Reversal of Rocuronium-induced Neuromuscular Block by the Selective Relaxant Binding Agent Sugammadex

2006 ◽  
Vol 104 (4) ◽  
pp. 667-674 ◽  
Author(s):  
Iben F. Sorgenfrei ◽  
Kathrine Norrild ◽  
Per Bo Larsen ◽  
Jakob Stensballe ◽  
Doris Østergaard ◽  
...  
Keyword(s):  
Placebo Group ◽  
Renal Excretion ◽  
Neuromuscular Block ◽  
Neuromuscular Blocking ◽  
Dependent Manner ◽  
Binding Agent ◽  
Train Of Four ◽  
Time Required ◽  
To Receive ◽  
Dose Dependent

Background Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block. Methods Twenty-seven male surgical patients aged 18-64 yr were randomly assigned to receive placebo or sugammadex (0.5, 1.0, 2.0, 3.0, or 4.0 mg/kg) for reversal of 0.6 mg/kg rocuronium-induced neuromuscular block. Anesthesia was induced and maintained using intravenous fentanyl and propofol. Neuromuscular function was assessed using acceleromyography. Sugammadex or placebo was administered at reappearance of T2 of the train-of-four. The primary efficacy variable was the time required for recovery to a train-of-four ratio of 0.9. Results Sugammadex decreased median recovery time in a dose-dependent manner from 21.0 min in the placebo group to 1.1 min in the group receiving 4.0 mg/kg sugammadex. Doses of sugammadex of 2.0 mg/kg or greater reversed rocuronium-induced neuromuscular block within 3 min. A median of 59-77% of sugammadex was excreted unchanged in the urine within 16 h, mostly in the first 8 h. Sugammadex increased the proportion of the rocuronium dose excreted unchanged in the urine (from a median of 19% in the placebo group to 53% in the 4.0-mg/kg group within 16 h). Sugammadex was safe and well tolerated. No evidence of recurarization was observed in any patient. Conclusion At doses of 2.0 mg/kg or greater, sugammadex safely reversed 0.6 mg/kg rocuronium-induced neuromuscular block in a dose-dependent manner. Sugammadex enhanced renal excretion of rocuronium and was excreted unchanged by the kidneys.

scholarly journals Reversal of Profound, High-dose Rocuronium–induced Meeting Abstracts by Sugammadex at Two Different Time Points

2008 ◽  
Vol 109 (2) ◽  
pp. 188-197 ◽  
Author(s):  
Friedrich K. Pühringer ◽  
Christopher Rex ◽  
Andreas W. Sielenkämper ◽  
Casper Claudius ◽  
Per Bo Larsen ◽  
...  
Keyword(s):  
Neuromuscular Blockade ◽  
Clinical Evidence ◽  
High Dose ◽  
Dependent Manner ◽  
Binding Agent ◽  
Residual Neuromuscular Blockade ◽  
Arterial Blood ◽  
Train Of Four ◽  
To Receive ◽  
Dose Dependent

Background Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade was evaluated. Methods A total of 176 adult patients were randomly assigned to receive sugammadex (2, 4, 8, 12, or 16 mg/kg) or placebo at 3 or 15 min after high-dose rocuronium (1.0 or 1.2 mg/kg) during propofol anesthesia. The primary endpoint was time to recovery of the train-of-four ratio to 0.9. Neuromuscular monitoring was performed using acceleromyography. Results Sugammadex administered 3 or 15 min after injection of 1 mg/kg rocuronium decreased the median recovery time of the train-of-four ratio to 0.9 in a dose-dependent manner from 111.1 min and 91.0 min (placebo) to 1.6 min and 0.9 min (16 mg/kg sugammadex), respectively. After 1.2 mg/kg rocuronium, sugammadex decreased time to recovery of train-of-four from 124.3 min (3-min group) and 94.2 min (15-min group) to 1.3 min and 1.9 min with 16 mg/kg sugammadex, respectively. There was no clinical evidence of reoccurrence of neuromuscular blockade or residual neuromuscular blockade. Exploratory analysis revealed that prolongation of the corrected QT interval considered as possibly related to sugammadex occurred in one patient. Another two patients developed markedly abnormal arterial blood pressure after sugammadex that lasted approximately 15 min. Conclusion Sugammadex provides a rapid and dose-dependent reversal of profound neuromuscular blockade induced by high-dose rocuronium (1.0 or 1.2 mg/kg) in adult surgical patients.

