Prevention of post-operative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: a pragmatic, randomized, double-blind, placebo-controlled trial.

BACKGROUND: After cardiac surgery, post-operative delirium (PoD) is acknowledged to have a significant negative impact on patient outcome. To date, there is no valuable and specific treatment for PoD. Critically ill patients often suffer from poor sleep condition. There is an association between delirium and sleep quality after cardiac surgery. This study aimed to establish whether promoting sleep using an overnight infusion of dexmedetomidine reduces the incidence of delirium after cardiac surgery. METHODS: Randomized, pragmatic, multicentre, double-blind, placebo controlled trial from January 2019 to July 2021. All adult patients aged 65 years or older requiring elective cardiac surgery were randomly assigned 1:1 either to the dexmedetomidine group or the placebo group on the day of surgery. Dexmedetomidine or matched placebo infusion was started the night after surgery from 8 pm to 8 am and administered every night while the patient remained in ICU, or for a maximum of 7 days. Primary outcome was the occurrence of postoperative delirium (PoD) within the 7 days after surgery. RESULTS: A total of 348 patients provided informed consent, of whom 333 were randomized: 331 patients underwent surgery and were analysed (165 assigned to dexmedetomidine and 166 assigned to placebo). The incidence of PoD was not significantly different between the two groups (12.6% vs. 12.4%, p = 0.97). Patients treated with dexmedetomidine had significantly more hypotensive events (7.3% vs 0.6%; p < 0.01). At 3 months, functional outcomes (Short-form 36, Cognitive failure questionnaire, PCL-5) were comparable between the two groups. CONCLUSION: In patients recovering from an elective cardiac surgery, an overnight infusion of dexmedetomidine did not decrease postoperative delirium. Trial registration This trial was registered on ClinicalTrials.gov (number: NCT03477344; date: 26th March 2018).

Perioperative Management and Outcomes in Patients With Autism Spectrum Disorder: A Retrospective Cohort Study.

BACKGROUND: Autism spectrum disorder (ASD) is a neurocognitive disorder characterized by impairments in communication and socialization. There are little data comparing the differences in perioperative outcomes in children with and without ASD. We hypothesized that children with ASD would have higher postoperative pain scores than those without ASD. METHODS: Pediatric patients undergoing ambulatory tonsillectomy/adenoidectomy, ophthalmological surgery, general surgery, and urologic procedures between 2016 and 2021 were included in this retrospective cohort study. ASD patients, defined by International Classification of Diseases-9/10 codes, were compared to controls utilizing inverse probability of treatment weighting based on surgical category/duration, age, sex, race and ethnicity, anesthetizing location, American Society of Anesthesiology physical status, intraoperative opioid dose, and intraoperative dexmedetomidine dose. The primary outcome was the maximum postanesthesia care unit (PACU) pain score, and secondary outcomes included premedication administration, behavior at induction, PACU opioid administration, postoperative vomiting, emergence delirium, and PACU length of stay. RESULTS: Three hundred thirty-five children with ASD and 11,551 non-ASD controls were included. Maximum PACU pain scores in the ASD group were not significantly higher than controls (median, 5; interquartile range [IQR], 0-8; ASD versus median, 5; IQR, 0-8 controls; median difference [95% confidence interval {CI}] of 0 [-1.1 to 1.1]; P = .66). There was no significant difference in the use of premedication (96% ASD versus 95% controls; odds ratio [OR], 1.5; [95% CI, 0.9-2.7]; P = .12), but the ASD cohort had significantly higher odds of receiving an intranasal premedication (4.2% ASD versus 1.2% controls; OR, 3.5 [95% CI, 1.8-6.8]; P < .001) and received ketamine significantly more frequently (0.3% ASD versus <0.1% controls; P < .001). Children with ASD were more likely to have parental (4.9% ASD versus 1.0% controls; OR, 5 [95% CI, 2.1-12]; P < .001) and child life specialist (1.3% ASD versus 0.1% controls; OR, 9.9 [95% CI, 2.3-43]; P < .001) presence at induction, but were more likely to have a difficult induction (11% ASD versus 3.4% controls; OR, 3.42 [95% CI, 1.7-6.7]; P < .001). There were no significant differences in postoperative opioid administration, emergence delirium, vomiting, or PACU length of stay between cohorts. CONCLUSIONS: We found no difference in maximum PACU pain scores in children with ASD compared to a similarly weighted cohort without ASD. Children with ASD had higher odds of a difficult induction despite similar rates of premedication administration, and significantly higher parental and child life specialist presence at induction. These findings highlight the need for future research to develop evidence-based interventions to optimize the perioperative care of this population.

