Reversal Of Vecuronium-induced Neuromuscular Blockade Research Articles

Pharmacokinetic and Pharmacodynamics of Sugammadex in Reversal of Vecuronium-induced Neuromuscular Blockade

Pharmacokinetic and Pharmacodynamics of Sugammadex in Reversal of Vecuronium-induced Neuromuscular Blockade

Reversal of Vecuronium-induced Neuromuscular Blockade with Low-dose Sugammadex at Train-of-four Count of Four: A Randomized Controlled Trial.

Rocuronium-induced neuromuscular block that spontaneously recovered to a train-of-four count of four can be reversed with sugammadex 0.5 or 1.0 mg/kg. We investigated whether these doses of sugammadex can also reverse vecuronium at a similar level of block. Sixty-five patients were randomly assigned, and 64 were analyzed in this controlled, superiority study. Participants received general anesthesia with propofol, sevoflurane, fentanyl, and vecuronium. Measurement of neuromuscular function was performed with acceleromyography (TOF-Watch-SX, Organon Teknika B.V., The Netherlands ). Once the block recovered spontaneously to four twitches in response to train-of-four stimulation, patients were randomly assigned to receive sugammadex 0.5, 1.0, or 2.0 mg/kg; neostigmine 0.05 mg/kg; or placebo. Time from study drug injection to normalized train-of-four ratio 0.9 and the incidence of incomplete reversal within 30 min were the primary outcome variables. Secondary outcome was the incidence of reparalysis (normalized train-of-four ratio less than 0.9). Sugammadex, in doses of 1.0 and 2.0 mg/kg, reversed a threshold train-of-four count of four to normalized train-of-four ratio of 0.9 or higher in all patients in 4.4 ± 2.3 min (mean ± SD) and 2.6 ± 1.6 min, respectively. Sugammadex 0.5 mg/kg reversed the block in 6.8 ± 4.1 min in 70% of patients (P < 0.0001 vs. 1.0 and 2.0 mg/kg), whereas neostigmine produced reversal in 11.3 ± 9.7 min in 77% of patients (P > 0.05 vs. sugammadex 0.5 mg/kg). The overall frequency of reparalysis was 18.7%, but this incidence varied from group to group. Sugammadex 1.0 mg/kg, unlike 0.5 mg/kg, properly reversed a threshold train-of-four count of four vecuronium-induced block but did not prevent reparalysis.

Reversal of Vecuronium-induced Neuromuscular Blockade with Sugammadex in a Child with Moebius Syndrome after Accidental Extubation

Sugammadex chemically encapsulates rocuronium and vecuronium, thereby rapidly terminating the neuromuscular blockade induced by these agents. Although the experience with the use of sugammadex in children under 2 years of age is limited, it may be considered in specific clinical contexts. We present a case where spontaneous efficient respiratory effort was resumed after reversal of vecuroniuminduced neuromuscular blockade with sugammadex in a child. A 21-month-old boy with a history of Moebius syndrome and obstructive sleep apnea needing night time noninvasive ventilation support was scheduled for adenotonsillectomy and bilateral myringotomy. Tracheal intubation was anticipated to be difficult and so it was performed using a videolaryngoscope. In the postoperative period the child remained intubated in the intensive care unit sedated and with a continuous infusion of vecuronium. On day 3 accidental extubation occurred. As it was considered an urgent situation, flumazenil, naloxone and sugammadex 2 mg.kg-1 were administered with rapid return of spontaneous respiration and consciousness, obviating the need of unnecessary airway manipulation and the inherent risks.

Effect of flucloxacillin on mouse hemi-diaphragm contractions after sub-optimal reversal of vecuroniuminduced neuromuscular blockade with sugammadex

Effect of flucloxacillin on mouse hemi-diaphragm contractions after sub-optimal reversal of vecuroniuminduced neuromuscular blockade with sugammadex

Sugammadex Provides Faster Reversal of Vecuronium-Induced Neuromuscular Blockade Compared with Neostigmine: A Multicenter, Randomized, Controlled Trial

Sugammadex, a specifically designed gamma-cyclodextrin, is a selective relaxant binding drug that rapidly reverses rocuronium-induced and, to a lesser extent, vecuronium-induced neuromuscular blockade. In this study, we compared the efficacy of sugammadex and neostigmine for the reversal of vecuronium-induced neuromuscular blockade in patients scheduled for elective surgery. Patients aged > or = 18 yr, ASA Class I-III, and scheduled for a surgical procedure under sevoflurane/opioid anesthesia received an intubating dose of vecuronium (0.1 mg/kg) and maintenance doses of 0.02-0.03 mg/kg at reappearance of the second twitch (T(2)) of train-of-four (TOF) if required. Neuromuscular blockade was monitored using acceleromyography (TOF-Watch SX, Schering-Plough Ireland, Dublin, Ireland). At end of surgery, at reappearance of T(2) after the last dose of vecuronium, patients were randomized to receive either sugammadex (2 mg/kg) or neostigmine (50 microg/kg) plus glycopyrrolate (10 microg/kg) i.v.. The primary efficacy end-point was time from start of administration of sugammadex or neostigmine to recovery of TOF ratio to 0.9. The geometric mean time to recovery of the TOF ratio to 0.9 was significantly faster with sugammadex compared with neostigmine (2.7 min [95% confidence interval {CI}]: 2.2-3.3) versus 17.9 min [95% CI: 13.1-24.3], respectively; P < 0.0001). The mean recovery times to a TOF ratio of 0.8 and 0.7 were also significantly shorter with sugammadex. No serious adverse events or unexpected side effects were reported with either drug. Sugammadex provided significantly faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine.

