Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278134 (anesthesia)
 110,339 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mivacurium chloride (Mivacron) is a new benzylisoquinolinium choline-like diester neuromuscular blocking drug with an onset of action at equipotent doses that is comparable to atracurium and vecuronium but slower than succinylcholine. Its clinical duration (injection-25% recovery and injection-95% recovery) is twice that of succinylcholine but one-half to one-third that of atracurium and vecuronium. Mivacurium is easy to use as a continuous infusion and when used this way its recovery characteristics are unchanged. It is readily antagonized by anticholinesterase drugs. The ED95 in adults under narcotic-based anesthesia is 0.07-0.08 mg/kg. At twice the ED95 (0.15 mg/kg) onset time is about 2 to 3 minutes, duration to 25% recovery is 15 to 20 minutes, and 5-95% recovery time about 14 minutes. The mean infusion rate in adults is 6 micrograms/kg/min (range 2-15) with a 5-95% recovery time of 14 minutes. Enflurane and isoflurane require a 20-30% decrease in dosage; halothane, enflurane, and isoflurane prolong the duration of mivacurium 25-30%. The ED95 in children 2 to 12 years of age is slightly higher (0.09-0.11 mg/kg) with a faster onset and shorter duration. In these young patients, a dose of 0.2 mg/kg has an onset comparable to succinylcholine. Being chemically related to atracurium, mivacurium may cause histamine release. When administered rapidly at doses of 0.2 mg/kg or greater in adults, histamine release and transient hypotension have been observed. Doses of 0.2 mg/kg or higher are not recommended by the manufacturer. Mivacurium is metabolized by plasma cholinesterase. In vitro, the rate is about 70% that of succinylcholine. In patients with normal or slightly less than normal plasma cholinesterase activity, no prolonged durations of action have been observed. In patients heterozygous for the atypical gene and at a dose of 0.2 mg/kg, 50% prolongation has been shown. Those individuals homozygous for the atypical gene are exquisitely sensitive to mivacurium and have a markedly prolonged blockade that is readily reversible. In these patients and those with acquired deficiencies, mivacurium should not be used. The duration of action in elderly patients is comparable to that in the young, while in prerenal transplant patients, its duration is prolonged by about 50%, and in prehepatic transplant patients, duration of block is increased threefold. Mivacurium possesses the advantages of short duration, unchanged recovery characteristics following infusions (without phase II block or tachyphylaxis), and precise control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical pharmacology of mivacurium chloride: a review. 137 87

We assessed the neuromuscular and cardiovascular effects of mivacurium chloride, a neuromuscular blocking agent, in 33 patients during propofol-nitrous oxide anaesthesia. Neuromuscular function was assessed with supramaximal stimuli of the ulnar nerve, using surface electrodes at the wrist, with repeat trains of four. Mivacurium given as a bolus of 0.15 mg.kg-1 (ED95 x 2) was found to be haemodynamically stable. Intubating conditions assessed at 2 and 2.5 min were either good or excellent. All patients developed a block of 100% in a mean (SD) time of 105 (34) s. There were mean (SD) intervals of 12 (2.4) min before the reappearance of the first twitch of the train of four (T1) following the bolus dose, and 15.8 (3.1) min for the T1 to reach 25% of its control value (TC). Seventeen patients received an infusion of mivacurium to maintain neuromuscular blockade (T1:TC 10-20%) with a mean (SD) infusion rate of 6.9 (2.2) micrograms.kg-1.min-1. Recovery from neuromuscular blockade was assessed with spontaneous offset or augmented with edrophonium following either the initial bolus or an infusion. Following a bolus it took a mean (SD) of 26.2 (3.7) min for the fourth twitch of the train of four (T4):T1 ratio to reach 0.7. In patients receiving an infusion with spontaneous offset it took a mean (SD) time of 12.0 (2.2) min to reach the T4:T1 ratio of 0.7 from a T1:TC value of 8.8. Edrophonium significantly decreased the recovery time in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Anaesthesia 1992 Aug
PMID:Mivacurium chloride: a study to evaluate its use during propofol-nitrous oxide anaesthesia. 138 65

