Application of Mivacurium in Fast-Track Anesthesia for Transthoracic Device Closure of Ventricular Septal Defects in Children

Abstract Introduction: The objective of this study was to investigate the effect of mivacurium in the application of fast-track anesthesia for transthoracic device closure of ventricular septal defects (VSDs) in children. Methods: The data of 108 children who underwent transthoracic device closure of VSDs from December 2018 to June 2020 were recorded and analyzed. All children were divided into group M (mivacurium group, n=55) and group C (cisatracurium group, n=53) according to the different muscle relaxant drug used. Results: No statistically significant differences in general preoperative data, intraoperative hemodynamic changes, or the incidence of adverse reactions were noted between the two groups (P>0.05). However, the intubation condition rating of children in group M was better than that in group C. The onset time, duration of clinical action and recovery index of the muscle relaxant, postoperative mechanical ventilation duration, and length of intensive care unit stay in group M were significantly lower than those in group C (P<0.05). Conclusion: It is safe and feasible to use mivacurium as a muscle relaxant in children undergoing fast-track cardiac anesthesia during transthoracic device closure of VSDs.

Comparison of efficacy of mivacurium versus cisatracurium in patients undergoing painless fiberoptic bronchoscopy / 中华麻醉学杂志

Objective:To compare the efficacy of mivacurium versus cisatracurium in patients undergoing painless fiberoptic bronchoscopy.Methods:A total of 100 patients of both sexes, aged 18-64 yr, of American Society of Anesthesiology physical status I or Ⅱ, scheduled for elective fiberoptic bronchoscopy were divided into 2 groups ( n=50 each) using a random number table method: mivacurium group (M group) and cisatracurium group (C group). Mivacurium 0.15 mg/kg was injected intravenously in group M, and cisatracurium 0.1 mg/kg was injected intravenously in group C. The onset time of neuromuscular block (ThD95), the duration of neuromuscular block (TOFR25), recovery index (RI), recovery time of autonomous respiration, extubation time and time of discharge from postanesthesia care unit (PACU) were recorded.The occurrence of intraoperative and postoperative adverse reactions and complications were recorded.The mean arterial pressure (MAP), heart rate (HR) and SpO 2 at restlessness at 10 min after entering the operating room (T 1), at loss of consciousness (T 2), when laryngeal mask airway was inserted (T 3), at the end of surgery (T 4), when laryngel mask airway was removed (T 5), and when the patients left the operating room (T 6). Results:Compared with group C, TOFR25, RI, recovery time of autonomous respiration, extubation time and time of discharge from PACU were significantly shortened, the total incidence of adverse reactions was decreased ( P<0.05), and no significant change was found in ThD95 in group M ( P>0.05). There was no significant difference in MAP, HR and SpO 2 at each time point between the 2 groups ( P>0.05). Conclusion:Mivacurium provides better efficacy than cisatracurium when used for painless fiberoptic bronchoscopy.

Maximum dose of continuous infusion of mivacurium for thyroid surgery under total intravenous anesthesia: a sequential trial of monitoring neurological function in 30 patients / 南方医科大学学报

OBJECTIVE@#To investigate the maximum dose of continuous mivacurium infusion for intraoperative neuromonitoring (IONM) and observe the adverse reactions during thyroid surgery under total intravenous anesthesia (TIVA).@*METHODS@#Thirty patients undergoing IONM during thyroid surgery received continuous infusion of mivacurium at the initial rate of 14.97 μg · kg@*RESULTS@#The EC@*CONCLUSIONS@#In patients undergoing thyroid surgery under TIVA, the EC

Sequential method for determining the maximum dose of mivacurium continuously infused for intraoperative neuromonitoring in thyroid surgery / 南方医科大学学报

OBJECTIVE@#To determine the maximum dose of continuously infused mivacurium for intraoperative neuromonitoring and observe its adverse effects in thyroid surgery.@*METHODS@#Twenty-eight patients undergoing thyroid surgery with intraoperative neuromonitoring received continuous infusion of mivacurium at the initial rate of 5.43 μg?kg?min, and the infusion rate for the next patient was adjusted based on the response of the previous patient according to the results of neurological monitoring. The depth of anesthesia was maintained with sevoflurane and remifentanil during the surgery. The LD50 and 95% of mivacurium were calculated using Brownlee's up-and-down sequential method.@*RESULTS@#The LD50 of continuously infused mivacurium was 8.94 μg?kg?min (95% : 8.89- 8.99 μg?kg?min) during thyroid surgery, which did not affect neurological function monitoring. Transient chest skin redness occurred after induction in 9 patients (32.1%). None of the patients experienced intubation difficulties or showed intraoperative body motions during the surgery.@*CONCLUSIONS@#In patients undergoing thyroid surgery under anesthesia maintained by inhalation and intravenous infusion, the LD50 of mivacurium was 8.94 μg?kg?min (95% : 8.89-8.99 μg?kg?min) for continuous infusion, which does not cause serious adverse effects during the operation.