Comparison of Remimazolam and Propofol on Postoperative Delirium in Elderly Patients Undergoing Radical Resection of Colon Cancer: A Single-Center Prospective Randomized Controlled Study.

BACKGROUND We compared the effect of remimazolam and propofol intravenous anesthesia on postoperative delirium in elderly patients undergoing laparoscopic radical resection of colon cancer. MATERIAL AND METHODS One hundred patients undergoing elective radical operation of colon cancer under general anesthesia were divided into a remimazolam group (group R) and propofol group (group P) by a random number table method. During anesthesia induction and maintenance, group R was intravenously injected with remimazolam to exert sedation; however, in group P, propofol was injected instead of remimazolam. The occurrence of postoperative delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit scale and postoperative pain was assessed with the visual analogue score (VAS). The primary outcome measures were the incidence and duration of delirium within 7 days following surgery. Secondary outcome measures included postoperative VAS scores, intraoperative anesthetic drug dosage, and adverse reactions, including nausea and vomiting, hypoxemia, and respiratory depression. RESULTS There was no significant difference in baseline data between the 2 groups (P>0.05). There was no statistically significant difference in the incidence and duration of postoperative delirium between the 2 groups (P>0.05). There were no significant differences in VAS scores, remifentanil consumption, and adverse reactions, including nausea and vomiting, hypoxemia, and respiratory depression between the 2 groups (P>0.05). CONCLUSIONS In elderly patients undergoing radical colon cancer surgery, remimazolam administration did not improve or aggravate the incidence and duration of delirium, compared with propofol.

Adverse drug reactions in paediatric surgery: prospective study on frequency and risk related factors.

BACKGROUND: Paediatric patients are especially prone to experiencing adverse drug reactions (ADRs), and the surgical environment gathers many conditions for such reactions to occur. Additionally, little information exists in the literature on ADRs in the paediatric surgical population. We aimed to quantify the ADR frequency in this population, and to investigate the characteristics and risk factors associated with ADR development. METHODS: A prospective observational study was conducted in a cohort of 311 paediatric patients, aged 1-16 years, admitted for surgery at a tertiary referral hospital in Spain (2019-2021). Incidence rates were used to assess ADR frequency. Odds ratios (ORs) were calculated to evaluate the influence of potential risk factors on ADR development. RESULTS: Distinct ADRs (103) were detected in 80 patients (25.7%). The most frequent being hypotension (N = 32; 35%), nausea (N = 16; 15.5%), and emergence delirium (N = 16; 15.5%). Most ADRs occurred because of drug-drug interactions. The combination of sevoflurane and fentanyl was responsible for most of these events (N = 32; 31.1%). The variable most robustly associated to ADR development, was the number of off-label drugs prescribed per patient (OR = 2.99; 95% CI 1.73 to 5.16), followed by the number of drugs prescribed per patient (OR = 1.26, 95% CI 1.13 to 1.41), and older age (OR = 1.26, 95% CI 1.07 to 1.49). The severity of ADRs was assessed according to the criteria of Venulet and the Spanish Pharmacovigilance System. According to both methods, only four ADRs (3.9%) were considered serious. CONCLUSIONS: ADRs have a high incidence rate in the paediatric surgical population. The off-label use of drugs is a key risk factor for ADRs development.

Postoperative Delirium after Dexmedetomidine versus Propofol Sedation in Healthy Older Adults Undergoing Orthopedic Lower Limb Surgery with Spinal Anesthesia: A Randomized Controlled Trial.

