Preoperative ketamine administration for prevention of postoperative neurocognitive disorders after major orthopedic surgery in elderly patients: A multicenter randomized blinded placebo-controlled trial.

BACKGROUND: Preventive anesthetic impact on the high rates of postoperative neurocognitive disorders in elderly patients is debated. The Prevention of postOperative Cognitive dysfunction by Ketamine (POCK) study aimed to assess the effect of ketamine on this condition. METHODS: This is a multicenter, randomized, double-blind, interventional study. Patients ≥60 years undergoing major orthopedic surgery were randomly assigned in a 1:1 ratio to receive preoperative ketamine 0.5 mg/kg as an intravenous bolus (n = 152) or placebo (n = 149) in random blocks stratified according to the study site, preoperative cognitive status and age. The primary outcome was the proportion of objective delayed neurocognitive recovery (dNR) defined as a decline of one or more neuropsychological assessment standard deviations on postoperative day 7. Secondary outcomes included a three-month incidence of objective postoperative neurocognitive disorder (POND), as well as delirium, anxiety, and symptoms of depression seven days and three months after surgery. RESULTS: Among 301 patients included, 292 (97%) completed the trial. Objective dNR occurred in 50 (38.8%) patients in the ketamine group and 54 (40.9%) patients in the placebo group (OR [95% CI] 0.92 [0.56; 1.51], p = 0.73) on postoperative day 7. Incidence of objective POND three months after surgery did not differ significantly between the two groups nor did incidence of delirium, anxiety, apathy, and fatigue. Symptoms of depression were less frequent in the ketamine group three months after surgery (OR [95% CI] 0.34 [0.13-0.86]). CONCLUSIONS: A single preoperative bolus of intravenous ketamine does not prevent the occurrence of dNR or POND in elderly patients scheduled for major orthopedic surgery. (Clinicaltrials.gov NCT02892916).

Sensitivity and Specificity of Strategies to Identify Patients with Haemostasis Abnormalities Leading to an Increased Risk of Bleeding Before Scheduled Intervention: the Hemorisk Study.

BACKGROUND: Preoperative identification of patients with haemostasis abnormalities leading to an increased bleeding risk was based on routine haemostasis tests: prothrombin time (PT), activated prothrombin time (aPTT), and platelet count. Because of their low predictive performance, guidelines recommend replacing them with structured bleeding risk questionnaires, but none is validated in this population. OBJECTIVES: To assess the diagnostic accuracy of 3 strategies, performed at the pre-anaesthesia visit before scheduled interventions, to identify patients with haemostasis abnormalities leading to an increased bleeding risk PATIENTS AND METHODS: Multicenter study in 7 French academic hospitals, involving patients scheduled for surgical intervention, without antiplatelet/anticoagulant treatment. The 3 strategies consisted of 1-a structured screening questionnaire; 2-PT, aPTT, and platelet count ordered in selected patients; 3-systematic PT, aPTT, and platelet count. The reference standard comprised von Willebrand factor activity/antigen, factors VIII, IX, and XI, platelet-function analyser, and, when required, FII, FV, FX, and FVII and haemostasis consultation. RESULTS: Eighteen (1.2%) of 1484 patients had a haemostasis abnormality leading to an increased bleeding risk according to reference standard. In the overall cohort, sensitivity of the questionnaire-based strategy was 50% (95%CI, 26-74; specificity 87% (95%CI, 85-88); sensitivity was 0 (95%CI, 0-41) in men vs 82% (95%CI, 48- 98) in women. For selective routine tests, sensitivity was 33% (95%CI, 13-59) and specificity 97% (95% CI, 96-98). Corresponding values for systematic routine tests were 44% (95%CI, 22-69) and 93% (95%CI, 91-94). CONCLUSIONS: Sensitivity was low for all 3 strategies investigated. The structured screening questionnaire had clinically acceptable diagnostic accuracy only in women.