Mivacurium chloride in infants and children

Mivacurium has been little studied in infants and children without a volatile anaesthetic agent. We analysed onset time and maximal neuromuscular response after mivacurium 0.1 mg/kg, and the infusion requirement of mivacurium to maintain a 50, 90, or 95% neuromuscular block in 76 infants and children under N₂O-O₂ alfentanil anaesthesia. Furthermore, we assessed the time course of potentiation of 1 MAC end-tidal halothane or isoflurane on the infusion requirement of mivacurium. Neuromuscular response was recorded by adductor pollicis electromyogram. The onset time of mivacurium was shorter in infants than in children (2.1 ± 0.6 and 3.2 ± 0.9 min (mean±SD); P =0.0001). The dose potency of mivacurium did not depend on the age of a paediatric patient. The estimated ED₉₅ of mivacurium was 136±46 μg/kg. The mivacurium requirement to maintain a 50, 90, or 95% neuromuscular block averaged 340, 730, and 900 μg/kg/h, respectively. Halothane and isoflurane decreased this hourly requirement by 35 and 70%, respectively. The decrease in the mivacurium infusion requirement was fastest in the youngest children. In conclusion, mivacurium is easy to administer as bolus doses or continuous infusion in paediatric patients because its potency is similar in all patients from 1 month to 15 years of age. Halothane and isoflurane produce their maximal potentiation of neuromuscular block only after 30–60 min of administration. This potentiation is similar in magnitude in all patients, but takes place fastest in the youngest children.     

Sevoflurane and isoflurane, but not propofol, decrease mivacurium requirements over time

PURPOSE: Volatile anesthetic agents potentiate neuromuscular blockade, but the magnitude of potentiation appears to be time dependent. The time course of this interaction was studied by measuring mivacurium infusion rates during sevoflurane, isoflurane and propofol anesthesia. METHODS: After informed consent, anesthesia was induced in 48 ASA physical status I-II adults with propofol, fentanyl and mivacurium 0.25 mg.kg(-1) and maintained with N(2)O (60%) and one of the three agents chosen at random: sevoflurane 1.9%; isoflurane 1.2%; or propofol 100-150 microgram.kg(-1).min(-1). Train-of-four stimulation was applied every 15 sec to the ulnar nerve. Neuromuscular blockade was monitored with accelerometry. At 5% recovery of the first twitch (T1), a mivacurium infusion was started and adjusted every five minutes to maintain 90-95% T1 depression. RESULTS: The time to 5% T1 recovery after the initial dose was similar in all groups (13-15 min). Fifteen minutes after the start of the infusion mivacurium requirements were greater (P < 0.05) in the propofol group (7.5 +/- 1.7 microgram.kg(-1).min(-1); mean +/- SD) than in either isoflurane (4.7 +/- 1.6 microgram.kg(-1).min(-1)) or sevoflurane (4.5 +/- 1.5 microgram.kg(-1).min(-1)) group. Then, the rate remained stable for propofol (6.2 +/- 1.4 microgram.kg(-1).min(-1) after 90 min of infusion) while it decreased with isoflurane to 2.9 +/- 1.6 microgram.kg(-1).min(-1) at 90 min (P < 0.05 vs propofol) and to 1.4 +/- 1.0 microgram.kg(-1).min(-1) in the sevoflurane group (P < 0.05 vs propofol and isoflurane). CONCLUSION: Sevoflurane and isoflurane do not prolong the effect of a bolus dose of mivacurium, but potentiation increases with time from 30-105 min of exposure. This interaction is greater with sevoflurane than isoflurane.     