scholarly journals Optimal neuromuscular blocking effects of remifentanil during tracheal intubation under general anesthesia

2018 ◽  
Vol 46 (8) ◽  
pp. 3097-3103 ◽  
Author(s):  
So Young Kwon ◽  
Si Wook Chung ◽  
Jin Deok Joo
Keyword(s):  
General Anesthesia ◽  
Elective Surgery ◽  
Neuromuscular Block ◽  
Onset Time ◽  
Neuromuscular Blocking ◽  
Blocking Effects ◽  
Train Of Four ◽  
The Times ◽  
Time Required ◽  
Retrospective Comparative Study

Objective This study was performed to determine the effect of the remifentanil dose on the onset time of rocuronium with electromyography. Methods This retrospective comparative study included 75 patients undergoing general anesthesia for elective surgery. Patients received lidocaine (40 mg) and propofol (2 mg/kg) followed by rocuronium (0.6 mg/kg) with either saline infusion (Group S), remifentanil at 0.5 µg/kg/minute (Group R 0.5), or remifentanil at 1.0 µg/kg/minute (Group R 1.0). Neuromuscular block was monitored by train-of-four (TOF) electromyography, and the times taken to reach TOF 0 and TOF ratio (TOFR) 25% were recorded. Results The times taken to reach TOF 0 and TOFR 25% were significantly higher in Groups R 0.5 and R 1.0 than in Group S. The time taken to reach TOF 0 was 130.0 ± 6.4 s in Group S, 142.6 ± 6.0 s in Group R 0.5, and 183.0 ± 11.6 s in Group R 1.0. The time taken to reach TOFR 25% was also higher in Groups R 0.5 and R 1.0 than in Group S. Conclusions As the remifentanil dose increases, the intubation time required to reach TOF 0 also increases. Remifentanil has an effect on the onset of rocuronium.

scholarly journals Nov način odmerjanja sugamadeksa za odpravo z vekuronijem povzročene nevromišične blokade

2015 ◽  
Vol 84 (6) ◽  
Author(s):  
Blaž Peček ◽  
Damjan Polh ◽  
Tea Priman
Keyword(s):  
Neuromuscular Block ◽  
Muscle Relaxation ◽  
Muscle Relaxants ◽  
Binding Agent ◽  
Know How ◽  
Economical Evaluation ◽  
Train Of Four ◽  
Dosage Regime ◽  
Time Required ◽  
Mean Time

Background and Goal of Study: Sugammadex is a selective binding agent that bindsaminosteroid muscle relaxants. Each molecule of sugammadex binds one molecule of musclerelaxant. To produce the same depth of the neuromuscular block (NMB) much less molecules ofvecuronium are needed than molecules of rocuronium. In theory less sugammadex would beneeded to neutralise the neuromuscular block if vecuronium was used to produce the neuromuscular block. Our aim was to compare reversal of vecuronium induced muscle relaxation between a new way of dosing sugammadex, which takes into account TOF value at the end of the surgery and the amount of vecuronium given during the surgery with neostigmine atropine combination. We also wanted to know how much this dosage regime can save compared to standard per kg dosage.Materials and Methods: 20 adult patients requiring a general anesthesia for surgery were analysed. The first group of 11 patients (SUG) received sugammadex at the end of the surgery according to the table one for NMB reversal. The second group of 9 patients (NEO) received neostigmine and atropine. Train of four (TOF) value was recorded at the end of the surgery and then continuously until the TOF value reached more than 0.9 and the patient was extubated. The time required for the TOF value reaching 0.9 was compared between the groups. For economical evaluation we compared the amount of sugammadex used in the SUG group to standard sugammadex per kg dosage.Results and Discussion: Mean time to recovery to a TOF ratio of 0.9 with sugammadex was 5.12min versus 12.6 min with neostigmine atropine (P < 0.05). No sign of postoperative residual curarisation was observed in the SUG group. For patients in our study 530 mg of sugammadex were used to neutralise the NMB. If standard per kg sugammadex dosing had been used we would have used 2420 mg for the NMB reversal.Conclusion(s): New dosing for sugammadex was successful in neutralising the NMB regardlessof the TOF value at the end of the surgery. The economic impact of the proposed dosing is significant as an average cost for the vecuronium NMB reversal is reduced from around 80 € to 20 € per patient.

