Propofol potentiates the neuromuscular blocking effects of vecuronium in man

The possible interaction between vecuronium and propofol has been investigated in 40 healthy (ASA I-II) patients. They were randomly allocated to two groups according to the method of anesthesia; continuous propofol infusion group (propofol) and droperidol and fentanyl group (control). The electromyographic response of abductor digiti minimi was monitored at 20-s interval after train-of-four stimulations of the ulnar nerve. The ED50 and ED95 (dose required to produce a 50% and 95% depression of twitch tension, respectively,) of vecuronium in the propofol group (n = 20) were 29.4 +/- 0.5 and 56.6 +/- 2.1 micrograms.kg-1 (mean +/- SEM), and in the control group (n = 20), 36.7 +/- 1.8 and 73.6 +/- 5.2 micrograms.kg-1, respectively. Under propofol anesthesia, the cumulative dose-response curves of vecuronium were shifted to the left when compared with control ED50 and the slope showed that propofol had potentiated the action of vecuronium.     

Atracurium and vecuronium: repeated bolus injection versus infusion.

The purpose of this study was to compare the characteristics of recovery from neuromuscular blockade after either atracurium or vecuronium given by intravenous infusion or by repeated injection. Four groups of 10 patients each were studied during nitrous oxide narcotic anesthesia. An initial intravenous dose of 2 x ED95 of either muscle relaxant was followed by an intravenous infusion started at 5% recovery of control twitch tension and adjusted for 95% block or by repeated injection of 0.6 x ED95 administered whenever twitch tension had returned to 25% of control. There were no significant differences between the maintenance doses required based on method of administration: atracurium repeated injection, 1.6 +/- 0.3 x ED95 h-1; atracurium infusion, 1.7 +/- 0.3 x ED95 h-1; vecuronium repeated injection, 1.8 +/- 0.5 x ED95 h-1; and vecuronium infusion, 1.6 +/- 0.4 x ED95 h-1. Nevertheless, differences of up to 20 min were noted in the recovery indices in the following order: atracurium repeated injection = atracurium infusion less than vecuronium repeated injection less than vecuronium infusion. A single dose of neostigmine (7 micrograms/kg) significantly reduced the recovery indices, thereby eliminating their differences.     

Mivacurium: dose-response relationship and administration by repeated injection or infusion.

The dose-response relationship and neuromuscular blockade after infusion or repeated injection of mivacurium were studied in 65 patients in nitrous oxide-narcotic anesthesia. The ED95 (twitch tension) was determined in 45 patients by intravenous injection of a single bolus of 30, 39, 47, 54, or 60 micrograms/kg (9 patients per dose). Another 20 patients received an initial bolus of 2 x ED95 followed either by an infusion started at 5% twitch recovery (i.e., 95% depression) and adjusted to sustain 95% twitch depression (n = 10) or by repeated injection of 0.6 x ED95 whenever twitch tension had recovered to 25% of control (n = 10). Five patients in each of these two groups received 7 micrograms/kg of neostigmine at 25% twitch recovery, and the others recovered twitch tension spontaneously. The mean ED95 was 73 micrograms/kg. A 2 x ED95 bolus was followed by complete twitch depression within 2.2 +/- 0.7 min. The mean infusion rate resulted in 6 +/- 2 micrograms.kg-1.min-1. The ensuing recovery index was 6 +/- 3 min. A 6 +/- 2 min recovery index was found after up to 10 repeat injections given every 9 +/- 3 min. There was no significant effect of neostigmine in both groups. In conclusion, the recovery indices after the infusion or repeat injection of near-equal doses of mivacurium were identical.     

Effect of volatile anesthetics on vecuronium-induced neuromuscular blockade in children

