title: Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg-1 for reversal of deep neuromuscular blockade in patients with severe renal impairment.
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.
  
  
  BACKGROUND
  NCT00702715.
authors.affiliation: Department of Anaesthesia, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
authors.forename: I F
authors.initials: IF
authors.lastname: Panhuizen
authors.affiliation: Department of Anaesthesia, Central Manchester University Hospitals NHS Foundation Trust UK, Manchester, UK.
authors.forename: S J A
authors.initials: SJ
authors.lastname: Gold
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, Feldkirch Hospital, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Buerkle
authors.affiliation: Department of Anaesthesia, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands m.snoeck@cwz.nl.
authors.forename: M M J
authors.initials: MM
authors.lastname: Snoeck
authors.affiliation: Department of Anaesthesia, Central Manchester University Hospitals NHS Foundation Trust UK, Manchester, UK.
authors.forename: N J N
authors.initials: NJ
authors.lastname: Harper
authors.affiliation: MSD, Oss, The Netherlands.
authors.forename: M J G H
authors.initials: MJ
authors.lastname: Kaspers
authors.affiliation: MSD, Oss, The Netherlands.
authors.forename: M W
authors.initials: MW
authors.lastname: van den Heuvel
authors.affiliation: Department of Anaesthesiology, University of Amsterdam (AMC), Amsterdam, The Netherlands.
authors.forename: M W
authors.initials: MW
authors.lastname: Hollmann
mesh_terms: D000732:Androstanols / Q000037:antagonists & inhibitors*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D019148:Neuromuscular Blockade / Q000379:methods*; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors*; D010146:Pain / Q000139:chemically induced; D051437:Renal Insufficiency / Q000601:surgery*; D000077123:Rocuronium; D000077122:Sugammadex; D016896:Treatment Outcome; D047408:gamma-Cyclodextrins / Q000009:adverse effects* / Q000493:pharmacokinetics*
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D000077123:Rocuronium
keywords: neuromuscular blockade; renal failure; rocuronium; sugammadex