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

Abstract

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. Randomized, placebo-controlled, pilot feasibility trial. Cardiac surgery department of a tertiary hospital. Forty patients undergoing combined valvular and coronary artery bypass surgery. Intravenous thiamine (600 mg on the day of surgery, and 400 mg/day on postoperative days 1, 2, and 3) or placebo. 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). 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.