Mivacurium infusion requirement and spontaneous recovery of neuromuscular transmission in children anaesthetized with nitrous oxide and fentanyl,halothane, isoflurane or sevoflurane

BACKGROUND: Forty children, aged 3-11 years, ASA I or II, were allocated at random to receive N2O/O2-fentanyl or 1 MAC halothane, isoflurane or sevoflurane-N2O/O2 anaesthesia. Mivacurium was used for muscle relaxation. METHODS: Electromyographic response of the adductor pollicis to train-of-four (TOF) stimulation, 2 Hz for 2 s, applied to the ulnar nerve at 10-s intervals was recorded using the Relaxograph (Datex, Helsinki, Finland). An intubating dose of mivacurium, 0.2 mg.kg-1 was given, and when T1 returned to 5%, muscle relaxation was maintained by continuous infusion of mivacurium, adjusted manually to maintain a stable 90-99% block. RESULTS: Halothane, isoflurane and sevoflurane groups had lower infusion requirements for mivacurium than the N2O-fentanyl group (P=0.000083). Mivacurium requirement was 18.8 +/- 6.8, 10.8 +/- 4.2, 6.9 +/- 3.9 and 9.6 +/- 5.6 microg.kg-1.min-1 for children receiving N2O/O2-fentanyl, halothane, isoflurane and sevoflurane anaesthesia, respectively. CONCLUSIONS: Spontaneous recovery from T1=10% to TOF ratio=0.7 was insignificantly prolonged from 6.3 to 12.5 min in the fentanyl group to 7-16.5 min in children anaesthetized with inhalational anaesthetics.     

Neuromuscular and cardiovascular effects of mivacurium chloride (BW B109OU) during nitrous oxide-narcotic, nitrous oxide-halothane and nitrous oxide-isoflurane anesthesia in surgical patients

One hundred seventeen adult surgical patients were studied to compare neuromuscular and cardiovascular effects of mivacurium chloride during nitrous oxide-narcotic (BAL, n = 45) nitrous oxide-halothane (HAL, n = 27) and nitrous oxide-isoflurane (ISF, n = 45) anesthesia. Anesthesia was maintained with nitrous oxide (60%-70%) and oxygen (30%-40%) with end-tidal concentrations of halothane or isoflurane to yield a total MAC of approximately 1.25, or with supplemental fentanyl and thiopental as clinically indicated. Twitch response of the adductor pollicis muscle was elicited by supramaximal square wave pulses of 0.2 msec duration at a frequency of 0.15 Hz (Grass S44 stimulator) to the ulnar nerve and quantitated by a Grass FT10 transducer. Nine patients in each of the HAL and ISF groups received one of four doses of mivacurium (0.03, 0.05, 0.10 or 0.15 mg/kg). Ninety patients in the balanced anesthesia group received one of seven doses of mivacurium (0.03, 0.04, 0.05, 0.08, 0.15, 0.20, 0.25 mg/kg). The ED50, ED75 and ED95 of mivacurium in each group were estimated from linear regression plots of log dose versus probit of maximum percentage depression of twitch height. The ED50, ED75 and ED95 for halothane and isoflurane are 0.040, 0.053 and 0.081 and 0.037, 0.043 and 0.053, respectively. The ED50, ED75, and ED95 for the balanced group are 0.039, 0.050, and 0.073 mg/kg respectively. There was no significant difference between the slopes of the HAL and BAL inhalation anesthetic dose-response curves. The slope of the ISF group was significantly than the slope of the BAL group. Intercepts of the HAL and BAL curves were not different. The isoflurane curve's intercept was significantly less than the other groups' intercepts, lying above the halothane curve, but below the BAL curve. For the 0.05 mg/kg dose, maximum block was greater in the ISF group (89.1 +/- 2.7%, n = 9) than in the HAL (70.3 +/- 7.6%, n = 9) or BAL (67.7 +/- 6.4%, n = 9) groups. At higher doses of mivacurium, isoflurane produces a greater potentiation of neuromuscular block than halothane or balanced anesthesia. There were no significant cardiovascular changes seen in any group following mivacurium doses up to 0.15 mg/kg (approximately 2xED95).     

