of delirium after transcatheter aortic valve implantation under general anesthesia: A retrospective exploratory study. Journal of Anesthesia 2023; 37:210–8

116.

Kang D, Kim M, Bae HB, Moon S, Kim J: Comparison of postoperative recovery between balanced and total intravenous anesthesia in patients undergoing off-pump coronary artery bypass (OPCAB) surgery: A prospective, single-blind randomized study. International Journal of Environmental Research and Public Health 2023; 20

117.

Ke Y, Chew S, Seet E, Wong WY, Lim V, Chua N, Zhang J, Lim B, Chua V, Loh NHW, Ti LK: Incidence and risk factors of delirium in post-anaesthesia care unit. Ann Acad Med Singap 2022; 51:87–95

118.

Kinouchi M, Mihara T, Taguri M, Ogura M: The efficacy of ramelteon to prevent postoperative delirium after general anesthesia in the elderly: A double-blind, randomized, placebo-controlled trial. American Journal of Geriatric Psychiatry 2023 doi:10.1016/j.jagp.2023.07.011

119.

Kishimoto M, Yamana H, Inoue S, Noda T, Akahane M, Inagaki Y, Matsui H, Yasunaga H, Kawaguchi M, Imamura T: Suspected periprosthetic joint infection after total knee arthroplasty under propofol versus sevoflurane anesthesia: A retrospective cohort study. Can J Anaesth 2018; 65:893–900

120.

Koch S, Blankertz B, Windmann V, Spies C, Radtke FM, Röhr V: Desflurane is risk factor for postoperative delirium in older patients’ independent from intraoperative burst suppression duration. Front Aging Neurosci 2023; 15:1067268

121.

Konishi Y, Evered LA, Scott DA, Silbert BS: Postoperative cognitive dysfunction after sevoflurane or propofol general anaesthesia in combination with spinal anaesthesia for hip arthroplasty. Anaesth Intensive Care 2018; 46:596–600

122.

Koo BW, Sim JB, Shin HJ, Kim DW, Kang SB, Do SH, Na HS: Surgical site infection after colorectal surgery according to the main anesthetic agent: A retrospective comparison between volatile anesthetics and propofol. Korean J Anesthesiol 2016; 69:332–40

123.

Kowalczyk M, Panasiuk-Kowalczyk A, Stadnik A, Guz M, Cybulski M, Jeleniewicz W, Stepulak A, Kwiatosz-Muc M: Dexmedetomidine increases MMP-12 and MBP concentrations after coronary artery bypass graft surgery with extracorporeal circulation anaesthesia without impacting cognitive function: A randomised control trial. International Journal of Environmental Research and Public Health 2022; 19

124.

Kuang Q, Zhong N, Ye C, Zhu X, Wei F: Propofol versus remimazolam on cognitive function, hemodynamics, and oxygenation during one-lung ventilation in older patients undergoing pulmonary lobectomy: A randomized controlled trial. J Cardiothorac Vasc Anesth 2023; 37:1996–2005

125.

Lai Y, Chen Q, Xiang C, Li G, Wei K: Comparison of the effects of dexmedetomidine and lidocaine on stress response and postoperative delirium of older patients undergoing thoracoscopic surgery: A randomized controlled trial. Clin Interv Aging 2023; 18:1275–83

126.

Larsen KA, Kelly SE, Stern TA, Bode RH, Jr. P, L. L. H, D. J. G, D. B, B. E. S, G. A. H, K. A. C, J. J. P: Administration of olanzapine to prevent postoperative delirium in elderly joint-replacement patients: A randomized, controlled trial. Psychosomatics 2022; 51:409–18

127.

Lee C, Lee CH, Lee G, Lee M, Hwang J: The effect of the timing and dose of dexmedetomidine on postoperative delirium in elderly patients after laparoscopic major non-cardiac surgery: A double blind randomized controlled study. J Clin Anesth 2018; 47:27–32

128.

Lee C, Lee J, Lee G, Lee H, Koh E, Hwang J: Pregabalin and dexmedetomidine combined for pain after total knee arthroplasty or total hip arthroplasty performed under spinal anesthesia. Orthopedics 2018; 41:365–70

129.

Lee KH, Kim JY, Kim JW, Park JS, Lee KW, Jeon SY: Influence of ketamine on early postoperative cognitive function after orthopedic surgery in elderly patients. Anesth Pain Med 2015; 5:e28844

130.

Leigheb M, De Sire A, Zeppegno P, Forni F, Sgreccia M, Gagliardi VP, Pogliacomi F, Sabbatini M: Delirium risk factors analysis post proximal femur fracture surgery in elderly. Acta Biomed 2022; 92:e2021569

131.

Lester PE, Ripley D, Grandelli R, Drew LA, Keegan M, Islam S: Interdisciplinary protocol for surgery in older persons: Development and implementation. J Am Med Dir Assoc 2022; 23:555–62

132.

Leung JM, Sands LP, Chen N, Ames C, Berven S, Bozic K, Burch S, Chou D, Covinsky K, Deviren V, Kinjo S, Kramer JH, Ries M, Tay B, Vail T, Weinstein P, Chang S, Meckler G, Newman S, Tsai T, Voss V, Youngblom E: Perioperative gabapentin does not reduce postoperative delirium in older surgical patients: A randomized clinical trial. Anesthesiology 2017; 127:633–44

133.

Li CJ, Wang BJ, Mu DL, Hu J, Guo C, Li XY, Ma D, Wang DX: Randomized clinical trial of intraoperative dexmedetomidine to prevent delirium in the elderly undergoing major non-cardiac surgery. British Journal of Surgery 2020; 107:e123–32

134.

Li JQ, Yuan H, Wang XQ, Yang M: Dexmedetomidine-induced anesthesia in elderly patients undergoing hip replacement surgery. World Journal of Clinical Cases 2023; 11:3756–64

135.

Li T, Li J, Yuan L, Wu J, Jiang C, Daniels J, Mehta RL, Wang M, Yeung J, Jackson T, Melody T, Jin S, Yao Y, Wu J, Chen J, Smith FG, Lian Q, Investigators RS: Effect of regional vs general anesthesia on incidence of postoperative delirium in older patients undergoing hip fracture surgery: The RAGA randomized trial. JAMA 2022; 327:50–8

136.

Li WX, Luo RY, Chen C, Li X, Ao JS, Liu Y, Yin YQ: Effects of propofol, dexmedetomidine, and midazolam on postoperative cognitive dysfunction in elderly patients: A randomized controlled preliminary trial. Chin Med J (Engl) 2019; 132:437–45

137.

Li X, Yang J, Nie XL, Zhang Y, Li XY, Li LH, Wang DX, Ma D: Impact of dexmedetomidine on the incidence of delirium in elderly patients after cardiac surgery: A randomized controlled trial. PLoS One 2017; 12:e0170757

138.

Li Y, Chen D, Wang H, Wang Z, Song F, Li H, Ling L, Shen Z, Hu C, Peng J, Li W, Xing W, Pan J, Liang H, Zhou Q, Cai J, He Z, Peng S, Zeng W, Zuo Z: Intravenous versus volatile anesthetic effects on postoperative cognition in elderly patients undergoing laparoscopic abdominal surgery. Anesthesiology 2021; 134:381–94

139.

Li Y, He R, Chen S, Qu Y: Effect of dexmedetomidine on early postoperative cognitive dysfunction and peri-operative inflammation in elderly patients undergoing laparoscopic cholecystectomy. Exp Ther Med 2015; 10:1635–42

140.