Effects of different doses of mivacurium chloride on muscle relaxation time- course and hemodynamics in children with different ages / 中国医师进修杂志

Objective To observe the effect of different doses of mivacurium chloride on muscle relaxation time-course and hemodynamics in children with different ages. Methods One hundred children of selective inguinal hernia repair under general anesthesia with endotracheal intubation from January 2016 to January 2017 were enrolled, and the age was 0.5 to 6.0 years. The children were divided into low age group (0.5 to 3.0 years) and high age group (3.1 to 6.0 years) according to the age, then the children were divided into low dose group (mivacurium chloride 0.20 mg/kg) and high dose group (mivacurium chloride 0.25 mg/kg) according to the doses of mivacurium chloride. Therefore, the children were divided into low age low dose group, low age high dose group, high age low dose group and high age high dose group with 25 cases each. The mean arterial pressure (MAP) and heart rates before anesthesia (T0) and 1 min (T1), 3 min (T2), 5 min (T3), 10 min (T4) after intravenous injection of mivacurium chloride were recorded. The times of first intravenous injection of mivacurium chloride to neuromuscular block 75% (ThD75), 90% (ThD90) and maximum (ThDmax) were recorded. The recovery index (RI) was recorded. The times of last intravenous injection of mivacurium chloride to onset of muscle convulsions (Th) and muscle convulsions recovery 10% (ThR10), 25% (ThR25), 75% (ThR75), 90% (ThR90) were recorded. The times of ratio of the fourth muscle twitch to the first muscle twitch (TOFR) recovery 75% (TOFR75) and 90% (TOFR90) were recorded. Results There were no statistical difference in MAP and heart rate among 4 groups (P＞0.05). The ThD75, ThD90 and ThDmax in low age low dose group were (126 ± 40), (163 ± 59) and (192 ± 49) s, those in low age high dose group were (73 ± 15), (115 ± 41) and (142 ± 37) s, those in high age low dose group were (149 ± 38), (193 ± 44) and (221 ± 47)s, and those in high age high dose group were (105 ± 32), (138 ± 35) and (167 ± 44)s. The ThD75, ThD90 and ThDmax in low age high dose group were significantly shorter than those in low age low dose group, those in high age high dose group were significantly shorter than those in high age low dose group, those in high age low dose group were significantly longer than those in low age low dose group, those in high age high dose group were significantly longer than those in low age high dose group, and there were statistical differences (P＜0.05). There were no statistical differences in Th, ThR10, ThR25, ThD75, ThD90, RI, TOFR75 and TOFR90 among low age low dose group and low age high dose group, high age low dose group and high age high dose group (P＞0.05). Conclusions In the children of 0.5 to 3.0 years, the effect of mivacurium chloride is significantly faster than that in the children of aged 3.1 to 6.0 years. Compared with 0.20 mg/kg of mivacurium chloride, 0.25 mg/kg of mivacurium chloride has less time to display muscle relaxation effect. The recovery time is not affected by age and induction dose. Mivacurium chloride has no significant effect on hemodynamics.

Effect of antagonism of neostigmine on residual neuromuscular blockade from mivacurium chloride in the elderly patients / 临床麻醉学杂志

Objective To investigate the effect of Neostigmine on Mivacurium Chloride in postoperative recovery of elderly patients with anesthesia.Methods A total of 46 patients (32 males,14 females,aged 60-73 years,ASA grade Ⅰ or Ⅱ) who underwent laparoscopic surgery for gastrointestinal tumor under general anesthesia,were randomly divided into two groups.Patients in the studying group (group A,n=22) were given a dosage of eostigmine 20 ug/kg after the end of surgery,and patients in control group (group B,n=24) were given 0.9% saline solution.Monitored the contract reaction of adductor pollicis through train-of-four ratio (TOFR) by stimulating ulnar nerve.Record condition of recovery from neuromuscular blocked,untoward effect after operation,the activity of the plasmacholinesterase at the time of induction of anaesthesia and extubation.Results The sex,age,height,weight,BMI,operation time,fluid volume,temperature,the activity of the plasmacholinesterase,recovery score and sedation score had no significant difference.Activity decline of the plasmacholinesterase is obviously related with infusion liquid volume,was statistically significant(P<0.05),group A is lower than group B obviously at the recovery of TOFR to 25%,to 70%,70% to 90%,onset time and recovery index time,was statistically significant (P<0.05),the difference of TOFR of the two groups was statistically significant at the time of 5 min、10 min、30 min after extubation (P<0.05).The difference of the incidence of TOFR<0.7 of the two groups at the time of 5 min,10 min,30 min after extubation and the difference of the incidence of TOFR<0.9 of the two groups at the time of 10 min,30 min after extubation were statistically significant (P<0.05).Conclusion There is obvious significance for neostigmine to resume muscle force in mivacurium chloride postoperative recovery in the elderly.