The effect of halothane on mivacurium infusion requirements in adult surgical patients

Background: The extent of interaction between volatile anaesthetics and neuromuscular blocking agents depends both on the inhalational anaesthetic and the muscle relaxant. Halothane has the weakest potentiating effect on neuromuscular blocking drugs and previous studies of the interaction between halothane and mivacurium have been contradictory. We were interested in determining the effect of different levels of halothane-nitrous oxide anaesthesia on infusion requirements of mivacurium. Methods: Sixty adult surgical patients were studied. Anaesthesia was induced with thiopentone and fentanyl and intubation facilitated with mivacurium 0.15 mg kg^-1. The patients were randomly assigned to one of four study groups. The control group received nitrous oxide in oxygen (2: 1) supplemented with fentanyl, while in the other groups halothane was administered at different end-tidal concentrations: 0.19% (Group 2), 0.37% (Group 3), 0.74% (Group 4), corresponding to 0.25, 0.5 and 1.0 MAC of halothane. Neuromuscular block was kept at 95% with a closed-loop feedback infusion of mivacurium and monitored with electromyography. Plasma cholinesterase concentrations and dibucaine numbers were determined. Results: Mivacurium infusion requirements (mean±SD) were 7.5±3.1 μg kg^-1 min^-1 with nitrous oxide-fentanyl anaesthesia. In the groups receiving 0.25, 0.5 or 1.0 MAC of halothane the steady-state infusion rates of mivacurium were reduced to 6.3±2.8, 5.6±1.4 and 5.7±2.5 μg-kg^-1min^-1 (P < 0.05), respectively. There was a linear relationship between mivacurium infusion requirements and plasma cholinesterase activity. Conclusion: Halothane anaesthesia reduces mivacurium infusion requirements by 15–25% compared to nitrous oxide-fentanyl anaesthesia. Interindividual differences in the extent of this interaction are great.     

Neuromuscular block and relative concentrations of mivacurium isomers under isoflurane versus propofol anaesthesia

BACKGROUND AND OBJECTIVE: The augmentation of the effect of neuromuscular blocking drugs with volatile anaesthetics is well documented, but the mechanism remains unclear. The pharmacological interaction and relative plasma concentrations of mivacurium isomers were investigated during either propofol- or isoflurane-maintained anaesthesia. METHODS: Forty-four patients were randomly assigned to one of two groups: isoflurane or propofol. All patients received an initial dose of mivacurium 0.1 mg kg(-1). After recovery of the first twitch (T1) response measured by acceleromyography to 5%, a T1 depression of 90-99% was maintained by infusion. After a steady state was reached, blood samples were taken after 10 and 30 min for analysis of mivacurium isomers. Recovery times for T1 to 251/50/75/90% (TW25-90), train-of-four ratio 25/70% and recovery index (time TW25-75) were recorded after stop of infusion. RESULTS: In the isoflurane group, lower infusion rates were needed (3.0 +/- 1.6 versus 3.6 +/- 1.6 microg kg(-1) min(-1)) and there was a slower recovery (significant for train-of-four ratio 70%: 21.9 versus 17.9 min). The plasma concentrations of mivacurium and its trans-trans isomer (in percentage of the total) were significantly higher in the isoflurane group (10 min: 52.6 versus 25.8%; 30 min: 49.6 versus 23.2%). CONCLUSIONS: For mivacurium, the phenomenon of 'potentiation' of the effect of muscle relaxants by volatile anaesthetics could be due to an increase in the plasma concentration of the potent trans-trans isomer.     

Potency and time course of mivacurium block during sevoflurane, isoflurane and intravenous anesthesia

PURPOSE: To determine the potency and time course of action of mivacurium neuromuscular block under routine clinical conditions during sevoflurane, isoflurane and intravenous anesthesia. METHOD: Patients were anesthetized with nitrous oxide 66% in oxygen and 1.5 MAC sevoflurane or isoflurane or a propofol infusion, neuromuscular block being monitored using mechanomyography. Potency was determined using administration of single doses of mivacurium of 40-100 micrograms.kg-1 and construction of dose-response curves (n = 72). The onset and duration of action were determined following a bolus dose of 0.2 mg.kg-1 of mivacurium (n = 30). RESULTS: The ED50 and ED95 (with 95% confidence limits) were estimated to be 42 (35-51) and 86 (74-98) micrograms.kg-1, 52 (45-60) and 89 (72-110) micrograms.kg-1, and 53 (45-62) and 95 (81-112) micrograms.kg-1 during sevoflurane, isoflurane and propofol anesthesia respectively (P < 0.05 between sevoflurane and propofol). Following administration of the 0.2 mg.kg-1 dose, neither the times (mean +/- SD) to maximum block (1.6 +/- 0.31, 1.7 +/- 0.21 and 1.6 +/- 0.45 min, respectively) nor the times to 25 and 90% recovery of T1 (20 +/- 4.5 and 33 +/- 8.8 min, 21 +/- 3.8 and 33 +/- 6.5 min, and 18 +/- 4.1 and 28 +/- 5.8 min respectively) were different among groups. The times to recovery of TOF ratio to 0.8 were 40 +/- 10.0, 36 +/- 8.5 and 29 +/- 5.5 min in the sevoflurane, isoflurane and propofol groups respectively (P = 0.017 between the sevoflurane and propofol groups). CONCLUSIONS: Under usual conditions of clinical anesthesia the potency of mivacurium was slightly enhanced during sevoflurane compared with intravenous anesthesia but the duration of action was only minimally prolonged during sevoflurane and isoflurane anesthesia.     