Li Y, Wang C, Bi M, Gao J, Zhang X, Tian H: Effect of dexmedetomidine on brain function and hemodynamics in patients undergoing lung cancer resection. Oncology Letters 2020; 20:1077–82

141.

Li Z, Yao S, Cheng M, Chen J: Evaluation of the effect of dexmedetomidine on postoperative cognitive dysfunction through aβand cytokines analysis. Iran J Pharm Res 2021; 20:515–22

142.

Liang C, Wei J, Cai X, Lin W, Fan Y, Yang F: Efficacy and safety of 3 different anesthesia techniques used in total hip arthroplasty. Med Sci Monit 2017; 23:3752–9

143.

Liang Y, Xin X, Wang H, Hua W, Wu Y, Wang X, Li P, Zhou T, Wang H: A novel predictive strategy for the incidence of postoperative neurocognitive dysfunction in elderly patients with mild cognitive impairment. Front Aging Neurosci 2022; 14:985406

144.

Liao YQ, Min J, Wu ZX, Hu Z: Comparison of the effects of remimazolam and dexmedetomidine on early postoperative cognitive function in elderly patients with gastric cancer. Frontiers in Aging Neuroscience 2023; 15

145.

Lindholm EE, Aune E, Norén CB, Seljeflot I, Hayes T, Otterstad JE, Kirkeboen KA: The anesthesia in abdominal aortic surgery (ABSENT) study: A prospective, randomized, controlled trial comparing troponin t release with fentanyl-sevoflurane and propofol-remifentanil anesthesia in major vascular surgery. Anesthesiology 2013; 119:802–12

146.

Liu J, Li J, Gao D, Wang J, Liu M, Yu D: High ASA physical status and low serum uric acid to creatinine ratio are independent risk factors for postoperative delirium among older adults undergoing urinary calculi surgery. Clin Interv Aging 2023; 18:81–92

147.

Liu T, Liu FC, Xia Y, Luo TJ, Wang F, Chen B, Wang C, Gao GK, Zhai WT, Liu W: Effect of dexmedetomidine on the montreal cognitive assessment in older patients undergoing pulmonary surgery. J Int Med Res 2022; 50:3000605221123680

148.

Liu T, Tuo J, Wei Q, Sun X, Zhao H, Zhao X, Qu M: Effect of perioperative dexmedetomidine infusion on postoperative delirium in elderly patients undergoing oral and maxillofacial surgery: A randomized controlled clinical trial. Int J Gen Med 2022; 15:6105–13

149.

Liu W, Wang Y, Chen K, Ye M, Lu W, Chen K, Shen X: Effect of intraoperative dexmedetomidine use on postoperative delirium in the elderly after laryngectomy: A randomized controlled clinical trial. Drug Design, Development and Therapy 2023; 17:2933–41

150.

Liu X, Zhang J, Xie G, Gao Y: The application of dexmetomidine hydrochloride inanaes the ticprocess of laparoscopic colorectal cancer in elderly patients. Anti-Tumor Pharmacy 2017; 7:739–42

151.

Liu Y, Ma L, Gao M, Guo W, Ma Y: Dexmedetomidine reduces postoperative delirium after joint replacement in elderly patients with mild cognitive impairment. Aging Clin Exp Res 2016; 28:729–36

152.

Lu J, Chen G, Zhou H, Zhou Q, Zhu Z, Wu C: Effect of parecoxib sodium pretreatment combined with dexmedetomidine on early postoperative cognitive dysfunction in elderly patients after shoulder arthroscopy: A randomized double blinded controlled trial. J Clin Anesth 2017; 41:30–4

153.

Lu Y, Fang PP, Yu YQ, Cheng XQ, Feng XM, Wong GTC, Maze M, Liu XS, Collaborators PS: Effect of intraoperative dexmedetomidine on recovery of gastrointestinal function after abdominal surgery in older adults: A randomized clinical trial. JAMA Netw Open 2022; 4:e2128886

154.

Luntz SP, Janitz E, Motsch J, Bach A, Martin E, Böttiger BW: Cost-effectiveness and high patient satisfaction in the elderly: Sevoflurane versus propofol anaesthesia. Eur J Anaesthesiol 2004; 21:115–22

155.

Lv Y, Gu L: Dexmedetomidine potential in attenuating postoperative delirium in elderly patients after total hip joint replacement. Rev Assoc Med Bras (1992) 2022; 68:1166–71

156.

Ma J, Wang F, Wang J, Wang P, Dou X, Yao S, Lin Y: The effect of low-dose esketamine on postoperative neurocognitive dysfunction in elderly patients undergoing general anesthesia for gastrointestinal tumors: A randomized controlled trial. Drug Des Devel Ther 2023; 17:1945–57

157.

Mahrose R, ElSerwi H, Maurice A, Elsersi M: Postoperative delirium after coronary artery bypass graft surgery: Dexmedetomidine infusion alone or with the addition of oral melatonin. Egyptian Journal of Anaesthesia 2021; 37:62–8

158.

Mandal S, Basu M, Kirtania J, Sarbapalli D, Pal R, Kar S, Kundu KK, Sarkar U, Gupta SD: Impact of general versus epidural anesthesia on early post-operative cognitive dysfunction following hip and knee surgery. J Emerg Trauma Shock 2011; 4:23–8

159.

Mangusan RF, Hooper V, Denslow SA, Travis L: Outcomes associated with postoperative delirium after cardiac surgery. Am J Crit Care 2015; 24:156–63

160.

Mansouri N, Nasrollahi K, Shetabi H: Prevention of cognitive dysfunction after cataract surgery with intravenous administration of midazolam and dexmedetomidine in elderly patients undergoing cataract surgery. Adv Biomed Res 2019; 8:6

161.

Marcantonio ER, Flacker JM, Wright RJ, Resnick NM: Reducing delirium after hip fracture: A randomized trial. J Am Geriatr Soc 2001; 49:516–22

162.

Mardani D, Bigdelian H: Prophylaxis of dexamethasone protects patients from further post-operative delirium after cardiac surgery: A randomized trial. Journal of Research in Medical Sciences 2013; 18:137–43

163.

Mazul-Sunko B, Hromatko I, Tadinac M, Sekulić A, Ivanec Z, Gvozdenović A, Tomasević B, Gavranović Z, Mladić-Batinica I, Cima A, Vrkić N, Lovricević I: Subclinical neurocognitive dysfunction after carotid endarterectomy-the impact of shunting. J Neurosurg Anesthesiol 2010; 22:195–201

164.

McDonald SR, Heflin MT, Whitson HE, Dalton TO, Lidsky ME, Liu P, Poer CM, Sloane R, Thacker JK, White HK, Yanamadala M, Lagoo-Deenadayalan SA: Association of integrated care coordination with postsurgical outcomes in high-risk older adults: The perioperative optimization of senior health (POSH) initiative. JAMA Surg 2018; 153:454–62

165.

Mei B, Meng G, Xu G, Cheng X, Chen S, Zhang Y, Zhang M, Liu X, Gu E: Intraoperative sedation with dexmedetomidine is superior to propofol for elderly patients undergoing hip arthroplasty: A prospective randomized controlled study. Clin J Pain 2018; 34:811–7

166.