BACKGROUND: Delirium is a critical postoperative complication in older patients. Based on the hypothesis that intraoperative dexmedetomidine sedation would lower postoperative delirium than propofol sedation would, the authors compared the incidence of postoperative delirium in older adults, using the mentioned sedatives. METHODS: This double-blinded, randomized controlled study included 748 patients, aged 65 yr or older, who were scheduled for elective lower extremity orthopedic surgery, between June 2017 and October 2021. Patients were randomized equally into two groups in a 1:1 ratio according to the intraoperative sedative used (dexmedetomidine vs. propofol). The postoperative delirium incidence was considered the primary outcome measure; it was determined using the confusion assessment method, on the first three postoperative days. The mean arterial pressure and heart rate were evaluated as secondary outcomes. RESULTS: The authors enrolled 732 patients in the intention-to-treat analyses. The delirium incidence was lower in the dexmedetomidine group than in the propofol group (11 [3.0%] vs. 24 [6.6%]; odds ratio, 0.42; 95% CI, 0.201 to 0.86; P = 0.036). During sedation, the mean arterial pressure (median [interquartile range] mmHg) was higher in the dexmedetomidine group (77 [71 to 84]) than in the propofol group (74 [69 to 79]; P < 0.001); however, it significantly fell lower (74 [68 to 80]) than that of the propofol group (80 [74 to 87]) in the postanesthesia care unit (P < 0.001). Lower heart rates (beats/min) were recorded with the use of dexmedetomidine than with propofol, both during sedation (60 [55 to 66] vs. 63 [58 to 70]) and in the postanesthesia care unit (64 [58 to 72] vs. 68 [62-77]; P < 0.001). CONCLUSIONS: Dexmedetomidine showed a lower incidence of postoperative delirium than propofol in healthy older adults undergoing lower extremity orthopedic surgery.

The Efficacy of Ramelteon to Prevent Postoperative Delirium After General Anesthesia in the Elderly: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: Postoperative delirium is common and serious in elderly patients. Several drugs have been proposed as potential prophylactic agents for postoperative delirium. Studies on melatonin receptor agonists showed heterogeneity in age, cognitive function, anesthesia, surgery, interventions, methodologies for assessing outcomes, and results. Our objective was to examine the effect of ramelteon to prevent postoperative delirium in elderly patients, including those with dementia. DESIGN: A stratified, double-blind, randomized, placebo-controlled trial (UMIN000028436, jRCTs031180054). SETTING: Tertiary medical center. PARTICIPANTS: Patients aged older than or equal to 65 years undergoing elective surgery under general anesthesia. INTERVENTION: Ramelteon (8 mg orally) or placebo (lactose) for six nights (the preoperative night and five consecutive nights from postoperative day 1 to 5) at around 9 P.M. MEASUREMENTS: Patients were screened for postoperative delirium using the Confusion Assessment Method for the Intensive Care Unit twice daily until the sixth postoperative day. Patients with positive results were referred to a consultant psychiatrist to establish the diagnosis of delirium. RESULTS: A total of 108 patients were randomly assigned to receive ramelteon (n = 55) or placebo (n = 53). Most of the patients' characteristics were reasonably well-balanced between the two groups. The stratified log-rank test showed no significant difference in preventing postoperative delirium between ramelteon and placebo (χ2 = 0.30, degrees of freedom = 1, p = 0.60). The Cox proportional hazard ratio for ramelteon compared to placebo was 1.40 (95% confidence interval: 0.40-4.85, χ2 for likelihood ratio test = 0.29, degrees of freedom = 1, p = 0.60). CONCLUSION: There was no significant difference in the incidence of postoperative delirium between ramelteon and placebo after general anesthesia in elderly patients.

Benzodiazepines and postoperative delirium: should we be as cautious as we are?

A recent systematic review and meta-analysis by Wang and colleagues in the British Journal of Anaesthesia calls into question the concept that perioperative benzodiazepine administration is associated with development of postoperative delirium in older individuals after anaesthesia and surgery. This editorial focuses on potential bias within the systematic review and addresses major concerns surrounding benzodiazepine use in the older perioperative population.

Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial.

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 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 anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).

Prevalence and risk factors of emergence agitation among pediatric patients undergo ophthalmic and ENT Surgery: a cross-sectional study.

