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PubMed1995

Edrophonium increases mivacurium concentrations during constant mivacurium infusion, and large doses minimally antagonize paralysis.

BACKGROUND: Mivacurium, a nondepolarizing muscle relaxant, is metabolized by plasma cholinesterase. Although edrophonium does not alter plasma cholinesterase activity, we have observed that doses of edrophonium that antagonize paralysis from other nondepolarizing muscle relaxants are less effective with mivacurium. We speculated that edrophonium might after metabolism of mivacurium, thereby hindering antagonism of paralysis. Accordingly, we determined the effect of edrophonium on neuromuscular function and plasma mivacurium concentrations during constant mivacurium infusion. METHODS: We infused mivacurium to maintain 90% depression of adductor pollicis twitch tension and then gave edrophonium in doses ranging from 125-2,000 micrograms/kg without altering the mivacurium infusion. Peak twitch tension after edrophonium was determined to estimate the dose of edrophonium antagonizing 50% of twitch depression for antagonism of mivacurium; plasma cholinesterase activity and mivacurium concentrations before and after edrophonium were measured. Additional subjects were given 500 micrograms/kg edrophonium to antagonize continuous infusions of d-tubocurarine and vecuronium. RESULTS: With mivacurium, edrophonium increased twitch tension in a dose-dependent manner: the dose of edrophonium antagonizing 50% of twitch depression was 2,810 micrograms/kg. The largest dose of edrophonium (2,000 micrograms/kg) produced only 45 +/- 7% antagonism. Edrophonium, 500 micrograms/kg, antagonized mivacurium markedly less than it antagonized d-tubocurarine and vecuronium. Edrophonium increased plasma concentrations of the two potent stereoisomers of mivacurium 48% and 79%, these peaking at 1-2 min; plasma cholinesterase activity was unchanged. CONCLUSIONS: Edrophonium doses that antagonize d-tubocurarine and vecuronium are less effective in antagonizing the neuromuscular effects of mivacurium during constant infusion. Edrophonium increases plasma mivacurium concentrations, partly or completely explaining its limited efficacy; the mechanism by which edrophonium increases mivacurium concentrations remains unexplained. Our results demonstrate that antagonism of mivacurium by edrophonium is impaired, and therefore we question whether edrophonium should be used to antagonize mivacurium.

Adolescent↗

PubMed2001

Equi-lasting doses of rocuronium, compared to mivacurium, result in improved neuromuscular blockade in patients undergoing gynecological laparoscopy : [Des doses de durée équivalente de rocuronium, comparé au mivacurium, améliorent la curarisation chez des patientes qui subissent une laparoscopie gynécologique].

PURPOSE: To compare equi-lasting doses of a short-acting (mivacurium) to an intermediate-acting (rocuronium) neuromuscular relaxant, with regard to intubating conditions, efficacy, number of maintenance doses, hemodynamic alterations, adverse events and costs, in patients undergoing laparoscopic gynecological surgery. METHODS: Sixty patients were randomly allocated to receive either 0.2 mg*kg(-1) (3 x ED(95)) mivacurium or 0.5 mg*kg(-1) (1.7 x ED(95)) rocuronium, under propofol/fentanyl anesthesia. T1, first twitch of the train-of-four (TOF) and TOF ratio (T4:T1) were used to evaluate neuromuscular block using the Relaxometer(R) mechanomyograph. The trachea was intubated when T1 was maximally suppressed. Neuromuscular block was maintained at 25% T1 with equi-lasting doses of 0.075 mg*kg(-1) mivacurium or 0.15 mg*kg(-1) rocuronium. RESULTS: Mean (min) +/- SD mivacurium onset time (1.9 +/- 0.4) was longer than that of rocuronium (1.3 +/- 0.3). This did not yield a statistical difference in intubating conditions between the two groups. Interval 25-75% T1 recovery and time to 0.8 TOF recovery were prolonged following rocuronium (11.9 +/- 3.9, 52.6 +/- 15.5 respectively) compared to mivacurium (6.7 +/- 2.3, 39.2 +/- 8.1 respectively). More patients, 22/30, required mivacurium maintenance doses compared to 14/30 patients in the rocuronium group. Arterial blood pressure declined and 13/30 patients manifested erythema following mivacurium administration. The acquisition costs of rocuronium (6.93 Euro/patient) were 23% lower compared to mivacurium (8.96 Euro/patient). CONCLUSION: Equi-lasting doses of rocuronium resulted in favourable intubating conditions more rapidly, improved hemodynamic stability, required less frequent administration of maintenance doses and were not associated with erythema, compared to mivacurium.

Adolescent↗

PubMed1994

Synergism between atracurium and mivacurium compared with that between vecuronium and mivacurium.