The significance of plasma cholinesterase (pChe) activity for the duration of action of mivacurium in phenotypically normal patients was evaluated in 35 patients during neurolept anaesthesia. The response to train-of-four nerve stimulation was recorded using a Myograph 2000. Ten patients with normal pChe (Group I) and five patients with decreased pChe activity (Group 2) were given a small test dose of mivacurium 0.03 mg kg-1. Mivacurium 0.1 mg kg-1 was administered following spontaneous recovery from the first dose. The mean suppression of the height of the first (T1) of the train-of-four responses following mivacurium 0.03 mg kg-1 patients with normal and decreased enzyme activity was 40% and 56%, respectively, and the mean T1 suppression after mivacurium 0.1 mg kg-1 was 100% in both groups. The times to different levels of twitch height recovery following the 0.1 mg kg-1 dose did not differ between the two groups of patients. Another 20 patients with normal or decreased pChe activity (Group 3) were given mivacurium 0.2 mg kg-1. In this group the time to maximum block was 1.4 min (1.0-4.0) mean (range) and the time to reappearance of the T1 response was 15.0 min (7.4-22.7) (range). An inverse relationship was found between the patients' pChe activity and the time to first response. It is concluded that mivacurium is short-acting in patients with normal pChe phenotype and normal to low-normal pChe activity. No patient with very low pChe activity was included in the study. A prolonged response to mivacurium may, however, be expected in these patients.
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PMID:Influence of plasma cholinesterase activity on recovery from mivacurium-induced neuromuscular blockade in phenotypically normal patients. 144 74

We were interested in determining the infusion rate of mivacurium required to maintain approximately 95% neuromuscular blockade during nitrous oxide-halothane (0.8% end-tidal) or nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity (Datex NMT) of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Mivacurium steady-state infusion requirements averaged 315 +/- 26 micrograms.m-2.min-1 during nitrous oxide-halothane anesthesia and 375 +/- 19 micrograms.m-2.min-1 (mean +/- SEM) during nitrous oxide-narcotic anesthesia. Higher levels of pseudocholinesterase activity were generally associated with a higher mivacurium infusion requirement. During both anesthetics, younger age was associated with a higher infusion requirement when the infusion requirement was calculated in terms of micrograms.kg-1.min-1. This difference was not present when the infusion rate was calculated in terms of micrograms.m-2.m-1. There was no evidence of cumulation during prolonged mivacurium infusion. There was no difference in the rates of spontaneous or reversal-mediated recovery between anesthetic groups. After the termination of the infusion, spontaneous recovery to T4/T1 greater than or equal to 0.75 occurred in 9.8 +/- 0.4 min, with a recovery index, T25-75, of 4.0 +/- 0.2 min (mean +/- SEM). In summary, pseudocholinesterase activity is the major factor influencing mivacurium infusion rate in children during nitrous oxide-narcotic or nitrous oxide-halothane (0.8% end-tidal) anesthesia.
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PMID:Mivacurium infusion requirements in pediatric surgical patients during nitrous oxide-halothane and during nitrous oxide-narcotic anesthesia. 214 69

Mivacurium is a new short-acting competitive neuromuscular blocking agent. Infusion requirements for the maintenance of a stable 90-99% muscle twitch depression were determined in 28 children anaesthetized with nitrous oxide and 1% halothane (inspired) in oxygen or nitrous oxide in oxygen and opioid. Neuromuscular block was assessed by monitoring the force of contraction of the adductor of the thumb during train-of-four (TOF) stimulation at 0.1 Hz. Infusion rate and twitch depression were analysed from 15 to 75 min and from 75 to 135 min after the start of the infusion. In the first period of evaluation, the mean infusion requirement was 10.4 (SEM 0.92) micrograms kg-1 min-1 during the halothane anaesthesia and 13 (1.4) micrograms kg-1 min-1 during the opiod anaesthesia (P less than 0.05). This difference was present also during the second 60-min period. There was no significant correlation between infusion rates required to maintain greater than 90% depression of the first twitch (T1) of the TOF and plasma cholinesterase concentrations. Regardless of the anaesthetic regimen, children recovered rapidly after discontinuing the infusion. The recovery index (25-75% recovery of T1) for all patients was 5.4 (0.57) min with no significant differences between the groups.
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PMID:Continuous infusion of mivacurium in children. 253 33

