Can sugammadex be used in patients with impaired renal function (creatinine clearance (CrCl) < 30 ml/min)?

Sugammadex Use in Patients with Severe Renal Impairment (CrCl < 30 ml/min)

Sugammadex is not recommended for use in patients with severe renal impairment (creatinine clearance < 30 ml/min) due to insufficient safety information and prolonged drug exposure in these patients. 1

Pharmacokinetic Considerations in Renal Impairment

• Sugammadex is substantially excreted by the kidneys (approximately 96% of the dose is excreted in urine) 1
• In patients with severe renal impairment (CrCl < 30 ml/min), the half-life of sugammadex is significantly prolonged to 19 hours (compared to 2 hours in patients with normal renal function) 1
• Exposure to sugammadex is increased 5-fold in patients with severe renal impairment compared to those with normal renal function 1
• The sugammadex-rocuronium complex remains detectable in plasma for at least 7 days in patients with severe renal impairment 2

Efficacy in Severe Renal Impairment

• Despite pharmacokinetic changes, sugammadex 4 mg/kg can effectively reverse deep rocuronium-induced neuromuscular blockade in patients with severe renal impairment 2
• However, the time to recovery is slower in patients with severe renal impairment compared to those with normal renal function (median time to T4/T1 ratio of 0.9 was 3.1 minutes vs. 1.9 minutes) 2
• A recent randomized controlled trial showed that even in patients with severe renal impairment, sugammadex provided significantly faster reversal of neuromuscular blockade compared to neostigmine (3.5 minutes vs. 14.8 minutes) 3

Safety Concerns

• The FDA label explicitly states that sugammadex is not recommended for use in patients with severe renal impairment due to insufficient safety information and prolonged drug exposure 1
• The prolonged presence of the sugammadex-rocuronium complex in the circulation raises concerns about potential long-term effects 2
• Current safety experience is insufficient to support the recommended use of sugammadex in this population 2
• There is limited data on the risk of recurarization, which could theoretically occur due to redistribution of the drug in patients with impaired elimination 4

Alternative Approaches

• For patients with severe renal impairment requiring neuromuscular blockade reversal:
  • Consider using benzylisoquinolinium-type neuromuscular blocking agents (e.g., cisatracurium) with neostigmine reversal when available 5
  • If sugammadex must be used (e.g., in countries where alternatives are unavailable), quantitative neuromuscular monitoring is essential 5
  • High-flux hemodialysis can effectively remove both sugammadex and the sugammadex-rocuronium complex (approximately 70% reduction after a 3-6 hour dialysis session) 6, 1

Recommendations for Clinical Practice

• Avoid sugammadex in patients with severe renal impairment (CrCl < 30 ml/min) whenever possible 1
• If sugammadex must be used in these patients:
  • Employ quantitative neuromuscular monitoring throughout the perioperative period 5
  • Monitor patients for a longer period postoperatively for signs of recurarization 4
  • Consider the potential for prolonged exposure to the sugammadex-rocuronium complex 2
  • For patients on dialysis, schedule high-flux hemodialysis postoperatively to remove the drug complex 6

Conclusion

While sugammadex can effectively reverse rocuronium-induced neuromuscular blockade in patients with severe renal impairment, its use is not recommended in this population due to significant pharmacokinetic alterations and insufficient safety data. The prolonged exposure to both sugammadex and the sugammadex-rocuronium complex raises concerns about potential long-term effects that have not been adequately studied.