Metoclopramida e ondansetrona alteram o bloqueio neuromuscular induzido por mivacurio? - um estudo randomizado / Do metoclopramide and ondansetrone alter mivacurium-induced neuromuscular blockade? - a randomised trial / La metoclopramida y la ondansetrona alteran el bloqueo neuromuscular inducido por mivacurio? - un estudio aleatorizado

Experiência: Objetivamos investigar os efeitos de metoclopramida e ondansetrona no bloqueio neuromuscular por mivacúrio. Métodos: Foram incluídos no estudo 75 pacientes ASA I-II, com idades entre 18 e 65 anos e agendados para cirurgia eletiva necessitando de intubação traqueal. Os pacientes receberam metoclopramida 10 mg, ondansetrona 4 mg ou salina normal 5 mL; grupo M, grupo O e grupo SN (n = 25) respectivamente. Antes da anestesia, os medicamentos em estudo foram administrados em um volume de 5 mL. O nível de colinesterase plasmática foram obtidos antes e 5 minutos depois da administração dos medicamentos em estudo e 5 minutos depois da administração de mivacúrio. Os tempos até o início e os níveis T25, T75, T25-75 e T90 foram comparados entre si, tendo sido investigadas as diferenças entre cada paciente. Depois de registrar T90, o estudo foi terminado, tendo início a cirurgia. Resultados: O tempo até o início foi significativamente mais breve no Grupo M versus os outros dois grupos. O tempo até o início no Grupo O foi significativamente mais breve versus grupo SN. No grupo M, T25, T75, T90 e os índices de recuperação foram significativamente maiores versus Grupo NS (p < 0,001). No Grupo O, T25 e T75 foram maiores versus Grupo NS (p < 0,01 e p < 0,05,respectivamente). No Grupo M, T75, T90 e índices de retorno da anestesia foram significativamente maiores versus Grupo O (p < 0,001, p < 0,01, p < 0,001, respectivamente). Nos Grupos M e O, os níveis plasmáticos de colinesterase diminuíram significativamente (p < 0,001). Depois da administração dos medicamentos em estudo e de mivacúrio. Houve também redução na colinesterase plasmática no Grupo NS 5 minutos após a administração de mivacúrio (p < 0,001). ...

Background: We aimed to investigate the effects of metoclopramide and ondansetrone on mivacurium neuromuscular blockade. Methods: Seventy five, ASA I-II patients, aged 18-65 and scheduled for elective surgery requiring tracheal intubation were included in the study. The patients received metoclopramide 10 mg, ondansetrone 4 mg or normal saline 5 mL; group M, group O, group NS (n = 25), respectively. Before anesthesia study drugs were administered in a volume of 5 mL. The level of plasma cholinesterase were obtained before and 5 minutes after the administration of study drugs and5 minutes after the administration of mivacurium. Onset time, T25, T75, T25-75, T90 levelswere compared with each other and differences between each patients were investigated. After recording T90, the study was terminated and surgery was started. Results: Onset time was significantly shorter in group M, than the other two groups. Onset time in group O was significantly shorter than in group NS. In Group M T25, T75, T90 and recovery indices were significantly greater than in Group NS (p < 0.001). In Group O T25, T75 were greater than Group NS (p < 0.01 and p < 0.05, respectively). In Group M T75, T90 and emergence indices were significantly higher than Group O (p < 0.001, p < 0.01, p < 0.001, respectively). In Groups M and O, plasma cholinesterase levels decreased significantly (p < 0.001) after administration of study drugs and mivacurium. Plasma cholinesterase also was reduced in Group NS 5 minutes after the administration of mivacurium (p < 0.001). Conclusion: Ondansetrone is believed to be more reliable agent than metoclopramide when used with mivacurium. .

