N-acetylcysteine is associated with increased blood loss and blood product utilization during cardiac surgery
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Published on: April 19, 2022
Duminda N Wijeysundera1, Keyvan Karkouti, Vivek Rao
1Department of Anesthesia, Toronto General Hospital and University of Toronto, Toronto, Ontario, Canada.
Insights
N-acetylcysteine use in cardiac surgery patients with renal insufficiency was linked to increased blood loss and red blood cell transfusions. This suggests potential impairment of hemostasis, requiring careful consideration by clinicians.
Area of Science:
- Cardiovascular Surgery
- Pharmacology
- Nephrology
Background:
- N-acetylcysteine (NAC) is used to prevent perioperative inflammation and ischemia-reperfusion injury.
- Potential adverse effects of NAC on hemostasis warrant investigation, particularly in vulnerable patient populations.
Purpose of the Study:
- To determine if NAC administration is associated with increased blood loss and blood product transfusion in cardiac surgery patients with moderate renal insufficiency.
- To analyze the impact of NAC on hemostasis markers and transfusion requirements post-cardiac surgery.
Main Methods:
- Post hoc analysis of a blinded, placebo-controlled randomized trial (NCT00188630) conducted at a tertiary care hospital.
- 177 patients with moderate renal insufficiency undergoing cardiac surgery received either intravenous NAC or placebo.
- Hemostasis was evaluated using laboratory markers, chest-tube blood loss, and blood product transfusion data.
Main Results:
- Patients receiving NAC had significantly higher mean 24-hour chest-tube blood loss (261 mL more) compared to placebo.
- NAC recipients required more red blood cell (RBC) transfusions (1.6 units more) during hospitalization.
- The risk of receiving ≥5 units of RBCs within 24 hours was significantly elevated in the NAC group (adjusted relative risk 2.09).
Conclusions:
- In cardiac surgery patients with moderate renal insufficiency, NAC is associated with increased blood loss and transfusion requirements.
- Clinicians should consider the potential for impaired hemostasis when using NAC perioperatively.
- Further research is needed to elucidate the mechanisms of NAC-induced hemostasis impairment and its risk-benefit profile for organ protection.
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
Interventions:
Eighty-nine patients were randomized to receive intravenous N-acetylcysteine (100 mg/kg bolus; 20 mg.kg.hr 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% CI 0.4-3.1 units, p = 0.02) during hospitalization. The risk of receiving >or=5 units of red blood cells within 24 hours of surgery was significantly higher with N-acetylcysteine (relative risk 1.85, 95% CI 1.06-3.21, p = 0.03; adjusted relative risk 2.09, 95% CI 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-acetylcysteine 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.
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