Effect of intraoperative dexmedetomidine on long-term survival in older patients after major noncardiac surgery: 3-year follow-up of a randomized trial.

STUDY OBJECTIVE: To assess the impact of intraoperative dexmedetomidine on long-term outcomes of older patients following major noncardiac surgery mainly for cancer. DESIGN: A long-term follow-up of patients enrolled in a randomized trial. SETTING: The initial trial was performed in a tertiary care hospital in Beijing, China. PARTICIPANTS: Patients aged 60 years or older who were scheduled for major noncardiac surgery. INTERVENTION: Participants were randomized to receive either dexmedetomidine (a loading dose of 0.6 µg/kg over 10 min, followed by a continuous infusion of 0.5 µg/kg/h until 1 h before end of surgery) or placebo during anesthesia. MEASUREMENTS: The primary endpoint was overall survival. Secondary endpoints included recurrence-free survival and event-free survival. Cox proportional hazard models were used to adjust for predefined confounding factors. Propensity score matching was employed for sensitive analysis. RESULTS: Among 620 patients who were randomized in the initial trial, 619 were included in the long-term analysis (mean age 69 years, 40% female, 77% oncological surgery). The median follow-up duration was 42 months (interquartile range 41 to 45). Overall survival did not differ between the two groups: there were 49/309 (15.9%) deaths with dexmedetomidine versus 63/310 (20.3%) with placebo (adjusted hazard ratio [HR] 0.78, 95% CI 0.53-1.13, P = 0.187). Recurrence-free survival was improved with dexmedetomidine (68/309 [22.0%] events with dexmedetomidine versus 98/310 [31.6%] with placebo; adjusted HR 0.67, 95% CI 0.49-0.92, P = 0.012). Event-free survival was also improved with dexmedetomidine (120/309 [38.8%] events with dexmedetomidine versus 145/310 [46.8%] with placebo; adjusted HR 0.78, 95% CI 0.61-1.00, P = 0.047). Results were similar after propensity-score matching and in the subgroup of cancer patients. CONCLUSIONS: In older patients having major noncardiac surgery mainly for cancer, intraoperative dexmedetomidine did not improve overall survival but was associated with improved recurrence-free and event-free survivals.

The effect of dexmedetomidine on intraoperative blood glucose homeostasis: secondary analysis of a randomized controlled trial.

PURPOSE: To investigate the effect of dexmedetomidine on intraoperative blood glucose hemostasis in elderly patients undergoing non-cardiac major surgery. METHODS: This was secondary analysis of a randomized controlled trial. Patients in dexmedetomidine group received a loading dose dexmedetomidine (0.6 µg/kg in 10 min before anaesthesia induction) followed by a continuous infusion (0.5 µg/kg/hr) till 1 h before the end of surgery. Patients in control group received volume-matched normal saline at the same time interval. Primary outcome was the incidence of intraoperative hyperglycemia (blood glucose higher than 10 mmol/L). RESULTS: 303 patients in dexmedetomidine group and 306 patients in control group were analysed. The incidence of intraoperative hyperglycemia showed no statistical significance between dexmedetomidine group and control group (27.4% vs. 22.5%, RR = 1.22, 95%CI 0.92-1.60, P = 0.167). Median value of glycemic variation in dexmedetomidine group (2.5, IQR 1.4-3.7, mmol) was slightly lower than that in control group (2.6, IQR 1.5-4.0, mmol), P = 0.034. In multivariable logistic analysis, history of diabetes (OR 3.007, 95%CI 1.826-4.950, P < 0.001), higher baseline blood glucose (OR 1.353, 95%CI 1.174-1.560, P < 0.001) and prolonged surgery time (OR 1.197, 95%CI 1.083-1.324, P < 0.001) were independent risk factors of hyperglycaemia. CONCLUSIONS: Dexmedetomidine presented no effect on intraoperative hyperglycemia in elderly patients undergoing major non-cardiac surgery. TRIAL REGISTRATION: Present study was registered at Chinese Clinical Trial Registry on December 1, 2015 ( www.chictr.org.cn , registration number ChiCTR-IPR-15007654).

The diagnostic threshold of Cornell assessment of pediatric delirium in detection of postoperative delirium in pediatric surgical patients.