Application of mivacurium in moden non-convulsively electuoconvulsive therapy / 临床麻醉学杂志

Objective To observe the effect of mivacurium,succinylcholine and atracurium in modified electric convulsive therapy (MECT).Methods Sixty ASA Ⅰ or Ⅱ patients with schizo-phrenia aged from 18 to 60 years old were randomly divided into 3 groups :mivacurium group (group A,n=20),succinylcholine group (group B,n=20),atracurium group (group C,n=20).The on-set time of muscle relaxation,the recovery time of spontaneous breathing after MECT,the awake time,as well as the changes of 5 min MAP,HR and SpO2 before and after MECT were observed re-spectively.Results The onset time of muscle relaxation and the recovery time of spontaneous breath-ing in group B were shorter than those in groups A and C (P <0.05).The onset time of muscle re-laxation and the recovery time of spontaneous breathing in group A were shorter than those in group C (P <0.05).Conclusion Mivacurium is a better alternative medicine in MECT in the situation of no succinylcholine or succnylcholine contraindication.

Clinical Comparison of Neuromuscular Pharmacodynamics of Different Dosage of Mivacurium Chloride in Infants during Sevoflurane Anesthesia / 昆明医科大学学报

Objective To investigate the neuromuscular blocking effects and clinical pharmacology of different dosage of mivacurium chloride in infants during sevoflurane anesthesia. Methods Forty ASA I infants undergoing sevoflurane general anesthesia were randomly assigned to tow groups according to the dose level of mivacurium: group1: 200 μg/kg ( n =20) and group2: 250 μg/kg ( n =20) . TOFs were determined synchronously. The onset time of mivacurium, recovery time of spontaneous breathing and cardiovascular reactions were measured. Results The onset time was significantly shortened in group 2 compared with group 1 (P<0.05) . There was no significant difference in the recovery time of spontaneous breathing between the two groups. 2 minutes after mivacurium was injected, DBP in group 2 decreased significantly compared with baseline and group 1. 3 minutes after mivacurium was injected,SBP in group 2 decreased significantly compared with baseline and group 1. Conclusion In infants undergoing sevoflurane general anesthesia, the onset time of mivacurium can be shortened when 250μg/kg was administered,but the depression of cardiovascular system may occurr simultaneously.

Neuromuscular Pharmacodynamics of Mivacurium in Patients with Major Burns / 대한마취과학회지

BACKGROUND: Burned patients sometimes require rapid onset of neuromuscular paralysis to secure the airway in full stomach patients or to treat laryngospasm. Because of poor lung function and hypermetabolic state, they desaturate quite rapidly. Burned patients are usually resistant to the effects of nondepolarizing relaxants. Mivacurium can be potentially a good alternative for rapid onset of paralysis, since it is metabolized by plasma cholinesterase, an enzyme often decreased in subject with major burns. This prospective study was conducted to define the neuromuscular pharmacodynamic profile of a single bolus dose of mivacurium in adult patients with major burns. METHODS: Adults (M/F = 22/8), aged 44.0 +/- 10.2 years, with total body surface area (TBSA) burn of 35.0 +/- 12.5% were studied at 39.8 +/- 28.9 post burn days. Age and sex matched 30 non-burned patients served as controls. Anesthesia was consisted of propofol and fentanyl infusion with nitrous oxide and oxygen. Mivacurium 0.2 mg/kg was administered as a bolus. Using TOF Watch, neuromuscular block was monitored with T1 response after the initial tetanic stimulation to recruit all muscle fibers. Onset time was defined as the interval from the beginning of drug administration to maximal twitch suppression. Intubation was attempted at 1 minute after the drug administration to simulate the rapid sequence induction with recording of either failure or success of intubation. By allowing spontaneous recovery without reversal drug, recovery profiles of neuromuscular paralysis were also measured. RESULTS: Patients demographics were similar in both groups except for the burn. Onset times and all recovery profiles were significantly prolonged in the burned versus non-burned groups. Attempts at intubation at 1 minute after the drug administration were successful with difficulty in approximately 70% of patients in both groups. CONCLUSIONS: Mivacurium 0.2 mg/kg demonstrated the conflicting dual responses in the burned patients. The prolonged onset time suggests resistance to neuromuscular effects. The prolonged recovery suggests increased sensitivity. This can be partially explained by the acetylcholine receptor proliferation and decreased level of plasma pseudocholinesterase. In view of the prolonged onset time of almost two minutes for maximal paralysis, mivacurium does not appear to be a good drug for rapid onset of paralysis in burns.

