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Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg-1 for reversal of deep neuromuscular blockade in patients with severe renal impairment.
Br J Anaesth. 2015 May; 114(5):777-84.BJ

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.

Authors+Show Affiliations

Department of Anaesthesia, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.Department of Anaesthesia, Central Manchester University Hospitals NHS Foundation Trust UK, Manchester, UK.Department of Anaesthesia and Intensive Care Medicine, Feldkirch Hospital, Austria.Department of Anaesthesia, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands m.snoeck@cwz.nl.Department of Anaesthesia, Central Manchester University Hospitals NHS Foundation Trust UK, Manchester, UK.MSD, Oss, The Netherlands.MSD, Oss, The Netherlands.Department of Anaesthesiology, University of Amsterdam (AMC), Amsterdam, The Netherlands.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25829395

Citation

Panhuizen, I F., et al. "Efficacy, Safety and Pharmacokinetics of Sugammadex 4 Mg Kg-1 for Reversal of Deep Neuromuscular Blockade in Patients With Severe Renal Impairment." British Journal of Anaesthesia, vol. 114, no. 5, 2015, pp. 777-84.
Panhuizen IF, Gold SJ, Buerkle C, et al. Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg-1 for reversal of deep neuromuscular blockade in patients with severe renal impairment. Br J Anaesth. 2015;114(5):777-84.
Panhuizen, I. F., Gold, S. J., Buerkle, C., Snoeck, M. M., Harper, N. J., Kaspers, M. J., van den Heuvel, M. W., & Hollmann, M. W. (2015). Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg-1 for reversal of deep neuromuscular blockade in patients with severe renal impairment. British Journal of Anaesthesia, 114(5), 777-84. https://doi.org/10.1093/bja/aet586
Panhuizen IF, et al. Efficacy, Safety and Pharmacokinetics of Sugammadex 4 Mg Kg-1 for Reversal of Deep Neuromuscular Blockade in Patients With Severe Renal Impairment. Br J Anaesth. 2015;114(5):777-84. PubMed PMID: 25829395.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg-1 for reversal of deep neuromuscular blockade in patients with severe renal impairment. AU - Panhuizen,I F, AU - Gold,S J A, AU - Buerkle,C, AU - Snoeck,M M J, AU - Harper,N J N, AU - Kaspers,M J G H, AU - van den Heuvel,M W, AU - Hollmann,M W, Y1 - 2015/03/31/ PY - 2013/09/30/accepted PY - 2015/4/2/entrez PY - 2015/4/2/pubmed PY - 2015/7/17/medline KW - neuromuscular blockade KW - renal failure KW - rocuronium KW - sugammadex SP - 777 EP - 84 JF - British journal of anaesthesia JO - Br J Anaesth VL - 114 IS - 5 N2 - 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. SN - 1471-6771 UR - https://www.unboundmedicine.com/medline/citation/25829395/Efficacy_safety_and_pharmacokinetics_of_sugammadex_4_mg_kg_1_for_reversal_of_deep_neuromuscular_blockade_in_patients_with_severe_renal_impairment_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0007-0912(17)31293-X DB - PRIME DP - Unbound Medicine ER -