The influence of halothane, isoflurane and sevoflurane on rocuronium infusion in children

BACKGROUND: Rocuronium is a non-depolarizing neuromuscular blocking agent with intermediate duration of action and without significant cumulative properties, suitable for continuous infusion. This study was designed to determine the infusion requirements in children under nitrous oxide and fentanyl, halothane, isoflurane or sevoflurane anaesthesia. METHODS: Forty children, 3-11 years old, ASA physical status group I or II were studied. They were randomly allocated to receive fentanyl-nitrous oxide, 1 MAC halothane-nitrous oxide, 1 MAC isoflurane-nitrous oxide or 1 MAC sevoflurane-nitrous oxide anaesthesia. Rocuronium, 0.6 mg(-1) was used to facilitate endotracheal intubation. Electromyographic response of adductor pollicis to train-of-four (TOF) stimulation, 2 Hz for 2 s, applied to the ulnar nerve at 10-s intervals was recorded using Relaxograph (Datex, Helsinki, Finland). Once the first twitch response (T1) returned to 5%, muscle relaxation was maintained by continuous infusion of rocuronium, adjusted automatically in a closed-loop system to maintain a stable 90-99% T1 depression. The block was considered stable if it changed by no more than 2% over a 10-min observation period. RESULTS: Halothane, isoflurane and sevoflurane groups had ower infusion requirements than the fentanyl-nitrous oxide group (P<0.00075). Rocuronium requirement (mean +/- SD) at one hour from the commencement of anaesthesia was 16.7+/-2.3, 13.6+/-3.7, 13.1+/-5.1 and 8.4+/-1.6 microg x kg(-1) x min(-1) for children receiving fentanyl-nitrous oxide, halothane, isoflurane and sevoflurane anaesthesia, respectively. CONCLUSIONS: The rocuronium infusion rate required to maintain stable 90-99% T1 depression was reduced by approximately 20% with halothane and isoflurane anaesthesia, and by 50% with evoflurane anaesthesia when compared to fentanyl-nitrous oxide anaesthesia. Significant patient-to-patient variability of infusion rate makes monitoring of neuromuscular transmission necessary.     

Comparison of the neuromuscular effects of mivacurium and suxamethonium in infants and children

We compared both the time course of neuromuscular blockade and the cardiovascular side-effects of suxamethonium and mivacurium during halothane and nitrous oxide anaesthesia in infants 2–12 months and children 1–12 years of age. Equipotent doses of mivacurium and suxamethonium were studied; 2.2×ED₉₅ was used in four groups of infants and children, while 3.4×ED₉₅ was used in two groups of children. Onset of neuromuscular block in infants was not significantly faster with suxamethonium than with mivacurium ( P =0.2). In all infants given suxamethonium, intubating conditions were excellent, while, in 6/10 infants given mivacurium, intubating conditions were excellent. Onset of complete neuromuscular block in children was significantly faster with suxamethonium, 0.9 min compared with mivacurium, 1.4 min ( P ×0.05). Increasing the dose of suxamethonium or mivacurium in children to 3.4×ED₉₅ did not change the onset of neuromuscular block. Recovery of neuromuscular transmission to 25% of initial twitch height (T₂₅) in infants and children was significantly faster after suxamethonium than after mivacurium, at 2.5 and 6 min, respectively ( P ×0.05). In children given 3.4×ED₉₅ of suxamethonium or mivacurium, recovery from neuromuscular block was almost identical with the dose of 2.2×ED₉₅, with spontaneous recovery to T₂₅ prolonged by only 0.5 min. No infant or child had hypotension after the mivacurium bolus dose.     