Mei B, Xu G, Han W, Lu X, Liu R, Cheng X, Chen S, Gu E, Liu X, Zhang Y: The benefit of dexmedetomidine on postoperative cognitive function is unrelated to the modulation on peripheral inflammation: A single-center, prospective, randomized study. Clin J Pain 2020; 36:88–95

167.

Mei X, Zheng H-L, Li C, Ma X, Zheng H, Marcantonio E, Xie Z, Shen Y: The effects of propofol and sevoflurane on postoperative delirium in older patients: A randomized clinical trial study. Journal of Alzheimer’s Disease 2020; 76:1627–36

168.

Memtsoudis S, Cozowicz C, Zubizarreta N, Weinstein SM, Liu J, Kim DH, Poultsides L, Berger MM, Mazumdar M, Poeran J: Risk factors for postoperative delirium in patients undergoing lower extremity joint arthroplasty: A retrospective population-based cohort study. Reg Anesth Pain Med 2019 doi:10.1136/rapm-2019-100700

169.

Meuret P, Bouvet L, Villet B, Hafez M, Allaouchiche B, Boselli E: Hypobaric unilateral spinal anaesthesia versus general anaesthesia in elderly patients undergoing hip fracture surgical repair: A prospective randomised open trial. Turk J Anaesthesiol Reanim 2018; 46:121–30

170.

Miyata R, Omasa M, Fujimoto R, Ishikawa H, Aoki M: Efficacy of ramelteon for delirium after lung cancer surgery. Interact Cardiovasc Thorac Surg 2017; 24:8–12

171.

Mohamed SA, Rady A, Youssry M, Abdelaziz Mohamed MR, Gamal M: Performance of melatonin as prophylaxis in geriatric patients with multifactorial risk for postoperative delirium development: A randomized comparative study. Turk J Anaesthesiol Reanim 2022; 50:178–86

172.

Mohamed S, Shaaban AR: The effect of dexmedetomidine on the incidence of postoperative cognitive dysfunction in elderly patients after prolonged abdominal surgery. Egyptian Journal of Anaesthesia 2014; 30:331–8

173.

Momeni M, Khalifa C, Lemaire G, Watremez C, Tircoveanu R, Van Dyck M, Kahn D, Rosal Martins M, Mastrobuoni S, De Kerchove L, Zango SH, Jacquet LM: Propofol plus low-dose dexmedetomidine infusion and postoperative delirium in older patients undergoing cardiac surgery. Br J Anaesth 2021; 126:665–73

174.

Mueller A, Spies CD, Eckardt R, Weiss B, Pohrt A, Wernecke KD, Schmidt M: Anticholinergic burden of long-term medication is an independent risk factor for the development of postoperative delirium: A clinical trial. J Clin Anesth 2020; 61:109632

175.

Mueller A, Spies CD, Eckardt R, Weiss B, Pohrt A, Wernecke KD, Schmidt M: Mueller_haloperidol. J Clin Anesth 2020; 61:109632

176.

Nandi S, Harvey WF, Saillant J, Kazakin A, Talmo C, Bono J: Pharmacologic risk factors for post-operative delirium in total joint arthroplasty patients: A case-control study. J Arthroplasty 2022; 29:268–71

177.

The effect of spinal versus general anesthesia on postoperative pain and analgesic requirements in patients undergoing peripheral vascular surgery. Coll Antropol 2012; 36:1301–5

178.

Neuman MD, Feng R, Carson JL, Gaskins LJ, Dillane D, Sessler DI, Sieber F, Magaziner J, Marcantonio ER, Mehta S, Menio D, Ayad S, Stone T, Papp S, Schwenk ES, Elkassabany N, Marshall M, Jaffe JD, Luke C, Sharma B, Azim S, Hymes RA, Chin KJ, Sheppard R, Perlman B, Sappenfield J, Hauck E, Hoeft MA, Giska M, Ranganath Y, et al.: Spinal anesthesia or general anesthesia for hip surgery in older adults. N Engl J Med 2022; 385:2025–35

179.

Neuman MD, Feng R, Ellenberg SS, Sieber F, Sessler DI, Magaziner J, Elkassabany N, Schwenk ES, Dillane D, Marcantonio ER, Menio D, Ayad S, Hassan M, Stone T, Papp S, Donegan D, Marshall M, Jaffe JD, Luke C, Sharma B, Azim S, Hymes R, Chin KJ, Sheppard R, Perlman B, Sappenfield J, Hauck E, Hoeft MA, Tierney A, Gaskins LJ, et al.: Pain, analgesic use, and patient satisfaction with spinal versus general anesthesia for hip fracture surgery: A randomized clinical trial. Ann Intern Med 2022; 175:952–60

180.

Neuman MD, Feng R, Ellenberg SS, Sieber F, Sessler DI, Magaziner J, Elkassabany N, Schwenk ES, Dillane D, Marcantonio ER, Menio D, Ayad S, Hassan M, Stone T, Papp S, Donegan D, Marshall M, Jaffe JD, Luke C, Sharma B, Azim S, Hymes R, Chin KJ, Sheppard R, Perlman B, Sappenfield J, Hauck E, Hoeft MA, Tierney A, Gaskins LJ, et al.: Pain, analgesic use, and patient satisfaction with spinal versus general anesthesia for hip fracture surgery. Annals of Internal Medicine 2022; 176:952–60

181.

Nishikawa K, Kimura S, Shimodate Y, Igarashi M, Namiki A: A comparison of intravenous-based and epidural-based techniques for anesthesia and postoperative analgesia in elderly patients undergoing laparoscopic cholecystectomy. J Anesth 2007; 21:1–6

182.

Nishikawa K, Nakayama M, Omote K, Namiki A: Recovery characteristics and post-operative delirium after long-duration laparoscope-assisted surgery in elderly patients: Propofol-based vs. Sevoflurane-based anesthesia. Acta Anaesthesiol Scand 2004; 48:162–8

183.

Nishikawa K, Yoshida S, Shimodate Y, Igarashi M, Namiki A: A comparison of spinal anesthesia with small-dose lidocaine and general anesthesia with fentanyl and propofol for ambulatory prostate biopsy procedures in elderly patients. J Clin Anesth 2007; 19:25–9

184.

O’Brien K, Feng R, Sieber F, Marcantonio ER, Tierney A, Magaziner J, Carson JL, Dillane D, Sessler DI, Menio D, Ayad S, Stone T, Papp S, Schwenk ES, Marshall M, Jaffe JD, Luke C, Sharma B, Azim S, Hymes R, Chin KJ, Sheppard R, Perlman B, Sappenfield J, Hauck E, Hoeft MA, Karlawish J, Mehta S, Donegan DJ, Horan A, et al.: Outcomes with spinal versus general anesthesia for patients with and without preoperative cognitive impairment: Secondary analysis of a randomized clinical trial. Alzheimer’s and Dementia 2023; 19:4008–19

185.

Oh ES, Leoutsakos JM, Rosenberg PB, Pletnikova AM, Khanuja HS, Sterling RS, Oni JK, Sieber FE, Fedarko NS, Akhlaghi N, Neufeld KJ: Effects of ramelteon on the prevention of postoperative delirium in older patients undergoing orthopedic surgery: The RECOVER randomized controlled trial. Am J Geriatr Psychiatry 2021; 29:90–100

186.

Oh TK, Kim J, Han S, Kim K, Jheon S, Ji E: Effect of sevoflurane-based or propofol-based anaesthesia on the incidence of postoperative acute kidney injury: A retrospective propensity score-matched analysis. Eur J Anaesthesiol 2019; 36:649–55

187.