We studied 60 children undergoing elective surgery to evaluate the effect of interactions between vecuronium and isoflurane or halothane on the potency and duration of neuromuscular blockade, as measured by electromyography. Vecuronium was first administered by a logarithm-based cumulative method (14, 22, 35, 56, 89 micrograms/kg) in 10 children anesthetized with thiopental (5 mg/kg), alfentanil (15 micrograms/kg first dose, then 10 micrograms/kg), and N2O/O2 (60:40) until a 95% +/- 2% twitch depression (ED95) was obtained. Thirty children given the same balanced anesthesia were then randomly assigned to three groups (n = 10 in each) to receive a single ED20 (21 micrograms/kg), ED50 (33 micrograms/kg), or ED80 (47 micrograms/kg) intravenous bolus of vecuronium calculated from the mean regression line of twitch responses of the first 10 children. In the second part of the study, 20 children were anesthetized with isoflurane (1.2%) or halothane (0.7%) and compared with the previous 10 children anesthetized with alfentanil-N2O. Potency of vecuronium determined by single-bolus or logarithm-based cumulative techniques was not significantly different. Isoflurane and halothane significantly decreased ED50 (22.3 +/- 1.6 and 25.4 +/- 1.4 micrograms/kg, respectively; mean +/- SE) and ED95 (41.5 +/- 3.3 and 46.7 +/- 3.2 micrograms/kg, respectively) compared with alfentanil-N2O (ED50: 32.8 +/- 0.8 micrograms/kg, ED95: 70.5 +/- 2.6 micrograms/kg). Recovery rate from vecuronium-induced neuromuscular blockade was significantly longer with isoflurane than with alfentanil-N2O or halothane. We conclude that in children single-bolus and logarithm-based cumulative techniques give similar potency estimates for vecuronium. Isoflurane and halothane increase by similar amounts the neuromuscular potency of vecuronium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical pharmacology of doxacurium chloride. A new long-acting nondepolarizing muscle relaxant

Doxacurium chloride (BW A938U) is a bis-quaternary benzylisoquinolinium diester nondepolarizing neuromuscular blocking compound that is minimally hydrolyzed by human plasma cholinesterase. The effect of bolus doses of doxacurium ranging from 10 to 80 micrograms/kg were studied in 81 consenting ASA physical status I and II patients anesthetized with nitrous oxide-oxygen-fentanyl-thiopental. The neuromuscular and cardiovascular effects of doxacurium were compared with those of eight patients receiving 100 micrograms/kg of pancuronium receiving identical anesthesia. The calculated ED95 for evoked twitch inhibition of the adductor pollicis at 0.15 Hz was 30 micrograms/kg. At 1.3 times the ED95 dose of doxacurium, recovery times to 5% and 25% of control twitch height were 59.2 +/- 4.1 (n = 23 of 26) and 75.7 +/- 5.6 (n = 23 of 26) min respectively. For pancuronium comparable recovery times were 81.7 +/- 10.3 (n = 8 of 8) and 83.0 +/- 8.4 (n = 5 of 8) min. Residual doxacurium blockade was readily antagonized by neostigmine. No dose-related effect on heart rate or mean arterial pressure was seen with doxacurium at doses up to and including 2.7 times the ED95 (80 micrograms/kg). Doxacurium administration did not result in any elevation of plasma histamine at doses up to and including 2.7 times the ED95. In this study doxacurium appears to be a long-acting nondepolarizing relaxant with readily reversible neuromuscular blocking effects and devoid of cardiovascular effects. This profile offers clinical advantages over current long-acting agents and further clinical trials seem appropriate.     

Recovery from vecuronium neuromuscular blockade following neostigmine administration in infants, children, and adults during halothane anesthesia

To determine whether neostigmine had different effects in pediatric patients during vecuronium neuromuscular blockade, the rate of recovery following neostigmine administration was compared in infants (n = 8), children (n = 10), and adults (n = 10) during nitrous oxide-halothane anesthesia. After induction of anesthesia, patients received 100 micrograms/kg of vecuronium. The EMG response of the adductor pollicis was monitored after train-of-four (TOF) stimulation of the ulnar nerve every 20 s. When the first twitch of TOF spontaneously recovered to 10% of control value, neostigmine was injected (40 micrograms/kg in adults, 30 micrograms/kg in infants and children). During the first few minutes following neostigmine administration, no differences were observed between the three groups. After the 8 min, recovery was more rapid in children than in infants and adults up to and including the 15th min. Ten minutes after neostigmine administration, the first twitch (mean +/- SD) reached 97 +/- 3%, 99 +/- 2%, and 97 +/- 5% of control value in infants, children, and adults, respectively; TOF ratio was greater in children (0.96 +/- 0.03) than in either adults (0.82 +/- 0.17) or in infants (0.83 +/- 0.14) (P less than 0.05). During the first minutes after neostigmine administration, the lack of difference in TOF recovery in the three groups suggests that neostigmine is the main factor of recovery. In contrast, the more complete recovery after the eighth minute in children could be due to the faster rate of spontaneous recovery from vecuronium induced neuromuscular blockade in children.     