Residual Block after Mivacurium with or without Edrophonium Reversal in Adults and Children

1996 ◽  
Vol 84 (2) ◽  
pp. 362-367. ◽  
Author(s):  
David R. Bevan ◽  
Raymond Kahwaji ◽  
John M. Ansermino ◽  
Eleanor Reimer ◽  
Michael F. Smith ◽  
...  
Keyword(s):  
Ulnar Nerve ◽  
Neuromuscular Block ◽  
Saline Group ◽  
Neuromuscular Blocking ◽  
Postanesthesia Care Unit ◽  
Random Allocation ◽  
Train Of Four ◽  
Residual Neuromuscular Block ◽  
Residual Block ◽  
Stimulation Of

Background The rapid recovery from mivacurium- induced neuromuscular block has encouraged omission of its reversal. The purpose of this study was to determine, in children and in adults, whether failure to reverse mivacurium neuromuscular block was associated with residual neuromuscular block on arrival in the postanesthesia care unit. Methods In 50 children, aged 2-12 yr, and 50 adults, aged 20-60 yr, anesthesia was induced and maintained with propofol and fentanyl, and neuromuscular block was achieved by an infusion of mivacurium, to maintain one or two visible responses to train-of-four (TOF) stimulation of the ulnar nerve. At the end of surgery, mivacurium infusion was stopped, and 10 min later, reversal was attempted with saline or 0.5 mg x kg(-1) edrophonium by random allocation. On arrival in the postanesthesia care unit, a blinded observer assessed patients clinically and by stimulation of the ulnar nerve with a Datex electromyogram in the uncalibrated TOF mode. Results Children arrived in the postanesthesia care unit 8.2 +/- 3-4 min after reversal of neuromuscular block and showed no sign of weakness, either clinically or by TOF stimulation. Although TOF ratio was greater in children who had received edrophonium (1.00 +/- 0.05 vs. 0.93 +/- 0.01, P&lt;0.01), TOF was &gt;0.7 in all children. Adults arrived in the postanesthesia care unit 12.9 +/- 5.3 min after reversal of neuromuscular block(P&lt;0.01 vs. children). Six in the saline group demonstrated weakness (two required immediate reversal of neuromuscular block, and TOF was &lt;0.7 in four others), compared with TOF &lt;0.7 in only one of the edrophonium group (P&lt;0.05). Conclusions This study demonstrated that, in adults, failure to reverse mivacurium neuromuscular block was associated with an increased incidence of residual block. Such weakness was not observed in children receiving similar anesthetic and neuromuscular blocking regimens.

scholarly journals The tof-guard neuromuscular transmission monitor and its use in horses

1999 ◽  
Vol 29 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Juliana Noda Bechara ◽  
Denise Tabacchi Fantoni ◽  
Paulo Sergio de Moraes Barros ◽  
Elton Rodrigues Migliati ◽  
Marcio Augusto Ferreira ◽  
...  
Keyword(s):  
Surgical Procedure ◽  
Neuromuscular Transmission ◽  
Medical Literature ◽  
Neuromuscular Block ◽  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agent ◽  
Neuromuscular Transmission Monitor ◽  
To Receive ◽  
Neuromuscular Transmission Monitoring

It has been emphasized in the human medical literature, that when using a neuromuscular blocking agent, it is of vital importance the monitoring of the neuromuscular block and that these agents should never be used without it. The purpose of this study was to evaluate the use of the neuromuscular transmission monitor TOF-Guard in horses. Twelve horses were randomly assigned whether to receive pancuronium or atracurium as the neuromuscular blocking agent. All horses were pre-medicated with romifidine, anaesthesia induced with diazepam and ketamine and maintenance with halothane. Abolition of spontaneous ventilation was accomplished by the administration of atracurium or pancuronium. The time from injection of the muscle relaxant agent to the onset of maximum block (T1=0), recovery of T1 to 25% and the recovery of TOF ratio to 0.7 were recorded, as was the time for recovery of T1 from 25 to 75%. It was concluded that it is very important the neuromuscular transmission monitoring during the use of a nondepolarizing neuromuscular blocking agent, since it provides a safer anaesthetic and surgical procedure with the use of adequate dosages and due to the impossibility of a superficialization of the neuromuscular blockade during a surgical procedure. The TOF-Guard showed to be a good option for neuromuscular monitoring in horses.

