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.

Effect of Duration of Lower Motor Neuron Injury on Mivacurium-induced Muscluar Relaxation in Rabbits / 대한마취과학회지

BACKGROUND: The purpose of this study was to investigate whether the effects of mivacurium on muscular relaxation were similar by the duration of more than 2 weeks after the injury of lower motor neurons in rabbits. METHODS: The animals were divided into five groups. The control group was without lower motor neuron injury. In the experimental groups, the lower motor neuron injury was made by denervating with 75 - 80% lesion on the common peroneal nerve to the right anterior tibialis muscle. The experimental groups were subdivided as 1, 2, 3 and 4 week groups (referred to ad the 1 wk, 2, 3 and 4 wks group) according to the durations of the denervation of common peroneal nerve, respectively. The dose-response relationship of mivacurium on the muscle twitches induced by TOF (train of four) stimulation (supramaximal stimulus of 0.2 ms duration, square-wave pulses, 2 Hz rate, repeated every 10 seconds) was studied by calculating ED50 and ED95 in the anterior tibialis muscles and compared between all groups. After recording the muscle twitches, microscopic findings were observed. RESULTS: The effective dose for 95% twitch depression (ED95) of mivacurium at 1week after denervation was significantly higher than that of the control group (P <0.05), but the ED95 of 2, 3 and 4wks groups were not significantly different from that of the control group. However, the ED95 of 3 and 4wks group were inclined to be lower than that of the control and significantly lower than 1wk group (P < 0.05). There was no significant difference in the effective dose for 50% twitch depression (ED50) of mivacurium in all groups. The size of the anterior tibialis muscle was significantly decreased at 4weeks after the lower motor neuron injury (P <0.05), but the number of its sarcoplasmic nuclei was increased, according to the duration after the denervation. CONCLUSIONS: Our results therefore suggest that neuromuscular response of denervated anterior tibial muscle was resistant to intravenous mivacurium in early periods of 1 or 2 weeks but sensitive 4 weeks after the lower motor neuron injury.

Effects of Pseudocholinesterase and/or Neostigmine, Pyridostigmine, Edrophonium and Galanthamine for Reversal of Mivacurium- or Succinylcholine-induced Paralysis in Vitro / 대한마취과학회지

BACKGROUND: The hydrolysis of mivacurium and succinylcholine is impaired in the presence of defects of pseudocholinesterase. Clinical reports are conflicting as to the utility of anticholinesterases, in the reversal of mivacurium- or succinylcholine-induced paralysis. In this study, the role of exogenous bovine pseudocholinesterases (BpChE) and/or neostigmine, pyridostigmine, edrophonium or galanthamine in the reversal of mivacurium- or succinylcholine-induced paralysis, were investigated with the rat phrenic nerve-diaphragm preparation. METHODS: Ninety five Sprague-Dawley rats (200 g, male) were divided into 14 groups (n = 10). The phrenic nerve-diaphragm preparation mounted in a bath containing oxygenated Krebs' solution. Twitch response from diaphragmatic muscle evoked by phrenic nerve stimulation were measured. After stabilization of the twitch responses, mivacurium (0.1 microgram/mlml) or succinylcholine (0.1 microgram/ml) was administered incrementally in the preparation to obtain more than 95% twitch inhibition. BpChE (0.1, 1.0 u/ml), and/or neostigmine (0.1, 1.0 microgram/ml), pyridostigmine (0.5, 5 microgram/ml), edrophonium (0.01, 0.1 microgram/ml) or galanthamine (0.1, 1.0 microgram/ml) were added for the reversal of mivacurium- and/or succinylcholine-induced block in each group and the twitch responses (0.1 Hz) were monitored for 60 min. The effect of BpChE (0.1 u/ml), in combination with each of the above four anticholinesterases at lower concentrations also were examined. Twitch heights more than 75% was considered an adequatereversal. RESULTS: BpChE 0.1 and 1.0 u/ml were effective in reversal of mivacurium-induced paralysis. When anticholinestrases were added, there was no effective improvement of twitch height at the end of 60 minutes. In succinylcholine-induced paralysis, BpChE was effective for reversal, but when anticholinesterases were added, BpChE potency was inhibited. CONCLUSIONS: BpChE will reverse mivacurium-induced block more effectively than anticholinesterase. BpChE is effective in reversing succinylcholine block. The addition of anticholinesterases inhibits the activity of pseudocholinesterase.