BACKGROUND: Some studies reported that pediatric patients undergoing otorhinolaryngology (ENT) and ophthalmic surgeries have higher incidences of emergence agitation (EA). Children with EA tend to carry the risk of self-harm, have longer periods of recovery and delayed hospital discharge. Consequently, EA needs to be monitored and risk factors ought to be emphasized to implement preventative measures. The objective of this study was to describe EA and to identify risk factors after pediatric ophthalmic or ENT surgery. METHODS: Between September 2021 and December 2021, a cross-sectional study was conducted in 100 children aged of 0-12 years who underwent ophthalmic or ENT surgery. The Watcha scale was used to observe and record EA, which was defined at levels of 3 or 4 at any time in the post-anesthesia care unit (PACU). The pain intensity was graded with the Face, Legs, Activity, Cry, Consolability (FLACC) Scale after surgery. Patient and surgery-related characteristics, the behavioral criteria of EA, the pharmacologic and non-pharmacologic interventions and recovery outcomes were objectively recorded. A binary logistic regression model was constructed to identify the associated factors of EA. RESULTS: From the 100 analyzed children, 58 were males and 42 were females, and 44 patients received ophthalmic surgery and 56 ENT surgery. The median age was 6 (IQR 4-7) years. The overall incidence of EA among pediatrics was 30% (34.5% for ENT and 24.4% for ophthalmic surgery). High preoperative modified Yale Preoperative Anxiety scale (m-YPAS) grade (OR = 1.19, 95%CI 1.06-1.33, P = 0.003) and high postoperative FLACC score (OR = 3.36, 95%CI 1.88-6.02, P < 0.001) were risk factors for EA. CONCLUSIONS: This study identified that preoperative anxiety and postoperative pain are associated with EA in children after ophthalmic or ENT surgery. Preoperative anxiety assessment and management, and administration of adjunct analgesic treatments should be considered in the routine care.

A Comparison of Dexmedetomidine and Propofol on Emergence Delirium in Children Undergoing Cleft Palate Surgery With Sevoflurane-Based Anesthesia.

ABSTRACT: Emergence delirium is a common complication after sevoflurane-anesthesia and have a serious impact on children undergoing cleft palate surgery. The aim of this study was to compare the effect of propofol and dexmedetomidine on emergence delirium in children. Ninety children aged 8 to 24 months, underwent cleft palate repair, were enrolled in the study. Children were randomly assigned to 3 groups after the induction: Group C (intravenous infusion 0.9% saline), Group P (intravenous infusion 2 mg/kg/hour propofol), and Group D (intravenous infusion 0.5 µg/kg/hour dexmedetomidine). Emergence delirium was diagnosed using the pediatric anesthesia emergence delirium scale and pain using the face, legs, activity, cry, consolability scale. Heart rate, mean arterial pressure, respiratory recovery time, extubation time, post anesthesia care unit observation time, and adverse events were also evaluated. A total of 86 patients were analyzed. The incidence of emergence delirium was 20.1% in group D, 58.6% in group P and 85.7% in group C (P < 0.05). A lower face, legs, activity, cry, consolability score was seen in group D than in group P and group C (3.9 + 1.1 versus 6.1 ±â€Š0.9 and 7.1 ±â€Š1.0, P < 0.05). The value of heart rate and mean arterial pressure during emergence in group P and group C were significantly higher than that in group D (All P < 0.05). These findings suggest that dexmedetomidine as a sedative, analgesic, and sympatholytic agent was superior to propofol in reducing the incidence of emergence delirium in children undergoing cleft palates surgery with sevoflurane-based anesthesia.

Adult Emergence Agitation: A Veteran-Focused Narrative Review.

Emergence agitation (EA) is a self-limited state of psychomotor excitement during awakening from general anesthesia. EA is confined to the emergence period as consciousness is restored, which sharply distinguishes it from other postoperative delirium states. Sporadic episodes of EA may become violent with the potential for harm to both patients and caregivers, but the long-term consequences of such events are not fully understood. Current literature on EA in adults is limited to small-scale studies with inconsistent nomenclature, variable time periods that define emergence, a host of different surgical populations, and conflicting diagnostic criteria. Therefore, true incidence rates and risk factors are unknown. In adult noncardiac surgery, the incidence of EA is approximately 19%. Limited data suggest that young adults undergoing otolaryngology operations with volatile anesthetic maintenance may be at the highest risk for EA. Currently suggested EA mechanisms are theoretical but might reflect underblunted sympathetic activation in response to various internal (eg, flashbacks or anxiety) or external (eg, surgical pain) stimuli as consciousness returns. Supplemental dexmedetomidine and ketamine may be utilized for EA prevention. Compared to the civilian population, military veterans may be more vulnerable to EA due to high rates of posttraumatic stress disorder (PTSD) manifesting as violent flashbacks; however, confirmatory data are limited. Nonetheless, expert military medical providers suggest that use of patient-centered rapport tactics, PTSD trigger identification and avoidance, and grounding measures may alleviate hyperactive emergence phenomena. Future research is needed to better characterize EA in veterans and validate prophylactic measures to optimize care for these patients. This narrative review provides readers with an important framework to distinguish EA from delirium. Furthermore, we summarize current knowledge of EA risk factors, mechanisms, and adult management strategies and specifically revisit them in the context of veteran perioperative health. The anesthesiology care team is ideally positioned to further explore EA and develop effective prevention and treatment protocols.