The neuromuscular and cardiovascular effects of mivacurium chloride were studied during nitrous oxide-oxygen narcotic (fentanyl) (n = 90) and nitrous oxide-oxygen isoflurane (ISO) anaesthesia (n = 45). In addition, a separate group (n = 9) received succinylcholine during fentanyl anaesthesia to compare its neuromuscular effects with mivacurium. Mivacurium was initially administered as a single bolus in doses from 0.03 mg.kg-1 to 0.25 mg.kg-1 to study the dose-response relationships, as well as the cardiovascular effects of mivacurium. Neuromuscular block (NMB) was measured by recording the twitch response of the adductor pollicis muscle following ulnar nerve stimulation (0.15 Hz, 0.2 ms supramaximal voltage). The ED95 values for mivacurium were estimated to be 0.073 mg.kg-1 and 0.053 mg.kg-1 in the fentanyl and ISO groups respectively. The duration of block (time from injection to 95 per cent recovery) for a dose of 0.05 mg.kg-1 mivacurium was 15.3 +/- 1.0 min and 21.5 +/- 1.3 min for fentanyl and ISO anaesthesia, respectively. The recovery index (25-75 per cent) between initial bolus dose (6.1 +/- 0.5 min), repeat bolus doses (7.6 +/- 0.6 min), mivacurium infusion (6.7 +/- 0.7 min) and succinylcholine infusion (6.8 +/- 1.8 min) were not significantly different. There was minimal change in mean arterial pressure (MAP) or heart rate (HR) following bolus doses of mivacurium up to 0.15 mg.kg-1. Bolus administration of 0.20 mg.kg-1 or 0.25 mg.kg-1 of mivacurium decreased MAP from 78.2 +/- 2.5 to 64.0 +/- 3.2 mmHg (range 12-59 per cent of control) (P less than 0.05). The same doses when administered slowly over 30 sec produced minimal change in MAP or HR.
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PMID:Neuromuscular and cardiovascular effects of mivacurium chloride in surgical patients receiving nitrous oxide-narcotic or nitrous oxide-isoflurane anaesthesia. 203 2

Mivacurium chloride (BW B1090U), a bis-benzylisoquinolinium diester compound, was found to undergo hydrolysis in vitro by purified human plasma cholinesterase in a pH-stat titrator at 88% of the rate of succinylcholine at pH 7.4, 37 degrees C and 5 microM substrate concentration. In 72 consenting ASA Physical Status I-II patients receiving nitrous oxide/oxygen-narcotic-thiopental anesthesia, the neuromuscular blocking effect of mivacurium was assessed following bolus doses from 0.03 to 0.30 mg/kg, as well as during and following continuous infusions from 35 to 324 min in length. The calculated ED95 for inhibition of adductor pollicis twitch evoked at 0.15 Hz was 0.08 mg/kg. At 0.1 mg/kg, 96% block developed, onset to maximum block required 3.8 +/- 0.5 min, and recovery to 95% twitch height occurred 24.5 +/- 1.6 (SE) min after injection. At 0.25 mg/kg, onset was 2.3 +/- 0.3 min; 95% recovery developed within 30.4 +/- 2.2 min, an increase in duration of action of only 24% versus 150% higher dosage. Comparative recovery indices from 5 to 95% or from 25 to 75% twitch heights did not differ significantly among all dosage groups from 0.1 to 0.3 mg/kg (range 12.9 to 14.7 and 6.6 to 7.2 min, respectively). In 38 patients who received mivacurium by continuous infusion (duration 88.1 +/- 7.1/47.1 min, SE/SD) for maintenance of 95 +/- 4% twitch inhibition, the mean 5-95% and 25-75% recovery indices after discontinuation of infusion were 14.4 +/- 0.6 and 6.5 +/- 0.3 min (P greater than 0.5 vs. all single bolus doses). The train-of-four (T4) ratio, within 2.6 +/- 0.5 min after 95% twitch recovery following bolus doses, averaged 79.5 +/- 1.8% (n = 32). Similarly, after discontinuation of infusions, the T4 ratio reached 73.4 +/- 1.9% within 3.4 +/- 1.9 min after 95% twitch recovery (n = 33). Antagonism of residual block was seldom indicated, but, to test ease of reversal, eight patients electively received neostigmine (0.06 mg/kg) with atropine (0.03 mg/kg) at 67 to 93 (76.6 +/- 3.5) % block. Twitch returned to 95% of control within 4.5 to 9.5 (6.3 +/- 0.5) min after neostigmine. Mivacurium may offer increased versatility in providing clinical muscle relaxation in a variety of situations. Further studies seem appropriate.
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PMID:The clinical neuromuscular pharmacology of mivacurium chloride (BW B1090U). A short-acting nondepolarizing ester neuromuscular blocking drug. 296 39

