Postoperative Neurocognitive Disorders After Closed-Loop Versus Manual Target Controlled-Infusion of Propofol and Remifentanil in Patients Undergoing Elective Major Noncardiac Surgery: The Randomized Controlled Postoperative Cognitive Dysfunction-Electroencephalographic-Guided Anesthetic Administration Trial.

BACKGROUND: The aim of the study was to investigate whether closed-loop compared to manual bispectral index (BIS)-guided target-controlled infusion of propofol and remifentanil could decrease the incidence of postoperative neurocognitive disorders after elective major noncardiac surgery. METHODS: Patients aged >50 admitted for elective major noncardiac surgery were included in a single-blind randomized (ratio 2:1) trial. The anesthetic protocol was allocated by randomization into either closed-loop or manual BIS-guided propofol and remifentanil titration. The BIS target range was 40-60. All patients had cognitive assessment the day before surgery and within 72 hours after surgery using a battery of neuropsychological tests. The primary outcome was the rate of postoperative neurocognitive disorders. Postoperative neurocognitive disorders were defined as a decrease >20% from baseline on at least 3 scores. Intergroup comparison of the primary outcome was performed using the χ2 test. RESULTS: A total of 143 and 61 patients were included in the closed-loop and manual groups, respectively (age: 66 [8] vs 66 [9] years). The primary outcome was observed in 18 (13%) and 10 (16%) patients of the closed-loop and manual groups, respectively (relative risk [95% confidence interval {CI}], 0.77 [0.38-1.57], P = .47). Intraoperative propofol consumption was lower (4.7 [1.4] vs 5.7 [1.4] mg·kg-1·h-1, mean difference [MD] [95% CI], -0.73 [-0.98 to -0.48], P < .0001) and the proportion of time within the BIS target range higher (84 [77-89] vs 74 [54-81]%, MD [95% CI], 0.94 [0.67-1.21], P < .0001) in the closed-loop group. CONCLUSIONS: Closed-loop compared to manual BIS-guided total intravenous anesthesia provided a significant reduction in episodes of an excessive depth of anesthesia while decreasing intraoperative propofol requirement but no evidence for a reduction of the incidence of postoperative neurocognitive disorders after elective major noncardiac surgery was observed.

Early post-operative cognitive dysfunction after closed-loop versus manual target controlled-infusion of propofol and remifentanil in patients undergoing elective major non-cardiac surgery: Protocol of the randomized controlled single-blind POCD-ELA trial.

INTRODUCTION: Post-operative cognitive dysfunction (POCD) is frequent in patients older than 60 years undergoing major non-cardiac surgery, and increases both morbidity and mortality. Anesthetic drugs may exert neurotoxic effects and contribute to the genesis of POCD. The hypothesis of the POCD-ELA trial was that closed-loop target-controlled infusion of propofol and remifentanil could reduce the occurrence of POCD by decreasing the risk of excessive depth of anesthesia and the dose of anesthetic drugs. METHODS AND ANALYSIS: We designed a single-center, single-blind, randomized, controlled, parallel trial and aim to include 204 patients aged >60 years undergoing elective major non-cardiac surgery. Patients will be randomized to receive closed-loop versus manual target-controlled infusion of propofol and remifentanil guided by bispectral index monitoring. Cognitive assessment will be performed the day before surgery (baseline) and within 72 hours after surgery, using a battery of validated neuropsychological tests. The primary outcome is the incidence of POCD within 72 hours after surgery. POCD is defined as a Z-score value > 1.96 for at least 2 different tests or a Z-score composite value >1.96. The calculation of the Z-score is based on data from an age-matched control population who did not undergo surgery or general anesthesia. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee (Comité de Protection des Personnes Est-II) and authorized by the French Health Products Agency (Agence Nationale de Sécurité des Médicaments, Saint-Denis, France). The University Hospital of Besancon is the trial sponsor and the holder of all data and publication rights. Results of the study will be submitted for publication in a peer-review international medical journal and for presentation in abstract (oral or poster) in international peer-reviewed congresses. REGISTRATION: The trial is registered with ClinicalTrials.gov (Identifier: NCT02841423, principal investigator: Prof Emmanuel Samain, date of registration: July 22, 2016). Last amendment of protocol: version 8.0 April 2018.