Risk factors for emergence agitation in adults after general anesthesia: A systematic review and meta-analysis.

BACKGROUND: Emergence agitation (EA) is an adverse post-operative complication that increases the risk for injury, self-extubation, hemorrhages, and prolonged hospitalization. This meta-analysis aims to define the risk factors for adult EA after general anesthesia and provide recommendations for clinical practice. METHODS: Embase, PubMed, Medline, and the Cochrane Library databases were comprehensive retrieved. Observational studies that reported the risk factors for adult EA were enrolled. Review Manager 5.4 was used to analyze the extracted data. RESULTS: Eighteen observational studies involving 16, 678 adult patients were enrolled in this study. Eighteen pre-operative and nineteen intraoperative factors with unadjusted data, and five pre-operative and five intraoperative factors with adjusted data were meta-analyzed separately. Among them, seven factors (age, male, smoking, history of substance misuse, inhalational anesthesia, urinary catheter, complain of pain, or need analgesic drug use in post-anesthetic care unit) were the risk factors no matter meta-analyzed by unadjusted data or adjusted data. Intraoperative use of benzodiazepines was the risk factor when meta-analyzed by adjusted data, but not unadjusted data. Moreover, age and inhalational anesthesia were not the risk factors when omitted one study for sensitivity analysis, and history of substance misuse could not do sensitivity analysis. CONCLUSION: Based on this meta-analysis, male, smoking, urinary catheter, and post-operative pain are the risk factors, while age, inhalational anesthesia, history of substance misuse, and intraoperative use of benzodiazepines are the possible risk factors for adult EA. EDITORIAL COMMENT: This systematic review and meta-analysis identify risk factors associated with the occurrence of agitation during emergence from general anesthesia. As might be expected, the strongest factors are generally things which are irritating or painful for patients, but cannot necessarily be avoided.

The frequency of emergence delirium in children undergoing outpatient anaesthesia for magnetic resonance imaging.

AIM: The aim of this study was to investigate the effect on the occurrence of emergence delirium of propofol and ketofol with intranasal dexmedetomidine and midazolam applied as premedication to paediatric patients during magnetic resonance imaging (MRI). METHODS: The study included children aged 2-10 years who received sedation for MRI, separated into four groups. Group MP (midazolam-propofol) received intranasal midazolam (0.2 mg/kg) for premedication and intravenous (IV) propofol (1 mg/kg) as the anaesthetic agent. Group MK (midazolam-ketofol) received intranasal midazolam (0.2 mg/kg) for premedication and IV ketofol (1 mg/kg) as the anaesthetic agent. Group DP (dexmedetomidine-propofol) received intranasal dexmedetomidine (1 mcg/kg) for premedication and IV propofol (1 mg/kg) as the anaesthetic agent. Group DK (dexmedetomidine-ketofol) received intranasal dexmedetomidine (1 mcg/kg) for premedication and IV ketofol (1 mg/kg) as the anaesthetic agent. The Paediatric Anaesthesia Emergence Delirium (PAED) scale was used to evaluate delirium. A PAED score ≥ 10 was accepted as delirium. RESULTS: Statistical analysis was made of 140 paediatric patients. Delirium developed in 1.42% of all the patients, and in 5.7% of Group MP. The mean Aldrete and PAED scores were lower and the length of stay in the recovery room was shorter in Group DP than in the other groups. The need for additional anaesthetic was highest in Group DP at 94.3% and lowest in Group DK at 14.3%. The groups administered ketofol were observed to have a lower requirement for additional anaesthetic. CONCLUSION: Delirium was seen at a very low rate only in the Group MP and it is difficult to say the best combination in terms of delirium frequency. However, intranasal dexmedetomidine and IV ketofol seem to be better and safer than the other groups in terms of the need for additional doses and the number of side effects. The addition of ketamine to propofol reduces the need for additional doses with a synergistic effect.

Dexmedetomidine vs. total intravenous anaesthesia in paediatric emergence delirium: A network meta-analysis.

