Reversal of Profound Rocuronium Meeting Abstracts by Sugammadex in Anesthetized Rhesus Monkeys

Background Reversal of neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a synthetic gamma-cyclodextrin derivative. The current study determined the feasibility of reversal of rocuronium-induced profound neuromuscular blockade with sugammadex in the anesthetized rhesus monkey using train-of-four stimulation. Methods Four female rhesus monkeys each underwent three experiments. In each experiment, first, a 100-microg/kg dose of rocuronium was injected and spontaneous recovery was monitored. After full recovery, a 500-microg/kg dose of rocuronium was injected. Up to this point, all three experiments in a single monkey were identical. One minute after this rocuronium injection, either one of the two tested dosages of sugammadex (1.0 or 2.5 mg/kg) was injected or saline was injected. Results Injection of 100 microg/kg rocuronium resulted in a mean neuromuscular blockade of 93.0% (SD = 4%), and profound blockade was achieved by injection of 500 microg/kg. In all experiments, a 100% neuromuscular blockade was achieved at this dose. After injection of the high rocuronium dose, the 90% recovery of the train-of-four ratio took 28 min (SD = 7 min) after saline, 26 min (SD = 9.5 min) after 1 mg/kg sugammadex, and 8 min (SD = 3.6 min) after 2.5 mg/kg sugammadex. Signs of residual blockade or recurarization were not observed. Injection of sugammadex had no significant effects on blood pressure or heart rate. Conclusions Chemical encapsulation of rocuronium by sugammadex is a new therapeutic mechanism allowing effective and rapid reversal of profound neuromuscular blockade induced by rocuronium in anesthetized rhesus monkeys.

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Comparison of the TOFscan and the TOF-Watch SX during Recovery of Neuromuscular Function

Anesthesiology ◽

10.1097/aln.0000000000002400 ◽

2018 ◽

Vol 129 (5) ◽

pp. 880-888 ◽

Cited By ~ 14

Author(s):

Glenn S. Murphy ◽

Joseph W. Szokol ◽

Michael J. Avram ◽

Steven B. Greenberg ◽

Torin D. Shear ◽

...

Keyword(s):

Neuromuscular Blockade ◽

Spontaneous Recovery ◽

Three Dimensional ◽

Tracheal Extubation ◽

Neuromuscular Function ◽

Neuromuscular Monitoring ◽

Limits Of Agreement ◽

Train Of Four ◽

Good Agreement

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Quantitative neuromuscular monitoring is required to ensure neuromuscular function has recovered completely at the time of tracheal extubation. The TOFscan (Drager Technologies, Canada) is a new three-dimensional acceleromyography device that measures movement of the thumb in multiple planes. The aim of this observational investigation was to assess the agreement between nonnormalized and normalized train-of-four values obtained with the TOF-Watch SX (Organon, Ireland) and those obtained with the TOFscan during recovery from neuromuscular blockade. Methods Twenty-five patients were administered rocuronium, and spontaneous recovery of neuromuscular blockade was allowed to occur. The TOFscan and TOF-Watch SX devices were applied to opposite arms. A preload was applied to the TOF-Watch SX, and calibration was performed before rocuronium administration. Both devices were activated, and train-of-four values were obtained every 15 s. Modified Bland–Altman analyses were conducted to compare train-of-four ratios measured with the TOFscan to those measured with the TOF-Watch SX (when train-of-four thresholds of 0.2 to 1.0 were achieved). Results Bias and 95% limits of agreement between the TOF-Watch SX and the TOFscan at nonnormalized train-of-four ratios between 0.2 and 1.0 were 0.021 and −0.100 to 0.141, respectively. When train-of-four measures with the TOF-Watch SX were normalized, bias and 95% limits of agreement between the TOF-Watch SX and the TOFscan at ratios between 0.2 and 1.0 were 0.015 and −0.097 to 0.126, respectively. Conclusions Good agreement between the TOF-Watch SX with calibration and preload application and the uncalibrated TOFscan was observed throughout all stages of neuromuscular recovery.