Vecuronium infusion dose requirements during fentanyl and halothane anesthesia in humans

Steady-state infusion rate requirements of vecuronium were determined in 29 patients during either halothane-nitrous oxide or fentanyl-nitrous oxide anesthesia at different levels of neuromuscular block. During N2O-halothane anesthesia (end-tidal concentration, 0.5%), the infusion rate necessary for a steady-state (defined as unchanging twitch height and infusion rate for at least 20 min) 50% depression of twitch force was 28.8 +/- 5.4 (mean +/- SD) (n = 8) and 47.6 +/- 9.7 micrograms . kg-1 . hr-1 (n = 6) at 90% reduction of twitch force. During N2O-fentanyl anesthesia, the steady-state infusion rate required for 50 and 90% decrease of twitch force was 56.3 +/- 20.0 (n = 9) and 74.8 +/- 16.0 micrograms . kg-1 . hr-1 (n = 6), respectively. The variances of vecuronium steady-state infusion dose requirements were smaller in the halothane groups than in the fentanyl anesthesia groups. The steady-state vecuronium infusion dose requirements during fentanyl anesthesia were greater than the mean infusion dose requirements during halothane anesthesia at equivalent levels of twitch depression.     

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 dose-response relationship and time course of the neuromuscular blockade by alcuronium

Although alcuronium has been in clinical use for almost 40 years, there is still considerable controversy in the literature regarding its neuromuscular blocking potency, the time course of the drug action and the side effects. The aim of this study was to investigate the dose-response relationship of alcuronium and to compare the time course of its neuromuscular effects with vecuronium following intubation doses of both compounds. METHODS. The study was carried out in two parts. In the first part 60 patients and in the second part 30 consenting ASA class I or II patients 20-60 years of age were included. The patients were undergoing elective gynecological or intra-abdominal operations. In the first part the patients received six different doses of alcuronium (60, 90, 120, 150, 180 or 210 micrograms/kg) in order to establish its dose-response relationship. Each dose was administered to ten patients. In the second part patients received either 300 micrograms/kg alcuronium (n = 15) or 100 micrograms/kg vecuronium (n = 15), and the time course of these two compounds (onset time, duration 25%, duration 75% and the recovery index) were compared. To test the reversibility, ten patients in each group received 30 micrograms/kg neostigmine at 25% recovery of T1. The neuromuscular effects of alcuronium and vecuronium were quantitated by EMG using the DATEX relaxograph. RESULTS. The log-logit analysis of the dose response data revealed an ED50 of 111 micrograms/kg and an ED95 of 250 micrograms/kg, which is in reasonable agreement with the measured effects following 120 micrograms/kg and 210 micrograms/kg alcuronium, resulting in 52 +/- 21% and 96 +/- 4% T1 depression, respectively. The onset time, duration 25%, duration 75% and spontaneous recovery index following 300 micrograms/kg alcuronium (5.0 +/- 3.4 min, 62 +/- 25 min, 119 +/- 38 min and 58 +/- 34 min) appeared to be significantly longer (P less than 0.05) than those observed after 100 micrograms/kg vecuronium (3.2 +/- 1.2 min, 33 +/- 7 min, 49 +/- 9 min and 18 +/- 7 min), respectively. The most striking finding of this study is the enormous individual variations observed in both neuromuscular potency and the time course of action of alcuronium. Following 150 micrograms/kg (routinely employed in daily clinical practice), the magnitude of T1 depression ranged between 19% and 100%. The same vast individual variations were observed in the time course of action following 300 micrograms/kg of alcuronium. The onset time, duration 25%, duration 75% and spontaneous recovery index ranged between 1.3 and 14 min, 22 and 110 min, 93 and 186 min and 32 and 116 min, respectively. CONCLUSIONS. The ED50 and ED95 values for alcuronium found in this study are in the same order of magnitude as 106.8 micrograms/kg and 135 micrograms/kg for ED50 and with 280 micrograms/kg for ED95, respectively, as reported by others. The long duration with slow recovery and the wide individual variation in the neuromuscular effects observed in our study have been reported earlier. Based on the above observations and because of the availability of better alternatives with fewer side effects, we conclude that alcuronium should be added to the list of obsolete neuromuscular blocking agents, together with gallamine and d-tubocurarine.     