BACKGROUND: Emergence delirium is a common complication in paediatric anaesthesia associated with significant morbidity. Total intravenous anaesthesia (TIVA) and intra-operative dexmedetomidine as an adjuvant to sevoflurane anaesthesia can both reduce the incidence of emergence delirium compared with sevoflurane alone, but no studies have directly compared their relative efficacy. OBJECTIVE: The study objective was to compare the effects of TIVA and dexmedetomidine on the incidence of paediatric emergence delirium. STUDY DESIGN: The current study is a systematic review and network meta-analysis (NMA) of randomised controlled trials. DATA SOURCES: We conducted a systematic search of 12 databases including Medline (Ovid) and Web of Science (Clarivate Analytics) from their respective inception to December 2020. ELIGIBILITY: Inclusion criteria were randomised controlled trials of paediatric patients undergoing general anaesthesia using sevoflurane, sevoflurane with dexmedetomidine or TIVA. Data were extracted by two reviewers according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and analysed using NMA methodology. Risk ratios and 95% credible intervals (CrI) were calculated for all outcomes [emergence delirium, postoperative nausea and vomiting (PONV), and time to emergence and extubation]. The protocol was registered with PROSPERO (CRD42018091237). RESULTS: The systematic review returned 66 eligible studies comprising 5257 patients with crude median emergence delirium incidences of 12.8, 9.1 and 40% in the dexmedetomidine with sevoflurane, TIVA and sevoflurane alone groups, respectively. NMA indicated that compared with TIVA, sevoflurane with adjuvant dexmedetomidine decreased the incidence of emergence delirium without statistical difference (risk ratio 0.88, 95% CrI 0.61 to 1.20, low quality of evidence), but resulted in a higher incidence of PONV (risk ratio: 2.3, 95% CrI 1.1 to 5.6, low quality of evidence). CONCLUSION: Clinical judgement, considering the patient's risk factors for the development of clinically significant outcomes such as emergence delirium and PONV, should be used when choosing between TIVA and sevoflurane with adjuvant dexmedetomidine. These findings are limited by the low quality of evidence (conditional recommendation).

Association between Use of Angiotensin-converting Enzyme Inhibitors or Angiotensin Receptor Blockers and Postoperative Delirium.

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improve cognitive function. The authors therefore tested the primary hypothesis that preoperative use of angiotensin inhibitors is associated with less delirium in critical care patients. Post hoc, the association between postoperative use of angiotensin system inhibitors and delirium was assessed. METHODS: The authors conducted a single-site cohort study of adults admitted to Cleveland Clinic critical care units after noncardiac procedures between 2013 and 2018 who had at least one Confusion Assessment Method delirium assessment. Patients with preexisting dementia, Alzheimer's disease or other cognitive decline, and patients who had neurosurgical procedures were excluded. For the primary analysis, the confounder-adjusted association between preoperative angiotensin inhibitor use and the incidence of postoperative delirium was assessed. Post hoc, the confounder-adjusted association between postoperative angiotensin system inhibitor use and the incidence of delirium was assessed. RESULTS: The incidence of delirium was 39% (551 of 1,396) among patients who were treated preoperatively with angiotensin system inhibitors and 39% (1,344 of 3,468) in patients who were not. The adjusted odds ratio of experiencing delirium during critical care was 0.98 (95% CI, 0.86 to 1.10; P = 0.700) for preoperative use of angiotensin system inhibitors versus control. Delirium was observed in 23% (100 of 440) of patients who used angiotensin system inhibitors postoperatively before intensive care discharge, and in 41% (1,795 of 4,424) of patients who did not (unadjusted P < 0.001). The confounder-adjusted odds ratio for experiencing delirium in patients who used angiotensin system inhibitors postoperatively was 0.55 (95% CI, 0.43 to 0.72; P < 0.001). CONCLUSIONS: Preoperative use of angiotensin system inhibitors is not associated with reduced postoperative delirium. In contrast, treatment during intensive care was associated with lower odds of delirium. Randomized trials of postoperative angiotensin-converting enzymes inhibitors and angiotensin receptor blockers seem justified.

Comparison of Bispectral Index-Guided Individualized Anesthesia with Standard General Anesthesia on Inadequate Emergence and Postoperative Delirium in Elderly Patients Undergoing Esophagectomy: A Retrospective Study at a Single Center.