Synergism exists between some combinations of nondepolarizing muscle relaxants. To test the possibility of synergism between mivacurium and atracurium or vecuronium, 60 children anesthetized with propofol-alfentanil-N2O-O2 were randomized to one of five groups. Three groups of 10 patients each received an ED50 dose of a parent drug atracurium (A), vecuronium (V), or mivacurium (M), respectively, and two other groups of 15 patients each received a single-dose combination of atracurium with mivacurium (cAM) or vecuronium with mivacurium (cVM). Dose combinations constituted 0.5 times an ED50 dose of each drug. Neuromuscular response was monitored by adductor pollicis electromyogram (EMG). Maximum neuromuscular block (NMB) established by a single parent drug did not differ between the groups or from 50% NMB. It averaged 5.03 +/- 0.12 probits (51.2% NMB). On the contrary, maximum NMB established by the two-dose combinations, cAM or cVM, was significantly more than NMB produced by either single parent drug of the particular combination (cAM vs A or M; P = 0.0035, and cVM vs V or M; P = 0.0004) without a statistically significant difference between groups cAM and cVM. Maximum NMB established by combinations averaged 6.15 +/- 0.21 probits (87.5% NMB). The onset of maximum NMB for mivacurium was significantly faster compared to that for atracurium or for vecuronium (2.8 +/- 0.3 vs 5.7 +/- 0.4 or 4.0 +/- 0.3 min, respectively; P = 0.0001). Our results indicate that both drug combinations are synergistic even though only vecuronium is markedly different in its molecular structure from mivacurium.

Atracurium↗

PubMed1996

Re-establishment of paralysis using mivacurium following apparent full recovery from mivacurium-induced neuromuscular block.

Recent published data suggest that despite apparently satisfactory recovery from nondepolarising block (train-of-four ratios in excess of 0.90), even very small doses of additional relaxant may re-establish significant paralysis. We sought to verify this observation and quantify its magnitude. Twelve adult patients were studied under nitrous oxide-propofol-opioid anaesthesia and neuromuscular block was monitored electromyographically. Train-of-four stimuli were delivered to the ulnar nerve every 20 s throughout the period of observation. After baseline stabilisation, an initial bolus of mivacurium 25 micrograms.kg-1 was administered and the twitch depression noted. When the twitch was stable for two consecutive stimuli, a second bolus, calculated to produce approximately 90% twitch depression, was administered. Recovery was then allowed to proceed spontaneously until the train-of-four ratio reached 0.95. At that time a second 25 micrograms.kg-1 dose was administered and the effect on twitch height recorded. Using the slope for the log-dose/logit dose-response relationship of mivacurium (5.5), it was possible to estimate any change in the ED50 of mivacurium. The control ED50 of mivacurium (calculated from the initial dose of mivacurium) averaged 43 micrograms.kg-1. When the same dose of drug was given at 95% recovery of the train-of-four ratio, the ED50 was reduced to 19 micrograms.kg-1 (p < 0.0001). Hence, there remains a considerable reduction in the neuromuscular margin of safety even at a train-of-four ratio of 0.95.

Adolescent↗

PubMed1994

Neuromuscular effects of rocuronium bromide and mivacurium chloride administered alone and in combination.

BACKGROUND: Rocuronium is a new nondepolarizing neuromuscular blocking agent with a rapid onset but with intermediate duration of action. Mivacurium, on the other hand, is a new short-acting nondepolarizing neuromuscular relaxant, but of slower onset of action. The current study was undertaken to characterize the interaction between rocuronium and mivacurium. METHODS: In the first study, the dose-response relations of rocuronium, mivacurium, and their combination were studied in ASA physical status 1 or 2 patients during thiopental-fentanyl-N2O anesthesia. One hundred ten patients, randomly assigned to 1 of 11 groups of 10 patients each, received mivacurium 30, 50, or 70 micrograms.kg-1; rocuronium 100, 200, 250, or 300 micrograms.kg-1; or an equieffective combination of both drugs (1 ED50 rocuronium + 1 ED50 mivacurium; 1/2 ED50 rocuronium + 1/2 ED50 mivacurium; 1/4 ED50 rocuronium + 1/4 ED50 mivacurium; or 1/8 ED50 rocuronium + 1/8 ED50 mivacurium, where ED50 is the dose producing 50% depression of the first twitch height). In the second study, 50 patients, ASA physical status 1 or 2, anesthetized with thiopental-fentanyl-N2O, were randomly allocated to 5 groups of 10 patients each to receive one of the following neuromuscular blocking drugs or drug combination: rocuronium 600 micrograms.kg-1 (group 1), mivacurium 150 micrograms.kg-1 (group 2) rocuronium 150 micrograms.kg-1 + mivacurium 37.5 micrograms.kg-1 (group 3), rocuronium 300 micrograms.kg-1 + mivacurium 75 micrograms.kg-1 ((group 4), or rocuronium 600 micrograms.kg-1 + mivacurium 150 micrograms.kg-1 (group 5). RESULTS: The calculated ED50 values and their 95% confidence intervals were 125 (122-129) and 37 (36-38) micrograms.kg-1 for the rocuronium and mivacurium groups, respectively. The interaction between rocuronium and mivacurium was found to be synergistic. The measured ED50 of the mixture was only 62% of the predicted value assuming a purely additive interaction. In the second study, rocuronium 600 micrograms.kg-1 group and group 3 had similar onset times (99 [74-123] and 114 [100-128] s, respectively), which were significantly shorter than that observed in the mivacurium 150 micrograms.kg-1 group (178 [149-206] s). Onset times in groups 4 and 5 were significantly shorter than that in each of the other study groups (69 [63-76] and 73 [65-80] s, respectively). Clinical duration of action (recovery of T1 to 25% of baseline twitch height) was significantly greater in group 5 (55 [51-60] min) than with all other doses and agents, and briefest (P < 0.01) with mivacurium 150 micrograms.kg-1 (14.5 [12.6-16.5] min) and group 3 (14.7 [13.4-16] min). CONCLUSIONS: The interaction between rocuronium and mivacurium was found to be synergistic.

