Correlation of NLRP3 With Cognitive Dysfunction Early After Heart Valve

90 consecutive patients scheduled for mitral valve replacement or aortic valve replacement under moderate hypothermic CPB gave written informed consent and were enrolled in this study.

In the operating room, patients received routine monitoring. Systemic arterial blood pressure was measured via radial artery catheterization. After induction of anesthesia, a central venous catheter was inserted for monitoring central venous pressure (CVP) and fluid management. Baseline readings of hemodynamics were taken every 5 to 10 min after radial artery cannulation was completed.

Induction of anesthesia was performed with target-controlled infusion of propofol. All patients received an infused scheme of several steps that started from a target plasma concentration (Cp) of 0.5 mg/mL that was increased stepwise by 0.5 mg/mL until the patient fell asleep and maintain BIS at 40-60. The interval between each step was 3 min. After loss of consciousness, cisatracurium (0.2 mg/kg) and fentanyl (10-15 mg/kg) were infused in all groups. The trachea was intubated and the lungs were ventilated with oxygenenriched air (fraction of inspired oxygen 0.6) to an end-tidal carbon dioxide partial pressure of 35 to 45 mmHg. The propofol target Cp was adjusted according to BIS. Intermittent IV boluses of fentanyl (10-15 mg/kg) were administered according to blood pressure and heart rate (HR) at the following time points: before the skin incision, before the onset of CPB, and after separation from CPB, for a total dose of 40 to 50 mg/kg. All patients received infusion of cisatracurium at 0.1 mg/kg/h throughout the surgery.

Surgery was conducted on all patients via a standard median sternotomy approach. Porcine heparin was administered at a dose of 300 IU/kg and supplemented when required to maintain an activated coagulation time of at least 480 s during CPB. Heparin was neutralized with 1 mg of protamine/100 IU of heparin administered after separation from CPB. Body temperature was cooled to 30℃-32℃ on CPB (moderate hypothermia). All patients were treated with an intermittent antegrade infusion of cooled high-potassium blood cardioplegia during continuous aortic cross-clamping (ACC) using a nonpulsatile flow rate of 1.8 to 2.8 L/min/m2 and a membrane oxygenator to keep the mixed venous saturation at more than 75% during CPB. Phenylephrine (bolus, 20-100 mg) or epinephrine (0.1 mg/kg/min) or both were used to restore systemic vascular resistance, and MAP was maintained at a target range of 60 to 80 mmHg. Patients were warmed to a bladder temperature of 36.5℃ before separation from CPB, with the highest temperature not exceeding 37℃. Blood remaining in the CPB circuit and from the surgical field was collected in a cell-saving device. After centrifuging and washing, it was infused to the patient within 4 hours after CPB. Hematocrit was maintained at more than 25%, with the addition of blood as necessary. Insulin therapy was initiated during the surgery to treat serum blood glucose levels higher than 150 mg/dL. Hemodynamic (pre- or post-CPB) management aimed to keep MAP at 60 to 100 mmHg. Hypertension was treated with an additional bolus dose of fentanyl (0.2-0.3 mg) or with nitroglycerin (0.1-0.5 mg/kg/min or with both). Hypotension was treated with fluid intake (including crystalloids, colloids, and blood products) or vasoactive drug administration (phenylephrine IV, 20-100 mg or concomitant use of epinephrine, o 0.1 mg/min). The vasoactive drug dosage, fluid intake, and output (urine and blood loss) were recorded when the surgery was finished.

As the surgeons began to close the skin, a 0.08 mg/kg bolus dose of midazolam was given intravenously and the infusion of propofol was stopped. After the surgery, all patients were admitted to the surgical intensive care unit (ICU). The patients were extubated when they were able to sustain adequate spontaneous respiration and required minimal oxygen support, as reflected by normal arterial blood gas levels. The patients then were discharged from the ICU when they were hemodynamically stable with blood gas variables within the normal range and when they did not need inotropic or oxygen support. The tracheal extubation time and the length of the ICU stay were recorded. For all patients, hemodynamic measurements were made and recorded at the following times: Before induction of anesthesia, before skin incision, after sternotomy, at the cessation of CPB (CPB-cessation), and at 1 (Post-CPB 1 h), 2 (Post-CPB 2 h), and 4 (Post-CPB 4 h) hours after CPB. At pre-incision, CPB-cessation, Post-CPB 2 h, and PostCPB 4 h, the radial arterial blood was sampled for blood gas analysis, as well as blood glucose and lactic acid analyses. Before induction of anesthesia, at the end of the operation, 7 days after the operation, peripheral venous blood was sampled to measure IL-1B, IL-18 and NLRP3 inflammatory protein expression in peripheral blood monocytes.