title: Sugammadex and neostigmine dose-finding study for reversal of residual neuromuscular block at a train-of-four ratio of 0.2 (SUNDRO20)†,.
abstract: BACKGROUND
  The aim of this dose-finding study was to evaluate the dose-response relationship of sugammadex and neostigmine to reverse a commonly observed level of incomplete recovery from rocuronium-induced neuromuscular block, that is, a train-of-four ratio (TOFR) ≥0.2.
  
  
  METHODS
  Ninety-nine anaesthetized patients received rocuronium 0.6 mg kg(-1) i.v. for tracheal intubation and, if necessary, incremental doses of 0.1-0.2 mg kg(-1). Neuromuscular monitoring was performed by calibrated electromyography. Once the TOFR recovered to 0.2, patients were randomized to receive sugammadex (0.25, 0.5, 0.75, 1.0, or 1.25 mg kg(-1) i.v.), neostigmine (10, 25, 40, 55, or 70 µg kg(-1) i.v.), or saline (n=9 per group). Primary and secondary end points were the doses necessary to restore neuromuscular function to a TOFR≥0.9 with an upper limit of 5 and 10 min for 95% of patients, respectively.
  
  
  RESULTS
  Neostigmine was not able to fulfil the end points. Based on the best-fitting model, the sugammadex dose estimation for recovery to a TOFR≥0.9 for 95% of patients within 5 and 10 min was 0.49 and 0.26 mg kg(-1), respectively.
  
  
  CONCLUSIONS
  A residual neuromuscular block of a TOFR of 0.2 cannot be reversed reliably with neostigmine within 10 min. In the conditions studied, substantially lower doses of sugammadex than the approved dose of 2.0 mg kg(-1) may be sufficient to reverse residual rocuronium-induced neuromuscular block at a recovery of TOFR≥0.2.
  
  
  BACKGROUND
  NCT01006720.
authors.affiliation: Klinik für Anaesthesiologie.
authors.forename: N
authors.initials: N
authors.lastname: Kaufhold
authors.affiliation: Klinik für Anaesthesiologie s.schaller@tum.de.
authors.forename: S J
authors.initials: SJ
authors.lastname: Schaller
authors.affiliation: Klinik für Anaesthesiologie.
authors.forename: C G
authors.initials: CG
authors.lastname: Stäuble
authors.affiliation: Klinik für Anaesthesiologie.
authors.forename: E
authors.initials: E
authors.lastname: Baumüller
authors.affiliation: Institut für Medizinische Statistik und Epidemiologie, Klinikum rechts der Isar, Technische Universität München, Ismaningerstraße 22, 81675 München, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Ulm
authors.affiliation: Klinik für Anaesthesiologie.
authors.forename: M
authors.initials: M
authors.lastname: Blobner
authors.affiliation: Klinik für Anaesthesiologie.
authors.forename: H
authors.initials: H
authors.lastname: Fink
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000732:Androstanols / Q000037:antagonists & inhibitors; D000762:Anesthesia Recovery Period; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004576:Electromyography / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009388:Neostigmine / Q000494:pharmacology*; D019148:Neuromuscular Blockade; D061886:Neuromuscular Monitoring / Q000706:statistics & numerical data*; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors*; D000077123:Rocuronium; D012965:Sodium Chloride / Q000008:administration & dosage; D000077122:Sugammadex; D055815:Young Adult; D047408:gamma-Cyclodextrins / Q000494:pharmacology*
chemical_list: D000732:Androstanols; D002800:Cholinesterase Inhibitors; D003473:Neuromuscular Nondepolarizing Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D009388:Neostigmine; D012965:Sodium Chloride; D000077123:Rocuronium
keywords: neostigmine; neuromuscular block; quantitative neuromuscular monitoring; reversal neuromuscular block; rocuronium; sugammadex