Adult↗

PubMed2003

Potentiation of mivacurium blockade by low dose of pancuronium: a pharmacokinetic study.

BACKGROUND: Mivacurium is potentiated by pancuronium to a much greater extent than other relaxants. In a previous investigation we suggested that this potentiation could be due to the ability of pancuronium to inhibit plasma cholinesterase activity, but we did not measure plasma concentrations of mivacurium. In the current study we performed a pharmacokinetic analysis by measuring the plasma concentration of mivacurium when preceded by administration of a low dose of pancuronium. METHODS: After induction of general anesthesia with propofol and fentanyl and orotracheal intubation, 10 patients (pancuronium-mivacurium group) received 15 microg/kg pancuronium followed 3 min later by 0.1 mg/kg mivacurium, whereas 10 other patients (mivacurium group) received saline followed by 0.13 mg/kg mivacurium 3 min later. Plasma cholinesterase activity was measured before and 3 and 30 min after pancuronium dosing in the pancuronium-mivacurium group and was measured before and after administration of saline in the mivacurium group. Arterial plasma concentrations of mivacurium and its metabolites were measured at 0.5, 1, 1.5, 2, 4, 10, 20, and 30 min after injection. Neuromuscular blockade was assessed by mechanomyography. RESULTS: Plasma cholinesterase activity decreased by 26% in the pancuronium-mivacurium group 3 min after injection of pancuronium (P < 0.01) and returned to baseline values 30 min later; however, no significant variation was observed in the mivacurium group. The clearances of the two most active isomers (Cis-Trans and Trans-Trans) were lower in the pancuronium-mivacurium group (17.6 +/- 5.1, 14.7 +/- 5.3 ml. min-1. kg-1, respectively) than in the mivacurium group (32.4 +/- 20.2, 24.8 +/- 13.5 ml. min-1. kg-1; P < 0.05). CONCLUSIONS: A subparalyzing dose of pancuronium decreased plasma cholinesterase activity and the clearance of the two most active isomers of mivacurium. Pancuronium potentiates mivacurium more than other neuromuscular blocking agents because, in addition to its occupancy of postsynaptic acetylcholine receptors, it slows down the hydrolysis of mivacurium.

Adolescent↗

PubMed1996

Mivacurium when preceded by pancuronium becomes a long-acting muscle relaxant.

