Reversal of Profound Neuromuscular Block by Sugammadex Administered Three Minutes after Rocuronium

Background Rocuronium in intubation doses provides similar intubation conditions as succinylcholine, but has a longer duration of action. This study compared time to sugammadex reversal of profound rocuronium-induced neuromuscular block with time to spontaneous recovery from succinylcholine. Methods One hundred and fifteen adult American Society of Anesthesiologists Class I-II surgical patients were randomized to this multicenter, safety-assessor-blinded, parallel group, active-controlled, Phase IIIa trial. Anesthesia was induced and maintained with propofol and an opioid. Neuromuscular transmission was blocked and tracheal intubation facilitated with 1.2 mg/kg rocuronium or 1 mg/kg succinylcholine. Sugammadex (16 mg/kg) was administered 3 min after rocuronium administration. Neuromuscular function was monitored by acceleromyography. The primary efficacy endpoint was the time from the start of relaxant administration to recovery of the first train-of-four twitch (T(1)) to 10%. Results One hundred and ten patients received study treatment. Mean times to recovery of (T(1)) to 10% and (T(1)) to 90% were significantly faster in the rocuronium-sugammadex group (4.4 and 6.2 min, respectively), as compared with the succinylcholine group (7.1 and 10.9 min, respectively; all P < 0.001). Timed from sugammadex administration, the mean time to recovery of (T(1)) to 10%, (T(1)) to 90%, and the train-of-four (T(4)/T(1)) ratio to 0.9 was 1.2, 2.9, and 2.2 min, respectively. Reoccurrence of the block was not observed. There were no serious adverse events related to study treatments. Conclusion Reversal of profound high-dose rocuronium-induced neuromuscular block (1.2 mg/kg) with 16 mg/kg sugammadex was significantly faster than spontaneous recovery from 1 mg/kg succinylcholine.

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Reversal of Rocuronium-induced (1.2 mg/kg) Profound Neuromuscular Block by Sugammadex

Anesthesiology ◽

10.1097/01.anes.0000270722.95764.37 ◽

2007 ◽

Vol 107 (2) ◽

pp. 239-244 ◽

Cited By ~ 116

Author(s):

Hans D. de Boer ◽

Jacques J. Driessen ◽

Marco A. E. Marcus ◽

Hans Kerkkamp ◽

Marten Heeringa ◽

...

Keyword(s):

Adverse Events ◽

Neuromuscular Blockade ◽

Recovery Time ◽

Neuromuscular Block ◽

Dependent Manner ◽

Physical Status ◽

Serious Adverse Events ◽

Train Of Four ◽

American Society ◽

American Society Of Anesthesiologists

Background Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified gamma-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular blockade at 5 min in American Society of Anesthesiologists physical status I and II patients. Methods Forty-five American Society of Anesthesiologists physical status I and II patients (aged 18-64 yr) scheduled to undergo surgical procedures (anticipated anesthesia duration >/= 90 min) were randomly assigned to a phase II, multicenter, assessor-blinded, placebo-controlled, parallel, dose-finding study. Anesthesia was induced and maintained with propofol and an opioid. Profound neuromuscular blockade was induced with 1.2 mg/kg rocuronium bromide. Sugammadex (2.0, 4.0, 8.0, 12.0, or 16.0 mg/kg) or placebo (0.9% saline) was then administered 5 min after the administration of rocuronium. Neuromuscular function was monitored by acceleromyography, using train-of-four nerve stimulation. Recovery time was the time from the start of administration of sugammadex or placebo, to recovery of the train-of-four ratio to 0.9. Safety assessments were performed on the day of the operation and during the postoperative and follow-up period. Results A total of 43 patients received either sugammadex or placebo. Increasing doses of sugammadex reduced the mean recovery time from 122 min (spontaneous recovery) to less than 2 min in a dose-dependent manner. Signs of recurrence of blockade were not observed. No serious adverse events related to sugammadex were reported. Two adverse events possibly related to sugammadex were reported in two patients (diarrhea and light anesthesia); however, both patients recovered without sequelae. Conclusions Sugammadex rapidly and effectively reversed profound rocuronium-induced neuromuscular blockade in humans and was well tolerated.