BACKGROUND: Cornell assessment of pediatric delirium (CAPD) showed advantage in diagnosis of pediatric delirium in Chinese critically ill patients. But its performance in surgical patients is still unclear. The present study was designed to validate the diagnostic performance of CAPD in surgical pediatric patients. METHODS: This is a prospective validation study. Pediatric patients who underwent selective surgery and general anesthesia were enrolled. Primary outcome was the incidence of delirium within postoperative three days. CAPD Chinese version was used to evaluate if the patient had delirium one time per day. At the meantime, a psychiatrist employed Diagnostic and Statistical Manual of Mental Disorders fifth edition to diagnose delirium, which was the "gold standard", and the result was considered as reference standard. Sensitivity, specificity and area under receiver operating characteristic (ROC) curve were calculated to investigate the performance of CAPD. RESULTS: A total of 170 patients were enrolled. Median age was 4 years old. As diagnosed by psychiatrist, 23 (13.5 %) patients experienced at least one episode of delirium during the follow-up period. When diagnostic threshold was set at 9, CAPD showed the optimal sensitivity (87.0 %, 95 %CI 65.3 %-96.6 %) and specificity (98.0 %, 95 %CI 93.7 %-99.5 %) in comparison with other diagnostic thresholds. ROC analysis showed that CAPD was a good delirium assessment instrument with area under curve of 0.911 (95 % CI 0.812 to 1.000, P < 0.001). Agreement between CAPD and reference standard was 0.849 (Kappa coefficient, P < 0.001). CONCLUSIONS: This study found that Cornell assessment of pediatric delirium could be used as an effective instrument in diagnosis of delirium in pediatric surgical patients. TRIAL REGISTRATION: www.chictr.org.cn Identifier: ChiCTR-DDD-17,012,231, August 3, 2017.

The sensitivity and specificity of statistical rules for diagnosing delayed neurocognitive recovery with Montreal cognitive assessment in elderly surgical patients: A cohort study.

Delayed neurocognitive recovery (DNR) is common in elderly patients after major noncardiac surgery. This study was designed to investigate the best statistical rule in diagnosing DNR with the Montreal cognitive assessment (MoCA) in elderly surgical patients.This was a cohort study. One hundred seventy-five elderly (60 years or over) patients who were scheduled to undergo major noncardiac surgery were enrolled. A battery of neuropsychological tests and the MoCA were employed to test cognitive function at the day before and on fifth day after surgery. Fifty-three age- and education-matched nonsurgical control subjects completed cognitive assessment with the same instruments at the same time interval. The definition of the international study of postoperative cognitive dysfunction (ISPOCD 1) was adopted as the standard reference for diagnosing DNR. With the MoCA, the following rules were used to diagnose DNR: the cut-off point of ≤26; the 1 standard deviation decline from baseline; the 2 scores decline from baseline; and the Z score of ≥1.96. The sensitivity and specificity as well as the area under receiver operating characteristic curve for the above rules in diagnosis of DNR were calculated.The incidence of DNR was 13.1% (23/175) according to the ISPOCD1 definition. When compared with the standard reference, the 2 scores rule showed the best combination of sensitivity (82.6%, 95% confidence interval [CI] 67.1%-98.1%) and specificity (82.2%, 95% CI 76.2%-88.3%); it also had the largest area under receiver operating characteristic curve (0.824, 95% CI 0.728-0.921, P < .001). The cut-off point rule showed high sensitivity (95.7%) and low specificity (37.5%), whereas the 1 standard deviation and the Z score rules showed low sensitivity (47.8% and 21.7%, respectively) and high specificity (93.4% and 97.3%, respectively).Compared with the ISPOCD1 definition, the 2 scores rule with MoCA had the best combination of sensitivity and specificity to diagnose DNR.

Impact of dexmedetomidine infusion during general anaesthesia on incidence of postoperative delirium in elderly patients after major non-cardiac surgery: study protocol of a randomised, double-blinded and placebo-controlled trial.

INTRODUCTION: Delirium is a common complication in the elderly after surgery and is associated with worse outcomes. Multiple risk factors are related with postoperative delirium, such as exposure to general anaesthetics, pain and postoperative inflammatory response. Preclinical and clinical studies have shown that dexmedetomidine attenuated neurotoxicity induced by general anaesthetics, improved postoperative analgesia and inhibited inflammatory response after surgery. Several studies found that intraoperative use of dexmedetomidine can prevent postoperative delirium, but data were inconsistent. This study was designed to investigate the impact of dexmedetomidine administered during general anaesthesia in preventing delirium in the elderly after major non-cardiac surgery. METHODS AND ANALYSIS: This is a randomised, double-blinded and placebo-controlled trial. 620 elderly patients (age ≥60 years) who are scheduled to undertake elective major non-cardiac surgery (with an expected duration ≥2 hours) are randomly divided into two groups. For patients in the dexmedetomidine group, a loading dose dexmedetomidine (0.6 µg/kg) will be administered 10 min before anaesthesia induction, followed by a continuous infusion at a rate of 0.5 µg/kg/hour until 1 hour before the end of surgery. For patients in the control group, normal saline will be administered with an identical rate as in the dexmedetomidine group. The primary endpoint is the incidence of delirium during the first five postoperative days. The secondary endpoints include pain intensity, cumulative opioid consumption and subjective sleep quality during the first three postoperative days, as well as the incidence of non-delirium complications and all-cause mortality within 30 days after surgery. ETHICS AND DISSEMINATION: The study protocol was approved by the Clinical Research Ethics Committee of Peking University First Hospital (2015-987) and registered at Chinese Clinical Trial Registry (http://www.chictr.org.cn) with identifier ChiCTR-IPR-15007654. The results of the study will be presented at academic conferences and submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCRR-IPR-15007654; Pre-results.