Olsson LE, Karlsson J, Berg U, Karrholm J, Hansson E: Person-centred care compared with standardized care for patients undergoing total hip arthroplasty–a quasi-experimental study. J Orthop Surg Res 2014; 9:95

188.

Ommundsen N, Wyller TB, Nesbakken A, Bakka AO, Jordhøy MS, Skovlund E, Rostoft S: Preoperative geriatric assessment and tailored interventions in frail older patients with colorectal cancer: A randomized controlled trial. Colorectal Dis 2018; 20:16–25

189.

Oriby ME, Elrashidy AA, Elsharkawy A, Ahmed SA: Effects of ketamine or dexmedetomidine on postoperative cognitive dysfunction after cataract surgery: A randomized controlled trial. Indian Journal of Anaesthesia 2023; 67:186–93

190.

Ornek D, Metin S, Deren S, Un C, Metin M, Dikmen B, Gogus N: The influence of various anesthesia techniques on postoperative recovery and discharge criteria among geriatric patients. Clinics (Sao Paulo) 2010; 65:941–6

191.

Ottens TH, Dieleman JM, Sauer AM, Peelen LM, Nierich AP, Groot WJ e, Nathoe HM, Buijsrogge MP, Kalkman CJ, Dijk D van, Group DE for CSS: Effects of dexamethasone on cognitive decline after cardiac surgery: A randomized clinical trial. Anesthesiology 2022; 121:492–500

192.

Özer E, Yilmaz R: Effect of different anesthetic techniques on mental outcome in elderly patients undergoing off-pump coronary artery bypass graft surgery. Turkiye Klinikleri Cardiovascular Sciences 2017; 29:17–22

193.

Paille M, Senage T, Roussel JC, Manigold T, Piccoli M, Chapelet G, Le Tourneau T, Karakachoff M, Berrut G, Decker L e, Boureau AS: Association of preoperative geriatric assessment with length of stay after combined cardiac surgery. Annals of Thoracic Surgery 2021; 112:763–9

194.

Pan CL, Chen Y, Wu YH: Dexmedetomidine combined with ulinastatin improves postoperative cognitive dysfunction in elderly patients after laparoscopic colorectal cancer surgery by regulating pro-inflammatory/antiinflammatory system. World Chinese Journal of Digestology 2016; 24:2755–61

195.

Papaioannou A, Fraidakis O, Michaloudis D, Balalis C, Askitopoulou H: The impact of the type of anaesthesia on cognitive status and delirium during the first postoperative days in elderly patients. Eur J Anaesthesiol 2005; 22:492–9

196.

Park CM, Inouye SK, Marcantonio ER, Metzger E, Bateman BT, Lie JJ, Lee SB, Levin R, Kim DH: Perioperative gabapentin use and in-hospital adverse clinical events among older adults after major surgery. JAMA Intern Med 2022; 182:1117–27

197.

Park JW, Kim EK, Lee HT, Park S, Do SH: The effects of propofol or dexmedetomidine sedation on postoperative recovery in elderly patients receiving lower limb surgery under spinal anesthesia: A retrospective propensity score-matched analysis. J Clin Med 2021; 10

198.

Park J, Lee SH, Lee JH, Min JJ, Kwon JH, Oh AR, Carriere K, Ahn J: Volatile versus total intravenous anesthesia for 30-day mortality following non-cardiac surgery in patients with preoperative myocardial injury. PLoS One 2020; 15:e0238661

199.

Parker MJ, Griffiths R: General versus regional anaesthesia for hip fractures. A pilot randomised controlled trial of 322 patients. Injury 2015; 46:1562–6

200.

Partridge JS, Harari D, Martin FC, Peacock JL, Bell R, Mohammed A, Dhesi JK: Randomized clinical trial of comprehensive geriatric assessment and optimization in vascular surgery. Br J Surg 2017; 104:679–87

201.

Pipanmekaporn T, Punjasawadwong Y, Wongpakaran N, Wongpakaran T, Suwannachai K, Chittawatanarat K, Mueankwan S: Risk factors and adverse clinical outcomes of postoperative delirium in thai elderly patients: A prospective cohort study. Perspect Psychiatr Care 2021; 57:1073–82

202.

Poeran J, Cozowicz C, Zubizarreta N, Weinstein SM, Deiner SG, Leipzig RM, Friedman JI, Liu J, Mazumdar M, Memtsoudis SG: Modifiable factors associated with postoperative delirium after hip fracture repair: An age-stratified retrospective cohort study. European Journal of Anaesthesiology 2020; 37:649–58

203.

Prakanrattana U, Prapaitrakool S: Efficacy of risperidone for prevention of postoperative delirium in cardiac surgery. Anaesth Intensive Care 2007; 35:714–9

204.

Prestmo A, Hagen G, Sletvold O, Helbostad JL, Thingstad P, Taraldsen K, Lydersen S, Halsteinli V, Saltnes T, Lamb SE, Johnsen LG, Saltvedt I: Comprehensive geriatric care for patients with hip fractures: A prospective, randomised, controlled trial. Lancet 2015; 385:1623–33

205.

Purwar B, Ismail KM, Turner N, Farrell A, Verzune M, Annappa M, Smith I, El-Gizawy Z, Cooper JC: General or spinal anaesthetic for vaginal surgery in pelvic floor disorders (GOSSIP): A feasibility randomised controlled trial. Int Urogynecol J 2015; 26:1171–8

206.

Qiao H, Chen J, Huang Y, Pan Y, Lu W, Huang Y, Li W, Shen X: Early neurocognitive function with propofol or desflurane anesthesia after laser laryngeal surgery with low inspired oxygen. Laryngoscope 2023; 133:640–6

207.

Qiao Y, Feng H, Zhao T, Yan H, Zhang H, Zhao X: Postoperative cognitive dysfunction after inhalational anesthesia in elderly patients undergoing major surgery: The influence of anesthetic technique, cerebral injury and systemic inflammation. BMC Anesthesiol 2015; 15:154

208.

Qin Y, Ni J, Kang L, Zhong Z, Wang L, Yin S: Sevoflurane effect on cognitive function and the expression of oxidative stress response proteins in elderly patients undergoing radical surgery for lung cancer. J Coll Physicians Surg Pak 2019; 29:12–5

209.

Qu JZ, Mueller A, McKay TB, Westover MB, Shelton KT, Shaefi S, D’Alessandro DA, Berra L, Brown EN, Houle TT, Akeju O: Nighttime dexmedetomidine for delirium prevention in non-mechanically ventilated patients after cardiac surgery (MINDDS): A single-centre, parallel-arm, randomised, placebo-controlled superiority trial. EClinicalMedicine 2023; 56:101796

210.

Rascón-Martı́nez DM, Fresán-Orellana A, Ocharán-Hernández ME, Genis-Zarate JH, Castellanos-Olivares A: The effects of ketamine on cognitive function in elderly patients undergoing ophthalmic surgery: A pilot study. Anesth Analg 2016; 122:969–75

211.

Rasmussen LS, Johnson T, Kuipers HM, Kristensen D, Siersma VD, Vila P, Jolles J, Papaioannou A, Abildstrom H, Silverstein JH, Bonal JA, Raeder J, Nielsen IK, Korttila K, Munoz L, Dodds C, Hanning CD, Moller JT: Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients. Acta Anaesthesiol Scand 2003; 47:260–6

212.