Pharmacokinetic-Pharmacodynamic Model for the Reversal of Neuromuscular Blockade by Sugammadex

Sugammadex selectively binds steroidal neuromuscular blocking drugs, leading to reversal of neuromuscular blockade. The authors developed a pharmacokinetic-pharmacodynamic model for reversal of neuromuscular blockade by sugammadex, assuming that reversal results from a decrease of free drug in plasma and/or neuromuscular junction. The model was applied for predicting the interaction between sugammadex and rocuronium or vecuronium. Noninstantaneous equilibrium of rocuronium-sugammadex complex formation was assumed in the pharmacokinetic-pharmacodynamic interaction model. The pharmacokinetic parameters for the complex and sugammadex alone were assumed to be identical. After development of a pharmacokinetic-pharmacodynamic model for rocuronium alone, the interaction model was optimized using rocuronium and sugammadex concentration data after administration of 0.1-8 mg/kg sugammadex 3 min after administration of 0.6 mg/kg rocuronium. Subsequently, the predicted reversal of neuromuscular blockade by sugammadex was compared with data after administration of up to 8 mg/kg sugammadex at reappearance of second twitch of the train-of-four; or 3, 5, or 15 min after administration of 0.6 mg/kg rocuronium. Finally, the model was applied to predict reversal of vecuronium-induced neuromuscular blockade. Using the in vitro dissociation constants for the binding of rocuronium and vecuronium to sugammadex, the pharmacokinetic-pharmacodynamic interaction model adequately predicted the increase in total rocuronium and vecuronium plasma concentrations and the time-course of reversal of neuromuscular blockade. Model-based evaluation supports the hypothesis that reversal of rocuronium- and vecuronium-induced neuromuscular blockade by sugammadex results from a decrease in the free rocuronium and vecuronium concentration in plasma and neuromuscular junction. The model is useful for prediction of reversal of rocuronium and vecuronium-induced neuromuscular blockade with sugammadex.

Reversal of vecuronium with neostigmine in patients with diabetes mellitus.

Reversal of vecuronium-induced neuromuscular blockade with neostigmine was compared in two groups of 16 subjects: patients with Type 2 diabetes mellitus and normal controls. When the first twitch of the train-of-four had returned to 25% of the control value, neostigmine 40 microg x kg(-1) and atropine 20 microg x kg(-1) were given to reverse the neuromuscular blockade. The train-of-four ratio was lower at 3 min, 6 min, 9 min, 12 min and 15 min after reversal in the diabetic group than in the control group but the differences did not reach statistical significance. Fifteen minutes after reversal, the number of patients in whom recovery from neuromuscular blockade was judged insufficient to guarantee good respiratory function (train-of-four ratio < 0.74) did not differ between the groups. However, 15 min after reversal, the number of patients with a train-of-four ratio < 0.9 was significantly higher in the Diabetic Group than in the Control Group (15 vs. 10, p = 0.033).

Inadequate Antagonism of Vecuronium-Induced Neuromuscular Block by Neostigmine During Sevoflurane or Isoflurane Anesthesia

To examine the effects of discontinuing sevoflurane or isoflurane anesthesia (1 minimum alveolar anesthetic concentration [MAC] of end-tidal concentrations, together with 66% N2O/O2) on the reversal of vecuronium-induced neuromuscular blockade (an initial dose = 100 micrograms/kg), the electromyographic response of the abductor digiti minimi was monitored at 20-s intervals after train-of-four (TOF) stimulation of the ulnar nerve in 192 ASA grades I and II patients. When the amplitudes of the first response (T1) had recovered to 10% of the control, neostigmine (0;spontaneous recovery, 10, 20, 30, 40, or 55 micrograms/kg, eight patients each) was given and the ratio of the fourth TOF to the first response (TOFR) was monitored at 1-min intervals for 15 min in the presence of the volatile anesthetics, or after discontinuation of anesthetic administration. Spontaneous TOFR recovery was also assessed in another eight patients who were anesthetized with 66% N2O/O2-fentanyl-diazepam. Adequate antagonisms (TOFR > 75%) were achieved after discontinuation of both administrations, but not during anesthetic administration at the neostigmine doses tested. The dose-response curves for neostigmine (10, 20, 30, and 40 micrograms/kg) were constructed using the TOFR values at 5-11 min, from which the ED50 values (a neostigmine dose required for a TOFR value of 50%) were derived. Sevoflurane impaired neostigmine antagonism more than isoflurane, as demonstrated by the significantly higher ED50 values at 7-11 min (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)