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Neuromuscular blockade effects of cisatracurium in 11 cats undergoing ophthalmological surgery anaesthetised with isoflurane

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x211021829 ◽

2021 ◽

pp. 1098612X2110218

Author(s):

Anne-Sophie Van Wijnsberghe ◽

Keila K Ida ◽

Petra Dmitrovic ◽

Alexandru Tutunaru ◽

Charlotte Sandersen

Keyword(s):

Neuromuscular Blockade ◽

Case Series ◽

Neuromuscular Function ◽

Duration Of Action ◽

Cardiovascular Side Effects ◽

Train Of Four ◽

Physical Classification ◽

The Mean ◽

American Society ◽

American Society Of Anesthesiologists

Case series summary This case series describes the neuromuscular blockade (NMB) following 0.15 mg/kg intravenous (IV) cisatracurium administration in 11 cats undergoing ophthalmological surgery and anaesthetised with isoflurane. Anaesthetic records were analysed retrospectively. Neuromuscular function was assessed by a calibrated train-of-four (TOF) monitor. Cats were 73 ± 53 months old, weighed 4 ± 1 kg and were of American Society of Anesthesiologists’ physical classification 2. Duration of anaesthesia and surgery were 144 ± 27 and 94 ± 24 mins, respectively. The lowest TOF count was zero in four cats, four in six cats and for one cat the TOF ratio never decreased below 31%. The time of onset was between 1 and 6 mins after the administration of cisatracurium and the mean duration of action was 20.4 ± 10.1 mins. Relevance and novel information Cisatracurium at a dose of 0.15 mg/kg IV did not consistently induce a TOF count of zero in all cats. The dose used in these cats did not produce any remarkable cardiovascular side effects. Although the NMB was not complete, the dose given was sufficient to produce central eyeball position, which was the goal of the ophthalmic surgeries.

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Effective Reversal of Moderate Rocuronium- or Vecuronium-induced Neuromuscular Block with Sugammadex, a Selective Relaxant Binding Agent

Anesthesiology ◽

10.1097/00000542-200702000-00016 ◽

2007 ◽

Vol 106 (2) ◽

pp. 283-288 ◽

Cited By ~ 128

Author(s):

Koen Suy ◽

Karl Morias ◽

Guy Cammu ◽

Pol Hans ◽

Wilbert G. F. van Duijnhoven ◽

...

Keyword(s):

Dose Response ◽

Neuromuscular Block ◽

Muscle Relaxation ◽

Dose Finding ◽

Reversal Agent ◽

Muscle Twitch ◽

Train Of Four ◽

The Mean ◽

American Society ◽

Mean Time

Background Sugammadex rapidly reverses rocuronium-induced neuromuscular block. This study explored the dose-response relation of sugammadex given as a reversal agent at reappearance of the second muscle twitch after rocuronium- and vecuronium-induced block. A secondary objective was to investigate the safety of single doses of sugammadex. Methods In this two-center, phase II, dose-finding study, 80 patients (age >or= 18 yr, American Society of Anesthesiologists physical status I or II, surgery >or= 60 min requiring muscle relaxation for intubation) were randomly assigned to receive rocuronium (0.60 mg/kg) or vecuronium (0.10 mg/kg). Sugammadex or placebo was administered at reappearance of the second muscle twitch. The primary efficacy endpoint was time from starting sugammadex administration until recovery of the train-of-four ratio to 0.9. Results Compared with placebo, sugammadex produced dose-dependent decreases in mean time to recovery for all train-of-four ratios in the rocuronium and vecuronium groups. The mean time for recovery of the train-of-four ratio to 0.9 in the rocuronium group was 31.8 min after placebo compared with 3.7 and 1.1 min after 0.5 and 4.0 mg/kg sugammadex, respectively. The mean time for recovery of the train-of-four ratio to 0.9 in the vecuronium group was 48.8 min after placebo, compared with 2.5 and 1.4 min after 1.0 and 8.0 mg/kg sugammadex, respectively. Sugammadex was well tolerated. Conclusion Sugammadex rapidly reversed rocuronium- or vecuronium-induced neuromuscular block at reappearance of the second muscle twitch and was well tolerated. A dose-response relation was observed with sugammadex for reversal of both rocuronium- and vecuronium-induced neuromuscular block.