Evaluation of Neuromuscular and Cardiovascular Effects of Two Doses of Rapacuronium (ORG 9487) versus Mivacurium and Succinylcholine 

1999 ◽  
Vol 91 (6) ◽  
pp. 1648-1648 ◽  
Author(s):  
Rafael Miguel ◽  
Thomas Witkowski ◽  
Hideo Nagashima ◽  
Robert Fragen ◽  
Richard Bartkowski ◽  
...  
Keyword(s):  
Neuromuscular Blockade ◽  
Cardiovascular Effects ◽  
Rapid Onset ◽  
Neuromuscular Blocking ◽  
Open Label ◽  
Org 9487 ◽  
Train Of Four ◽  
Pressure Changes ◽  
To Receive ◽  
Nondepolarizing Muscle Relaxant

Background This study compares the neuromuscular blocking and cardiovascular effects of rapacuronium (ORG 9487), a new aminosteroid nondepolarizing muscle relaxant, to recommended intubating doses of succinylcholine and mivacurium. Methods Adult patients were randomized in an open-label fashion to receive 1-5 microg/kg fentanyl before 1.5 mg/kg propofol induction followed by 1.5 or 2.5 mg/kg rapacuronium, 1.0 mg/kg succinylcholine, or 0.25 mg/kg mivacurium (i.e., 0.15 mg/kg followed by 0.1 mg/kg 30 s later). Results Patient neuromuscular blockade status was monitored by measuring the train-of-four response to a supramaximal stimulus at the ulnar nerve every 12 s. Percentage of the first twitch of the train-of-four (T1) at 60 s was similar in patients receiving 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine and was significantly less than in patients in the mivacurium group (26, 16, and 18%, respectively, vs. 48%; P &lt; 0.01). Times to 80% T1 depression were also similar among patients in the 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine groups and significantly longer in the mivacurium group (62, 54, and 54 s, respectively, vs. 112 s; P &lt; 0.01). Clinical duration was longer in all groups compared with the succinylcholine group; however, clinical duration in the 1.5 mg/kg rapacuronium group was shorter compared with the mivacurium group (15 vs. 21 min, respectively; P &lt; 0.01). Heart rate changes were mild in the 1.5 mg/kg rapacuronium, succinylcholine, and mivacurium groups. The patients in the 2.5 mg/kg rapacuronium group had significantly higher heart rates compared with patients in the mivacurium group. No differences were found in blood pressure changes among patients in the four groups. Conclusions Rapacuronium, 1.5 and 2.5 mg/kg, produced neuromuscular blockade as rapidly as succinylcholine and significantly faster than mivacurium. Although succinylcholine continued to show the shortest duration, 1.5 mg/kg rapacuronium used a rapid onset and a relatively short duration and may be considered an alternative to succinylcholine.

Pharyngeal Function and Breathing Pattern during Partial Neuromuscular Block in the Elderly

2014 ◽  
Vol 120 (2) ◽  
pp. 312-325 ◽  
Author(s):  
Anna I. Hårdemark Cedborg ◽  
Eva Sundman ◽  
Katarina Bodén ◽  
Hanne Witt Hedström ◽  
Richard Kuylenstierna ◽  
...  
Keyword(s):  
Neuromuscular Block ◽  
The Elderly ◽  
Pulmonary Complications ◽  
Neuromuscular Blocking ◽  
Residual Effects ◽  
Airway Protection ◽  
Healthy Elderly ◽  
Increased Risk ◽  
Train Of Four ◽  
Pharyngeal Function