The Effect of Mivacurium on Onset and Recovery According to the Durations of Lower Motor Neuron Injury / 대한마취과학회지

BACKGROUND: The purpose of this study was to investigate whether the effects of mivacurium on onset and recovery were affected by the duration of more than 2 weeks after injury of the lower motor neuron in rabbits. METHODS: The animals were divided into five groups. The control group was without lower motor neuron injury. In the experimental groups, the lower motor neuron injury was made by denervating with a 75 - 80% lesion on the common peroneal nerve to the right anterior tibialis muscle. The experimental groups were subdivided as 1, 2, 3 and 4 week groups (named group 1 wk, 2, 3 and 4 wks) according to the duration of the denervation of the common peroneal nerve. The response relationship of mivacurium on the muscle twitches induced by TOF (train of four) stimulation (supramaximal stimulus of 0.2 ms duration, square-wave pulses, 2 Hz rate and 10 mA, repeated every 10 seconds) was studied in the anterior tibialis muscles and compared between all groups. Neuromuscular responses (onset, recovery time to T1(1), T1(25), T1(75), T1(95) and recovery index) of muscle twitches to intravenous mivacurium (0.18 mg/kg) were studied. After recording the muscle twitches, macroscopic findings were observed. RESULTS: The recovery time, T1(1) of group 4 wks was significantly longer than those of group 1, 2 and 3 wks (P < 0.05), but not different from the control group. The recovery time, T1(25), T1(75) and T1(95) of group 4 wks was significantly longer than those of all other groups (P < 0.05), but the onset times of all groups were not significantly different. The recovery index of group 4 wks was significantly higher than that of the control group (P < 0.05), but those of groups 1, 2 and 3 wks were not significantly different from that of the control group. The mass of the anterior tibialis muscle was significantly decreased at 4 weeks after the lower motor neuron injury (P < 0.05). CONCLUSIONS: Our results therefore suggest that the neuromuscular response to intravenous mivacurium on recovery in rabbits becomes prolonged according to the durations of the denervation and represents sensitivity at 4 weeks after the lower motor neuron injury.

A Comparison of Recovery from Mivacurium during Enflurane or Propofol Anesthesia in Children / 대한마취과학회지

BACKGROUND: Mivacurium is a new, short acting, nondepolarizing muscle relaxant of the benzylisoquinolinium type. Enflurane produces relaxation and augments the neuromuscular blockade from muscle relaxation, but propofol does not produce muscle relaxation. We compared maintenance infusion rates, recovery index and correlations of recovery index to maintenance infusion rates and infusion duration after mivacurium during enflurane or propofol anesthesia in children. METHODS: Maintenance infusion rates, and the recovery index after mivacurium were studied in 30 pediatric patients in enflurane anesthesia (n = 15) and propofol anesthesia (n = 15). The ulnar nerve was stimulated at the wrist by repeated single twitch (1Hz) stimulus using the peripheral nerve stimulator (Model ST5 MaxiStimTM, Life-Tech , Inc, Texas, USA). We recorded the contraction of adductor pollicis longus via mechanomyography (MYOTRACE, Life-Tech, Inc, Texas, USA). RESULTS: The infusion rates of mivacurium for the maintenance of muscle relaxation (below 10% of control) were 9.6 0.80 microgram/kg/min in the enflurane anesthesia, and 11.04 1.22 microgram/kg/min in the propofol anesthesia. There was a significant difference between the groups. The recovery index was shorter in the propofol anesthesia, but regarding this index, there was no significant difference between both groups. The correlation between the recovery index and the infusion duration was significantly different in the enflurane anesthesia. CONCLUSIONS: We conclude that maintenance infusion rates are significantly lower in the enflurane anesthesia, the recovery index is insignificantly shorter in the propofol anesthesia, that there is a significant correlation between the maintenance infusion rates and recovery index in the enflurane anesthesia.