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Comparison of Train of Four Measurements with Kinemyography NMT DATEX and Accelerography TOFscan

Medical Sciences ◽

10.3390/medsci9020021 ◽

2021 ◽

Vol 9 (2) ◽

pp. 21

Author(s):

Cyrus Motamed ◽

Migena Demiri ◽

Nora Colegrave

Keyword(s):

Neuromuscular Blockade ◽

Lower Limit ◽

Elective Surgery ◽

Orotracheal Intubation ◽

Neuromuscular Blocking ◽

Physical Status Classification ◽

Train Of Four ◽

Surgery First ◽

American Society ◽

American Society Of Anesthesiologists

Introduction: This study was designed to compare the Datex neuromuscular transmission (NMT) kinemyography (NMTK) device with the TOFscan (TS) accelerometer during the onset and recovery of neuromuscular blockade. Patients and methods: This prospective study included adult patients who were scheduled to undergo elective surgery with general anesthesia and orotracheal intubation. The TS accelerometer was randomly placed at the adductor pollicis on one hand, and the NMTK was placed on the opposite arm. Anesthesia was initiated with remifentanil target-controlled infusion (TCI) and 2.0–3.0 mg/kg of propofol. Thereafter, 0.5 mg/kg of atracurium or 0.6 mg/kg of rocuronium was injected. If needed, additional neuromuscular blocking agents were administered to facilitate surgery. First, we recorded the train of four (TOF) response at the onset of neuromuscular blockade to reach a TOF count of 0. Second, we recorded the TOF response at the recovery of neuromuscular blockade to obtain a T4/T1 90% by both TS and NMTK. Results: There were 32 patients, aged 38–83 years, with the American Society of Anesthesiologists (ASA) Physical Status Classification I–III included and analyzed. Surgery was abdominal, gynecologic, or head and neck. The Bland and Altman analysis for obtaining zero responses during the onset showed a bias (mean) of 2.7 s (delay) of TS in comparison to NMTK, with an upper/lower limit of agreement of [104; −109 s] and a bias of 36 s of TS in comparison to NMTK, with an upper/lower limit of agreement of [−21.8, −23.1 min] during recovery (T4/T1 > 90%). Conclusions: Under the conditions of the present study, the two devices are not interchangeable. Clinical decisions for deep neuromuscular blockade should be made cautiously, as both devices appear less accurate with significant variability.

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Reversal of Meeting Abstracts by Sugammadex after Continuous Infusion of Rocuronium in Patients Randomized to Sevoflurane or Propofol Maintenance Anesthesia

Anesthesiology ◽

10.1097/aln.0b013e3181a51cb0 ◽

2009 ◽

Vol 111 (1) ◽

pp. 30-35 ◽

Cited By ~ 36

Author(s):

Christopher Rex ◽

Stefanie Wagner ◽

Claudia Spies ◽

Jens Scholz ◽

Henk Rietbergen ◽

...