Abstract Background: Intact pharyngeal function and coordination of breathing and swallowing are essential for airway protection and to avoid respiratory complications. Postoperative pulmonary complications caused by residual effects of neuromuscular-blocking agents occur more frequently in the elderly. Moreover, elderly have altered pharyngeal function which is associated with increased risk of aspiration. The purpose of this study was to evaluate effects of partial neuromuscular block on pharyngeal function, coordination of breathing and swallowing, and airway protection in individuals older than 65 yr. Methods: Pharyngeal function and coordination of breathing and swallowing were assessed by manometry and videoradiography in 17 volunteers, mean age 73.5 yr. After control recordings, rocuronium was administered to obtain steady-state train-of-four ratios of 0.70 and 0.80 followed by spontaneous recovery to greater than 0.90. Results: Pharyngeal dysfunction increased significantly at train-of-four ratios 0.70 and 0.80 to 67 and 71%, respectively, compared with 37% at control recordings, and swallowing showed a more severe degree of dysfunction during partial neuromuscular block. After recovery to train-of-four ratio of greater than 0.90, pharyngeal dysfunction was not significantly different from the control state. Resting pressure in the upper esophageal sphincter was lower at all levels of partial neuromuscular block compared with control recordings. The authors were unable to demonstrate impaired coordination of breathing and swallowing. Conclusion: Partial neuromuscular block in healthy elderly individuals causes an increased incidence of pharyngeal dysfunction from 37 to 71%, with impaired ability to protect the airway; however, the authors were unable to detect an effect of partial neuromuscular block on coordination of breathing and swallowing.

Early Reversal of Rapacuronium with Neostigmine 

1999 ◽  
Vol 91 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Robert Purdy ◽  
David R. Bevan ◽  
Francois Donati ◽  
Lance J. Lichtor
Keyword(s):  
Neuromuscular Block ◽  
Rapid Onset ◽  
Force Of Contraction ◽  
Mean Values ◽  
Neuromuscular Relaxant ◽  
Treatment Groups ◽  
Nitrous Oxide Oxygen ◽  
Train Of Four ◽  
To Receive ◽  
Different Doses

Background Rapacuronium is a rapid-onset, short-acting neuromuscular relaxant. This multiple-center study determined neuromuscular recovery when neostigmine was given 2 or 5 min after rapacuronium. Methods One hundred seventeen patients were randomized to receive two different doses of rapacuronium and to receive neostigmine in two different doses and at two different times. During propofol anesthesia with nitrous oxide, oxygen, and fentanyl, 1.5 or 2.5 mg/kg rapacuronium was given 1 min before tracheal intubation. Neuromuscular block was measured by train-of-four ulnar nerve stimulation every 12 s: The adductor pollicis force of contraction was recorded mechanomyographically. Two or five minutes after rapacuronium was administered, 0.05 or 0.07 mg/kg neostigmine was administered and recovery was compared with that of control patients who received no neostigmine. Results Both doses of rapacuronium produced 100% block in all but one patient, who exhibited 97% block. Neostigmine accelerated recovery in all groups. After 1.5 mg/kg rapacuronium, the time to 25% T1 twitch recovery decreased from a mean of 16 min in control patients to mean values of 8-10 min in the treatment groups: The time to train-of-four ratio of 0.7 decreased from 38 min to 17-19 min. After 2.5 mg/kg rapacuronium, the time to 25% T1 was reduced from 23 min to 11-12 min, and the time to train-of-four ratio of 0.7 decreased from 54 min to 26-32 min. Recovery was not different among the the groups that received different doses and timing of neostigmine. Conclusions Recovery of intense rapacuronium block was accelerated by early neostigmine administration. When given 2 min after rapacuronium, neostigmine was as effective as after 5 min, and 0.05 mg/kg neostigmine was comparable to 0.07 mg/kg neostigmine.

scholarly journals Reversal of Vecuronium-induced Neuromuscular Blockade with Low-dose Sugammadex at Train-of-four Count of Four

2017 ◽  
Vol 127 (3) ◽  
pp. 441-449 ◽  
Author(s):  
László Asztalos ◽  
Zoltán Szabó-Maák ◽  
András Gajdos ◽  
Réka Nemes ◽  
Adrienn Pongrácz ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Low Dose ◽  
Neuromuscular Block ◽  
Study Drug ◽  
Neuromuscular Function ◽  
Secondary Outcome ◽  
Drug Injection ◽  
Train Of Four ◽  
Study Participants ◽  
To Receive

Abstract Background 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. Methods 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). Results 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 &lt; 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 &gt; 0.05 vs. sugammadex 0.5 mg/kg). The overall frequency of reparalysis was 18.7%, but this incidence varied from group to group. Conclusions 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.

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