BACKGROUND: To ensure rapid recovery of neuromuscular block, it might be useful to administer a short-acting relaxant after a long-acting one. Therefore, the interaction between pancuronium and mivacurium was investigated when mivacurium was administered during the recovery from pancuronium block. METHODS: After written informed consent, 41 adult patients were studied during propofol/alfentanil/nitrous oxide/oxygen anesthesia. Neuromuscular function was monitored using an electromyographic (EMG) method. AFter a stable EMG calibration response, cumulative doses of pancuronium were given to establish a 95% neuromuscular block. In the control group, and ED95 dose of 100 microg/kg mivacurium was administered instead of pancuronium. When the EMG response after pancuronium or mivacurium had recovered to 25% of the baseline, a single randomized intravenous bolus dose of 10 or 70 microg/kg mivacurium was given. Thereafter, spontaneous recovery of the neuromuscular function was recorded. RESULTS: The time from pancuronium until T1 25% EMG recovery was 38 +/- 12 min (mean +/- SD). The respective times after 10 or 70 microg/kg mivacurium were 28 +/- 8 and 54 +/- 7 min in the pancuronium group or 3 +/- 1 (n=3) and 10 +/- 4 min in the mivacurium group (P=0.0001). Times to 95% EMG recovery after 10 or 70 microgm/kg mivacurium were 77 +/- 14 and 97 +/- 16 min in the pancuronium group and 11 +/- 3 and 20 +/- 7 min in the mivacurium group, respectively (P<0.0001). Recovery indexes after 10 or 70 microg/kg mivacurium group, respectively (P<0.0001). Recovery indexes after 10 or 70 microg/kg mivacurium wre 26 +/- 4 and 22 +/- 6 min in the pancuronium group or 7 +/- 3 (n=3) and 5+/- 2 min in the mivacurium group, respectively (P<0.0001). Times from the administration of 10 or 70 microg/kg mivacurium until train-of-four ration 0.7 were 94 +/- 16 and 111 +/- 14 min in the pancuronium group and 12 +/- 4 and 22 +/- 8 min in the mivacurium group, respectively (P<0.0001). CONCLUSIONS: After pancuronium, mivacurium is not a short acting neuromusclar blocking agent.

Adult↗

PubMed1995

The effect of neostigmine on twitch tension and muscle relaxant concentration during infusion of mivacurium or vecuronium.

BACKGROUND: An investigation suggested that neostigmine may not effectively antagonize mivacurium, presumably because neostigmine impairs mivacurium's metabolism. However, the effect of neostigmine on mivacurium's metabolism in vivo has not been reported. Therefore, the effect of neostigmine on neuromuscular function and plasma mivacurium concentrations during constant mivacurium infusion was determined. METHODS: Mivacurium was infused in five patients to maintain 90% depression of adductor pollicis twitch tension, then 50 micrograms/kg intravenous neostigmine was administered without altering the mivacurium infusion. Peak twitch tension after neostigmine, plasma cholinesterase activity, and mivacurium concentrations before and after neostigmine were measured. Five additional patients were given 50 micrograms/kg neostigmine to antagonize block due to continuous infusions of vecuronium. RESULTS: Neostigmine produced less antagonism of mivacurium (39 +/- 11%) than of vecuronium (54 +/- 9%, P < 0.05). Neostigmine decreased plasma cholinesterase activity and increased plasma concentrations of the trans-trans and cis-trans stereoisomers of mivacurium (P < 0.05). CONCLUSIONS: Neostigmine is less effective at antagonizing the neuromuscular effect of mivacurium than that of vecuronium during constant infusion. Neostigmine increases plasma mivacurium concentrations, likely explaining its limited efficacy. Our results confirm that neostigmine impairs the metabolism of mivacurium in vivo and may explain the observation that neostigmine may not effectively antagonize mivacurium-induced block.

Adolescent↗

PubMed1999

The nature of spontaneous recovery from mivacurium-induced neuromuscular block.

UNLABELLED: The hypothesis of this study was that, in a given patient, recovery from a tracheal intubating dose of mivacurium would indicate the time course of spontaneous recovery after discontinuation of an infusion of mivacurium. Thirty-eight male patients consented to participate in the study. After induction of anesthesia and endotracheal intubation, the ulnar nerve was stimulated with train-of-four (TOF) stimuli at 12-s intervals. Patients received 0.3 mg/kg mivacurium in two evenly divided doses of 0.15 mg/kg each, separated by 30 s. Complete ablation of TOF responses occurred in most patients. Once the first twitch in the TOF (T ) had recovered to 25% of its baseline height, a mivacurium infusion was begun to maintain 95% suppression of T1. As surgery was nearing completion, the infusion was discontinued, and neuromuscular function was allowed to recover spontaneously. Data were analyzed for recovery intervals after the administration of the initial doses of mivacurium and after discontinuation of the infusion. Analysis of variance was used to determine the strength of correlation between the time from administration of the initial 0.3 mg/kg dose to 5% recovery of T1 and the times to recovery of TOF ratios of 70% and 90%. The 25%-75% recovery interval after discontinuation of the infusion ranged from 2.8 to 11.3 min. The time interval after administration of mivacurium 0.3 mg/kg to 5% recovery of T1 correlated with both the time to recovery of a TOF ratio of 70% and 90%. Recovery to a TOF of 90% after discontinuation of the infusion required approximately the same amount of time as recovery to 5% T1 after the administration of 0.3 mg/kg mivacurium. Each patient's recovery of neuromuscular function after discontinuation of a mivacurium infusion was related to his recovery after the administration of 0.3 mg/kg mivacurium. Therefore, the need for pharmacologic antagonism of block can be anticipated well before the end of an anesthetic. IMPLICATIONS: Mivacurium (0.3 mg/kg) was administered to 38 patients. As they began to recover muscle strength, a mivacurium infusion was begun and later discontinued as surgery was nearing completion. Each patient's early recovery (administration to 5% recovery of T1) after the initial dose of mivacurium correlated well with more complete recovery of muscle strength after discontinuation of an infusion. This relationship enables early prediction of recovery speed after a mivacurium infusion.

