Target-achieved propofol concentration during on-pump cardiac surgery: a pilot dose-finding study

Abstract

Purpose Propofol concentrations that produce laboratory-based cardioprotective effects are generally greater than those produced under routine anesthesia during cardiac surgery. It is unknown whether experimental cardioprotective propofol concentrations can routinely be achieved during cardiopulmonary bypass (CPB) using continuous infusion. Methods Twenty-four patients scheduled for primary aortocoronary bypass grafting with CPB were allocated to receive one of three propofol infusion rates; 50, 100, or 150 lg Á kg -1 Á min -1 in an open-label pilot study. Data were described using a line of best fit to derive an experimental clinical maneuver predicted to produce a whole blood concentration of 5 lg Á mL -1 at reperfusion. A predetermined interim analysis of 30 patients who were receiving the derived maneuver in an ongoing study was used to evaluate the maneuver. Cardiac index (CI), systemic vascular resistance index (SVRI), and left ventricular stroke work index (LVSWI) were recorded. Results The infusion rate-concentration curve had an equation of y = 0.215e 0.0279x , where y represents the whole blood concentration and x represents the infusion rate (r 2 = 0.781). The predicted infusion rate to achieve a mean concentration of 5 lg Á mL -1 was 113 lg Á kg -1 Á min -1 . The nearest practical rate is 120 lg Á kg -1 Á min -1 , producing a concentration of 5.39 (1.45) lg Á mL -1 . The values for CI, SVRI, and LVSWI were similar between groups at corresponding time periods. Conclusions An infusion rate of 120 lg Á kg -1 Á min -1 is clinically practical and capable of achieving experimental cardioprotective propofol concentrations at reperfusion. RésuméObjectif Les concentrations de propofol qui provoquent des effets cardioprotecteurs lors des tests de laboratoire sont en ge´ne´ral plus e´leve´es que celles produites sous une anesthe´sie de routine lors d'une chirurgie cardiaque. Nous ne savons pas si des concentrations expe´rimentales cardioprotectrices de propofol peuvent eˆtre atteintes de façon routinie`re pendant la circulation extracorporelle (CEC) avec une perfusion continue. Méthode Vingt-quatre patients devant subir un pontage aortocoronarien avec CEC ont e´te´randomise´s à recevoir l'un des trois vitesses de perfusion de propofol suivantes : 50, 100 ou 150 lgÁkg -1 Ámin -1 dans une e´tude pilote ouverte. Les donne´es ont e´te´de´crites a`l'aide d'une droite de re´gression afin de de´river une manoeuvre clinique expe´rimentale qui devrait produire une concentration de sang total de 5 lgÁmL -1 au moment de la reperfusion. Une

Anesthetics influence the incidence of acute kidney injury following valvular heart surgery

“…Although propofol concentrations producing renoprotection are unknown, that for cardioprotection has been reported to between 25 and 50 mmol/l (4.5-8.9 mg/ml) and the predicted infusion rate to achieve a mean plasma concentration of 5 mg/ml was 113 mg/kg per min during CPB. 20 Propofol at relatively low concentrations could not counteract oxygen free radical production, which is greatly increased during reperfusion or CPB. 21 In the previous study, 19 only a broad propofol target concentration of 1-8 mg/ml was presented and not the actual target concentration or the total consumption of propofol during surgery.…”

Propofol protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via Akt activation and Bcl-2 up-regulation

“…The concentration of H 2 O 2 (400μM) applied was determined from pilot studies by our group and based on similar methods described in the scientific literature [14]. The concentration of propofol (50μM) applied was determined based on similar methods described in the scientific literature [8] and the average blood propofol concentration during human cardiac surgery in our clinical project [15]. Cells were cultured in 24-well plates and treated according to the protocol.…”

Propofol cardioprotection for on-pump aortocoronary bypass surgery in patients with type 2 diabetes mellitus (PRO-TECT II): a phase 2 randomized-controlled trial

“…Our study intervention was derived from prior in vitro and in vivo studies of the concentration and time-dependent effects of propofol which define a therapeutic window that we correlate with cyto-and cardioprotection (4.2-8.4 lgÁmL ). 16,17,23 These concentrations were achieved in the systemic circulation at reperfusion in 87% of participants where aortic cross-clamp intervals exceeded 60 min. Our technique enriches blood cardioplegia.…”

“…22 This report presents the effects of a propofol infusion designed to achieve drug concentrations in patients during cardiopulmonary bypass (CPB) that alleviate experimental oxidative injury. 23 Accordingly, in this study, we investigated the concentration and time-dependent effects of propofol (whole blood concentration 4-12 lgÁmL -1 ) compared with isoflurane on cyto-and cardioprotective measures of oxidative injury. 16,17 We hypothesized that propofol would decrease 15-F 2t -isoprostane release and, as a result, reduce the incidence of LCOS.…”