Mivacurium infusion during nitrous oxide-isoflurane anesthesia: a comparison with nitrous oxide-opioid anesthesia.

STUDY OBJECTIVE: To determine the potentiation of the neuromuscular blockade induced by a titrated infusion of mivacurium in the presence of isoflurane versus a nitrous oxide (N2O)-opioid anesthesia. DESIGN: An open-label, controlled study. SETTING: The inpatient anesthesia service of two university medical centers. PATIENTS: Thirty adults divided into two groups. INTERVENTION: An intravenous infusion of mivacurium during anesthesia with N2O-opioid or N2O-isoflurane. MEASUREMENTS AND MAIN RESULTS: A neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. The mivacurium infusion rate was significantly less in the presence of isoflurane [4.0 +/- 0.8 micrograms/kg/min (mean +/- SEM)] than during N2O-opioid anesthesia (6.4 +/- 0.6 micrograms/kg/min). The recovery rates did not differ between anesthetic groups. After the termination of the infusion, spontaneous recovery to T4/T1 of at least 0.75 occurred in an average of 17.9 +/- 1.5 minutes, with a mean recovery index (T25-75) of 6.0 +/- 0.7 minutes. CONCLUSION: Isoflurane anesthesia reduces the infusion rate of mivacurium required to produce about 95% depression of neuromuscular function.     

Neuromuscular and cardiovascular effects of mivacurium chloride in surgical patients receiving nitrous oxide-narcotic or nitrous oxide-isoflurane anaesthesia

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.     

The influence of isoflurane on a continuous infusion of mivacurium

Sixty surgical patients were studied to evaluate the neuromuscular effects of mivacurium 0.l5 mg.kg^-1 (2 × ED₉₅)for tracheal intubation. After intubation the patients were randomly allocated to receive alfentanil with either propofol (starting with 9mg.kg^-1 h^-1, reducing to 6mg.kg^-1 h^-1 after 20min) or isoflurane (0.5% end-tidal). In addition, all the patients were given a continuous infusion of mivacurium 10 μg.kg^-1 min^-1 after tracheal intubation which was adjusted to maintain 90% depression of T₁. Following mivacurium 0.15 mg.kg^-1 T₁ decreased below 25% in all but four patients. Mean (SD) percentage maximum block attainedwas 92.9% (12.5) after 309 (89)s. Tracheal intubation was completed 232 (155) s after administration of the relaxant and intubating conditions were graded as‘excellent’ or‘good’ in 56 patients. Although the mean (SD) mivacurium infusion rate for maintaining T₁ at 10% was higher in the propofol group, 4.8 (2.1) compared with 4.4 (2.0) μg.kg^-1 min^-1 in the isoflurane group, this was not significantly different (p > 0.05). The mean (SD) recovery index was prolonged in the isoflurane patients, 757 (508)s, compared to those receiving propofol, 466 (219)s (p < 0.05).     

Atracurium infusion requirements in children during halothane, isoflurane, and narcotic anesthesia

We were interested in determining the dose-response relationship of atracurium in children (2-10 yr) during nitrous oxide-isoflurane anesthesia (1%) and the atracurium infusion rate required to maintain about 95% neuromuscular blockade during nitrous oxide-halothane (0.8%), nitrous oxide-isoflurane (1%), or nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 sec at 10-sec intervals. To estimate dose-response relationships, three groups of five children received 80, 100, 150 micrograms/kg atracurium, respectively. During isoflurane anesthesia, the neuromuscular block produced by 80 micrograms/kg was 23.6% +/- 6.5 (mean +/- SEM), by 100 micrograms/kg was 45% +/- 7.2, and by 150 micrograms/kg was 64% +/- 8.7. The ED50 and ED95 (estimated from linear regression plots of log dose vs probit of effect) were 120 micrograms/kg and 280 micrograms/kg, respectively. At equipotent concentrations, halothane and isoflurane augment atracurium neuromuscular block to the same extent, compared to narcotic anesthesia. Atracurium steady-state infusion requirements averaged 6.3 +/- 0.6 micrograms . kg-1 . min-1 during halothane or isoflurane anesthesia; the requirements during balanced anesthesia were 9.3 +/- 0.8 micrograms . kg-1 . min-1 (P less than 0.05). There was no evidence of cumulation during prolonged atracurium infusion.     

