Abstract 1567: N-Acetylcysteine and Impaired Hemostasis in Cardiac Surgery
BACKGROUND: N-acetylcysteine is an anti-inflammatory and anti-oxidant agent that has been evaluated to prevent inflammation and ischemia-reperfusion injury during cardiac surgery. However, N-acetylcysteine may also impair hemostasis by inhibiting platelets and coagulation factors. We therefore retrospectively reviewed a recent randomized controlled trial to determine if N-acetylcysteine affected blood loss and blood product transfusion.
METHODS: Between 2003 and 2005, 177 patients with preoperative renal insufficiency (estimated glomerular filtration rate < 60 mL/min) were recruited into a triple-blinded placebo-controlled randomized trial in cardiac surgery at a quaternary-care hospital. Eighty-nine patients were randomized to IV N-acetylcysteine (100 mg/kg bolus; 20 mg/kg/h infusion until 4 hours after cardiopulmonary bypass), and 88 to placebo. Laboratory markers (hemoglobin, platelets, coagulation profile), chest-tube blood loss, and blood product transfusion were used to measure hemostasis. Safety outcomes included mortality, re-operation, and adverse effects.
RESULTS: Compared to placebo, patients receiving N-acetylcysteine arm experienced 24 h chest-tube blood loss that was 261 mL higher (95% CI 64 – 458 mL; P = 0.01), and were transfused 1.6 more units of red cell concentrate (95% CI 0.3–2.9 units; P = 0.02) during hospitalization. The risk of receiving 5 or more units of red cell concentrate within 1 day of surgery was significantly higher with N-acetylcysteine [odds ratio (OR) 2.24; 95% CI 1.10 – 4.58; P = 0.02]. After adjustment for confounding, the magnitude of this risk increased (OR 3.62; 95% CI 1.52–9.30; P = 0.005). Despite this increased blood loss, all-cause mortality was lower in the N-acetylcysteine arm (0% vs. 8%).
CONCLUSIONS: In cardiac surgery patients with preoperative renal insufficiency, N-acetylcysteine has important effects on blood loss and blood product transfusion. Although N-acetylcysteine was associated with favorable effects on mortality in this study, clinicians and researchers should consider the potential for impaired hemostasis when using N-acetylcysteine in the perioperative setting. Further research is needed to elucidate mechanisms by which N-acetylcysteine may impair hemostasis.