What is the recommended N-acetylcysteine (NAC) infusion dosage for organ protection during cardiopulmonary bypass (CPB) in cardiac surgery?

N-Acetylcysteine Dosing for Organ Protection During Cardiopulmonary Bypass

The perioperative use of intravenous NAC may be considered in patients with chronic kidney disease to reduce acute kidney injury after cardiac surgery, but routine use for all patients undergoing CPB is not recommended due to weak evidence and potential bleeding complications. 1

Guideline-Based Recommendation

The most recent 2024 EACTS/EACTAIC/EBCP guidelines provide a Class IIb recommendation (Level B evidence) for perioperative NAC use specifically in patients with pre-existing chronic kidney disease (CKD) to reduce acute kidney injury after cardiac surgery. 1 This weak recommendation reflects the limited and conflicting evidence base, indicating that NAC may be considered but is not strongly endorsed.

Evidence-Based Dosing Protocol (When Used)

When NAC is administered for renal protection in CKD patients undergoing cardiac surgery with CPB, the highest quality evidence supports the following regimen:

High-Dose Protocol (Most Effective)

• Loading dose: 150 mg/kg IV bolus administered before surgical incision 2
• Maintenance infusion: 50 mg/kg IV infusion over 6 hours (starting after the bolus) 2
• Vehicle: Diluted in 0.9% normal saline 2

This high-dose protocol demonstrated a significant reduction in acute kidney injury incidence from 57.1% to 28.6% (p=0.016) in CKD patients (stage 3-4) undergoing CABG surgery. 2 The protective effect was particularly pronounced in patients requiring CPB, where NAC reduced AKI incidence from 63% to 46%. 2

Alternative Moderate-Dose Protocol

• Loading dose: 100 mg/kg IV bolus 3
• Maintenance infusion: 20 mg/kg/hr until 4 hours after CPB completion 3
• Oral pretreatment: 600 mg orally the day before and morning of surgery (optional adjunct) 4

Target Population for NAC Use

NAC should only be considered in patients with:

• Pre-existing chronic kidney disease (estimated GFR ≤60 mL/min) 1, 2
• Undergoing cardiac surgery requiring cardiopulmonary bypass 2
• No contraindications to NAC administration 1

NAC is NOT recommended for:

• Routine prophylaxis in patients with normal renal function 1
• Patients without pre-existing renal impairment 1

Critical Safety Considerations and Pitfalls

Bleeding Risk

NAC significantly increases bleeding complications and transfusion requirements. 5 In a randomized trial of 177 cardiac surgery patients with moderate renal insufficiency:

• Mean 24-hour chest tube blood loss increased by 261 mL (95% CI 93-488 mL, p=0.008) 5
• Red blood cell transfusion increased by 1.6 units (95% CI 0.4-3.1 units, p=0.02) 5
• Risk of requiring ≥5 units of RBCs within 24 hours increased significantly (adjusted RR 2.09,95% CI 1.24-3.83, p=0.005) 5

This bleeding risk must be weighed against potential renal benefits, particularly in patients at high bleeding risk or those with coagulopathy. 5

Conflicting Efficacy Data

Multiple studies show no clinical benefit from NAC in cardiac surgery:

• A 100-patient RCT found no differences in death, myocardial infarction, bleeding, transfusion requirements, or biochemical markers between NAC and placebo groups 4
• A 177-patient trial showed no statistically significant improvement in postoperative estimated GFR (median 5.2% better, 95% CI -2.4% to 12.1%, p=0.22) 3

However, the same study noted lower all-cause mortality in the NAC arm (0% vs 8%, p=0.007), though this was a secondary outcome. 3

Mechanism and Rationale

When effective, NAC provides organ protection through:

• Abolishing oxidative stress during CPB 2
• Reducing systemic inflammatory response 6
• Preserving antioxidant capacity (glutathione, superoxide dismutase, catalase) 6
• Mitigating the negative effects of CPB on renal function 2

Alternative Renal Protection Strategies

The 2024 guidelines provide stronger recommendations for other renal protective measures:

• Balanced amino acid infusion perioperatively (Class IIa, Level B): Should be considered to reduce AKI occurrence 1
• Goal-directed perfusion (Class I, Level A): Recommended to reduce early-stage AKI, maintaining DO₂ ≥280 mL/min/m² 1
• Avoid routine high MAP targeting (Class III, Level A): Routinely targeting high MAP with vasoconstrictors is not recommended 1

Clinical Decision Algorithm

1. Assess baseline renal function: If eGFR >60 mL/min → NAC not indicated 1
2. If eGFR ≤60 mL/min: Consider NAC use with high-dose protocol (150 mg/kg bolus + 50 mg/kg over 6 hours) 2
3. Evaluate bleeding risk: If high bleeding risk, coagulopathy, or thrombocytopenia → reconsider NAC use given increased transfusion requirements 5
4. Implement proven strategies: Prioritize goal-directed perfusion and balanced amino acid infusion regardless of NAC decision 1
5. Monitor outcomes: Track chest tube drainage, transfusion requirements, and renal function markers postoperatively 5