Long-term succinylcholine infusion during isoflurane anesthesia

The characteristics of the neuromuscular blockade produced by prolonged succinylcholine infusion were compared in 40 patients anesthetized with either nitrous-oxide-isoflurane (0.75-1.50% inspired) or nitrous-oxide-fentanyl. Neuromuscular transmission was monitored using train-of-four stimulation and the infusion rate was adjusted to keep the first twitch at 10-15% of its control value. Initially, all patients exhibited a depolarizing-type block, and the infusion rates were similar in the isoflurane (61 micrograms . kg-1 . min-1) and fentanyl (57 micrograms . kg-1 . min-1) groups. Tachyphylaxis developed in both groups and correlated well with the onset of non-depolarizing (phase II) block. Both occurred sooner and at a lower cumulative dose in the isoflurane groups. After 90 min, infusion rates were similar in both groups (isoflurane: 107 micrograms . kg-1 . min-1, fentanyl;: 93 micrograms. kg-1 . min-1). After the infusion was stopped, the recovery of the train-of-four ratio was inversely related to the dose and duration of exposure to succinylcholine, and was slower with nitrous-oxide-isoflurane anesthesia. After 10 min of recovery, patients receiving isoflurane exhibited train-of-four ratios of 0.5 or less after 8.5 mg/kg succinylcholine and 103 min. Corresponding figures for fentanyl patients were 13 mg/kg and 171 min. The block in all 13 patients (eight with isoflurane, five with fentanyl) who did not recover spontaneously was antagonized successfully with atropine and neostigmine. It was concluded that with succinylcholine infusion of 90 min or less, isoflurane accelerates the onset of tachyphylaxis and phase II neuromuscular block without affecting succinylcholine requirements. These results, with isoflurane, were similar to those reported previously with enflurane or halothane.     

Vecuronium-induced neuromuscular blockade during enflurane, isoflurane, and halothane anesthesia in humans

To determine the effect of the commonly used volatile anesthetics on a vecuronium-induced neuromuscular blockade, the authors studied 54 patients anesthetized with 1.2 MAC or 2.2 MAC enflurane, isoflurane, or halothane (MAC value includes contribution from 60% nitrous oxide). During 1.2 MAC enflurane, isoflurane, and halothane, the ED50S (the doses depressing twitch tension 50%) for vecuronium were 12.8, 14.7, and 16.9 micrograms/kg, respectively. During 2.2 MAC enflurane, isoflurane, and halothane, the ED50S for vecuronium were 6.3, 9.8, and 13.8 micrograms/kg, respectively (P less than 0.05). Time from injection to peak effect was the same for each anesthetic group (6.5 +/- 0.5 min, mean +/- SD), except for the group given 2.2 MAC enflurane (9.7 +/- 0.6 min) (P less than 0.05). The duration of a 50% block from injection to 90% recovery was the same for each group (mean 20 +/- 4 min), except for the group given 2.2 MAC enflurane (46.5 min) (P less than 0.05). The authors conclude that enflurane is the most potent volatile anesthetic, followed by isoflurane and then halothane, in augmenting a vecuronium-induced neuromuscular blockade. Increasing the concentration of volatile anesthetic has less effect on a neuromuscular blockade produced by vecuronium than on one produced by other nondepolarizing relaxants (e.g., pancuronium and d-tubucurarine).     