Pharmacodynamic Changes of Mivacurium in Liver Cirrhosis Model in Rabbits Using Carbon Tetrachloride Intoxication / 대한마취과학회지

BACKGROUND: A reproducible animal model of liver cirrhosis by administering multiple doses of carbon tetrachloride (CCl4) is highly desirable for appropriate metabolic and therapeutic studies. The current study was undertaken to evaluate the neuromuscular blockade of mivacurium in CCl4 induced liver cirrhosis in rabbits. METHODS: Cirrhosis was induced in rabbits by CCl4 treatment for 11 weeks. Rabbits were randomly assigned to two groups; control group: corn oil 0.5 ml/kg/2 days IM for 11 weeks; study group: CCl4 0.5 ml/kg/2 days mixed 1:1 with corn oil IM for 11 weeks. In the first study, the dose-response relations of mivacurium were studied in twenty rabbits during thiopental anesthesia. They received mivacurium 10, 20, and 30 microgram/kg in control group, and mivacurium 20, 30, and 40 microgram/kg in study group, respectively. In the second study, time course of mivacurium 0.18 mg/kg in twenty rabbits was evaluated in each groups. Three fragments of each liver lobe at the end of the experimental period were performed for the histological examination. RESULTS: Eleven-weeks CCL4 treatment resulted in liver cirrhosis, decreased pseudocholinesterase to 1/6 of control level, and increased AST and ALT compared with controls. In the first study, There were significant differences between two groups. In the second study, There were significant differences between two groups. CONCLUSIONS: It is suggested that mivacurium should be used with caution in patients with hepatic insufficiency and that, in such patients, monitoring of neuromuscular function is desirable.

Pharmacodynamic and Pharmacokinetic Study on the Neuromuscular Blocking Action of Rapacuronium: a Comparison with Other Muscle Relaxants / 대한마취과학회지

BACKGROUND: We evaluated the pharmacodynamic and pharmacokinetic properties of rapacuronium, a new non-depolarizing muscle relaxant. METHODS: The EC50 and EC95 values of rapacuronium, vecuronium, and rocuronium were determined on rat hemidiaphragm, and reversal effects were determined using edrophonium or pyridostigmine. In 57 healthy adults, neuromuscular transmission was monitored at the adductor pollicis. Patients received a single dose of succinylcholine (1.0 mg/kg), rapacuronium (1.5 mg/kg), rocuronium (0.6 mg/kg), or mivacurium (0.16 mg/kg). Onset time, clinical duration, recovery index (RI), total duration (TD), train of four (TOF) ratio at over 95% recovery of control first twitch height, cardiovascular effect, and intubation scores were measured. RESULTS: By in vitro study, the EC50 and EC95 of rapacuronium were 4 to 10 fold larger than those of vecuronium and rocuronium, and by clinical study, the onset time of rapacuronium was similar to those of succinylcholine. The clinical duration of rapacuronium was not different from those of succinylcholine and mivacurium. RI and TD of rapacuronium (9.6 +/- 3.5 min and 30.9 +/- 10.7 min) were longer than those of succinylcholine (3.5 +/- 1.1 min and 18.1 +/- 4.4 min) and mivacurium (6.5 +/- 0.9 min and 23.0 +/- 4.4 min) for spontaneous recovery, but not different during reversal by pyridostigmine (5.0microgram/kg). The TOF ratio was increased after pyridostigmine than during spontaneous recovery. Intubation conditions of rapacuronium were similar to those of succinylcholine. Heart rates were significantly increased (15% of control) within 2 min, but not mean arterial pressure after rapacuronium was administration. CONCLUSIONS: Rapacuronium can be considered a valid alternative to succinylcholine and had no observed cardiovascular effect.

Neuromuscular Blockade of Mivacurium Following the Duration of Isepamicin Intramuscular Injection in Rabbits / 대한마취과학회지

BACKGROUND: Isepamicin, a new aminoglycoside antibiotic, was usually administered to patients for prophylactic use. Mivacurium has a short duration of action. The current study was undertaken to evaluate the neuromuscular blockade of mivacurium following the duration of an intramuscular injection of isepamicin 20 mg/kg/d in rabbits. METHODS: In the first study, the dose-response relations of mivacurium were studied in forty rabbits during thiopental anesthesia. Rabbits were randomly assigned to four groups; group 1: normal saline 2 ml/d IM for 7 days; group 2: isepamicin 20 mg/kg/d IM for 1 day; group 3: isepamicin 20 mg/kg/d IM for 3 days; group 4: isepamicin 20 mg/kg/d IM for 7 days. They received mivacurium 10, 20 and 30ng/kg in groups 1, 2 and 3; mivacurium 20, 30 and 40ng/kg in group 4, respectively. In the second study, time courses of action of mivacurium 0.18 mg/kg in forty rabbits were evaluated in each group. RESULTS: The calculated ED50 for mivacurium in groups 1, 2, 3 and 4 were 19.2 +/- 3.1ng/kg, 15.4 +/- 3.7ng/kg, 20.1 +/- 3.5ng/kg and 31.2 +/- 4.4ng/kg, respectively and corresponding ED95 was 29.9 +/- 3.7ng/kg, 22.1 +/- 4.5ng/kg, 30.1 +/- 5.9ng/kg and 43.4 +/- 5.1ng/kg, respectively. There were significant differences between group 4 and the others (P < 0.05). In the second study, the times after mivacurium 0.18 mg/kg until 95% twitch recovery in groups 1, 2, 3 and 4 were 35.1 +/- 5.1 min, 42.2 +/- 6.2 min, 32.8 +/- 4.9 min and 24.9 +/- 3.6 min, respectively. There were significant differences between group 2 and others, and between group 4 and group 1 or 3, respectively (P < 0.05). CONCLUSIONS: Mivacurium when used as a bolus isepamicin therapy, has both an increased potency and a longer duration of action, but when used during concurrent isepamicin therapy, has both a decreased potency and a shorter duration of action.