Keyword(s):

Single Dose ◽

Continuous Infusion ◽

Neuromuscular Blockade ◽

Recovery Time ◽

Clinical Effect ◽

Parallel Group ◽

Median Plasma ◽

Train Of Four ◽

American Society ◽

Posttetanic Count

Background Sugammadex rapidly reverses neuromuscular blockade induced by bolus rocuronium doses, but it has not been investigated after continuous rocuronium infusion in surgical patients. We therefore examined the clinical effect of sugammadex for neuromuscular blockade induced by continuous rocuronium infusion in adults undergoing surgery under maintenance anesthesia with sevoflurane or propofol. Methods This four-center, comparative, parallel-group study, randomly assigned 52 adult patients (American Society of Anesthesiologists Class I-III) to maintenance anesthesia with sevoflurane or propofol. Neuromuscular blockade was induced by bolus injection of 0.6 mg/kg rocuronium followed by continuous infusion of 7 microg x kg(-1) x min(-1) rocuronium adjusted to maintain a neuromuscular blockade depth of zero response to train-of-four and a posttetanic count of no more than 10 responses. A single dose of 4 mg/kg sugammadex was administered at first twitch (T1) 3-10%. The primary clinical effect variable was recovery time to a train-of-four ratio of 0.9. Results Median recovery time from start of sugammadex administration to a train-of-four ratio of 0.9 in the sevoflurane and propofol groups was 1.3 and 1.2 min, respectively. The estimated difference in recovery time between groups was 9 s (95% confidence interval -6 to 20 s), entirely within the predefined equivalence interval. Median plasma rocuronium concentration just before sugammadex administration was 33% lower during maintenance anesthesia with sevoflurane than with propofol. Sugammadex was well tolerated. One adverse event (procedural hypotension) was considered to be probably related to sugammadex. Conclusions Single-dose sugammadex (4 mg/kg) after continuous rocuronium infusion is equally effective and well tolerated during maintenance anesthesia with sevoflurane or propofol.

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Antagonism of Low Degrees of Atracurium-induced Meeting Abstracts

Anesthesiology ◽

10.1097/aln.0b013e3181c53863 ◽

2010 ◽

Vol 112 (1) ◽

pp. 34-40 ◽

Cited By ~ 60

Author(s):

Thomas Fuchs-Buder ◽

Claude Meistelman ◽

François Alla ◽

Arnaud Grandjean ◽

Yann Wuthrich ◽

...

Keyword(s):

Neuromuscular Block ◽

Dose Effect ◽

High Dose ◽

Residual Paralysis ◽

Train Of Four ◽

Clinical Interest ◽

Low Degrees ◽

Dose Recommendations ◽

Relationship Of ◽

Anesthesia Time

Background Low degrees of residual paralysis (i.e., a train-of-four [TOF] ratio > 0.4) are relatively frequent, difficult to detect, and still potentially harmful. Unfortunately, the appropriate dose of anticholinesterase for this situation has not been determined. This may be of clinical interest because a high dose of neostigmine given at a shallow level of neuromuscular block may produce neuromuscular weakness. The purpose of this study was to investigate the dose-effect relationship of neostigmine to antagonize residual paralysis corresponding to a TOF ratio of 0.4 and 0.6. Methods Recovery after 10, 20, 30 microg/kg neostigmine or placebo given at either 0.4 or 0.6 TOF ratio was assessed by acceleromyography in 120 patients undergoing intravenous anesthesia. Time to a 0.9 and 1.0 TOF ratio was measured, and the probability of successful reversal within 10 min after the respective neostigmine doses was calculated. In addition, the dose of neostigmine needed to achieve the recovery targets in 5 or 10 min was also determined. Results When given at a TOF ratio of either 0.4 or 0.6, time to 0.9 and 1.0 TOF ratio was significantly shorter with any dose of neostigmine than without. The probability of successful reversal after 20 microg/kg neostigmine was 100% when a TOF ratio of 0.9 was the target; for a TOF ratio of 1.0, the probability was 93% and 67%, dependent on whether the dose of neostigmine was given at TOF ratio of 0.6 or 0.4, respectively. With a dose of 30 microg/kg, a TOF ratio of 1.0 is expected to be reached within approximately 5 min. Low doses of neostigmine are required to reach a TOF ratio of 0.9 or to accept an interval of 10 min. Conclusion Reduced doses (10-30 microg/kg) of neostigmine are effective in antagonizing shallow atracurium block. For successful reversal within 10 min, as little as 20 microg/kg neostigmine may be sufficient. These dose recommendations are specific for atracurium and an intravenous anesthetic background.

