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

2005 ◽  
Vol 102 (6) ◽  
pp. 1124-1132 ◽  
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.

The Influence of Drug-induced Low Plasma Cholinesterase Activity on the Pharmacokinetics and Pharmacodynamics of Mivacurium

2000 ◽  
Vol 92 (6) ◽  
pp. 1581-1587 ◽  
Author(s):  
Doris Østergaard ◽  
Søren N. Rasmussen ◽  
Jørgen Viby-Mogensen ◽  
Niels A. Pedersen ◽  
Rikke Boysen
Keyword(s):  
Nerve Stimulation ◽  
Cholinesterase Activity ◽  
Elimination Rate ◽  
Plasma Cholinesterase ◽  
Effect Compartment ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Duration Of Action ◽  
Plasma Cholinesterase Activity ◽  
Elimination Half ◽  
Train Of Four

Background The short duration of action of mivacurium results from its rapid hydrolysis by plasma cholinesterase. Bambuterol, an oral bronchodilator, has an inhibiting effect on plasma cholinesterase. The purpose of this study was to evaluate the effect of bambuterol-induced low plasma cholinesterase activity on the pharmacokinetics and pharmacodynamics of mivacurium. Methods Fourteen patients received 20 mg bambuterol and 14 patients received placebo orally 2 h before induction of anesthesia. During anesthesia the neuromuscular block was monitored at the thumb using train-of-four nerve stimulation every 12 s and mechanomyography. The times to different levels of neuromuscular recovery after 0.2 mg/kg mivacurium were measured. The concentrations in venous blood of the three isomers and the metabolites of mivacurium were measured using high-performance liquid chromatography. Results Plasma cholinesterase activity was inhibited a median of 90% (range, 67-97%) after bambuterol. The time to first response to train-of-four nerve stimulation was 15 min (range, 9-21 min) and 59 min (range, 32-179 min) in patients receiving placebo and bambuterol, respectively. The estimated clearances of the isomers were significantly lower and the elimination half-lives of all three isomers significantly prolonged in patients receiving bambuterol. No difference was seen in elimination half-lives of the metabolites. The elimination rate constant from the effect compartment and the potency of mivacurium was not affected by bambuterol. Conclusion A 90% inhibition of plasma cholinesterase activity significantly reduced clearance of the isomers of mivacurium. Correspondingly, the duration of action of 0.2 mg/kg mivacurium was prolonged three- to fourfold, compared with patients not administered bambuterol.

Temperature-dependent Pharmacokinetics and Pharmacodynamics of Vecuronium

2000 ◽  
Vol 92 (1) ◽  
pp. 84-84 ◽  
Author(s):  
James E. Caldwell ◽  
Tom Heier ◽  
Peter M. C. Wright ◽  
Sean Lin ◽  
Gerald McCarthy ◽  
...  
Keyword(s):  
Core Temperature ◽  
Mechanical Response ◽  
Population Based ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Duration Of Action ◽  
Effect Site ◽  
Mixed Effects Modeling ◽  
Arterial Blood ◽  
First Response ◽  
Train Of Four

Background The authors evaluated the influence of temperature on the pharmacokinetics and pharmacodynamics of vecuronium because mild core hypothermia doubles its duration of action. Methods Anesthesia was induced with alfentanil and propofol and maintained with nitrous oxide and isoflurane in 12 healthy volunteers. Train-of-four stimuli were applied to the ulnar nerve, and the mechanical response of the adductor pollicis was measured. Volunteers were actively cooled or warmed until their distal esophageal temperatures were in one of four ranges: < 35.0 degrees C, 35.0-35.9 degrees C, 36.0-36.9 degrees C, and > or = 37.0 degrees C. With temperature stabilized, vecuronium was infused at 5 microg x kg(-1) x min(-1) until the first response of each train-of-four had decreased by 70%. Arterial blood (for vecuronium analysis) was sampled at intervals until the first response recovered to at least 90% of its prevecuronium level. Vecuronium, 20 microg x kg(-1) x min(-1), was then infused for 10 min, and arterial blood was sampled at intervals for up to 7 h. Population-based nonlinear mixed-effects modeling was used to examine the effect of physical characteristics and core temperature on vecuronium pharmacokinetics and pharmacodynamics. Results Decreasing core temperature over 38.0-34.0 degrees C decreases the plasma clearance of vecuronium (11.3% per degrees C), decreases the rate constant for drug equilibration between plasma and effect site (0.023 min(-1) per degrees C), and increases the slope of the concentration-response relationship (0.43 per degrees C). Conclusions Our results show that reduced clearance and rate of effect site equilibration explain the increased duration of action of vecuronium with reducing core temperature. Tissue sensitivity to vecuronium is not influenced by core temperature.

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

2005 ◽  
Vol 102 (3) ◽  
pp. 503-508 ◽  
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.