Effects of Edrophonium and/or Pseudocholinesterase for the Reversal of Mivacurium-Induced Paralysis in vitro / 대한마취과학회지

BACKGROUND: Mivacurium is a nondepolarizing neuromuscular blocking agent hydrolyzed by pseudocholinesterase. Anticholinesterase used in the reversal of mivacurium-induced muscle relaxation may also inhibit plasma pseudocholinesterase, and delay hydrolysis of mivacurium. In this study, the effects of edrophonium and/or bovine pseudocholinesterase (BpChE) in the reversal of mivacurium were investigated with the rat phrenic nerve-diaphragm preparation. METHODS: Fifty Sprague-Dawley rats (150 - 200 g) were randomly allocated into 10 groups based on the dosage of edrophonium and BpChE. Each animal was anesthetized with thiopental sodium (40 mg/kg I.P.). The phrenic nerve-diaphragm was dissected and mounted in a bath containing an oxygenated Krebs' solution at 32degreesC. The phrenic nerve was stimulated at supramaximal intensity and the single twitch responses and train of four (TOF) ratio were measured. After stabilization of the twitch responses, mivacurium (1ng/ml) was administered incrementally to obtain more than 95% twitch inhibition. Reversal of the mivacurium-induced block by edrophonium (0.01, 0.1, 1, or 10ng/ml) and/or BpChE (0.1 u, or 1.0 u/ml) were tested. A single twitch height more than 75% of the baseline value was considered an adequate reversal. RESULTS: Mivacurium-induced paralysis was recovered more effectively by BpChE 1.0 u/ml than the other groups. Edrophonium improved a single twitch in a dose dependent manner. CONCLUSIONS: Mivacurium-induced paralysis can be more effectively reversed by BpChE than edrophonium. Inhibition of pseudocholinesterase was not observed by increasing the dose of edrophonium.

Effects of Mivacurium in the Strips of Rat Thoracic Aortic Rings / 대한마취과학회지

BACKGROUND: The hypotensive effects of muscle relaxants has traditionally been associated with a ganglion block and histamine release. However, it was exhibited that the ability of certain analogues of the steroidal muscle relaxant directly caused relaxation of isolated vascular smooth muscles. The ability of mivacurium to elicit a direct relaxant effect on vascular smooth muscle has been studied using isolated rat thoracic aortic rings contracted with phenylephrine (PE). METHODS: Each ring of the thoracic aorta was suspended on wire supports in a 20 ml tissue bath under 2 gm of resting tension. All tissues were bathed in a Tris Tyrode solution at 37oC and 100% oxygen was supplied. RESULTS: Mivacurium 3 X 10 5 M and 10 3 M inhibited PE induced contractions of the aortic rings significantly (P < 0.05) and shifted the cumulative concentration-effect curves of PE to the right. The maximum contractile response from 81.9% to 55.0% (with PE 10 6 M) was the same as that seen with mivacurium 10 3 M pretreatment. Relaxation of aortic ring with mivacurium 10 3 M was not reversed with L-NAME pretreatment. Methylene blue reversed the relaxation of the aortic rings with mivacurium 10 3 M and shifted the cumulative concentration-effect curve of PE to the left. Indomethacine enhanced the relaxation of the aortic rings with mivacurium 10 3 M and shifted this curve to the right. Mivacurium 10 3 M inhibited the influx of extracellular Ca2+. CONCLUSIONS: The results suggest that the relaxation effects of mivacurium is related with the endothelium and at least, in part, cyclooxygenase inhibition and guanylate cyclase activation are related with this relaxation effect. Also, mivacurium inhibited extracelluar calcium influx.