The influence of the duration of isoflurane anaesthesia on neuromuscular effects of mivacurium

Background: The pharmacodynamic profile of muscle relax-ants is usually changed by volatile anaesthetics. These changes seem to be time-dependent, even though few data are available to substantiate this.
Methods: We studied neuromuscular effects of a single dose of mivacurium (0.2 mg·kg^-1) during short and intermediate duration of isoflurane anaesthesia. Forty-five children 1–10 years of age were randomized to receive 1.5% end-tidal concentration of isoflurane in N₂O/O₂ for 10 or 30 min (groups Iso-10 and Iso-30, respectively) or to receive nitrous oxide in oxygen for 10 min (Group N₂O) before 0.2 mg · kg^-1 of mivacurium was given. Neuromuscular response was recorded by adductor pollicis electromyogram.
Results: The onset time of mivacurium was shorter in Group Iso-30, 1.7 (1.0–2.3) min than in Group Iso-10, 2.3 (1.7-3.3) rnin or Group N₂O, 2.3 (1.7-3.3) min (median with 10–90% percen-tiles) ( P <0.05). In Group Iso-30 the recovery time of the first EMG response was significantly longer than in groups Iso-10 and N₂O ( P <0.0001). Groups Iso-10 and N₂O did not differ from each other.
Conclusions: Our results indicate that the duration of a constant concentration of isoflurane anaesthesia influences significantly the pharmacodynamics of mivacurium. The duration of a volatile anaesthesia is critical when potentiation of NMB is evaluated or compared in neuromuscular studies.     

Decreased mivacurium infusion rate and delayed neuromuscular recovery after metoclopramide: a randomized double blind placebo-controlled study

BACKGROUND AND OBJECTIVE: Metoclopramide is an antiemetic drug which inhibits plasma cholinesterase activity. We have compared the mivacurium infusion requirements and neuromuscular recovery after administration of metoclopramide to a group of adults compared to a control group. METHODS: Forty-five patients were randomized into three groups. Two groups received either 10 or 20 mg of intravenous (i.v.) metoclopramide and the third group received i.v. saline. Metoclopramide and saline were given 5 min before i.v. induction of anaesthesia. Plasma cholinesterase activity was measured before induction and 30 min after metoclopramide or saline injection. Neuromuscular block was monitored by accelerography using single and train-of-four (TOF) stimulation. The mivacurium intubation dose was followed by an infusion titrated every 5 min to maintain 95% block until the end of surgery when the infusion was stopped. Recovery from mivacurium was then monitored until complete. RESULTS: Mivacurium infusion rates were significantly lower in the metoclopramide groups. After 45 min of infusion, the infusion rates were 1.82 +/- 0.8 and 2.1 +/- 1 microg kg(-1) min(-1) in the 20 and 10 mg metoclopramide groups, respectively, and 6.8 +/- 2.7 in the saline group. Time to recovery of TOF to greater than 90% was significantly prolonged in both metoclopramide groups compared to the saline group: 33.2 +/- 7.2 and 29.5 +/- 10.3 min in the metoclopramide 20 and 10 mg groups, respectively, compared to 22 +/- 3.9 in the saline group (P < 0.001 for the 20 mg group compared to control). CONCLUSION: Metoclopramide enhances the effect of a mivacurium infusion.     

Protective effects of volatile agents against acetylcholine-induced bronchoconstriction in isolated perfused rat lungs

BACKGROUND: Bronchoactive properties of volatile agents against lung constriction are well established. The purpose of this study was to investigate the ability of halothane (Hal), isoflurane (Iso), sevoflurane (Sev) and desflurane (Des) to alter the lung mechanics in the absence of an airway tone and during acetylcholine (Ach)-induced bronchoconstriction. METHODS: Low-frequency pulmonary impedance data (ZL) were collected from isolated, normo-perfused rat lungs under baseline conditions and following the injection of Ach (0.1 mg/kg) into the pulmonary artery. Measurements were performed without the administration of any anaesthetic agent in the first phase of the experiments and during inhalation without any volatile agent (control group, n = 6) or during inhalation of Hal (n = 6), Iso (n = 9), Sev (n = 6) or Des (n = 8) at 1 minimum alveolar concentration (MAC). The airway resistance (Raw) and parenchymal damping and elastance were estimated from the Z(L) data by model fitting. RESULTS: Under baseline conditions, the basic value of Raw was significantly decreased by Des (- 31.2 +/- 3.8%) and Sev (- 18.0 +/- 4.5%) administration, whereas Hal and Iso did not have a statistically significant effect on Raw (- 3.3 +/- 5.1% and - 8.6 +/- 2.4%, respectively). Moreover, all four inhalation anaesthetics prevented the increase in Raw following Ach administration, the findings ranging between - 14.3 +/- 11.4% for Hal and - 37.5 +/- 10.9% for Sev. CONCLUSIONS: Our results on a denervated isolated perfused lung model demonstrate the potential of Des and Sev to decrease the basal airway tone, whereas Iso and Hal are ineffective in this regard. All of these volatile agents markedly protect against Ach-induced bronchoconstriction.     