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Response to Mivacurium in Patients Carrying the K Variant in the Butyrylcholinesterase Gene

Anesthesiology ◽

10.1097/00000542-200503000-00005 ◽

2005 ◽

Vol 102 (3) ◽

pp. 503-508 ◽

Cited By ~ 14

Author(s):

Mona R. Gätke ◽

Jørgen Viby-Mogensen ◽

Doris Østergaard ◽

Jens R. Bundgaard

Keyword(s):

Nerve Stimulation ◽

Dna Analysis ◽

Neuromuscular Block ◽

Nucleotide Sequencing ◽

Wild Type ◽

Duration Of Action ◽

Prolonged Duration ◽

Train Of Four ◽

K Variant

Background Mivacurium is hydrolyzed by the butyrylcholinesterase enzyme, and patients with hereditary changes of the enzyme often have prolonged duration of action of mivacurium. In this study, the authors investigated the significance of the most commonly occurring variant, the Kalow (K) variant, established using DNA analysis, for the response to mivacurium. Methods A total of 58 patients carrying either the wild-type butyrylcholinesterase or different combinations of the atypical (A) variant and the K variant were included. Patients who were homozygous for the A variant were given 0.03 mg/kg mivacurium. All other patients received 0.2 mg/kg mivacurium. The neuromuscular block was measured using train-of-four nerve stimulation and mechanomyography. Genotyping was performed with complete nucleotide sequencing. Results Heterozygosity of the K variant prolonged the time to train-of-four 0.70 from 26.6 to 34.5 min (30%; not significant) as compared with the wild type. Heterozygosity of the K variant linked to the A variant prolonged the corresponding time from 32 to 42.7 min (33%; P = 0.03) as compared with patients who were heterozygous for solely an A allele. For eight patients who were homozygous for both the A and K variants, the time to 25% recovery was 78-89 min as compared with 44-57 min in patients who were homozygous for the A variant or had only one linked K variant. Conclusion The K variant prolongs the duration of action of mivacurium. The current results indicate that the effect is modest when the K variant occurs heterozygously with the wild type or the A variant but is marked in patients who are homozygous for both the A and K variants.

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Sensitivity to Rocuronium-Induced Neuromuscular Block and Reversibility with Sugammadex in a Patient with Myotonic Dystrophy

Case Reports in Anesthesiology ◽

10.1155/2012/107952 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Akihiro Kashiwai ◽

Takahiro Suzuki ◽

Setsuro Ogawa

Keyword(s):

General Anesthesia ◽

Myotonic Dystrophy ◽

Neuromuscular Blockade ◽

Spontaneous Recovery ◽

Neuromuscular Block ◽

High Sensitivity ◽

Additional Dose ◽

Fast Recovery ◽

Train Of Four ◽

The Times

We report a patient with myotonic dystrophy who showed prolonged rocuronium-induced neuromuscular blockade, although with a fast recovery with sugammadex. During general anesthesia with propofol and remifentanil, the times to spontaneous recovery of the first twitch (T1) of train of four to 10% of control values after an intubating dose of rocuronium 1 mg/kg and an additional dose of 0.2 mg/kg were 112 min and 62 min, respectively. Despite the high sensitivity to rocuronium, sugammadex 2 mg/kg administered at a T1 of 10% safely and effectively antagonized rocuronium-induced neuromuscular block in 90 s.

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Comparative Clinical Pharmacology of Rocuronium, Cisatracurium, and Their Combination

Anesthesiology ◽

10.1097/00000542-199811000-00011 ◽

1998 ◽

Vol 89 (5) ◽

pp. 1116-1124 ◽

Cited By ~ 27

Author(s):

Mohamed Naguib ◽

Abdulhamid H. Samarkandi ◽

Adel Ammar ◽

S. R. Elfaqih ◽

Salem Al-Zahrani ◽

...