Anesthetic Management with Mivacurium in the Myasthenic Patients: Two cases / 대한마취과학회지

We have used mivacurium in two myasthenic patients, a generalized myasthenia gravis (MG) patient presenting for thymectomy and a Lambert-Eaton myasthenic (LEM) patient for mediastinoscopic lymph node biopsy. Both of them received nitrous oxide/oxygen (1:1)-narcotic-enflurane anesthesia with mivacurium as a muscle relaxant and the neuromuscular blocking effect of mivacurium was monitored continuously through the operation as well as before the induction of anesthesia. The dose of mivacurium for MG patient was 5.5 mg and LEM patient was 12 mg, because MG patient showed more severe clinical symptoms. The response to train-of-four (TOF) ulnar nerve stimulation was recorded using accelography. The onset times to maximal block in MG and LEM patients were 30 and 120 sec, respectively after injection and the recovery times to 25% from maximal block were 117 and 76 min, respectively. Mivacrium would be safe and appropriate for use in myasthenic patients, with relatively small dose under the neuromuscular monitoring.

The Pharmacodynamics and Infusion Rate of Mivacurium in Patients with Liver Cirrhosis or Cholestasis / 대한마취과학회지

BACKGROUND: Action of mivacurium varies in condition with reduced plasma cholinesterase activity. The aim of this study is to evaluate the pharmacodynamics of mivacurium and to obtain the infusion rate of mivacurium in patients with liver cirrhosis or cholestasis. METHOD: We allocated into three groups. Healthy subjects without hepatobiliary disease(Group I, n=10), patients with liver cirrhosis(Group II, n=5), and patients with cholestasis(Group III, n=9) received 5 mg/kg thiopental sodium and 1~2g/kg fentanyl. They were ventilated by mask with 2.5~3% enflurane(in O2/N2O 50%) until I/E ratio of enfurane concentration gt; or = 0.8, and then received 3 ED95 mivacurium(0.18 mg/kg). Accelerographic responses to train-of-four(TOF) stimulation of ulnar nerve at 15 seconds interval were used for neuromuscular monitoring. The onset time, the duration, recovery indices and infusion rate of mivacurium were compared among groups. RESULT: The durations from the injection of mivacurium to 10% single twitch recovered (Dur10) in group II(16.5+/-4.3 min) and III(17.1+/-0.6 min) were longer significantly than that in group I(10.7+/-5.3 min). The infusion rates to maintain a steady twitch height at 5~10% for 20 min in group II(1.9+/-1.5 microgram/kg/min) and III(1.6+/-0.7g/kg/min) were lower than that in group I(3.5+/-1.3 g/kg/min). However, there was no significant difference between group II and III. CONCLUSION: Clinical duration of relaxation with 3 ED95 mivacurium is prolonged significantly and infusion rate to maintain the steady twitch height at 5~10% is lower in patient with liver cirrhosis or cholestasis than in patient without hepatobiliary disease.

Neuromuscular Interactions between Mivacurium and Rocuronium in Rabbits / 대한마취과학회지

BACKGROUND: Mivacurium has a considerably shorter duration of action than any other currently used nondepolarizing agent. Rocuronium, on the other hand, has a brief onset but an intermediate duration of action. The current study was undertaken to characterize the interaction between mivacurium and rocuronium in rabbits. METHODS: In the first study, the dose-response relations of mivacurium, rocuronium and their combination were studied in thirty rabbits during thiopental anesthesia. Rabbits, randomly assigned to three groups (n=10), received mivacurium 10, 20, or 30 microgram/kg; rocuronium 50, 70, or 90 microgram/kg; or an equieffective combination of both drugs (0.3 ED50 mivacurium 0.3 ED50 rocuronium; 0.5 ED50 mivacurium 0.5 ED50 rocuronium; or 0.7 ED50 mivacurium 0.7 ED50 rocuronium, where ED50 is the dose producing 50% depression of the twitch height). In the second study, twenty rabbits were randomly allocated to two groups (n=10) to receive mivacurium 0.18 mg/kg or rocuronium 0.6 mg/kg. When the twitch height recovered to 25%, each rabbit received mivacurium 16.4 microgram/kg. RESULTS: The calculated ED95 and ED50 for mivacurium were 29.1 4.2 (mean SD) and 16.4 3.3 microgram/kg, respectively. Corresponding rocuronium was 95.1 6.7 and 61.5 5.3 microgram/kg, respectively. The interaction between mivacurium and rocuronium was found to be synergistic. The measured ED50 of the mixture was only 54% of the predicted value assuming a purely additive interaction. In the second study, the times after mivacurium until 95% in mivacurium and rocuronium group were 18.1 4.6 min and 37.7 5.7 min, respectively (p<0.0001). CONCLUSIONS: The combination of mivacurium and rocuronium is synergistic interaction and after rocuronium induced neuromuscular block, mivacurium becomes a longer acting agent than the shorter agent.