Vecuronium dose-response and maintenance requirements in patients with myasthenia gravis

Eleven myasthenia gravis and seven control patients were studied during N2O/O2-fentanyl anesthesia to determine the ED50, ED95, and maintenance requirement of vecuronium using both mechanomyography and electromyography. The ED95 of vecuronium was 17 (range 8-34) micrograms/kg in patients with myasthenia gravis, and this was significantly related to patient's acetylcholine receptor antibody titer (r = -0.75, P less than 0.01). The average ED95 value was 250% greater in control than in myasthenic patients (P less than 0.01). The hourly requirement of vecuronium to maintain an 80-90% neuromuscular blockade was 38 +/- 10 micrograms/kg in myasthenic and 120 +/- 27 micrograms/kg in control patients (P less than 0.001). When these requirements were related to individual ED95 doses, they were comparable indicating similar time durations of effect of vecuronium following an equipotent dose in myasthenic and in control patients.     

The neuromuscular blocking and cardiovascular effects of doxacurium chloride in patients receiving nitrous oxide narcotic anesthesia

The purpose of this study was to evaluate neuromuscular and cardiovascular effects of doxacurium chloride, a new long-acting neuromuscular blocking agent, during a stable state of nitrous oxide and narcotic anesthesia. Ninety-three ASA physical status I or II patients were studied after informed written consent had been obtained. Eighty-one patients (group A) received doxacurium. The 81 patients were divided into nine subgroups according to the dose of doxacurium administered (0.01-0.06 mg.kg-1). Patients in a control group (group B) (n = 12) received pancuronium. To assess neuromuscular responses, a force displacement transducer recorded the twitch response of the adductor pollicis muscle following ulnar nerve stimulation. The ED50 and ED95 for doxacurium were estimated to be 0.013 mg.kg-1 and 0.023 mg.kg-1, respectively. The time to maximum twitch suppression following a dose of 1.0 (ED95) and 1.7 (ED95) was 10.3 +/- 1.3 min and 7.6 +/- 0.8 min, respectively. After an ED95 dose of doxacurium the time to spontaneous recovery to 95% of control twitch height was 73.7 +/- 8.7 min. With larger doses of doxacurium, 0.04 mg.kg-1 (1.7 X ED95) and 0.05 mg.kg-1 (2.2 X ED95), the time to spontaneous recovery to 95% of control twitch height was 125.8 +/- 24.8 and 204.0 +/- 21.2 minutes, respectively. When 25% twitch height recovery or more was present the reversal of doxacurium induced neuromuscular blockade was prompt.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacodynamics of high-dose vecuronium in children during balanced anesthesia.

To compare the speed of onset, intubating conditions, duration of action, and recovery from neuromuscular blockade with vecuronium to those with succinylcholine, 40 ASA physical status 1 or 2 children (ages 2-9 yr) were studied during N2O-O2-opioid anesthesia. Each child was randomly assigned to receive a bolus dose of one of the following muscle relaxants: succinylcholine 2.0 mg/kg (n = 10), vecuronium 0.1 mg/kg (n = 10), vecuronium 0.2 mg/kg (n = 10), or vecuronium 0.4 mg/kg (n = 10). The evoked electromyogram of the abductor digiti minimi to train-of-four stimulation was monitored. We found that with succinylcholine, the time to 95% twitch depression (speed of onset, mean +/- SD), 24 +/- 7 s, was significantly less than that with each dose of vecuronium: 0.1 mg/kg, 83 +/- 21 s; 0.2 mg/kg, 58 +/- 17 s; and 0.4 mg/kg, 39 +/- 11 s, respectively (P less than 0.05). The time to laryngoscopy and intubation did not differ significantly between succinylcholine (48 +/- 10 s) and vecuronium 0.4 mg/kg (57 +/- 13 s); however, both were significantly less than than with vecuronium 0.1 and 0.2 mg/kg (P less than 0.005). The intubating conditions were excellent in 100% of patients. The duration of action was least with succinylcholine (5.7 +/- 1.5 min) and increased with increasing doses of vecuronium: 0.1 mg/kg, 23.9 +/- 5.1 min; 0.2 mg/kg, 55.2 +/- 11.6 min; and 0.4 mg/kg, 74.6 +/- 9.9 min, respectively (P less than 0.001). The recovery index was most rapid with succinylcholine (1.6 +/- 0.4 min) and was slowest with vecuronium 0.4 mg/kg (22.6 +/- 2.1 min) (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Duration of action of vecuronium after an intubating dose of rapacuronium, vecuronium, or succinylcholine