Adult↗

PubMed1997

Comparison of suxamethonium and different combinations of rocuronium and mivacurium for rapid tracheal intubation in children.

The use of suxamethonium in children is associated with undesirable side effects. The synergistic effect of a rocuronium-mivacurium combination can be considered as an acceptable alternative to suxamethonium in clinical practice. The calculated ED50 of the rocuronium-mivacurium mixture was only 62% of the predicted value assuming a purely additive interaction. The use of this combination has not been evaluated in children. In this two-part study, we assessed the intubating conditions and pharmacodynamics of suxamethonium, rocuronium, mivacurium or a rocuronium-mivacurium combinations in children. We studied 120 ASA I children of both sexes, aged 3-10 yr. Children were premedicated with trimeprazine 2 mg kg-1 orally, and received fentanyl 2 micrograms kg-1 and propofol 2 mg kg-1 for induction of anaesthesia. They were allocated randomly to receive one of the following drugs or drug combinations: suxamethonium 1.0 mg kg-1, mivacurium 0.2 mg kg-1, rocuronium 0.6 or 0.9 mg kg-1, mivacurium 0.1 mg kg-1 with rocuronium 0.3 mg kg-1 or mivacurium 0.15 mg kg-1 with rocuronium 0.45 mg kg-1. In part 1, 60 s after administration of the neuromuscular blocking drug or drug combination, tracheal intubation was performed in 60 children by mimicking rapid sequence induction, and intubating conditions were evaluated by a blinded investigator according to a standard score. In part 2, neuromuscular monitoring was established before administration of neuromuscular blocking agent(s) and the time from injection of drug or drug combination until complete ablation of T1 (onset) and recovery of T1 to 25% (duration) were recorded in another 60 children. The frequency of distribution of excellent or good intubating conditions in the higher dose of rocuronium and the combination groups were similar to those in the suxamethonium group, but significantly different (P < 0.05) from those in the mivacurium group. Mean onset time was faster in the suxamethonium (55.1 (SD 11.4) s), rocuronium 0.9 mg kg-1 (70.5 (37.7) s), mivacurium 0.1 mg kg-1 with rocuronium 0.3 mg kg-1 (67 (35.9) s) and mivacurium 0.15 mg kg-1 with rocuronium 0.45 mg kg-1 (55 (26.7) s) groups compared with the mivacurium 0.2 mg kg-1 (116 (26.8) s) and rocuronium 0.6 mg kg-1 (97.9 (29) s) groups. This study demonstrated that the combination of rocuronium 0.45 mg kg-1 and mivacurium 0.15 mg kg-1 could possibly be considered as an acceptable alternative to suxamethonium when rapid sequence induction of anaesthesia is indicated in children because it provides uniform excellent intubating conditions and complete neuromuscular block in < 60 s.

Androstanols↗

PubMed1989

Comparison of tracheal intubating conditions and neuromuscular blocking profiles after intubating doses of mivacurium chloride or succinylcholine in surgical outpatients.

Thirty ASA physical status I or II outpatients scheduled to undergo short procedures (less than 1 hr in duration) requiring tracheal intubation received either 1.0 mg/kg succinylcholine or 0.20 mg/kg (2.5 x ED95) or 0.25 mg/kg (3 x ED95) mivacurium. A N2O/O2/narcotic anesthetic technique was utilized and the ulnar nerve was stimulated with subcutaneous electrodes placed at the wrist. Tracheal intubation was attempted in all patients either 2 min after mivacurium or 1 min after succinylcholine. Intubation conditions were not different between the succinylcholine and mivacurium groups or between the two mivacurium groups. The onset and duration of neuromuscular blockade were shorter with succinylcholine than with mivacurium. Suppression of the T1 response to 90% of baseline occurred in 0.9 min with 1.0 mg/kg succinylcholine and at 2.2 and 1.5 min respectively, with 0.20 mg/kg and 0.25 mg/kg mivacurium. Initial recovery of the T1 response occurred at 6.4 min after 1.0 mg/kg succinylcholine and 12.7 and 13.6 min respectively after 0.20 mg/kg and 0.25 mg/kg mivacurium. Subsequent to initial recovery from the intubating dose of relaxant, infusions of mivacurium or succinylcholine were administered to maintain approximately 95% block. The mean infusion rates were 6.6 micrograms.kg-1.min-1 mivacurium and 41.2 micrograms.kg-1.min-1 for succinylcholine. Spontaneous recovery from neuromuscular blockade occurred more quickly after succinylcholine than after mivacurium: the time from cessation of infusion to recovery of T1 to 95% of baseline was 6.5 min in patients given succinylcholine and 16.7 min in patients given mivacurium. When reversal was in order, residual mivacurium-induced blockade was readily antagonized by 0.045 mg/kg neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

[Intubation conditions and circulatory effects 90 seconds after a divided mivacurium dose with three different TIVA induction methods].