The Effect of Cyclosporine on the Neuromuscular Blocking Action Induced by Rocuronium and Mivacurium in Rabbit / 대한마취과학회지

BACKGROUND: Cyclosporine, an immune suppressive agent has been reported to potentiate the neuromuscular blockade induced by vecuronium and atracurium. And the potentiation degree was more prominent in the vecuronium. Rocuronium and mivacurium have been introduced into clinical practice recently and there is no report whether the cyclosporine potentiates the neuromuscular blocking effects of these agents. We, therefore studied the effect of Sandimun (cyclosporine in cremophor-ethanol) on the neuromuscular blockade action of rocuronium and mivacurium in rabbits. METHOD: The effect of Sandimun on the rocuronium and mivacurium were investigated in anesthetized 30 rabbits. The rabbits were divided into five groups; rocuronium group (rocuronium bromide 1 mg/kg iv), rocuronium - Sandimun group (rocuronium bromide 0.1 mg/kg iv after Sandimun 5 mg/kg iv), mivacurium group (mivacurium chloride 0.064 mg/kg iv), mivacurium - Sandimun group (mivacurium chloride 0.064 mg/kg iv after Sandimun 5 mg/kg iv) and Sandimun group (Sandimun 5 mg/kg iv). Neuromuscular block was assessed by measuring the response of anterior tibial muscle to 0.1Hz single twitch stimulation of the common peroneal nerve. Onset time, duration of muscle relaxation and recovery index were compared among the groups. RESULTS: There were no significant differences in onset time and recovery indices among the groups. Significant difference was found in duration between the rocuronium group and the rocuronium-Sandimun group (p<0.05). CONCLUSION: Sandimun potentiates the rocuronium - induced neuromuscular blockade but not the neuromuscular blocking action of mivacurium.

The Neuromuscular Blocking Effect of Mivacurium in Isolated Rat Phrenic-Hemidiaphragm with Long-term Phenytoin Pretreatment / 대한마취과학회지

BACKGROUND: Long-term phenytoin therapy induces resistance to the neuromuscular blocking effects of metocurine, atracurium, doxacurium, and pipecuronium. This study examine neuromuscu-lar blocking effect and recovery of mivacurium in isolated rat phrenic-hemidiaphragm with two-weeks phenytoin pretreatment. METHOD: After the administration of 14 days of phenytoin 40 mg/kg, administered intraperitoneally twice daily (n=10), ED90, antagonism of neostigmine and 4-aminopyridine on the electrically evoked twitch response and train-of-four (TOF) stimulation were compared to control groups in isolated rat phrenic-hemidiaphragm preparation. RESULTS: ED90 was significantly greater in the phenytoin group than in the control group (319 +/- 39.5 g vs. 209.5 +/- 52.2 g, respectively). After the administration of neostigmine 0.75 M, the recovery of the single twitch and TOF ratio were significantly lesser in the phenytoin group than in the control group (single twitch; 19.6 +/- 6.6% vs. 69.2 +/- 9.4%, TOF ratio; 0.258 +/- 0.149 vs. 0.543 +/- 0.1, respectively). After the administration of 4-aminopyridine 40uM, the recovery of the single twitch and TOF ratio were no significant differrence between the phenytoin group and the control group (twitch; 118.1 +/- 25.3% vs. 122.6 +/- 24.8%, TOF ratio; 0.937 +/- 0.051 vs. 0.949 +/- 0.067, respectively). CONCLUSION: Long-term phenytoin therapy induces resistance to the neuromuscular blocking effects of mivacurium.