Rapacuronium (RAP) is a new, rapid-onset, short-duration, nondepolarizing neuromuscular blocker. If RAP is used to facilitate endotracheal intubation, what will the duration of a subsequent maintenance dose of vecuronium (VEC) be? We investigated the duration of action of a maintenance dose of VEC after intubation with RAP, VEC, or succinylcholine (SUC). Adult surgical patients under general anesthesia were randomly allocated to receive a tracheal intubating dose of RAP 1.5 mg/kg, VEC 0.1 mg/kg, or SUC 1 mg/kg. The anesthetic was induced with propofol and maintained with propofol, nitrous oxide, and oxygen. Neuromuscular function was monitored with electromyography. Recovery of the intubating dose of neuromuscular blocker was allowed to occur spontaneously until the first twitch of the train-of-four (T1) reached 50% of baseline, and then VEC 0.025 mg/kg (0.5 x 95% effective dose [ED(95)]) was administered. The onset, duration, and recovery to T1 = 25% and 50% were recorded. The durations of action (recovery of T1 25%) after intubating doses of RAP, VEC, and SUC were 13.7 +/- 5.3, 43.2 +/- 13.2, and 9.2 +/- 3.7 min (mean +/- SD), respectively (P < 0.0001). The times to maximum depression of T1 after a maintenance dose of VEC (0.5 x ED(95)) were 5.4 +/- 2.9, 5.1 +/- 2.5, and 5.3 +/- 2.8 min (mean +/- SD) for the RAP, VEC, and SUC groups, respectively. Recoveries to T1 25% after VEC for the RAP, VEC, and SUC groups were 18.9 +/- 11.5, 21.5 +/- 8.03, and 12.8 +/- 8.4 min, and at T1 50% they were 21.5 +/- 9.1, 30.8 +/- 9.5, and 15.5 +/- 9.7 min (mean +/- SD), respectively (P < 0.001, RAP and VEC versus SUC). The duration of action of a maintenance dose of VEC was similar after an intubating dose of RAP or VEC but was shortened when preceded by an intubating dose of SUC. IMPLICATIONS: The duration of action of a maintenance dose of vecuronium was longer after an endotracheal intubating dose of rapacuronium compared with succinylcholine.     

Dose-response relationships for edrophonium and neostigmine as antagonists of atracurium and vecuronium neuromuscular blockade

To determine the potencies of edrophonium and neostigmine as antagonists of nondepolarizing neuromuscular blockade produced by atracurium and vecuronium, dose-response curves were constructed for both antagonists when given at 10% spontaneous recovery of first twitch height. Ninety ASA physical status 1 and 2 adults were given either 0.4 mg/kg atracurium or 0.08 mg/kg vecuronium during thiopental-nitrous oxide-enflurane anesthesia. Train-of-four stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0.1, 0.2, 0.4, or 1 mg/kg) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg/kg) was administered by random allocation. Neuromuscular function in another ten subjects was allowed to recover spontaneously. Assisted recovery was defined as actual recovery minus mean spontaneous recovery observed in patients who were not given antagonists. First twitch recovery was initially more rapid when vecuronium was antagonized compared with atracurium, but no difference was detected after 10 min. At 10 min the neostigmine ED80 was 0.022 +/- 0.003 (SEM) mg/kg after atracurium and 0.024 +/- 0.003 mg/kg after vecuronium. The edrophonium ED80 was 0.44 +/- 0.11 mg/kg with atracurium and 0.46 +/- 0.12 mg/kg with vecuronium, giving a neostigmine:edrophonium potency ratio of 20. Atracurium train-of-four fade could be antagonized more easily with edrophonium, whereas that of vecuronium was more easily antagonized by neostigmine. It is concluded that edrophonium and neostigmine are not equally effective against atracurium and vecuronium.     