Remérand F, Le Tendre C, Baud A, Couvret C, Pourrat X, Favard L, Laffon M, Fusciardi J: The early and delayed analgesic effects of ketamine after total hip arthroplasty: A prospective, randomized, controlled, double-blind study. Anesth Analg 2009; 109:1963–71

213.

Ren WX, Wu RR: Effect of general and sub-arachnoid anesthesia on the incidence of postoperative delirium and cognitive impairments in elderly chinese patients. Tropical Journal of Pharmaceutical Research 2021; 20:433–9

214.

Richter HE, Redden DT, Duxbury AS, Granieri EC, Halli AD, Goode PS: Pelvic floor surgery in the older woman: Enhanced compared with usual preoperative assessment. Obstet Gynecol 2005; 105:800–7

215.

Rohan D, Buggy DJ, Crowley S, Ling FK, Gallagher H, Regan C, Moriarty DC: Increased incidence of postoperative cognitive dysfunction 24 hr after minor surgery in the elderly. Can J Anaesth 2005; 52:137–42

216.

Romano LU, Rigoni M, Torri E, Nella M, Morandi M, Casetti P, Nollo G: A propensity score-matched analysis to assess the outcomes in pre-and post-fast-track hip and knee elective prosthesis patients. Journal of Clinical Medicine 2021; 10:1–13

217.

Royse CF, Saager L, Whitlock R, Ou-Young J, Royse A, Vincent J, Devereaux PJ, Kurz A, Awais A, Panjasawatwong K, Sessler DI: Impact of methylprednisolone on postoperative quality of recovery and delirium in the steroids in cardiac surgery trial: A randomized, double-blind, placebo-controlled substudy. Anesthesiology 2017; 126:223–33

218.

Salonia A, Crescenti A, Suardi N, Memmo A, Naspro R, Bocciardi AM, Colombo R, Da Pozzo LF, Rigatti P, Montorsi F: General versus spinal anesthesia in patients undergoing radical retropubic prostatectomy: Results of a prospective, randomized study. Urology 2004; 64:95–100

219.

Salonia A, Suardi N, Crescenti A, Colombo R, Rigatti P, Montorsi F: General versus spinal anesthesia with different forms of sedation in patients undergoing radical retropubic prostatectomy: Results of a prospective, randomized study. Int J Urol 2006; 13:1185–90

220.

Sauer AM, Slooter AJ, Veldhuijzen DS, Eijk MM van, Devlin JW, Dijk D van: Intraoperative dexamethasone and delirium after cardiac surgery: A randomized clinical trial. Anesth Analg 2022; 119:1046–52

221.

Sciberras SC, Vella AP, Vella B, Spiteri J, Mizzi C, Borg-Xuereb K, Laferla G, Grech G, Sammut F: A randomized, controlled trial on the effect of anesthesia on chronic pain after total knee arthroplasty. Pain Management 2022; 12:711–23

222.

Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, Chen J: Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: A randomized controlled trial (DEXmedetomidine COmpared to morphine-DEXCOM study). Anesthesiology 2009; 111:1075–84

223.

Shen L, Chen JQ, Yang XL, Hu JC, Gao W, Chai XQ, Wang D: Flurbiprofen used in one-lung ventilation improves intraoperative regional cerebral oxygen saturation and reduces the incidence of postoperative delirium. Frontiers in Psychiatry 2022; 13

224.

Shi H, Du X, Wu F, Hu Y, Xv Z, Mi W: Dexmedetomidine improves early postoperative neurocognitive disorder in elderly male patients undergoing thoracoscopic lobectomy. Exp Ther Med 2020; 20:3868–77

225.

Shi Y: Effects of melatonin on postoperative delirium after PCI in elderly patients: A randomized, single-center, double-blind, placebo-controlled trial. Heart Surg Forum 2022; 24:E893–7

226.

Shimizu K, Hirose M, Mikami S, Takamura K, Goi T, Yamaguchi A, Morioka K, Ichikawa T, Shigemi K: Effect of anaesthesia maintained with sevoflurane and propofol on surgical site infection after elective open gastrointestinal surgery. J Hosp Infect 2010; 74:129–36

227.

Shin HJ, Woo Nam S, Kim H, Yim S, Han SH, Hwang JW, Do SH, Na HS: Postoperative delirium after dexmedetomidine versus propofol sedation in healthy older adults undergoing orthopedic lower limb surgery with spinal anesthesia: A randomized controlled trial. Anesthesiology 2023; 138:164–71

228.

Shin S, Kim SH, Park KK, Kim SJ, Bae JC, Choi YS: Effects of anesthesia techniques on outcomes after hip fracture surgery in elderly patients: A prospective, randomized, controlled trial. J Clin Med 2020; 9

229.

Shyu Y-IL, Liang J, Wu C-C, Su J-Y, Cheng H-S, Chou S-W, Chen M-C, Yang C-T: Interdisciplinary intervention for hip fracture in older taiwanese: Benefits last for 1 year. The Journals of Gerontology: Series A 2008; 63:92–7

230.

Shyu Y-IL, Liang J, Wu C-C, Su J-Y, Cheng H-S, Chou S-W, Yang C-T: A pilot investigation of the short-term effects of an interdisciplinary intervention program on elderly patients with hip fracture in taiwan. Journal of the American Geriatrics Society 2005; 53:811–8

231.

Silbert BS, Evered LA, Scott DA: Incidence of postoperative cognitive dysfunction after general or spinal anaesthesia for extracorporeal shock wave lithotripsy. Br J Anaesth 2014; 113:784–91

232.

Siripoonyothai S, Sindhvananda W: Comparison of postoperative delirium within 24 hours between ketamine and propofol infusion during cardiopulmonary bypass machine: A randomized controlled trial. Ann Card Anaesth 2021; 24:294–301

233.

Slor CJ, Jonghe JF e, Vreeswijk R, Groot E, Ploeg TV, Gool WA van, Eikelenboom P, Snoeck M, Schmand B, Kalisvaart KJ: Anesthesia and postoperative delirium in older adults undergoing hip surgery. J Am Geriatr Soc 2011; 59:1313–9

234.

Smoor RM, Dongen EPA van, Daeter EJ, Emmelot-Vonk MH, Cremer OL, Vernooij LM, Noordzij PG: The association between preoperative multidisciplinary team care and patient outcome in frail patients undergoing cardiac surgery. Journal of Thoracic and Cardiovascular Surgery 2023 doi:10.1016/j.jtcvs.2023.05.037

235.

Soh S, Shim JK, Song JW, Bae JC, Kwak YL: Effect of dexmedetomidine on acute kidney injury after aortic surgery: A single-centre, placebo-controlled, randomised controlled trial. British Journal of Anaesthesia 2020; 124:386–94

236.

Souwer ETD, Bastiaannet E, Bruijn S e, Breugom AJ, Bos F van den, Portielje JEA, Dekker JWT: Comprehensive multidisciplinary care program for elderly colorectal cancer patients: "From prehabilitation to independence". Eur J Surg Oncol 2018; 44:1894–900

237.

Spence J, Belley-Côté E, Jacobsohn E, Lee SF, Whitlock R, Bangdiwala S, Syed S, Sarkaria A, MacIsaac S, Lengyel A, Long S, Um K, McIntyre WF, Kavosh M, Fast I, Arora R, Lamy A, Connolly S, Devereaux PJ: Restricted versus liberal intraoperative benzodiazepine use in cardiac anaesthesia for reducing delirium (b-free pilot): A pilot, multicentre, randomised, cluster crossover trial. Br J Anaesth 2020; 125:38–46

238.

