What evidence supports the use of acetaminophen (paracetamol) to prevent Acute Kidney Injury (AKI) in adult and pediatric patients after cardiac surgery?

Acetaminophen for Prevention of Acute Kidney Injury After Cardiac Surgery

Current evidence does not strongly support the routine use of acetaminophen specifically for prevention of acute kidney injury (AKI) in adult or pediatric patients after cardiac surgery, though emerging research suggests potential benefit that warrants further investigation.

Evidence for Acetaminophen in Preventing Post-Cardiac Surgery AKI

Pediatric Population

• Retrospective cohort studies suggest early postoperative acetaminophen exposure may be associated with reduced risk of AKI in pediatric cardiac surgery patients 1
• In a retrospective study of pediatric cardiac surgery patients, those who received higher doses of acetaminophen in the first 48 postoperative hours had lower rates of AKI compared to those who received lower doses 1
• However, network meta-analyses of preventive strategies for AKI after pediatric cardiac surgery have not demonstrated significant efficacy for most interventions, including acetaminophen 2

Adult Population

• Recent retrospective data from 2024 suggests perioperative acetaminophen administration is associated with decreased incidence of AKI in adults undergoing cardiac surgery 3
• Analysis of two large clinical registries found that early postoperative acetaminophen administration was independently associated with 14-16% lower risk of severe AKI in adults recovering from cardiac surgery 4
• The mechanism may involve acetaminophen's antioxidant properties inhibiting hemoprotein-catalyzed lipid peroxidation, which could reduce oxidative stress-related kidney injury 4

Current Guideline Recommendations for AKI Prevention in Cardiac Surgery

Recommended Strategies

• The 2024 EACTS/EACTAIC/EBCP guidelines for cardiopulmonary bypass in adult cardiac surgery recommend:
  • Considering intravenous infusion of a balanced mixture of amino acids perioperatively to reduce AKI occurrence (Class IIa recommendation) 5
  • Considering perioperative intravenous N-acetylcysteine (NAC) in patients with chronic kidney disease to reduce AKI after cardiac surgery (Class IIb recommendation) 5

Not Recommended Strategies

• Routinely targeting high mean arterial pressure using vasoconstrictors during cardiopulmonary bypass is not recommended to reduce AKI (Class III recommendation) 5
• Routine use of mannitol in the priming solution is not recommended 5
• Low-dose dopamine, fenoldopam, and recombinant human IGF-1 are not recommended for AKI prevention 6

Acetaminophen's Role in Perioperative Care

• Acetaminophen is recommended as a cornerstone of multimodal analgesia after cardiac surgery, with potential additional benefit for kidney protection 7
• Standard dosing for adults after cardiac surgery is 1g every 6 hours, with intravenous administration preferred until gut function recovers 7
• Acetaminophen has fewer adverse effects on renal function compared to NSAIDs, which are associated with renal dysfunction after cardiac surgery 7
• It provides opioid-sparing effects, reducing risks of opioid-related adverse effects such as respiratory depression and ileus 7, 5

Practical Approach to AKI Prevention in Cardiac Surgery

Risk Assessment

• AKI complicates 22-36% of cardiac surgical procedures in children and is associated with increased morbidity and mortality 6, 8
• Risk factors include abnormal baseline creatinine, cardiopulmonary bypass exposure, and post-cardiac arrest acidosis 6

Recommended Preventive Strategies

• Avoid nephrotoxic agents in at-risk patients 6, 8
• Discontinue ACE inhibitors and ARBs for 48 hours post-surgery 6, 8
• Use isotonic crystalloids rather than colloids for volume expansion 6, 8
• Implement goal-directed fluid therapy with standardized algorithms 6, 8
• Avoid starch-containing fluids 6
• Monitor and optimize cardiac output to ensure adequate renal perfusion 6, 8

Conclusion on Acetaminophen for AKI Prevention

• While acetaminophen is widely used for pain management after cardiac surgery and has a favorable safety profile compared to NSAIDs and opioids 5, 7, current guidelines do not specifically recommend it for AKI prevention
• Emerging retrospective evidence suggests potential benefit in both pediatric and adult populations 1, 3, 4, but prospective randomized trials are needed to establish causality and determine optimal dosing regimens
• The potential renoprotective mechanism may involve acetaminophen's antioxidant properties that reduce oxidative stress from hemolysis during cardiopulmonary bypass 1, 4

Research Gaps and Future Directions

• Prospective randomized controlled trials are needed to determine if acetaminophen truly prevents or reduces severity of AKI after cardiac surgery 3, 4
• Optimal timing, dosing, and duration of acetaminophen administration for potential renoprotective effects need to be established 1, 4
• Investigation of mechanisms by which acetaminophen may protect against AKI would help inform targeted prevention strategies 4