Keyword(s):

Clinical Pharmacology ◽

Time Course ◽

Time Profile ◽

Neuromuscular Blocking ◽

Combination Group ◽

Onset Of Action ◽

Recovery Times ◽

Train Of Four ◽

American Society ◽

American Society Of Anesthesiologists

Background The comparative clinical pharmacology of cisatracurium and rocuronium and their combinations has not been reported. In this study, the authors compared the relative potency and the clinical profile and characterized the interaction of both drugs. Methods Two hundred twenty adults classified as American Society of Anesthesiologists physical status I and anesthetized with propofol-fentanyl-nitrous oxide were studied. In part 1, the neuromuscular-blocking effects of cisatracurium and rocuronium were assessed after administration of bolus doses of 20-50 microg/kg and 100-300 microg/kg, respectively. In part 2, we compared the time course of 1xED50, 1, 1.5, and 2xED95 doses of both drugs (where ED50 and ED95 are, respectively, the doses producing 50% and 95% depression of the first twitch height [T1]). In part 3, equieffective combinations of both drugs were studied to characterize their interaction. Results The calculated ED50 values and their 95% confidence intervals were 111 (107-115) and 26.2 (25.8-26.5) microg/kg [corrected] for rocuronium and cisatracurium, respectively. Compared with equipotent doses of cisatracurium, rocuronium had a faster onset, and a faster spontaneous T1 and train-of-four recovery times that were significant except at maximum recovery with the 2xED95 dose. The interaction between rocuronium and cisatracurium was synergistic, and the time profile of the combination group was different from that of the single-dose groups. Conclusions Cisatracurium is four to five times more potent than rocuronium. Rocuronium had a faster onset of action, a shorter clinical duration, and a faster spontaneous recovery rate compared with equipotent doses of cisatracurium.

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Pharmacokinetics and Pharmacodynamics of Mivacurium in Patients Phenotypically Homozygous for the Atypical Plasma Cholinesterase Variant

Anesthesiology ◽

10.1097/00000542-200506000-00011 ◽

2005 ◽

Vol 102 (6) ◽

pp. 1124-1132 ◽

Cited By ~ 12

Author(s):

Doris Østergaard ◽

Jørgen Viby-Mogensen ◽

Søren N. Rasmussen ◽

Mona R. Gätke ◽

France Varin

Keyword(s):

Neuromuscular Block ◽

Elimination Rate ◽

Plasma Cholinesterase ◽

Pharmacokinetics And Pharmacodynamics ◽

Duration Of Action ◽

First Response ◽

Train Of Four ◽

The Times ◽

Human Cholinesterase ◽

Different Levels

Background In patients homozygous for atypical plasma cholinesterase, mivacurium causes a long-lasting neuromuscular block, but injection of human cholinesterase has been proven effective in antagonizing the block. The purpose of this study was to evaluate the pharmacodynamics and pharmacokinetics of mivacurium in such patients, as well as the effect of cholinesterase injected early or late after mivacurium. Methods Eleven patients phenotypically homozygous for the atypical variant received 0.075 mg/kg (1 patient) or 0.15 mg/kg (10 patients) mivacurium. The neuromuscular block was monitored using train-of-four nerve stimulation and mechanomyography. Cholinesterase, 2.8-10.0 mg/kg, was administered approximately 30 or 120 min after mivacurium. The times to different levels of neuromuscular recovery and the venous concentrations of the isomers of mivacurium were measured. Results Injection of cholinesterase increased plasma cholinesterase activity to normal and the clearances of the active isomers and the elimination rate constants by a factor of 10-15. The first response was seen in 13.5 min (3.7-44.2 min). Time to a train-of-four ratio of 0.8 ranged from 30 to 60 min (n = 6). Neostigmine injected after cholinesterase shortened recovery further, and a train-of-four ratio of 0.8 was reached in 10-30 min. Conclusion As expected, the duration of action of mivacurium is markedly prolonged in homozygous atypical patients. Injection of cholinesterase significantly increases the metabolism of mivacurium, leading to a shorter duration of action. Injection of neostigmine after the administration of cholinesterase speeds up recovery.

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