BACKGROUND Elderly patients are susceptible to general anesthetics, with a higher bispectral index (BIS) at loss of consciousness (LOC) achieved by propofol infusion compared with young patients. Overexposure to general anesthetics can have adverse effects such as inadequate emergence and postoperative delirium (PD). This study aimed to compare the effects of BIS-guided individualized anesthesia with standard general anesthesia on emergence and delirium after esophagectomy. MATERIAL AND METHODS Data on 161 elderly patients undergoing esophagectomy for cancer were retrospectively obtained from electronic medical records. We performed propensity score matching analysis between patients receiving individualized anesthesia (BIS value maintained at about 10 less than the value at LOC) and those receiving standard anesthesia (BIS value maintained at 40-60). In addition, we conducted univariate and multivariate logistic -analyses in the entire cohort. RESULTS Patients receiving individualized anesthesia had higher BIS values and a lower propofol requirement during surgery than those receiving standard general anesthesia (P<0.05). The overall incidences of inadequate emergence and PD were 37.9% and 18.0% (n=161), respectively. Logistic regression analysis revealed that the independent risk factors for PD were organic brain disease (odds ratio [OR] 6.308; 95% confidence interval [CI] 2.458-16.187) and inadequate emergence (OR 4.063; 95% CI 1.645-10.033). CONCLUSIONS BIS-guided individualized anesthesia (lighter) does not reduce inadequate emergence or PD compared with standard general anesthesia in elderly patients undergoing esophagectomy. Independent risk factors for PD include organic brain disease and inadequate emergence.

Comparative efficacy of ancillary drugs in sevoflurane-related emergence agitation after paediatric adenotonsillectomy: A Bayesian network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: The comparative efficacy of ancillary drugs on sevoflurane-related emergence agitation (EA) in paediatric anaesthesia for adenotonsillectomy remains unclear. The purpose of this Bayesian network meta-analysis was to investigate the efficacy of ancillary drugs on sevoflurane-related EA in paediatric anaesthesia for adenotonsillectomy. METHODS: MEDLINE, Embase, the Cochrane Library and Web of Science databases were electronically searched to identify randomized controlled trials (RCTs) of different ancillary drugs used in adenotonsillectomy from inception to April 2019. Two reviewers independently screened the literature, extracted data and assessed the risk of bias in included studies. Subsequently, a network meta-analysis was performed using the R software and RevMan 5.3 software. RESULTS AND DISCUSSION: We included 25 RCTs, involving 2151 participants. The proportion of patients with sevoflurane-related EA was significantly lower in the dexmedetomidine, ketamine, propofol, fentanyl, midazolam, sufentanil, remifentanil and clonidine groups than in the placebo group (P < .05). Fentanyl was superior to sufentanil (P < .05), whereas dexmedetomidine was superior to fentanyl (P < .05). Among ancillary drugs, dexmedetomidine (90.04%) showed the highest possibility of reducing the risk of EA, followed by fentanyl (87.45%), remifentanil (63.85%), ketamine (52.07%), midazolam (51.27%), clonidine (49.94%), propofol (29.89%), sufentanil (21.38%) and placebo (4.09%). WHAT IS NEW AND CONCLUSION: Evidence suggests that the effects of dexmedetomidine in reducing the risk of sevoflurane-related EA in paediatric anaesthesia for adenotonsillectomy were better than the effects of other drugs. However, large, high-quality RCTs are required to further confirm this.

Intraoperative electroencephalogram suppression at lower volatile anaesthetic concentrations predicts postoperative delirium occurring in the intensive care unit.

BACKGROUND: Postoperative delirium is a common complication associated with increased morbidity and mortality. A recently-reported association between intraoperative electroencephalogram suppression and postoperative delirium might be mediated in some patients by a heightened sensitivity to volatile anaesthetics. METHODS: This retrospective cohort study included 618 elective surgery patients with planned intensive care unit admission, who also received intraoperative electroencephalogram monitoring and had delirium assessments documented in the medical record. Sensitivity to volatile anaesthetics was assessed using a mixed effects model predicting the likelihood of electroencephalogram suppression at each time point based on the current end-tidal anaesthetic concentration. Patients with a random intercept above the population median (electroencephalogram suppression at lower anaesthetic concentrations) were classified as having heightened sensitivity to volatile anaesthetics. Delirium was defined as a positive Confusion Assessment Method for the Intensive Care Unit assessment anytime in the first five postoperative days. RESULTS: Postoperative delirium was observed in 162 of 618 patients (26%). Patients who experienced electroencephalogram suppression at lower volatile anaesthetic concentrations had a higher incidence of postoperative delirium [109/309 (35%)] than other patients [53/309 (17%)] [unadjusted odds ratio 2.63; 95% confidence interval (CI), 1.81-3.84, P<0.001]. This association remained significant after adjusting for patient characteristics, surgical variables, and duration of electroencephalogram suppression (adjusted odds ratio 2.13; 95% CI 1.24-3.65, P=0.006). CONCLUSIONS: These data support the hypothesis that patients with electroencephalogram suppression at lower volatile anaesthetic concentrations have an increased incidence of postoperative delirium. Such patients appear to exhibit a phenotype of anaesthetic sensitivity, which might predispose them to adverse cognitive outcomes.