Staiger RD, Curley D, Attwood NV, Haile SR, Arulampalam T, Simpson JC: Surgical outcome improvement by shared decision-making: Value of a preoperative multidisciplinary target clinic for the elderly in colorectal surgery. Langenbecks Arch Surg 2023; 408:316

239.

Subramaniam B, Shankar P, Shaefi S, Mueller A, O’Gara B, Banner-Goodspeed V, Gallagher J, Gasangwa D, Patxot M, Packiasabapathy S, Mathur P, Eikermann M, Talmor D, Marcantonio ER: Effect of intravenous acetaminophen vs placebo combined with propofol or dexmedetomidine on postoperative delirium among older patients following cardiac surgery: The DEXACET randomized clinical trial. Jama 2019; 321:686–96

240.

Sultan SS: Assessment of role of perioperative melatonin in prevention and treatment of postoperative delirium after hip arthroplasty under spinal anesthesia in the elderly. Saudi J Anaesth 2010; 4:169–73

241.

Sun Y, Peng HP, Wu TT: Postoperative c-reactive protein predicts postoperative delirium in colorectal cancer following surgery. Clinical Interventions in Aging 2023; 18:559–70

242.

Sun Y, Zhang J, Feng S: Remimazolam supplemented to general anesthesia alleviates stress and cognitive impairment in elder patients after hip surgery. Psychiatry Investigation 2023; 20:301–6

243.

Tan Y, Ouyang W, Tang Y, Fang N, Fang C, Quan C: Effect of remimazolam tosilate on early cognitive function in elderly patients undergoing upper gastrointestinal endoscopy. J Gastroenterol Hepatol 2022; 37:576–83

244.

Tanaka P, Goodman S, Sommer BR, Maloney W, Huddleston J, Lemmens HJ: The effect of desflurane versus propofol anesthesia on postoperative delirium in elderly obese patients undergoing total knee replacement: A randomized, controlled, double-blinded clinical trial. J Clin Anesth 2017; 39:17–22

245.

Tang N, Ou C, Liu Y, Zuo Y, Bai Y: Effect of inhalational anaesthetic on postoperative cognitive dysfunction following radical rectal resection in elderly patients with mild cognitive impairment. J Int Med Res 2014; 42:1252–61

246.

Tang Y, Liu J, Huang X, Ding H, Tan S, Zhu Y: Effect of dexmedetomidine-assisted intravenous inhalation combined anesthesia on cerebral oxygen metabolism and serum Th1/Th2 level in elderly colorectal cancer patients. Front Surg 2022; 8:832646

247.

Tanifuji T, Otsuka I, Okazaki S, Horai T, So R, Shiroiwa K, Mouri K, Tanaka M, Ohmoto N, Sora I, Hirai M, Fukumoto T, Ku Y, Hishimoto A: Preventive effects of preoperative ramelteon on postoperative delirium in asian elderly population: A randomized, double-blind, placebo-controlled trial, and a systematic review and meta-analysis. Asian J Psychiatr 2022; 78:103282

248.

Tarazona-Santabalbina FJ, Llabata-Broseta J, Belenguer-Varea A, Alvarez-Martinez D, Cuesta-Peredo D, Avellana-Zaragoza JA: A daily multidisciplinary assessment of older adults undergoing elective colorectal cancer surgery is associated with reduced delirium and geriatric syndromes. J Geriatr Oncol 2019; 10:298–303

249.

Tian HT, Duan XH, Yang YF, Wang Y, Bai QL, Zhang X: Effects of propofol or sevoflurane anesthesia on the perioperative inflammatory response, pulmonary function and cognitive function in patients receiving lung cancer resection. European Review for Medical and Pharmacological Sciences 2021; 21:5515–22

250.

Tu W, Yuan H, Zhang S, Lu F, Yin L, Chen C, Li J: Influence of anesthetic induction of propofol combined with esketamine on perioperative stress and inflammatory responses and postoperative cognition of elderly surgical patients. American Journal of Translational Research 2021; 13:1701–9

251.

Turan A, Duncan A, Leung S, Karimi N, Fang J, Mao G, Hargrave J, Gillinov M, Trombetta C, Ayad S, Hassan M, Feider A, Howard-Quijano K, Ruetzler K, Sessler DI, Group DS: Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): A randomised placebo-controlled trial. Lancet 2020; 396:177–85

252.

Tzimas P, Samara E, Petrou A, Korompilias A, Chalkias A, Papadopoulos G: The influence of anesthetic techniques on postoperative cognitive function in elderly patients undergoing hip fracture surgery: General vs spinal anesthesia. Injury 2018; 49:2221–6

253.

Ushida T, Yokoyama T, Kishida Y, Hosokawa M, Taniguchi S, Inoue S, Takemasa R, Suetomi K, Arai YC, McLaughlin M, Tani T: Incidence and risk factors of postoperative delirium in cervical spine surgery. Spine (Phila Pa 1976) 2022; 34:2500–4

254.

Valentin LSS, Pereira VFA, Pietrobon RS, Schmidt AP, Oses JP, Portela LV, Souza DO, Vissoci JRN, Da Luz VF, De Souza Trintoni LMDA, Nielsen KC, Carmona MJC: Effects of single low dose of dexamethasone before noncardiac and nonneurologic surgery and general anesthesia on postoperative cognitive dysfunction - a phase III double blind, randomized clinical trial. PLoS ONE 2016; 11

255.

Van Grootven B, Detroyer E, Devriendt E, Sermon A, Deschodt M, Flamaing J, Dubois C, Milisen K: Is preoperative state anxiety a risk factor for postoperative delirium among elderly hip fracture patients? Geriatr Gerontol Int 2016; 16:948–55

256.

Norden J van, Spies CD, Borchers F, Mertens M, Kurth J, Heidgen J, Pohrt A, Mueller A: The effect of peri-operative dexmedetomidine on the incidence of postoperative delirium in cardiac and non-cardiac surgical patients: A randomised, double-blind placebo-controlled trial. Anaesthesia 2021; 76:1342–51

257.

Vidán M, Serra JA, Moreno C, Riquelme G, Ortiz J: Efficacy of a comprehensive geriatric intervention in older patients hospitalized for hip fracture: A randomized, controlled trial. J Am Geriatr Soc 2005; 53:1476–82

258.

Villalobos D, Reese M, Wright MC, Wong M, Syed A, Park J, Hall A, Browndyke JN, Martucci KT, Devinney MJ, Acker L, Moretti EW, Talbot L, Colin B, Ohlendorf B, Waligorska T, Shaw LM, Whitson HE, Cohen HJ, Mathew JP, Berger M: Perioperative changes in neurocognitive and alzheimer’s disease-related cerebrospinal fluid biomarkers in older patients randomised to isoflurane or propofol for anaesthetic maintenance. British Journal of Anaesthesia 2023; 131:328–37

259.

Vochteloo AJ, Moerman S, Burg BL van der, Boo M e, Vries MR e, Niesten DD, Tuinebreijer WE, Nelissen RG, Pilot P: Delirium risk screening and haloperidol prophylaxis program in hip fracture patients is a helpful tool in identifying high-risk patients, but does not reduce the incidence of delirium. BMC Geriatr 2011; 11:39

260.