Interaction between Mivacurium and Nitroglycerin / 대한마취과학회지

BACKGROUND: The neuromuscular blocking effects of a nondepolarizing neuromuscular blocker (NDNM) during a nitroglycerin (NTG) infusion were significantly potentiated and prolonged. NTG reduced the requirement of a NDNM in surgical patients. We investigated the influence of a NTG single bolus injection on a mivacurium nuromuscular blockade. METHODS: We studied 36 adult surgical patients, ASA physical status I or II, between 15 and 53 years old. Neuromuscular monitoring was measured by TOF-GUARD (Biometer Co., Denmark). Anesthesia was induced by thiopental sodium 3-5 mg/kg and fentanyl 3 microgram/kg, and maintained with 3 L/min N2O, 2 L/min O2 and 1 vol.% isoflurane. Patients were randomly assigned to 3 groups: 1) Control group (mivacurium 0.16 mg/kg), 2) N100 group (mivacurium 0.16 mg/kg, NTG 100 microgram), 3) N200 group (mivacurium 0.16 mg/kg, NTG 200 microgram). We measured the train-of-four (TOF) response from the beginning of recovery to the complete regaining of muscle twitch. RESULTS: NTG produced a prolongation of the neuromuscular blocking effect by mivacurium. T1 (contro group: 12.1 +/- 0.5, N100 group: 15.8 +/- 0.4 and N200 group: 11.6 +/- 0.4 min), T25 (16.4 +/- 0.4, 20.5 +/- 0.5 and 14.9 +/- 1.0 min), T75 (22.5 +/- 0.9, 29.4 +/- 0.7 and 20.1 +/- 1.0 min), T95 (27.3 +/- 0.6, 39.6 +/- 0.7 and 24.6 +/- 1.5 min) and the recovery index (6.1 +/- 0.6, 9.0 +/- 0.4 and 5.3 +/- 0.7 min) were significantly prolonged in the N100 and N200 groups (P < 0.05). CONCLUSION: These results suggest that a NTG bolus injection prolonged the neuromuscular blocking effect of mivacurium, dose relatively.

Neuromuscular Blocking and Vagolytic Effects of Atracurium, Cisatracurium, and Mivacurium in the Anesthetized Cat / 대한마취과학회지

BACKGROUND: Atracurium is a benzylisoquinolium nondepolarizing neuromuscular blocking drug. It releases histamine upon the rapid administration of more than 2 x ED95. Cisatracurium is about three to four times more potent than atracurium, less likely to release histamine, and has weaker cardiovascular or autonomic effects. Mivacurium releases histamine to about the same degree as atracurium at the same dose. This study was undertaken to reevaluate the experimental model for the evaluation of effects on the autonomic nervous system, and to determine the neuromuscular blocking profiles and the vagolytic effects of atracurium, cisatracurium and mivacurium in cats. METHODS: Cats, either sex, anesthetized with pentobarbital, were used. Neuromuscular blocking effects were assessed using the effects on the anterior tibialis muscle twitch evoked with supramaximal stimuli (0.2 ms-duration, 0.1 Hz). Inhibition of the parasympathetic nervous system was assessed in response to bradycardia to vagal nerve stimulation with ten-second trains of square-waves (0.5 ms-duration, 20 Hz). The dose-response curves for both neuromuscular blocking and vagolytic actions were determined for each animal. The dose-response curves were constructed in cumulative fashion. The response for vagal stimuli was measured two minute after each dosing. Vagal ID50 (The doses that produced 50% inhibition of the response to vagus nerve stimulation) were determined. RESULTS: NMB ED95 and NMB ED50, respectively, were 102.0 +/- 28.3 and 143.7 +/- 40.5 microgram/kg for atracurium, 81.4 +/- 13.3 and 110.7 +/- 18.8 microgram/kg for cisatracurium, and 56.8 +/- 17.4 and 74.2 +/- 25.0 microgram/kg for mivacurium. Vagal ID50 was 2,654 +/- 1,651 microgram/kg for atracurium, 655 +/- 389 microgram/kg for cisatracurium, and 606 +/- 182 microgram/kg for mivacurium. The vagal ID50/NMB ED95 and vagal ID50/NMB ED50 were 18.5 and 26.0 for atracurium, 5.9 and 8.1 for cisatracurium, and 8.2 and 10.7 for mivacurium. CONCLUSIONS: Atracurium has a wider margin of safety only for vagal stimulation as compared with cisatracurium and mivacurium. However, we couldn't exclude that either sympathetic stimulation or histamine release might contribute to heart rate.