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Reversal of Neuromuscular Blockade with Sugammadex at the Reappearance of Four Twitches to Train-of-four Stimulation

Anesthesiology ◽

10.1097/aln.0b013e318297ce95 ◽

2013 ◽

Vol 119 (1) ◽

pp. 36-42 ◽

Cited By ~ 44

Author(s):

Adrienn Pongrácz ◽

Szilárd Szatmári ◽

Réka Nemes ◽

Béla Fülesdi ◽

Edömér Tassonyi

Keyword(s):

Neuromuscular Blockade ◽

Study Drug ◽

Similar Degree ◽

Drug Injection ◽

Stimulation Threshold ◽

Double Blind ◽

Randomized Controlled ◽

Upper Limit ◽

Rapid Reversal ◽

Train Of Four

Abstract Background: Doses of sugammadex required to reverse deep, moderate, and shallow rocuronium-induced neuromuscular blockade have been established. However, no adequate doses for the reversal of reappearance of four twitches of train-of-four (TOF) stimulation (threshold TOF-count-four) have been established. Methods: This single-center, randomized, controlled, double-blind, four-groups parallel-arm study included 80 patients undergoing general anesthesia with propofol, sevoflurane, fentanyl, and rocuronium. Neuromuscular monitoring was performed with calibrated acceleromyography. Once rocuronium-induced neuromuscular blockade recovered spontaneously to threshold TOF-count-four, patients randomly received 0.5, 1.0, 2.0 mg/kg of sugammadex or 0.05 mg/kg of neostigmine. The time between study drug injection and reversal of TOF ratios to 1.0 was measured. Rapid reversal (≤2.0 min average, upper limit of 5.0 min) was the primary endpoint and slower reversal (≤5.0 min average, upper limit of 10 min) was the secondary endpoint of the study. Results: Sugammadex, in doses of 1.0 and 2.0 mg/kg, reversed threshold TOF-count-four to TOF ratios of 1.0 in 2.1 ± 0.8 min (mean ± SD) and 1.8 ± 0.9 min, respectively. Sugammadex, 0.5 mg/kg, induced a similar degree of reversal in 4.1 ± 1.9 min (P < 0.001 vs. 1.0 and 2.0 mg/kg). Neostigmine, 0.05 mg/kg, reversed TOF ratios to 1.0 in 8.5 ± 3.5 min (P < 0.001 vs. sugammadex groups). Conclusion: Sugammadex, 1.0 mg/kg, rapidly and effectively reverses rocuronium-induced block that has recovered spontaneously to a threshold TOF-count-four. A dose of 0.5 mg/kg was equally effective, but satisfactory antagonism took as long as 8 min to take place.

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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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Comparison of Cisatracurium and Vecuronium by Infusion in Neonates and Small Infants after Congenital Heart Surgery

Anesthesiology ◽

10.1097/00000542-200411000-00011 ◽

2004 ◽

Vol 101 (5) ◽

pp. 1122-1127 ◽

Cited By ~ 18

Author(s):

David L. Reich ◽

Ingrid Hollinger ◽

Donna J. Harrington ◽

Howard S. Seiden ◽

Sephali Chakravorti ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Neuromuscular Blockade ◽

Congenital Heart ◽

Heart Surgery ◽

Spontaneous Recovery ◽

Congenital Heart Surgery ◽

Pharmacokinetic Analysis ◽

Train Of Four ◽

Neonates And Infants

Background Neonates and infants often require extended periods of mechanical ventilation facilitated by sedation and neuromuscular blockade. Methods Twenty-three patients aged younger than 2 yr were randomly assigned to receive either cisatracurium or vecuronium infusions postoperatively in a double-blinded fashion after undergoing congenital heart surgery. The infusion was titrated to maintain one twitch of a train-of-four. The times to full spontaneous recovery of train-of-four without fade, extubation, intensive care unit discharge, and hospital discharge were documented after drug discontinuation. Sparse sampling after termination of the infusion and a one-compartment model were used for pharmacokinetic analysis. The Mann-Whitney U test and Student t test were used to compare data between groups. Results There were no significant differences between groups with respect to demographic data or duration of postoperative neuromuscular blockade infusion. The median recovery time for train-of-four for cisatracurium (30 min) was less than that for vecuronium (180 min) (P < 0.05). Three patients in the vecuronium group had prolonged train-of-four recovery: Two had long elimination half-lives for vecuronium, and one had a high concentration of 3-OH vecuronium. There were no differences in extubation times, intensive care unit stays, or hospital stays between groups. Conclusions Our results parallel data from adults demonstrating a markedly shorter recovery of neuromuscular transmission after cisatracurium compared with vecuronium. Decreased clearance of vecuronium and the accumulation of 3-OH vecuronium may contribute to prolonged spontaneous recovery times. Cisatracurium is associated with faster spontaneous recovery of neuromuscular function compared with vecuronium but not with any differences in intermediate outcome measures in neonates and infants.

