Sustained High-dose Thiamine Supplementation in High-risk Cardiac Patients Undergoing Cardiopulmonary Bypass: A Pilot Feasibility Study (The APPLY trial).

OBJECTIVE: To test the feasibility and investigate possible cardiovascular effects of a sustained high-dose intravenous thiamine protocol in patients undergoing combined valvular and coronary artery bypass graft surgery. DESIGN: Randomized, placebo-controlled, pilot feasibility trial. SETTING: Cardiac surgery department of a tertiary hospital. PARTICIPANTS: Forty patients undergoing combined valvular and coronary artery bypass surgery. INTERVENTIONS: Intravenous thiamine (600 mg on the day of surgery, and 400 mg/day on postoperative days 1, 2, and 3) or placebo. MEASUREMENTS AND MAIN RESULTS: The primary feasibility endpoints were recruitment rate and protocol compliance. Secondary endpoints included markers of possible biological and physiological effects. The mean recruitment rate was 8 patients per month and protocol compliance was 97.5%. There were no differences in median peak postoperative lactate (2.7 mmol/L [interquartile range [IQR] 1.4-4.6] for thiamine v 2.5 mmol/L [IQR 1.4-3.6] for placebo; p = 0.53), median peak postoperative creatinine (104 µmol/L [IQR 92.5-129] for thiamine v 99 µmol/L [IQR 86.5-109.5] for placebo; p = 0.53), median nadir postoperative cardiac index (1.8 L/min/m2 [IQR 1.5-2.1] for thiamine v 2.2 L/min/m2 [IQR 1.5-2.5] for placebo; p = 0.25), or the number of patients on vasopressor/inotropic agents (thiamine, 12 [63%]; placebo, 12 [60%]; p = 0.80), or in the total inotrope/vasopressor dose 0.14 µg/kg for thiamine v 0.12 µg/kg for placebo; p = 0.88). CONCLUSIONS: A double-blind trial of sustained high-dose intravenous thiamine supplementation in higher-risk cardiac surgery patients was feasible and appeared to be safe. However, such treatment did not demonstrate evidence of biological or physiological effects.

A randomized controlled trial of levosimendan to reduce mortality in high-risk cardiac surgery patients (CHEETAH): Rationale and design.

OBJECTIVE: Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. DESIGN: Double-blind, placebo-controlled, multicenter randomized trial. SETTING: Tertiary care hospitals. INTERVENTIONS: Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 µg/[kg min]) or placebo for 24-48 hours. MEASUREMENTS AND MAIN RESULTS: The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. CONCLUSIONS: This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery.

Randomized trial of fish oil infusion to prevent atrial fibrillation after cardiac surgery: data from an implantable continuous cardiac monitor.

OBJECTIVE: To test the hypothesis that perioperative OMEGA-3 polyunsaturated fatty acid infusion would reduce the incidence of postoperative atrial fibrillation in patients after coronary artery bypass grafting as assessed by an implantable continuous cardiac monitor. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Tertiary cardiothoracic referral center. PARTICIPANTS: Thirty-nine patients with coronary artery disease who underwent surgery with cardiopulmonary bypass. INTERVENTIONS: Patients were assigned randomly to receive either OMEGA-3 polyunsaturated fatty acids (200 mg/kg/day starting before anesthesia induction for 24 hours followed by 100 mg/kg/day for 7 days) or placebo. The primary outcome was freedom from atrial fibrillation at 2-year follow-up. Reveal(®) cardiac monitor was implanted subcutaneously in all patients. Data from the cardiac monitor were collected on the 10th day and 3, 6, 12, and 24 months postoperatively. MEASUREMENT AND MAIN RESULTS: Postoperative atrial fibrillation developed in 4 (19%) patients in the control group and in 5 (27.8%) patients in the study group at 10-day follow-up (p = 0.88). At 2-year follow-up, 5 (27.8%) patients in the control group and 6 (35.3%) patients in the study group had atrial fibrillation (p = 0.9). Atrial fibrillation duration predicted risk of cardiovascular hospitalization at the 2-year follow-up (regression coefficient estimate = 0.24, standard error 0.02, p<0.0001; R(2) = 0.74). CONCLUSIONS: Infusion of OMEGA-3 polyunsaturated fatty acids failed to prevent the occurrence of atrial fibrillation in 2 years after coronary artery bypass grafting surgery. The cumulative atrial fibrillation duration registered by the continuous cardiac monitor at the 2-year follow-up was a significant predictor of an adverse outcome.

Hypertonic solution decreases extravascular lung water in cardiac patients undergoing cardiopulmonary bypass surgery.

OBJECTIVE: To test the hypothesis that the infusion of hypertonic solution would decrease extravascular lung water postoperatively and thus improve pulmonary function. DESIGN: Prospective, randomized, blinded trial. SETTING: Tertiary cardiothoracic referral center. PARTICIPANTS: Twenty-six patients with coronary artery disease who underwent surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: Patients were allocated randomly to receive 4 mL/kg of 7.2% NaCl/hydroxyethyl starch, 200/0.5 (HSH group) or an equal volume of 0.9% NaCl (control group) for 30 minutes starting after anesthesia induction. The extravascular lung water index, hemodynamic and biochemical data, and the rate of complications were analyzed. MEASUREMENTS AND MAIN RESULTS: The extravascular lung water index was significantly lower (7 v 9.5 mL/kg) in the HSH group at the first postoperative day (p < 0.01). The index of arterial oxygenation efficiency was significantly higher at 5 minutes and 2 and 4 hours after cardiopulmonary bypass (CPB) in the HSH group (p < 0.05). The alveolar-arterial oxygen tension difference was significantly lower at 5 minutes and 2 and 4 hours after CPB in the HSH group (p < 0.01). The cardiac index was significantly higher at 5 minutes after infusion in the HSH group (p < 0.05). CONCLUSIONS: The infusion of HSH leads to significant decreases in the extravascular lung water index during and after cardiac surgery and is associated with better preservation of pulmonary function and transient increases in the cardiac index. Further trials are needed to clarify the clinical advantages of hypertonic solution administration in patients undergoing surgery with CPB.