Flucloxacillin and diclofenac do not cause recurrence of neuromuscular blockade after reversal with sugammadex.
BACKGROUND
Sugammadex, a modified γ-cyclodextrin, facilitates rapid reversal of rocuronium- and vecuronium-induced neuromuscular blockade (NMB). Cyclodextrins are known for their ability to form inclusion complexes with various drugs. Theoretically, molecules with a high affinity for sugammadex could interact and displace sugammadex from the sugammadex-rocuronium or sugammadex-vecuronium complex, potentially resulting in the recurrence of NMB due to recirculation of free rocuronium or vecuronium.


OBJECTIVE
This study aimed to evaluate whether the administration of high doses of flucloxacillin or diclofenac can result in recurrence of NMB through displacement of sugammadex from its complex with rocuronium or vecuronium, following successful reversal of NMB by a suboptimal dose of sugammadex 2 mg/kg. Flucloxacillin has previously been identified using a modelling approach as a drug with displacement potential, while diclofenac was assessed due to its common intravenous use in the peri-operative and post-surgery setting.


METHODS
This was a randomized, open-label, parallel, single-centre study conducted at SGS Life Services-CPU, Antwerp, Belgium. Twenty-four healthy, propofol-anaesthetized, adult volunteers were randomized to either rocuronium 0.6 mg/kg or vecuronium 0.1 mg/kg, followed by a suboptimal dose of sugammadex 2 mg/kg 15 minutes after induction of NMB. Five minutes after successful sugammadex reversal, subjects received either diclofenac 75 mg (15-minute infusion) or flucloxacillin 2 g (5-minute infusion) according to randomization. The suboptimal dose of sugammadex and relatively high doses of diclofenac and flucloxacillin were applied to create favourable conditions for the potential displacement of sugammadex from the sugammadex-rocuronium or sugammadex-vecuronium complex, and thus possible recurrence of NMB due to recirculation of free rocuronium or vecuronium. Possible recurrence of NMB was assessed by neuromuscular monitoring, performed with acceleromyography, and was continued until ∼90 minutes after the start of diclofenac or flucloxacillin administration. Recurrence of NMB was concluded if three consecutive train-of-four (TOF) ratios were <0.8.


RESULTS
Following successful reversal with a suboptimal dose of sugammadex 2 mg/kg administered 15 minutes after NMB induction, subsequent administration of diclofenac or flucloxacillin did not result in recurrence of NMB in any subject based on measurement of TOF ratios during anaesthesia and neuromuscular function tests upon awakening. There were no adverse events considered to be related to sugammadex.


CONCLUSIONS
Administration of flucloxacillin or diclofenac does not result in recurrence of NMB through displacement of sugammadex from the sugammadex-rocuronium or sugammadex-vecuronium complex.
Merck Sharp & Dohme Corp., Whitehouse Station, NJ 07065-0900, USA. pieter-jan.de.kam@merck.com
Pieter-Jan de
PJ
Kam
Michiel W van den
MW
Heuvel
Peter
P
Grobara
Alex
A
Zwiers
Jean-Luc
JL
Jadoul
Erik de
Ed
Clerck
Steven
S
Ramael
Pierre A M
PA
Peeters
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004008:Diclofenac / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D005436:Floxacillin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019148:Neuromuscular Blockade / Q000379:methods*; D012008:Recurrence; D000077122:Sugammadex; D047408:gamma-Cyclodextrins / Q000493:pharmacokinetics / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D047408:gamma-Cyclodextrins; D004008:Diclofenac; D000077122:Sugammadex; D005436:Floxacillin