The Effects of Succinylcholine on the Neuromuscular Block of Mivacurium / 대한마취과학회지

BACKGROUND: We studied the interaction between Succinylcholine (SCh) and mivacurium when mivacurium was administered during early and late recovery from SCh block was investigated. METHODS: Eighty patients undergoing elective surgery under general anesthesia were studied. General anesthesia was induced and maintained with propofol under TCI control. Neuromuscular function was measured in response to TOF stimulation of the ulnar nerve using an electromyographic method. The patients were allocated randomly to the following four groups; group 1 (n = 20): a bolus intravenous injection of 0.08 mg/kg mivacurium; group 2 (n = 20): intravenous injection of 0.08 mg/kg mivacurium after 2 minutes of 1 mg/kg SCh injection; group 3 (n = 20): intravenous injection of 0.08 mg/kg mivacurium after 25% recovery of initial twitch height from twitch height depression induced by 1 mg/kg SCh; group 4 (n = 20): intravenous injection of 0.08 mg/kg mivacurium after 75% recovery of initial twitch height from twitch height depression induced by 1 mg/kg SCh. The onset and duration of neuromuscular blockade, recovery rate and TOF ratio at T75% were measured. RESULTS: The onset of block in groups 3 and 4 were slower than in group 1 (5.2 +/- 0.7 and 2.3 +/- 0.6 vs 2.5 +/- 0.4 min P < 0.05). The clinical duration in groups 2 and 3 were longer than in groups 1 and 4 (12.5 +/- 2.1 min and 11.3 +/- 1.7 min vs 17.0 +/- 3.0 min and 18.5 +/- 2.6 min, p < 0.05). There was no difference in recovery index all groups. The TOF ratio of groups 2, 3 and 4 were smaller than for group 1 (38.2 +/- 5.3, 32.3 +/- 5.6 and 31.5 +/- 4.2 vs 56.0 +/- 7.3, P < 0.05). CONCLUSIONS: The Previous 1 mg/kg SCh injection was affected the time course of action of mivacurium 0.08 mg/kg-induced neuromuscular block.

The Effects of Mivacurium on Isolated Rat Tracheal Muscle / 대한마취과학회지

BACKGROUND: Neuromuscular blocking drugs are designed to specifically block nicotinic cholinergic receptors at the neuromuscular junction, but many bind to muscarinic cholinergic receptors on ganglia, nerve endings, and smooth muscles, thereby altering parasymphathetically mediated airway caliber and heart rate. METHODS: We studied the effects of mivacurium on the tension of tracheal smooth muscle by using an isolated rat tracheal preparation. We studied the cumulative effect of acetylcholine after pretreating the tracheal smooth muscle with mivacurium at different concentrations, as well as the effect of L-NAME and propranolol on the tension of tracheal smooth muscle after pretreating with mivacurium. RESULTS: Mivacurium shifted the acetylcholine dose-response curve to the right. L-NAME and propranolol had no effect on the tension of tracheal smooth muscle after pretreating with mivacurium. CONCLUSIONS: We have found that mivacurium relaxes isolated rat tracheal smooth muscle and this effect has no relationship to beta-receptors or nitric oxide.

Comparative Study of Pharmacokinetics in the Onset and Offset of Mivacurium and Other Muscle Relaxants / 대한마취과학회지

BACKGROUND: The purpose of this study was to evaluate mivacurium in the pharmacokinetics of onset and offset. METHODS: In 127 adult patients of ASA physical status I or II without any factors involving the neuromuscular function under general anesthesia, onset time (lag and manifest time) and clinical duration were measured after bolus or divided doses of ED95 x 2 of succinylcholine (SCC), rocuronium (ROC), atracurium (ATR), mivacurium (MIV), pancuronium (PAN) or vecuronium (VEC). Recovery time was defined as the recovery index and total duration measured after subsequent ED95 of MIV at 25% recovery of control twitch height from neuromuscular block induced by ED95 x 2 of ATR, MIV, PAN or VEC. Plasma cholinesterase (PChE) levels were measured following PAN or ATR. RESULTS: Onset time was faster with SCC and ROC, the low potency drugs, than with ATR, MIV, PAN or VEC, the high potent drugs. Manifest time was shorter in low potency drugs but longer in high potency drugs than lag time after bolus or divided doses of muscle relaxants given. Divided doses of various drugs induced a shortened onset time, but the patterns of relationship between lag and manifest time associated with drug potency did not alter. The recovery times with administered MIV were slowest after PAN pretreatment, and fastest after MIV pretreatment. PChE levels decreased significantly from 3 min to over 180 min after PAN administeration but not ATR. CONCLUSIONS: The onset time of MIV was not improved due to high drug potency as other nondepolarizing neuromuscular blockers. However, in spite of high potency, the recovery time of MIV was faster than other drugs. This results may be depend upon PChE activity rather than drug potency. Additionally, the prolonged recovery of MIV was not only under the influence of low PChE activity but also other some factors such as: the first relaxants administered before MIV dominated the neuromuscular block so that the duration of MIV given subsequently changed to resemble that of the first. The longer elimination half-life of the underlying relaxant prolonged the effects of subsequentshorter acting MIV. Structural similarities or dis-similarities between the interacting MIV and other drugs may have effects more potent in dis-similarity than in similarity.