Neuromuscular effect of pipecuronium bromide in infants and children during nitrous oxide-alfentanil anesthesia

To determine in infants and children the neuromuscular effect of pipecuronium during alfentanil-N2O/O2 anesthesia, the authors studied 32 ASA Physical Status 1 and 2 pediatric patients undergoing minor elective surgery, divided into three groups according to their age: group 1 included 12 infants, 1.9 +/- 0.2 months old (mean +/- SE; range, 20 days to 3 months), weighing 5.2 +/- 0.3 kg; group 2, 10 infants, 6.1 +/- 0.9 months old (range, 3-11 months), 6.9 +/- 0.4 kg; and group 3, 10 children 5.6 +/- 0.9 yr old (range, 2-9 yr), 19.6 +/- 2.2 kg. Neuromuscular blockade at the ulnar nerve-adductor pollicis muscle was measured by electromyography. Incremental iv doses of pipecuronium were given (one 20 micrograms/kg first dose, followed by 10 micrograms/kg increments) to reach a 95 +/- 2% twitch depression (ED95). In children ED50 and ED95 of pipecuronium were 45.0 +/- 5.8 micrograms/kg (mean +/- SE) and 70.5 +/- 9.3 micrograms/kg, respectively. In 3- to 12-month-old infants ED50 and ED95 were 25.8 +/- 1.5 micrograms/kg and 48.7 +/- 3.5 micrograms/kg, respectively, and both significantly (P less than 0.05) less than those in children. In 0- to 3-month-old infants ED50 and ED95 were 23.7 +/- 1.7 micrograms/kg and 46.5 +/- 2.9 micrograms/kg, respectively, and also significantly (P less than 0.05) less than those measured in children. Time from maximal initial neuromuscular blockade to 75% recovery was 64.5 +/- 8.8 min in children and significantly shorter (P less than 0.05) in the two infant groups (0- to 3-month-old: 38.7 +/- 5.7 min, 3- to 12-month-old: 43.8 +/- 5.3 min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

The clinical neuromuscular pharmacology of mivacurium chloride (BW B1090U). A short-acting nondepolarizing ester neuromuscular blocking drug

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.     

Clinical pharmacology of pipecuronium bromide

The neuromuscular blocking and cardiovascular effects of pipecuronium, in doses ranging 2-3 times its ED95, were evaluated in 46 patients during thiopental, fentanyl, N2O/O2 anesthesia. The neuromuscular blocking effect of pipecuronium was evaluated by recording of the mechanical twitch of the adductor pollicis muscle in response to stimulation of the ulnar nerve at the wrist. Heart rate, systolic and diastolic blood pressures, and cardiac output were non-invasively measured during the onset of the neuromuscular blockade and compared to a saline control group to separate the effect of anesthesia from those of pipecuronium. The mean +/- SD time from administration of pipecuronium to 90% suppression of the first twitch (T1) of the train-of-four was 2.6 +/- 0.8, 2.0 +/- 0.6, and 2.1 +/- 0.6 min following the 70 micrograms/kg, 85 micrograms/kg, and 100 micrograms/kg dose, respectively. There was no significant difference between the different doses of pipecuronium in the time to 90% suppression of T1. In general, all three doses of pipecuronium provided good to excellent intubating conditions within 3 minutes after its administration. The time from the administration of pipecuronium to 5% recovery of T1 was 52.3 +/- 18.2 min in the group given 70 micrograms/kg. This was significantly longer in patients given 85 micrograms/kg (71.9 +/- 15.7 min) or 100 micrograms/kg (71.8 +/- 22.1 min). Times to the start of recovery of T1 and to 25% recovery of T1 showed a similar significant pattern.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of bolus administration of ORG-9426 in children during nitrous oxide-halothane anesthesia.

ORG-9426 is a new steroidal nondepolarizing neuromuscular blocking drug. We determined the dose-response relationship of ORG-9426 in 62 children (aged 1-5 yr) during nitrous oxide-halothane anesthesia by means of log-probit transformation and least-squares linear regression of the initial dose and response. Twelve additional patients received a bolus of 600 micrograms/kg (2 X the dose estimated to produce 95% depression of neuromuscular function [ED95]) of ORG-9426. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. To determine the dose-response relationship, patients randomly received initial bolus doses of 120 (n = 15), 160 (n = 16), 200 (n = 16), or 240 (n = 15) micrograms/kg ORG-9426. The resulting dose estimated to produce 50% depression of neuromuscular function (ED50) and ED95 were 179 and 303 micrograms/kg, respectively. Time from administration of 600 micrograms/kg to onset of 90% and 100% neuromuscular block was 0.8 +/- 0.1 (0.5-1.3) and 1.3 +/- 0.2 (0.7-2.8) min. The time to recovery of neuromuscular transmission to 25% (T25) was 26.7 +/- 1.9 (17.2-39.0) min. The recovery index (T25-75) was 11.0 +/- 1.6 (6.0-22.8) min, and the time to complete recovery of the magnitude of the fourth response to a train-of-four stimuli divided by the magnitude of the first response (T4/T1) greater than or equal to 0.75 was 41.9 +/- 3.2 (26.5-57.7) min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Delayed recovery of vecuronium neuromuscular block in diabetic patients during sevoflurane anesthesia