The Potency of Mivacurium during Halothane or Enflurane Anesthesia in Infants and Preschool Children / 대한마취과학회지

BACKGROUND: The dose-responses of neuromuscular blocking agents may be influenced by many factors including age and inhalation anesthetics. This study was designed to determine the dose-response relationships of a new, short-acting muscle relaxant, mivacurium during nitrous oxide-halothane or nitrous oxide-enflurane anesthesia in two age groups, infants and 1 to 6 years old preschool children. METHODS: Neuromuscular blockade was monitored by recording the accelerographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate dose-response relationships, 24 infants or children of two anesthetic subgroups for each age group received single bolus doses of 45~100 g/kg of mivacurium. The ED50 and ED95 were estimated from linear regression plots of log-dose vs probit of twitch depression. The lag time, onset time and maximal depression of twitch height for the selective medium dose were mesured. RESULTS: The ED50 and ED95 for the infants group were 38.2 and 53.3 g/kg during halothane anesthesia, and 29.8 and 48.6 g/kg during enflurane anesthesia, respectively. And, those for preschool children group were 49.4 and 90.7 g/kg during halothane anesthesia, and 32.3 and 81.4 g/kg during enflurane anesthesia, respectively. There was a parallelism of the dose-response curve between halothane and enflurane anesthesia in either age group. Also, there was statistically significant difference in the maximal twitch depression for the selective medium dose of mivacurium between halothane and enflurane anesthesia in either group. CONCLUSIONS: The potency of mivacurium during enflurane anesthesia is higher than that during halothane anesthesia in infants and preschool children, and during either inhalation anesthesia the dose of mivacurium is less required in infants than preschool children.

The Effects of Cholestasis and Hepatic Failure on Mivacurium - induced Neuromuscular Blockade in the Cat / 대한마취과학회지

BACKGROUND: Duration of action varies in conditions with reduced plasma cholinesterase activity. To evaluate the action duration and recovery of mivacurium under the experimental hepatic failure and cholestasis, the pharmacodynamic studies were done. METHODS: The pharmacodynamic studies were done using a common peroneal nerve-anterior tibialis muscle preparation in 18, either sex, adult cats (weight, 2.0~4.0 kg). For the hepatic failure, galactosamine chloride (4.25 mmol/kg) was given 16 hours prior to the pharmacodynamic study. The cholestasis was made by the ligation of CBD and cystic duct 8 days prior to the pharmacodynamic study. All the cat had 4XED95 of mivacurium. The action durations and recovery indices were measured. And plasma cholinesterase activities were checked. RESULTS: The duration of mivacurium was prolonged significantly with either hepatic failure (14.96 4.44 min.) or cholestasis (11.21+/- 5.11 min.) group compared to control group (5.27 +/-0.67 min.) and also the recovery indices were significantly increased in the hepatic failure (4.58+/- 1.40 min.) and cholestasis (3.21+/- 1.00 min.) groups, as compaired with the control group (1.57+/- 0.40 min.). CONCLUSION: The mivacurium-induced neuromuscular blockade is prolonged by the experimental hepatic failure and cholestasis, and the effects may be caused by the hepatic dysfunction, impairment of direct biliary excretion.

Comparison of Onset Time of Mivacurium by Priming Principle with Succinylcholine during Endotracheal Intubation / 대한마취과학회지

BACKGROUND: Mivacurium has a characteristics of rapid onset and the shortest duration of non- depolarizing neuromuscular relaxants and the onset of action could be accelerate more rapidly by using priming principle. The purpose of this study was to compare the onset time of mivacurium by priming principle with succinylcholine during rapid endotracheal intubation. METHODS: 36 patients were randomly divided into 3 groups: mivacurium group by priming principle (Group 1), mivacurium group by bolus injection (Group 2) and succinylcholine group (Group 3). In Group 1, subparalyzing dose of 0.02 mg/kg was administered 2 minutes before principle dose of 0.25 mg/kg was given. Onset time and intubating conditions were observed when twitch tension was reduced by 25% block in each group. RESULTS: The onset of Group 1 (75 sec) was significantly faster than that of Group 2 (90 sec) (p<0.05) but was significantly slower than that of Group 3 (37.5 sec) (p<0.05). Intubating conditions were excellent in all groups. CONCLUSIONS: The attempts of priming principle with mivacurium could accelerate the onset of action of mivacurium compared with that of bolus injection but their onsets were shorter than those produced by succinylcholine.