SummaryCardiac surgery with cardiopulmonary bypass is associated with the development of a systemic inflammatory response that can often lead to dysfunction of major organs. We hypothesised that the highly selective a 2 -adrenergic agonist, dexmedetomidine, attenuates the systemic inflammatory response. Forty-two patients were randomly assigned to receive dexmedetomidine or saline after aortic cross-clamping). The mean (SD) levels of the nuclear protein plasma high-mobility group box 1 increased significantly from 5.1 (2.2) ng.ml À1 during (16.6 (7.3) ng.ml À1) and after (14.3 (8.2) ng.ml À1 ) cardiopulmonary bypass in the saline group. In the dexmedetomidine group, the levels increased significantly only during cardiopulmonary bypass (4.0 (1.9) ng.ml À1 baseline vs 10.8 (2.7) ng.ml À1 ) but not after (7.4 (3.8) ng.ml À1). Dexmedetomidine infusion also suppressed the rise in mean (SD) interleukin-6 levels after cardiopulmonary bypass (a rise of 124.5 (72.0) pg.ml À1 vs 65.3 (30.9) pg.ml À1 ). These suppressive effects of dexmedetomidine might be due to the inhibition of nuclear factor kappa B activation and suggest that intra-operative dexmedetomidine may beneficially inhibit inflammatory responses associated with ischaemia-reperfusion injury during cardiopulmonary bypass.

Purpose To analyze the cause of prolonged recovery from general anesthesia with remimazolam. Methods We studied 65 patients under general anesthesia with remimazolam. According to time to extubation, patients were divided into short period (SP) (n = 34, < 15 min) and long period (LP) (n = 31, ≥ 15 min) groups. Variables affecting time to extubation such as age, sex, height, body weight, body mass index (BMI), plasma albumin concentration, ASA class, duration of surgery, and total duration of general anesthesia, and total dose of remimazolam were compared between SP and LP groups. At the end of remimazolam infusion and upon extubation, predictive remimazolam concentrations were calculated using pharmacokinetic/pharmacodynamic three compartment modeling. Results LP group showed significantly higher BMI, older age, and lower plasma albumin concentration compared with those of SP group. Logistic regression analysis showed that the probability of time to extubation of ≥ 15 min was higher in patients with BMI greater than 22.0 kg/m2 (AUC 0.668, 95% CI 0.533‒0.803), ages older than 79.0 years (AUC 0.662, 95% CI 0.526‒0.798), and plasma albumin concentrations lower than 3.60 g/dl (AUC 0.720, 95% CI 0.593‒0.847). LP group showed significantly lower predicted remimazolam concentration than SP group upon extubation despite no difference in concentration between both groups at the end of infusion. Pharmacological analysis estimates that LP group is more sensitive to remimazolam than SP group through amplified responses. Conclusions Lower remimazolam doses should be considered for the overweight patients, elderly, and those with lower plasma albumin concentration.

No abstract