Mivacurium could be a useful agent as a final dose of a muscle relaxant following pancuronium if only additivity exists between these agents. We examined the interaction between mivacurium and pancuronium in 70 patients (ASA I-II) during propofol-alfentanil-N2O-O2 anaesthesia. Neuromuscular function was monitored by adductor pollicis EMG. Firstly we established dose-response curves for mivacurium and pancuronium. Thereafter, 20 patients received a combination of 0.5 times the ED50 doses of mivacurium and pancuronium (cMP) determined in the first part of this study. Patients were randomized to receive the cMP to the same IV-line (n = 10) or to two separate IV-lines in opposite hands (n = 10). ED50 values for mivacurium and pancuronium were 57.7 and 37.1 micrograms kg-1, respectively. Maximal neuromuscular block following the cMP was 91.8 +/- 5.0% (mean +/- SD). This was highly significantly different from the estimated 50% NMB if only additivity exists between mivacurium and pancuronium (P = 0.0001). After the cMP, the 25-75% recovery time was 9.4 +/- 1.3 min and the time to train-of-four ratio of 0.70 was 35.8 +/- 5.4 min. There was no statistical difference in any recorded neuromuscular parameter between the two subgroups receiving mivacurium and pancuronium to the same or to opposite hands (P > 0.40). We conclude that a significant synergism exists between mivacurium and pancuronium which may indicate that mivacurium does not produce a short-acting NMB if given after pancuronium. We do not recommend using mivacurium together with pancuronium.
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PMID:Synergism between mivacurium and pancuronium in adults. 748 25

This study was designed to compare the effectiveness of antagonism of mivacurium blockade with either neostigmine, edrophonium, or spontaneous recovery. Thirty ASA physical status I or II patients provided informed consent and were randomized to one of the following groups: Group 1, placebo saline; Group 2, edrophonium (1 mg/kg); and Group 3, neostigmine (70 micrograms/kg) (n = 10/group). All studied patients had anesthesia induced with propofol and maintained with propofol/N2O/fentanyl. Mivacurium bolus of 0.2 mg/kg was used for endotracheal intubation and an infusion titrated to maintain deep levels of block (T1% = 1%-5%) (T1% = first response/control response x 100). The antagonist was injected at a deep level of the block (T1% = 1%-8%) and neuromuscular (NM) recovery was evaluated by train-of-four twitches (TOF). T1% was used during maintenance, whereas both T1% and TOF% (fourth response/first response x 100) were used during recovery. Investigators were blinded to the antagonist used. Plasma cholinesterase activity was measured prior to antagonist administration (0 min), as well as 15, 30, and 60 min after. Plasma cholinesterase activity was decreased to 29% of control at 15 min and remained at approximately 60% of the control after neostigmine administration. Edrophonium did not affect plasma cholinesterase activity. Clinically adequate spontaneous recovery (TOF% > or = 70%) of the mivacurium block with placebo required 15-18 min. On average, clinically adequate antagonism of mivacurium by edrophonium was 50% faster than placebo and 30%-40% faster than with neostigmine. In summary, the speed of antagonism with edrophonium is faster than with neostigmine when antagonizing deep mivacurium NM block.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antagonism of mivacurium neuromuscular block: neostigmine versus edrophonium. 748 38

We have examined the effects of different benzyl-isoquinolinium and steroidal neuromuscular blocking compounds on plasma concentrations of histamine, heart rate and arterial pressure in surgical patients. A single, rapid (5-s) bolus of mivacurium 0.2 mg kg-1, atracurium 0.6 mg kg-1, tubocurarine 0.5 mg kg-1, vecuronium 0.1 mg kg-1 or rocuronium 0.6 mg kg-1 was administered to 75 patients (n = 15 in each group). Anaesthesia was induced with thiopentone 6 mg kg-1 i.v. and maintained with isoflurane and 70% nitrous oxide in oxygen. Venous blood samples were obtained before induction, 1 min after thiopentone and 1, 3 and 5 min after administration of the neuromuscular blocking drug. Mivacurium, atracurium and tubocurarine caused 370%, 234% and 252% increases in plasma histamine concentrations at 1 min, respectively. Corresponding values at 3 min were 223%, 148% and 157%, respectively. These changes were significant (P < 0.01) at 1 and 3 min. In contrast, the rocuronium and vecuronium groups had no significant changes in either plasma histamine concentrations or haemodynamic variables.
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PMID:Histamine-release haemodynamic changes produced by rocuronium, vecuronium, mivacurium, atracurium and tubocurarine. 878 57


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