N-acetylcysteine is associated with increased blood loss and blood product utilization during cardiac surgery

Objective: When used to prevent perioperative inflammation and ischemia-reperfusion injury, N-acetylcysteine may inadvertently impair hemostasis. We, therefore, performed a post hoc analysis of a recent randomized controlled trial in cardiac surgery to determine whether N-acetylcysteine was associated with increased blood loss and blood product transfusion. Design: Blinded (patients, caregivers, outcome assessors) placebo-controlled parallel group randomized trial (www.ClinicalTrials.gov ID NCT00188630). Setting: Tertiary care hospital in Toronto, Ontario, Canada (September 2003 to October 2005). Patients. A total of 177 patients with preexisting moderate renal insufficiency (estimated glomerular filtration rate <= 60 mL/min) and undergoing cardiac surgery. Interventions: Eighty-nine patients were randomized to receive intravenous N-acetylcysteine (100 mg/kg bolus; 20 mg . kg(-1) . hr(-1) infusion until 4 hours after cardiopulmonary bypass), and 88 were randomized to receive placebo. Measurements and Main Results. We used laboratory markers (hemoglobin, platelets, coagulation), chest-tube blood loss, and blood product transfusion to evaluate hemostasis. Compared with placebo, patients who received N-acetylcysteine arm experienced a mean 24-hour chest-tube blood loss that was 261 mL higher (95% confidence interval [CI] 93-488 mL, p = 0.008), and were transfused 1.6 more units of red blood cells (95% Cl 0.4-3.1 units, p = 0.02) during hospitalization. The risk of receiving >= 5 units of red blood cells within 24 hours of surgery was significantly higher with N-acetylcysteine (relative risk 1.85, 95% Cl 1.06-3.21, p = 0.03; adjusted relative risk 2.09, 95% Cl 1.24-3.83, p = 0.005). Conclusions: In patients who have preexisting moderate renal insufficiency and are undergoing cardiac surgery, N-acetylcysteine was associated with important effects on blood loss and blood product transfusion. Clinicians and researchers should, therefore, consider the potential for impaired hemostasis when using N-acetyleysteine in the perioperative setting. Further research is needed to elucidate mechanisms by which N-acetylcysteine may impair hemostasis, and the risk-benefit profile of N-acetylcysteine for perioperative organ protection. (Crit Care Med 2009; 37:1929-1934)