UNLABELLED: The aim of this study was to compare the intubating conditions of a mivacurium-induced neuromuscular block 90 s after a divided administration with three different methods of induction of anaesthesia. METHODS: After approval by the local ethics committee, we investigated 36 ASA I and II patients undergoing a 2-h scheduled, elective surgery, in whom a TIVA was induced by one of three different drugs, edomidate, methohexital or propofol. After stable anaesthesia was reached, 0.15 mg/kg and 0.1 mg/kg of mivacurium, spaced 30 s apart, was injected. Endotracheal intubation was performed 90 s after the first micacurium injection and the intubation conditions were graded (1: excellent, 2: good, 3: poor; 4: impossible). The neuromuscular function was stimulated every 20 s by a nerve stimulator in a train-of-four (TOF) pattern, and the time to complete distinction of a TOF response as well as the time of reoccurrence of the first twitch was taken. A minute prior to injection of the relaxant and every minute for 5 min, the systolic and diastolic blood pressure, mean arterial pressure (MAP) and heart rate were measured. The neuromuscular block was maintained with a mivacurium infusion on a level of one twitch response. After cessation of the mivacurium infusion we recorded the time of reappearance of the second, third and fourth twitch responses. RESULTS: All patients could be intubated 90 s after mivacurium except for one, who was excluded for abnormal difficult intubation conditions. The etomidate group had significantly (chi 2 test) worse intubation grades than the methohexital group. In none of the groups did we observe any significant cardiovascular response due to the mivacurium injection, neither in blood pressure nor in heart rate. All groups showed similar onset of the maximal neuromuscular block (4 +/- 1.8 min) and recovery of the first TOF reaction (11.3 +/- 3.4 min). There was no difference in recovery from neuromuscular block maintained by infusion at the end of surgery. CONCLUSIONS: A dose of mivacurium 3.57 times the ED95 does not produce any haemodynamic instability, if it is divided into two parts to induce a TIVA. After this dose, all patients could be safely intubated within 90 s. A prolongation of the neuromuscular block after higher mivacurium doses could not be seen, and this dose did not produce a more rapid onset of the maximal block in any group. The time for recovery from a mivacurium infusion did not differ among the groups. Etomidate, due to its short half-life, seems not ideal for induction of a TIVA together with mivacurium in the dosage used. Mivacurium meets the demands of good controllability as required for a TIVA and can be recommended for a 90-s injection-intubation interval as well as for maintenance of the neuromuscular block.

Anesthesia, Intravenous↗

PubMed2000

Mivacurium or vecuronium for paediatric ENT surgery. Clinical experience and cost analysis.

BACKGROUND: The present study compared the quality of neuromuscular block and costs after equipotent doses of mivacurium and vecuronium in the context of paediatric ENT surgery. METHODS: A total of 30 children undergoing elective tonsillectomy were included and randomised in two groups (n = 15 for each) according to the neuromuscular blocking agent (NMBA) used. Anaesthesia was induced with alfentanil (15 micrograms/kg), propofol (3 mg/kg) and either 0.2 mg/kg mivacurium or 0.14 mg/kg vecuronium. For maintenance of anaesthesia propofol (8-12 mg/kg/h) was given. Neuromuscular block was assessed by electromyography using train-of four stimulation and the following parameters were quantified: Twitch height (T1) 2 min after the initial bolus of the myorelaxant; duration until recovery to 10% T1, number and duration of bolus injections of the myorelaxant needed to maintain neuromuscular block to a T1 < 10%. In addition, the intubating conditions, number of patients needing pharmacological reversal at the end of surgery, adverse reactions and the costs for neuromuscular block and pharmacological antagonization were assessed. RESULTS: Intubation conditions were comparable between both study groups: mivacurium--excellent: 7, good: 5, not acceptable: 1; vecuronium--excellent: 11, good: 4 (n.s.). T1 at 2 min was 16 (15)% for mivacurium and 6 (9)% for vecuronium (P < 0.05). Time to 10% T1 recovery was 6.1 (1.7) min for mivacurium and 21.8 (3.7) min for vecuronium (P < 0.01). In the mivacurium group 7 repetitive doses (range: 4-18) were needed to maintain T1 < 10% during surgery, whereas children treated with vecuronium needed only 1 maintenance dose (range: 0-2) (P < 0.01). Two children in the mivacurium group and 11 in the vecuronium group required pharmacological reversal of the NMB at the end of surgery (P < 0.01). The overall costs of NMB were significantly higher in the mivacurium group as compared to vecuronium 12.88 (4.5) Euro vs 9.96 (2.4) Euro; P < 0.05. CONCLUSIONS: In conclusion, mivacurium-induced NMB is of very short duration in paediatric patients, and therefore repetitive doses are required to maintain a deep neuromuscular block. Nevertheless, residual paralysis is less frequent after mivacurium. The neuromuscular block after mivacurium was more expensive and residual paralysis less frequent compared to vecuronium.