Vovk Racman P, Kšela J, Racman M, Žerjav U, Šoštarič M: Comparison of procedural sedation with propofol and dexmedetomidine during transcatheter aortic valve replacement using the transfemoral approach. Journal of Cardiothoracic and Vascular Anesthesia 2023; 37:1894–900

261.

Wang F, Xie D, Xu H, Ye Q, Wu L, Gao XP: The effects of remifentanil-propofol combined with dexmedetomidine on cognitive dysfunction in elderly patients after ureteroscopic holmium laser lithotripsy: A double-blind randomized controlled trial. Trials 2022; 23:192

262.

Wang L, Zhang T, Huang L, Peng W: Comparison between dexmedetomidine and midazolam for sedation in patients with intubation after oral and maxillofacial surgery. Biomed Res Int 2020; 2020:7082597

263.

Wang ML, Min J, Sands LP, Leung JM: Midazolam premedication immediately before surgery is not associated with early postoperative delirium. Anesth Analg 2021; 133:765–71

264.

Wang Q, Lin F, Huang B, Pan LH: The effectiveness and safety of general and spinal anesthesia on systemic inflammatory response in patients with tumor-type total knee arthroplasty. Oncol Res Treat 2020; 43:428–34

265.

Wang S, Pei L, Xue Z: Effects of different doses of dexmedetomidine on postoperative cognitive function in elderly colon cancer patients. Cancer Research and Clinic 2020; 33:767–71

266.

Wang W, Feng N, Zhao W, Luo F, Zhu X, Zhao W, Liu Z, Xu L: Dexmedetomidine reduces brain neuronal injuries but not clinical neurocognitive function in the elderly, compared to midazolam. International Journal of Clinical and Experimental Medicine 2019; 12:4210–7

267.

Wang W, Li HL, Wang DX, Zhu X, Li SL, Yao GQ, Chen KS, Gu XE, Zhu SN: Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: A randomized controlled trial*. Crit Care Med 2022; 40:731–9

268.

Wang W, Ma Y, Liu Y, Wang P, Liu Y: Effects of dexmedetomidine anesthesia on early postoperative cognitive dysfunction in elderly patients. ACS Chem Neurosci 2022; 13:2309–14

269.

Wang Y, Zhang J, Zhang S: Influence of different anesthetic and analgesic methods on early cognitive function of elderly patients receiving non-cardiac surgery. Pak J Med Sci 2016; 32:369–72

270.

Wang Z, Shen Z, Wang H, Zhang L, Dong R: Effect of dexmedetomidine on the cognitive function of patients undergoing gastric cancer surgery by regulating the PI3K/AKT signaling pathway. Oncology Letters 2020; 19:1151–6

271.

Watne LO, Torbergsen AC, Conroy S, Engedal K, Frihagen F, Hjorthaug GA, Juliebo V, Raeder J, Saltvedt I, Skovlund E, Wyller TB: The effect of a pre- and postoperative orthogeriatric service on cognitive function in patients with hip fracture: Randomized controlled trial (oslo orthogeriatric trial). BMC Med 2014; 12:63

272.

Weinstein SM, Poultsides L, Baaklini LR, Mörwald EE, Cozowicz C, Saleh JN, Arrington MB, Poeran J, Zubizarreta N, Memtsoudis SG: Postoperative delirium in total knee and hip arthroplasty patients: A study of perioperative modifiable risk factors. Br J Anaesth 2018; 120:999–1008

273.

Whitlock RP, Devereaux PJ, Teoh KH, Lamy A, Vincent J, Pogue J, Paparella D, Sessler DI, Karthikeyan G, Villar JC, Zuo Y, Avezum A, Quantz M, Tagarakis GI, Shah PJ, Abbasi SH, Zheng H, Pettit S, Chrolavicius S, Yusuf S, Investigators S: Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): A randomised, double-blind, placebo-controlled trial. Lancet 2022; 386:1243–53

274.

Wittwer ED, Cerhan JH, Schroeder DR, Schaff HV, Mauermann WJ: Impact of ketamine versus propofol for anesthetic induction on cognitive dysfunction, delirium, and acute kidney injury following cardiac surgery in elderly, high-risk patients. Ann Card Anaesth 2023; 26:274–80

275.

Wongyingsinn M, Kohmongkoludom P, Trakarnsanga A, Horthongkham N: Postoperative clinical outcomes and inflammatory markers after inguinal hernia repair using local, spinal, or general anesthesia: A randomized controlled trial. PLoS One 2020; 15:e0242925

276.

Wu LP, Kang WQ: Effect of dexmedetomidine for sedation and cognitive function in patients with preoperative anxiety undergoing carotid artery stenting. J Int Med Res 2020; 48:300060520938959

277.

Xiang XB, Chen H, Wu YL, Wang K, Yue X, Cheng XQ: The effect of preoperative methylprednisolone on postoperative delirium in older patients undergoing gastrointestinal surgery: A randomized, double-blind, placebo-controlled trial. J Gerontol A Biol Sci Med Sci 2022; 77:517–23

278.

Xie K, Chen J, Tian L, Gu F, Pan Y, Huang Z, Fang J, Yu W, Zhou H: Postoperative infusion of dexmedetomidine via intravenous patient-controlled analgesia for prevention of postoperative delirium in elderly patients undergoing surgery. Aging Clinical and Experimental Research 2023; 35:2137–44

279.

Xie S, Xie M: Effect of dexmedetomidine on postoperative delirium in elderly patients undergoing hip fracture surgery. Pak J Pharm Sci 2018; 31:2277–81

280.

Xin X, Chen J, Hua W, Wang H: Intraoperative dexmedetomidine for prevention of postoperative delirium in elderly patients with mild cognitive impairment. Int J Geriatr Psychiatry 2021; 36:143–51

281.

Xing C, Yan C: Effects of dexmedetomidine on the incidence of postoperative delirium and plasma s-100βprotein levels following hip surgery in the elderly population. International Journal of Gerontology 2021; 15:207–11

282.

Xu CS, Qu XD, Qu ZJ, Wang G, Wang HJ: Effect of subarachnoid anesthesia combined with propofol target-controlled infusion on blood loss and transfusion for posterior total hip arthroplasty in elderly patients. Chin Med J (Engl) 2020; 133:650–6

283.

Xu HY, Fu GH, Wu GS: Effect of dexmedetomidine-induced anesthesia on the postoperative cognitive function of elder patients after laparoscopic ovarian cystectomy. Saudi J Biol Sci 2017; 24:1771–5

284.

Xu T, Chen X, Li X, Wang M, Wang M: Effect of dexmedetomidine-assisted ultrasound-guided lower extremity nerve block on postoperative cognitive function in elderly patients undergoing hip surgery. Am J Transl Res 2022; 14:7977–84

285.

Yamasaki M, Fukuda Y, Tanimoto A, Narahara M, Kawaguchi Y, Ushiroda H, Fukuda S, Murakami T, Maeda Y: Reduction in the rate of postoperative delirium by switching from famotidine to omeprazole in japanese hepatectomized recipients. J Pharm Health Care Sci 2022; 5:10

286.

Yan C, Ti-jun D: Effects of intraoperative dexmedetomidine infusion on postoperative delirium in elderly patients undergoing total hip arthroplasty. International Surgery 2021; 105:328–35

287.