PURPOSE: To study recovery from vecuronium-induced neuromuscular block in diabetic patients during total iv or sevoflurane anesthesia. METHODS: 30 diabetic patients were assigned to diabetes mellitus (DM)-total iv anesthesia (TIVA); (n = 15) or DM-sevoflurane (S) groups (n = 15). Thirty healthy patients were divided into control-TIVA (n = 15) or control-S groups (n = 15). In the DM-TIVA or control-TIVA groups and DM-S or control-S groups, anesthesia was maintained with propofol and fentanyl, and nitrous oxide-oxygen-sevoflurane 1.7%, respectively. After receiving vecuronium 0.1 mg.kg(-1)iv, recovery of the train-of-four (TOF) was compared among the four groups. RESULTS: Times to the return of T2, T3, or T4 in the DM-TIVA and DM-S groups were longer than in the control-TIVA and control-S groups (46.9 +/- 13.8 vs 32.2 +/- 10.7 and 32.6 +/- 8.7 min for T2, P < 0.05). T1/control in the DM-S group was less than in the control-TIVA and DM-TIVA groups 50 to 120 and 70 to 120 min after receiving vecuronium, respectively (P < 0.05). T1/control in the control-S group was less than in the control-TIVA group 80 to 120 min after receiving vecuronium (P < 0.05). TOF ratio in the DM-S group was less than in the control-TIVA, DM-TIVA, and control-S groups, 60 to 120, 80 to 120, and 80 to 120 min after receiving vecuronium, respectively (P < 0.05). CONCLUSION: In diabetic patients receiving vecuronium, recovery of T1/control and TOF ratio are delayed during sevoflurane anesthesia, but not in association with total iv anesthesia.     

Intramuscular rapacuronium in infants and children: dose-ranging and tracheal intubating conditions.

BACKGROUND: Intravenous rapacuronium's rapid onset and short duration suggest that intramuscular rapacuronium might facilitate tracheal intubation without prolonged paralysis. Accordingly, the authors injected rapacuronium into the deltoid muscle to determine the optimal dose and time for intubation in pediatric patients. METHODS: Unpremedicated patients (aged, 2 months to 3 yr) were studied. Part I: Spontaneous minute ventilation (V(E)) and twitch tension were measured during N2O/halothane anesthesia. Rapacuronium (2.2-5.5 mg/kg, given intramuscularly, n = 23), succinylcholine (4 mg/kg, given intramuscularly, n = 12), or vecuronium (0.1 mg/kg, given intravenously, n = 15) was given. Time to 50% depression of V(E) and 10% recovery of twitch were measured. Dose for each patient was changed 10-20% according to the previous patient's response. Part II: In 22 patients anesthetized with 0.82-1.0% halothane, the optimal rapacuronium dose determined in part I (infants, 2.8 mg/kg; children, 4.8 mg/kg) was given intramuscularly. Laryngoscopy was scored. Time to laryngoscopy was increased or decreased 0.5 min according to the previous patient's response. RESULTS: Part I: Rapacuronium typically depressed ventilation in < or = 2 min with 10% twitch recovery in 20-60 min. With succinylcholine, median time to ventilatory depression was 1.3 and 1.1 min for infants and children, respectively; for vecuronium, 0.7 and 0.6 min. Part I: Intubating conditions were good-excellent at 3.0 and 2.5 min in infants and children, respectively; time to 10% twitch recovery (mean +/- SD) was 31 +/- 14 and 36 +/- 14 min in the two groups. CONCLUSIONS: This pilot study indicates that deltoid injection of rapacuronium, 2.8 mg/kg in infants and 4.8 mg/kg in children, permits tracheal intubation within 2.5-3.0 min, despite a light plane of anesthesia. Duration of action is intermediate.