Child↗

PubMed2000

The mechanism of pancuronium potentiation of mivacurium block: use of the isolated-arm technique.

UNLABELLED: The neuromuscular blocking effects of mivacurium are greatly enhanced when mivacurium is preceded by a subparalyzing dose of pancuronium. The mechanism of this potentiation has not been elucidated. This study investigated the effects of the anticholinesterase activity of a small dose of pancuronium on the neuromuscular blocking effects of mivacurium. Forty patients were enrolled in the study. The neuromuscular effects of 7.5 and 15 microg/kg pancuronium, followed by 50 and 100 microg/kg mivacurium, were assessed in Groups PM1 and PM2 (n = 20), respectively. The neuromuscular effects of 65 and 130 microg/kg mivacurium were assessed in Groups M1 and M2 (n = 20), respectively. One arm was excluded from circulation with a tourniquet, which was inflated before the injection of pancuronium and deflated 3 min after the injection of mivacurium. The plasma cholinesterase activity was measured before induction for all patients and 3 min after the injection of pancuronium for Groups PM1 and PM2. The plasma cholinesterase activity was decreased by 16% and 33% after pancuronium administration in Groups PM1 and PM2, respectively. In the nonexcluded arm, pancuronium significantly potentiated the effects of mivacurium. In the excluded arm, no significant block was detected for Groups M1 and M2, whereas the maximal degree of neuromuscular block was 79% and 100% for Groups PM1 and PM2, respectively. Using the isolated-arm technique, we suggest that pancuronium potentiation of the neuromuscular blocking effects of mivacurium is more likely attributable to an increase in the effective plasma concentration of mivacurium than to occupancy of postsynaptic acetylcholine receptors. IMPLICATIONS: Using the isolated-arm technique, we suggest that pancuronium potentiation of the neuromuscular blocking effects of mivacurium is more likely attributable to an increase in the effective plasma concentration of mivacurium than to occupancy of postsynaptic acetylcholine receptors.

Adolescent↗

PubMed1994

Mivacurium after atracurium in children.

The effect of mivacurium after atracurium was evaluated in 36 children anesthetized with halothane-nitrous oxide-oxygen by measuring the force of contraction of the adductor pollicis during train-of-four stimulation at 0.1 Hz. The children were evaluated in two main groups. In Group 1 the effect of bolus doses of mivacurium after equipotent repeat doses of atracurium were evaluated. When the first twitch of the train-of-four response (T1) had recovered to 25% of control after a tracheally intubating dose of atracurium, a repeat dose of atracurium was given, on subsequent recovery to 25%, an equipotent dose of mivacurium was administered. In Group 2 when T1 had recovered to > 10% from 0.5 mg/kg atracurium, a mivacurium infusion was started; the initial infusion rate was 4 micrograms.kg-1.min-1 with adjustments made to maintain 90%-99% depression of T1. Patients were allowed to recover spontaneously from the effect of the relaxants. In Group 1 prolongation of the effect of mivacurium was noted after atracurium; the recovery indices (25%-75% and 5%-95%) of mivacurium were longer than those seen when mivacurium is the sole relaxant but shorter than atracurium. In Group 2, 15 min after the start of the mivacurium infusion, the dose requirement was 3.7 +/- 0.3 micrograms.kg-1.min-1 (approximately about one-third that required after a tracheally intubating dose of mivacurium). The infusion requirement increased gradually (P < 0.0001) until, at 90 min of infusion, it was 7.4 +/- 0.8 micrograms.kg-1.min-1. In Group 2 the recovery indices were similar to those seen when mivacurium is the sole relaxant given. When mivacurium is given after atracurium, evidence of the residual neuromuscular effects of the atracurium are detected beyond the usual recovery range.

Adolescent↗

PubMed1993

Pharmacodynamic and hemodynamic effects of mivacurium in infants anesthetized with halothane and nitrous oxide.