Yang JJ, Lei L, Qiu D, Chen S, Xing LK, Zhao JW, Mao YY, Yang JJ: Effect of remimazolam on postoperative delirium in older adult patients undergoing orthopedic surgery: A prospective randomized controlled clinical trial. Drug Design, Development and Therapy 2023; 17:143–53

288.

Yang L, Chen Z, Xiang D: Effects of intravenous anesthesia with sevoflurane combined with propofol on intraoperative hemodynamics, postoperative stress disorder and cognitive function in elderly patients undergoing laparoscopic surgery. Pakistan Journal of Medical Sciences 2022; 38

289.

Yin L, Yuan H, Chen X, Liao M, Lu F: Mechanism of action of dexmedetomidine on hemodynamics, analgesic and sedative effects and postoperative delirium in elderly patients undergoing hip fracture surgery. International Journal of Clinical and Experimental Medicine 2020; 13:6703–9

290.

Yoo SH, Jue MJ, Kim YH, Cho S, Kim WJ, Kim KM, Han JI, Lee H: The effect of dexmedetomidine on the mini-cog score and high-mobility group box 1 levels in elderly patients with postoperative neurocognitive disorders undergoing orthopedic surgery. Journal of Clinical Medicine 2023; 12

291.

Yoshimura M, Hidaka Y, Morimoto Y: Association between the use of midazolam during cardiac anesthesia and the incidence of postoperative delirium: A retrospective cohort study using a nationwide database. Journal of Cardiothoracic and Vascular Anesthesia 2023 doi:10.1053/j.jvca.2023.08.147

292.

Yoshimura M, Shiramoto H, Morimoto Y, Koga M: Comparison of total intravenous with inhalational anesthesia in terms of postoperative delirium and complications in older patients: A nationwide population-based study. J Anesth 2022; 36:698–706

293.

Yu DN, Zhu Y, Ma J, Sun Q: Comparison of post-anesthesia delirium in elderly patients treated with dexmedetomidine and midazolam maleate after thoracic surgery. Biomedical Research (India) 2017; 28:6852–5

294.

Yuan X, Dang C, Sun F, Wang Y, Zhang Y: Effects of dexmedetomidine on early cognitive function after laparoscopic colonic surgery in elderly patients. Anti-Tumor Pharmacy 2018; 8:411–4

295.

Yuefeng N, Li Z, Jun C: Effects of dexmedetomidine on short-term prognosis of elderly patients with gastric cancer after laparoscopic radical gastrectomy. Cancer Research and Clinic 2021; 33:134–7

296.

Zangrillo A, Testa V, Aldrovandi V, Tuoro A, Casiraghi G, Cavenago F, Messina M, Bignami E, Landoni G: Volatile agents for cardiac protection in noncardiac surgery: A randomized controlled study. J Cardiothorac Vasc Anesth 2011; 25:902–7

297.

Zarour S, Weiss Y, Kiselevich Y, Iacubovici L, Karol D, Shaylor R, Davydov T, Matot I, Cohen B: The association between midazolam premedication and postoperative delirium - a retrospective cohort study. Journal of Clinical Anesthesia 2023 doi:10.1016/j.jclinane.2023.111113

298.

Zeng Y, Wang Q, Hu J, Yang J: Adding dexamethasone to adductor canal block combined with iPACK block improve postoperative analgesia of total knee arthroplasty. Clinical Journal of Pain 2022; 38:575–81

299.

Zhang H, Wu Z, Zhao X, Qiao Y: Role of dexmedetomidine in reducing the incidence of postoperative cognitive dysfunction caused by sevoflurane inhalation anesthesia in elderly patients with esophageal carcinoma. J Cancer Res Ther 2018; 14:1497–502

300.

Zhang J, Liu G, Zhang F, Fang H, Zhang D, Liu S, Chen B, Xiao H: Analysis of postoperative cognitive dysfunction and influencing factors of dexmedetomidine anesthesia in elderly patients with colorectal cancer. Oncol Lett 2019; 18:3058–64

301.

Zhang L, Zhu B, Zhang L, Tian Z, Zhang X, Lin F: Effects of different doses of dexmedetomidine on stress responses and postoperative cognitive function in spine surgery for elderly patients. International Journal of Clinical and Experimental Medicine 2020; 13:6868–76

302.

Zhang W, Wang T, Wang G, Yang M, Zhou Y, Yuan Y: Effects of dexmedetomidine on postoperative delirium and expression of IL-1β, IL-6, and TNF-αin elderly patients after hip fracture operation. Front Pharmacol 2020; 11:678

303.

Zhang X, Dong Q, Fang J: Impacts of general and spinal anaesthesia on short-term cognitive function and mental status in elderly patients undergoing orthopaedic surgery. J Coll Physicians Surg Pak 2019; 29:101–4

304.

Zhang Y, Shan GJ, Zhang YX, Cao SJ, Zhu SN, Li HJ, Ma D, Wang DX: Propofol compared with sevoflurane general anaesthesia is associated with decreased delayed neurocognitive recovery in older adults. Br J Anaesth 2018; 121:595–604

305.

Zhang Z, Li W, Jia H: Postoperative effects of dexmedetomidine on serum inflammatory factors and cognitive malfunctioning in patients with general anesthesia. J Healthc Eng 2021; 2021:7161901

306.

Zhao W, Hu Y, Chen H, Wang X, Wang L, Wang Y, Wu X, Han F: The effect and optimal dosage of dexmedetomidine plus sufentanil for postoperative analgesia in elderly patients with postoperative delirium and early postoperative cognitive dysfunction: A single-center, prospective, randomized, double-blind, controlled trial. Front Neurosci 2020; 14:549516

307.

Zhao W, Li J, Wang J, Liu M, Yu D: Effect of dexmedetomidine on postoperative cognitive dysfunction and the t helper 17/regulatory t cell balance in geriatric patients undergoing orthopedic surgery: A randomized controlled study. American Journal of Translational Research 2023; 15:2634–44

308.

Zhou M, Lyu Y, Zhu Y, Jiang T, Wu C, Yang J, Wang L: Effect of ulinastatin combined with dexmedetomidine on postoperative cognitive dysfunction in patients who underwent cardiac surgery. Frontiers in Neurology 2019; 10

309.

Zhou Y, Xu T: Effect of propofol and sevoflurane on perioperative and postoperative outcomes in lung cancer patients after thoracoscopic surgery. Tropical Journal of Pharmaceutical Research 2021; 20:873–9

310.

Zhou ZJ, Tang J, Li WH, Tao WD: Preoperative intravenous flurbiprofen reduces postoperative pain and inflammatory cytokines in elderly patients after hip arthroplasty. Exp Ther Med 2019; 17:354–8

311.

Zhu T, Yu J, Ma Y, Qin Y, Li N, Yang H: Effectiveness of perioperative comprehensive evaluation of hip fracture in the elderly. Comput Intell Neurosci 2022; 2022:4124354

312.

Zhu Y, Le G: The effect of dexmedetomidine combined with epidural anesthesia on post-operative cognitive dysfunction in elderly patients after orthopedic surgery. Am J Transl Res 2022; 13:12058–64

313.

Zhu Y, Yao R, Li Y, Wu C, Heng L, Zhou M, Yan L, Deng Y, Zhang Z, Ping L, Wu Y, Wang S, Wang L: Protective effect of celecoxib on early postoperative cognitive dysfunction in geriatric patients. Front Neurol 2018; 9:633