Org 25969 (sugammadex), a selective relaxant binding agent for antagonism of prolonged rocuronium-induced neuromuscular block.
BACKGROUND
Org 25969 is a cyclodextrin compound designed to reverse a rocuronium-induced neuromuscular block. The aim of this study was to explore the efficacy, dose-response relation and safety of Org 25969 for reversal of a prolonged rocuronium-induced neuromuscular block.


METHODS
Thirty anaesthetized adult patients received rocuronium 0.6 mg kg(-1) as an initial dose followed by increments to maintain a deep block at a level of <10 PTCs (post-tetanic counts) recorded every 6 min. Neuromuscular monitoring was carried out using accelerometry, in a train-of-four (TOF) mode using TOF-WatchSX. At recovery of T2, following at least 2 h of neuromuscular block, patients received their randomly assigned dose of 0.5, 1.0, 2.0, 4.0 or 6.0 mg kg(-1) of Org 25969. Anaesthesia and neuromuscular monitoring were continued for a minimum period of 30 min after Org 25969 administration. The main end-point of the study was the time to achieve a sustained recovery of TOF ratio to 0.9. Patients were followed up for 7 days after anaesthesia.


RESULTS
The results showed a dose-related decrease in the average time taken to attain a TOF ratio of 0.9 from 6:49 (min:s) with the 0.5 mg kg(-1) dose to 1:22 with the 4.0 mg kg(-1) dose. Weighted non-linear regression analysis showed the fastest achievable time to TOF ratio of 0.9 to be 1:35. Org 25969 produced no major adverse effects.


CONCLUSIONS
Org 25969 effectively reversed a deep and prolonged neuromuscular block induced by rocuronium. The effective reversal dose appears to be 2-4 mg kg(-1).
Shields
M
M
Department of Anaesthetics and Intensive Care Medicine, Queen's University of Belfast, Northern Ireland, UK.
Giovannelli
M
M
Mirakhur
R K
RK
Moppett
I
I
Adams
J
J
Hermens
Y
Y
D000328:Adult; D000368:Aged; D000732:Androstanols / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000762:Anesthesia Recovery Period; D000768:Anesthesia, General; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative / Q000379:methods; D009213:Myography; D019148:Neuromuscular Blockade; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000077123:Rocuronium; D000077122:Sugammadex; D047408:gamma-Cyclodextrins / Q000009:adverse effects / Q000494:pharmacology*
D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D000077123:Rocuronium