Clinical pharmacology of mivacurium chloride (BW B1090U) in children during nitrous oxide-halothane and nitrous oxide-narcotic anesthesia

We determined the dose-response relationships of mivacurium (BW B1090U) in children (2-10 years) during nitrous oxide-halothane anesthesia (0.8% end-tidal) and during nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic 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, for each anesthetic background four subgroups of nine patients received single bolus doses of 20-120 micrograms/kg mivacurium. The ED50 and ED95 (estimated from linear regression plots of log-dose vs. probit of effect) were 52 micrograms/kg and 89 micrograms/kg during halothane anesthesia and 62 micrograms/kg and 103 micrograms/kg during narcotic anesthesia. Nine additional patients in each anesthetic group received 250 micrograms/kg mivacurium. Three of the 18 patients given 250 micrograms/kg mivacurium developed cutaneous flushing; in one of these mean arterial pressure decreased 32% for less than 1 minute; no significant changes in heart rate occurred. With the increase in mivacurium dose from 120 micrograms/kg to 250 micrograms/kg the times to onset of 90% and maximum neuromuscular block decreased by 0.5 to 1 minute, and the times to recovery of neuromuscular transmission to 5% (T5) or 25% (T25) increased by 2-4 minutes. The recovery index (T25-75) in patients anesthetized with halothane was 4.3 +/- 1.5 minute (mean +/- SD); the time to complete recovery (T4:1 greater than or equal to 0.75) was 19.8 +/- 7.4 minutes.     

Neuromuscular and haemodynamic effects of mivacurium in elderly and young adult patients

We have studied the neuromuscular effects of mivacurium andchanges in heart rate and arterial pressure in 40 elderly (aged70 yr) and 20 young adult (aged 18–40yr) patients anaesthetizedwith thiopentone, fentanyl, nitrous oxide in oxygen and halothane.Neuromuscular block was monitored by train-of-four (TOF) stimulationof the ulnar nerve and recording of the force of contractionof the adductor pollicis muscle using a force displacement transducerand a neuromuscular function analyser (Myograph 2000, BiometerLtd). Twenty elderly and 10 young adults received single closesof mivacurium 0.15 mg kg^–1 and spontaneous recovery wasrecorded. The other 20 elderly and 10 adults received the samedose but an infusion was started at T1 (first response in TOF)of 10% and the block maintained at this level. Haemodynamiceffects were studied after administration of mivacurium over15 or 5 s in elderly (n=10 each) and over 5 s in adult (n=10)patients. Onset of maximum block occurred at a mean time of122 (sd 32) and 125 (49) s in elderly and young adults, respectively.Recovery of T1 to 25% occurred in 22.0 (5.7) and 17.2 (4.4)min, and T1 to 90% in 32.8 (6.9) and 24.4 (5.8) min in elderlyand adult subjects, respectively. Recovery of the TOF ratioto 0.7 occurred in 32.8 (7.1) and 26.0 (15.0) min in the elderlyand young subjects, respectively (all P<0.05 between youngand elderly). Mean mivacurium requirements by continuous infusionfor maintenance of 90% block were 3.67 and 5.50 ng kg^–1min^–1 in elderly and the young adults, respectively (P< 0.05). In the elderly, neuromuscular effects were prolongedby approximately 30% and infusion requirements reduced by 38%.Residual neuromuscular block was antagonized easily with edrophoniumor neostigmine. Except for small changes in systolic arterialpressure, mivacurium exhibited good haemodynamic stability inboth groups. Cutaneous flushing was observed in six elderly(1 5%) and six young adults (30%).