Train-of-four ratio recovery often precedes twitch recovery when neuromuscular block is reversed by sugammadex.

BACKGROUND: Sugammadex reverses rocuronium-induced neuromuscular block (NMB). In all published studies investigating sugammadex, the primary outcome parameter was a train-of-four (TOF) ratio of 0.9. The recovery time of T1 was not described. This retrospective investigation describes the recovery of T1 vs. TOF ratio after the reversal of NMB with sugammadex. METHODS: Two studies were analyzed. In study A, a phase II dose-finding study, ASA I-II patients received an intravenous (IV) dose of rocuronium 1.2 mg/kg, followed by an IV dose of sugammadex (2.0, 4.0, 8.0, 12.0 or 16.0 mg/kg) or placebo (0.9% saline) after 5 min. In study B, a phase III trial comparing patients with renal failure and healthy controls, rocuronium 0.6 mg/kg was used to induce NMB; sugammadex 2.0 mg/kg was administered at reappearance of T2. Neuromuscular monitoring was performed by acceleromyography and TOF nerve stimulation. The primary efficacy variable was time from the administration of sugammadex to recovery of the TOF ratio to 0.9. Retrospectively, the time to recovery of T1 to 90% was calculated. RESULTS: After the reversal of rocuronium-induced NMB with an optimal dose of sugammadex [16 mg/kg (A) or 2 mg/kg (B)], the TOF ratio recovered to 0.9 significantly faster than T1 recovered to 90%. Clinical signs of residual paralysis were not observed. CONCLUSION: After the reversal of NMB by sugammadex, full recovery of the TOF ratio is possible when T1 is still depressed. The TOF ratio as the only measurement for the adequate reversal of NMB by sugammadex may not always be reliable. Further investigations for clinical implications are needed.

Reduced clearance of rocuronium and sugammadex in patients with severe to end-stage renal failure: a pharmacokinetic study.

BACKGROUND: Sugammadex is a selective relaxant binding agent designed to encapsulate the neuromuscular blocking agent, rocuronium. The sugammadex-rocuronium complex is eliminated by the kidneys. This trial investigated the pharmacokinetics (PKs) of sugammadex and rocuronium in patients with renal failure and healthy controls. METHODS: Fifteen ASA class II-III renal patients [creatinine clearance (CL(CR)) <30 ml min(-1)] and 15 ASA I-II controls (CL(CR) > or =80 ml min(-1)) were included. After induction of anaesthesia, a single i.v. dose of rocuronium 0.6 mg kg(-1) was given, followed by a single i.v. dose of sugammadex 2.0 mg kg(-1) at reappearance of the second twitch of the train-of-four response. Plasma concentrations of rocuronium and sugammadex were estimated and PK variables determined using non-compartmental analyses. Percentages of sugammadex and rocuronium excreted in the urine were measured. RESULTS: PK data were obtained from 26 patients. Mean total plasma clearance (CL) of sugammadex was 5.5 ml min(-1) in renal patients and 95.2 ml min(-1) in controls (P<0.05). Rocuronium CL was 41.8 ml min(-1) in renal patients and 167 ml min(-1) in controls (P<0.05). The median amount of sugammadex and rocuronium excreted in the urine over 72 h in renal patients was 29% and 4%, respectively, and 73% and 42% over 24 h in controls. CONCLUSIONS: Large differences in the PKs of sugammadex and rocuronium between patients with renal failure and healthy controls were observed. The effect of renal impairment on the PK variables of rocuronium was less than with sugammadex. Urinary excretion of both drugs was reduced in renal patients.

Multicentre, parallel-group, comparative trial evaluating the efficacy and safety of sugammadex in patients with end-stage renal failure or normal renal function.

BACKGROUND: Sugammadex, a modified gamma-cyclodextrin, is the first selective relaxant binding agent that specifically encapsulates the steroidal neuromuscular blocking agent, rocuronium. The action of rocuronium is prolonged in patients with renal failure. As sugammadex is primarily cleared renally, this phase III trial investigated the efficacy and safety of sugammadex for reversal of rocuronium-induced neuromuscular block (NMB) in patients with end-stage renal failure. METHODS: Thirty adult patients were studied: 15 renally impaired [creatinine clearance (CL(CR)) <30 ml min(-1)] and 15 controls (CL(CR)>80 ml min(-1)). Anaesthesia was induced and maintained using i.v. opiates and propofol. Neuromuscular monitoring was performed by acceleromyography and train-of-four (TOF) nerve stimulation. Rocuronium (0.6 mg kg(-1)) was given, followed by a single i.v. dose of sugammadex (2.0 mg kg(-1)) at reappearance of the second twitch of the TOF. The primary efficacy variable was time from administration of sugammadex to recovery of the TOF ratio to 0.9. Safety variables included clinical evidence of reoccurrence of NMB. RESULTS: After sugammadex administration, the mean (sd) time to recovery of the TOF ratio to 0.9 was 2.0 (0.72) min in renal patients and 1.65 (0.63) min in controls (NS). Recurrence of NMB was not observed in any patient. No sugammadex-related serious adverse events were reported. CONCLUSIONS: Sugammadex administered at reappearance of T(2) rapidly and effectively reverses NMB induced by rocuronium in renal failure and healthy patients. Sugammadex was well tolerated by all patients. Further safety studies on sugammadex in patients with severe renal impairment are warranted.