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The Effect of Preload on Electromyographic Train-Of-Four Ratio at the First Dorsal Interosseous Muscle during Spontaneous Recovery from Neuromuscular Blockade

Anaesthesia and Intensive Care ◽

10.1177/0310057x1804600613 ◽

2018 ◽

Vol 46 (6) ◽

pp. 614-619

Author(s):

A. Bansal ◽

P. A. Stewart ◽

S. Phillips ◽

S. Liang ◽

X. Wang

Keyword(s):

Neuromuscular Blockade ◽

Spontaneous Recovery ◽

Repeated Measurements ◽

First Dorsal Interosseous ◽

Reversal Agent ◽

Residual Neuromuscular Blockade ◽

Train Of Four ◽

First Dorsal Interosseous Muscle ◽

Induction Of Anaesthesia ◽

Dorsal Interosseous Muscle

Accurate and reliable quantitative neuromuscular function monitoring is desirable for the optimal management of neuromuscular blockade, selection of the most appropriate reversal agent and dosage, and assessing the completeness of reversal to exclude residual neuromuscular blockade. Applying preload to the thumb may affect the precision of electromyography. This study compared the precision and agreement of electromyography with and without preload during recovery from non-depolarising neuromuscular blockade. After induction of anaesthesia and before neuromuscular blockade, the supramaximal current required at the first dorsal interosseous muscle with and without preload was determined. During recovery, train-of-four ratios were recorded using electromyography every 20 seconds. Alternating pairs of measurements (with and without preload) were obtained until spontaneous recovery was achieved. The preload device applied a resting tension of 75–150 g to the thumb. Bland–Altman analysis for repeated measurements was used to assess precision and agreement of electromyography responses with and without muscle preload. Two hundred and seventy-five sets of repeated measurements were collected from 35 participants. The repeatability coefficient for train-of-four ratios recorded by electromyography with a preload was 0.030 (95% confidence intervals, CI, 0.028 to 0.031) versus 0.068 (95% CI 0.064 to 0.072) without. Train-of-four ratios with preload demonstrated a bias of +0.038 (95% CI 0.037 to 0.042) compared to electromyography without, with 95% limits of agreement of 0.035–0.111. Preload significantly improved the precision of electromyographic train-of-four ratios, with 95% of consecutive measurements differing by less than 3%. Furthermore, electromyography with preload demonstrated a positive bias of 0.04 compared with electromyography alone, the clinical significance of which requires further research.

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Effects of Prenatal Cocaine Exposure on Brain Dopamine Receptor Function, Behavior, and Cocaine Reinforcement in Adult Male and Female Rhesus Monkeys

PsycEXTRA Dataset ◽

10.1037/e654422011-001 ◽

2011 ◽

Author(s):

Michael A. Nader

Keyword(s):

Dopamine Receptor ◽

Adult Male ◽

Rhesus Monkeys ◽

Receptor Function ◽

Cocaine Exposure ◽

Brain Dopamine ◽

Prenatal Cocaine Exposure ◽

Male And Female ◽

Prenatal Cocaine ◽

Female Rhesus

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Estradiol, progesterone, and sex hormone‐binding globulin in female rhesus monkeys ( Macaca mulatta )

Journal of Medical Primatology ◽

10.1111/j.1600-0684.1993.tb00678.x ◽

1993 ◽

Vol 22 (5) ◽

pp. 320-324

Author(s):

C. Longcope ◽

C. Bukowski ◽

J. Tast

Keyword(s):

Macaca Mulatta ◽

Rhesus Monkeys ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Hormone Binding ◽

Female Rhesus

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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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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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