BACKGROUND: The newly developed neuromuscular blocking agent, mivacurium, has been evaluated in adults and children, but there are no data on its effects in infants. This study was designed to evaluate the neuromuscular effects of mivacurium by dose-response analysis, and its cardiovascular effects in 90 infants 2-11 months of age anesthetized with 1% halothane and nitrous oxide:oxygen. METHODS: The neuromuscular response was measured by recording the force of contraction of the adductor pollicis during train-of-four stimulation at 0.1 Hz. The infants were divided according to age into two equal groups of 45; group A infants were 2-6 months of age, and group B infants were 7-11 months of age. Each group was further subdivided into five subgroups of nine. Infants in group A received mivacurium at sequential doses of 40, 50, 55, 75, and 150 micrograms/kg, while those in group B received mivacurium at doses 40, 50, 60, 75, and 150 micrograms/kg. The first four doses in each group were used to determine dose-response relationships. The last two doses of 75 and 150 micrograms/kg were based on the observed preceding dose-response data to approximate the ED95 and 2XED95. Heart rate and blood pressure were determined every minute for a minimum of 3 min after mivacurium. RESULTS: The effective doses for 50% depression of the first twitch response of the train-of-four (ED50) were 44-50 micrograms/kg (confidence limits 29-74 micrograms/kg), without any significant difference between groups A and B. In both groups, a larger dose of mivacurium, 150 micrograms/kg, caused complete ablation of the twitch response in 1.3 +/- 0.2 min (mean +/- SE) with recovery to 5, 25, and 95% of control in 7.6 +/- 0.5, 9.4 +/- 0.6, and 16.2 +/- 0.9 min, respectively. In infants, the 25-75% recovery index was 3.8 +/- 0.4 min, and the 5-95% recovery index was 8.5 +/- 0.8 min. In 28 infants, in whom surgical relaxation was required for more than 20 min, the infusion requirements to maintain 90-99% neuromuscular block in infants 2-6 and 7-11 months of age were 12.1 +/- 1 and 9.9 +/- 1 micrograms.kg-1.min-1, respectively (NS). No significant changes of heart rate of blood pressure occurred in infants, except in the subgroup of infants 7-11 months of age who received 150 micrograms/kg mivacurium. In this group, a 13-mmHg increase in mean systolic blood pressure was seen without any significant change in diastolic pressure or heart rate. In addition, in 7 of 36 patients receiving 75-150 micrograms/kg mivacurium, a greater than 29% change in systolic or diastolic pressure occurred. One infant with cholinesterase deficiency had a prolonged neuromuscular block from mivacurium. CONCLUSIONS: The ED50 duration of action and infusion requirements of mivacurium in infants 2-6 months of age are comparable with those of infants 7-11 months of age.

Anesthesia, Inhalation↗

PubMed1997

Pharmacokinetics of mivacurium isomers and their metabolites in healthy volunteers after intravenous bolus administration.

BACKGROUND: Previous studies report the pharmacokinetics of mivacurium isomers after an infusion using venous blood sampling. Although the extent of the mivacurium arterial-venous gradient is not known, the sampling site is likely to influence mivacurium pharmacokinetic parameters because the drug is rapidly metabolized as it traverses the circulation. The objectives of this study were (1) to determine the pharmacokinetics of mivacurium isomers in healthy persons after intravenous bolus administration using intensive arterial blood sampling, and (2) to characterize the formation and elimination of mivacurium metabolites in human plasma. METHODS: Eight persons classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled to undergo elective surgery under balanced anesthesia received 0.15 mg/kg mivacurium chloride as an intravenous bolus. Arterial blood samples were collected every 10 s during the first 2 min and at frequent intervals for 4 h thereafter. Plasma concentrations of mivacurium isomers and their metabolites were determined by two stereoselective high-performance liquid chromatographic methods coupled with fluorometric detection and noncompartmental pharmacokinetic parameters. RESULTS: Mean elimination half-lives of the trans-trans, cis-trans, and cis-cis isomers were 2.4, 2, and 28.5 min, respectively, with corresponding mean plasma clearances of 29.2, 45.7, and 6.7 ml.min 1.kg-1. The volumes of distribution at steady state of the trans-trans, cis-trans, and cis-cis isomers were 0.047, 0.054, and 0.189 l/kg, respectively. Plasma concentrations of monoester and alcohol metabolites peaked 25 s (median) after mivacurium injection, with half-lives in the range of 90 min, except for the cis alcohol metabolite, which was only negligibly and transiently formed. CONCLUSIONS: Substantial hydrolysis of mivacurium isomers by cholinesterases was confirmed by the rapid appearance of mivacurium metabolites in plasma. The intensive arterial sampling proved to be critical for the trans-trans and cis-trans isomers because the area under the curve between 0 and 2 min accounted for 75% and 86% of the total, respectively.

Adolescent↗

PubMed1995

Synergism between mivacurium and pancuronium in adults.

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.

Adolescent↗