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

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
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.

scholarly journals Prolonged onset and duration of action of rocuronium after accidental subcutaneous injection in a patient with chronic renal failure—a case report

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Akira Doshu-Kajiura ◽  
Junko Suzuki ◽  
Takahiro Suzuki
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Neuromuscular Block ◽  
Subcutaneous Administration ◽  
Upper Airway ◽  
Duration Of Action ◽  
Case Presentation ◽  
Slow Development ◽  
Prolonged Duration ◽  
Train Of Four

Abstract Background Drugs administered subcutaneously have delayed onset and prolonged duration of action versus those given intravenously. Since the duration of action of rocuronium is prolonged in patients with renal dysfunction, subcutaneous administration of rocuronium to such patients might significantly prolong its effect. Case presentation A 51-year-old female with chronic renal failure was accidentally administered 1.04 mg/kg rocuronium subcutaneously. Marked prolongation of onset and duration of action of rocuronium were detected on acceleromyography. Slow development of the neuromuscular block was still observed at 100 min after injection. Administration of 4.5 mg/kg sugammadex at 140 min after rocuronium injection facilitated recovery from a train-of-four (TOF) count of 2 to a TOF ratio of 100% within 5 min. No symptoms of postoperative recurarization and upper airway obstruction were observed. Conclusion Neuromuscular monitoring is necessary to evaluate the progress and depth of neuromuscular block, particularly when rocuronium is inadvertently administered subcutaneously.

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

2009 ◽  
Vol 110 (5) ◽  
pp. 1020-1025 ◽  
Author(s):  
Chingmuh Lee ◽  
Jonathan S. Jahr ◽  
Keith A. Candiotti ◽  
Brian Warriner ◽  
Mark H. Zornow ◽  
...  
Keyword(s):  
Spontaneous Recovery ◽  
Neuromuscular Block ◽  
High Dose ◽  
Serious Adverse Events ◽  
Duration Of Action ◽  
Parallel Group ◽  
Train Of Four ◽  
American Society ◽  
American Society Of Anesthesiologists ◽  
Mean Time

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.

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 Cysatracurium dosing in gynecological laparoscopic surgery in obese patients

2020 ◽  
Vol 27 (4) ◽  
pp. 62-71
Author(s):  
E. V. Polovnikov ◽  
N. L. Elizar’eva ◽  
A. N. Kolosov ◽  
A. N. Shmakov ◽  
V. N. Kokhno ◽  
...  
Keyword(s):  
Body Weight ◽  
Laparoscopic Surgery ◽  
Recovery Time ◽  
Neuromuscular Block ◽  
Ideal Body Weight ◽  
Obese Patients ◽  
Total Consumption ◽  
Duration Of Action ◽  
First Response ◽  
Ideal Body

Aim. Substantiation of cisatracurium dosing in routine gynaecological laparoscopic surgery in obese patients based on comparative development time and duration of the neuromuscular block.Materials and methods. The assay included 24 women with class II-III obesity and routine laparoscopic gynaecological surgery divided into two cohorts. In cohort 1, cisatracurium was dosed at 0.15 mg/kg ideal body weight estimated with the Lorentz formula. In cohort 2, cisatracurium dosing was 0.15 mg/kg real body weight.Results. Tracheal intubation and total operation doses of the relaxant were higher when rated for real body weight. Time between cysatracurium administration and maximal neuromuscular transmission inhibition was less in cohort 2, and recovery time of the first response to stimulation — in cohort 1. Neuromuscular block recovery time to 25% TOF count and the recovery index did not differ significantly between the cohorts.Conclusion. Cysatracurium dosage rated for ideal body weight resulted in a better controlled course of the neuromuscular block, whilst rating for real body weight resulted in a dose-dependent increase of the duration of action and total consumption rate of the relaxant.

scholarly journals Recovery from Mivacurium Block with or without Anticholinesterase following Continuous Infusion in Obstetric Patients

1996 ◽  
Vol 24 (5) ◽  
pp. 585-589 ◽  
Author(s):  
G. S. K. Jan ◽  
W. N. Tong ◽  
A. M. H. Chan ◽  
T. W. C. Hui ◽  
J. W. R. Lo
Keyword(s):  
Nitrous Oxide ◽  
Cholinesterase Activity ◽  
Spontaneous Recovery ◽  
Neuromuscular Block ◽  
Plasma Cholinesterase ◽  
Nerve Stimulator ◽  
Group I ◽  
Group Time ◽  
Train Of Four ◽  
Recovery Group

Neostigmine antagonism after suxamethonium followed by mivacurium chloride bolus and infusion was studied. Thirty ASA group I or II patients were given mivacurium 0.15 mg/kg followed by infusion during nitrous oxide-enflurane-pethidine anaesthesia. Train of four (TOF) stimuli were applied to the ulnar nerve at the wrist and TOF twitch height and ratio measured by TOF-GUARD nerve stimulator. Mivacurium infusion was titrated to give a 90% block of first twitch height. Patients were randomized into two groups. Group I patients recovered from the mivacurium block spontaneously while Group II patients were given neostigmine 0.05 mg/kg and atropine 0.02 mg/kg. Time to reach train of four ratio (TOFR) of 25%, 50% and 70% were measured. This study demonstrated a mean infusion rate of 5.1±1.8 μg/kg/min to maintain a 90% neuromuscular block. In the spontaneous recovery group, time to reach TOFR of 25%, 50% and 70% were 9.3±2.7 min, 13.5±3.0 min and 16.7±3.0 min respectively while the corresponding times in the neostigmine group were 5.2±1.7 min, 10.9±2.2 min and 16.1±7.4 min respectively. There were significant differences in the time taken to TOFR of 25% (P<0.0001) and 50% (P<0.05) but no difference in the time taken for TOFR to return to 70%. We concluded that mivacurium is suitable for use in caesarean section despite a decrease in plasma cholinesterase activity. Neostigmine antagonism is not required as a routine.

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