Delineating the Trajectory of Cognitive Recovery From General Anesthesia in Older Adults: Design and Rationale of the TORIE (Trajectory of Recovery in the Elderly) Project.

BACKGROUND: Mechanistic aspects of cognitive recovery after anesthesia and surgery are not yet well characterized, but may be vital to distinguishing the contributions of anesthesia and surgery in cognitive complications common in the elderly such as delirium and postoperative cognitive dysfunction. This article describes the aims and methodological approach to the ongoing study, Trajectory of Recovery in the Elderly (TORIE), which focuses on the trajectory of cognitive recovery from general anesthesia. METHODS: The study design employs cognitive testing coupled with neuroimaging techniques such as functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labeling to characterize cognitive recovery from anesthesia and its biological correlates. Applying these techniques to a cohort of age-specified healthy volunteers 40-80 years of age, who are exposed to general anesthesia alone, in the absence of surgery, will assess cognitive and functional neural network recovery after anesthesia. Imaging data are acquired before, during, and immediately after anesthesia, as well as 1 and 7 days after. Detailed cognitive data are captured at the same time points as well as 30 days after anesthesia, and brief cognitive assessments are repeated at 6 and 12 months after anesthesia. RESULTS: The study is underway. Our primary hypothesis is that older adults may require significantly longer to achieve cognitive recovery, measured by Postoperative Quality of Recovery Scale cognitive domain, than younger adults in the immediate postanesthesia period, but all will fully recover to baseline levels within 30 days of anesthesia exposure. Imaging data will address systems neuroscience correlates of cognitive recovery from general anesthesia. CONCLUSIONS: The data acquired in this project will have both clinical and theoretical relevance regardless of the outcome by delineating the mechanism behind short-term recovery across the adult age lifespan, which will have major implications for our understanding of the effects of anesthetic drugs.

Effects of remifentanil maintenance during recovery on emergence delirium in children with sevoflurane anesthesia.

BACKGROUND: Emergence delirium is a common complication of sevoflurane anesthesia in children. AIMS: We examined the effects of maintaining remifentanil infusion during the recovery period on the incidence of emergence delirium in preschool-age children undergoing strabismus surgery under sevoflurane anesthesia. METHODS: Eighty children (aged 3-7 years) were randomly assigned to either the control group (group C; intraoperative remifentanil infusion) or the intervention group (group R; intraoperative remifentanil infusion followed by remifentanil maintenance during the recovery phase). Intraoperative remifentanil infusion (0.2 µg/kg/min) was discontinued upon surgery completion in the group C, and was maintained until the discharge criteria were met at a dose of 0.05 µg/kg/min in the group R. The incidence of emergence delirium was assessed using a five-point agitation scale and the Pediatric Anesthesia Emergence Delirium scale after arrival in the postanesthesia care unit. Postoperative pain was assessed using the Children's Hospital of Eastern Ontario Pain Scale. RESULTS: The incidence of emergence delirium according to the five-point agitation scale (scores ≥ 4) was lower in the group R (33.3%) compared to the group C (68.3%) (odds ratio 0.206; 95% CI 0.080 to 0.531; P = 0.002). Similar results were obtained using the Pediatric Anesthesia Emergence Delirium scale (scores > 12), with an incidence of 5.1% in the group R and 34.0% in the control group (odds ratio 0.104; 95% CI 0.022 to 0.497; P = 0.001). The Children's Hospital of Eastern Ontario Pain Scale scores and occurrence of postoperative adverse events including laryngospasm, desaturation, nausea, and vomiting were similar between the two groups. CONCLUSION: Maintaining a low dose of remifentanil (0.05 µg/kg/min) throughout the recovery phase attenuated the incidence of emergence delirium in children undergoing strabismus surgery under sevoflurane anesthesia.