Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg−1 for reversal of deep neuromuscular blockade in patients with severe renal impairment

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Abstract

Background

This study evaluated efficacy and safety of sugammadex 4 mg kg−1 for deep neuromuscular blockade (NMB) reversal in patients with severe renal impairment (creatinine clearance [CLCR] <30 ml min−1) vs those with normal renal function (CLCR ≥80 ml min−1).

Methods

Sugammadex 4 mg kg−1 was administered at 1–2 post-tetanic counts for reversal of rocuronium NMB. Primary efficacy variable was time from sugammadex to recovery to train-of-four (T4/T1) ratio 0.9. Equivalence between groups was demonstrated if two-sided 95% CI for difference in recovery times was within −1 to +1 min interval. Pharmacokinetics of rocuronium and overall safety were assessed.

Results

The intent-to-treat group comprised 67 patients (renal n=35; control n=32). Median (95% CI) time from sugammadex to recovery to T4/T1 ratio 0.9 was 3.1 (2.4–4.6) and 1.9 (1.6–2.8) min for renal patients vs controls. Estimated median (95% CI) difference between groups was 1.3 (0.6–2.4) min; thus equivalence bounds were not met. One control patient experienced acceleromyography-determined NMB recurrence, possibly as a result of premature sugammadex (4 mg kg−1) administration, with no clinical evidence of NMB recurrence observed. Rocuronium, encapsulated by Sugammadex, was detectable in plasma at day 7 in 6 patients. Bioanalytical data for sugammadex were collected but could not be used for pharmacokinetics.

Conclusions

Sugammadex 4 mg kg−1 provided rapid reversal of deep rocuronium-induced NMB in renal and control patients. However, considering the prolonged sugammadex-rocuronium complex exposure in patients with severe renal impairment, current safety experience is insufficient to support recommended use of sugammadex in this population.

Clinical trial registration

NCT00702715.

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