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.     

Conditions of intubation and neuromuscular block induced by mivacurium: comparison with succinylcholine]

OBJECTIVE: To compare the clinical conditions for intubation and neuromuscular parameters after a high dose of mivacurium (0.25 mg/kg; 3 x SD95) administered in 30 s to those obtained after use of the usual dose of succinylcholine (1 mg/kg). PATIENTS AND METHODS: Eighty-two patients, 37 in the succinylcholine group and 45 in the mivacurium group, were studied. Intubating conditions were assessed on a scale of 3 to 12 points analyzing ease of laryngoscopy, relaxation of vocal cords and presence of cough 60 seconds after administration of the drug. Neuromuscular parameters were acceleration of the thumb induced by supramaximal train-of-four stimulation of the cubital nerve. Heart rate and non-invasive mean blood pressure were recorded throughout surgery. Cutaneous flush was looked for after administration of the relaxant. RESULTS: Time to onset of effect (159 s versus 82 s) and times to recovery after mivacurium were significantly longer than with succinylcholine. Mivacurium afforded excellent/good conditions for intubation in 95.6% of cases, with a neuromuscular blockade at intubation of 52.68%. No significant hemodynamic changes or side effects were observed. CONCLUSIONS: Given the moderate conditions of intubation achieved at 60 s, mivacurium can not be recommended as a relaxant in situations that require a rapid induction sequence. In elective surgery, 0.25 mg/kg of mivacurium can, however, be considered an alternative to succinylcholine.     

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.     

Evaluation of neuromuscular and cardiovascular effects of two doses of rapacuronium (ORG 9487) versus mivacurium and succinylcholine

BACKGROUND: This study compares the neuromuscular blocking and cardiovascular effects of rapacuronium (ORG 9487), a new aminosteroid nondepolarizing muscle relaxant, to recommended intubating doses of succinylcholine and mivacurium. METHODS: Adult patients were randomized in an open-label fashion to receive 1-5 microg/kg fentanyl before 1.5 mg/kg propofol induction followed by 1.5 or 2.5 mg/kg rapacuronium, 1.0 mg/kg succinylcholine, or 0.25 mg/kg mivacurium (i.e., 0.15 mg/kg followed by 0.1 mg/kg 30 s later). RESULTS: Patient neuromuscular blockade status was monitored by measuring the train-of-four response to a supramaximal stimulus at the ulnar nerve every 12 s. Percentage of the first twitch of the train-of-four (T1) at 60 s was similar in patients receiving 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine and was significantly less than in patients in the mivacurium group (26, 16, and 18%, respectively, vs. 48%; P < 0.01). Times to 80% T1 depression were also similar among patients in the 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine groups and significantly longer in the mivacurium group (62, 54, and 54 s, respectively, vs. 112 s; P < 0.01). Clinical duration was longer in all groups compared with the succinylcholine group; however, clinical duration in the 1.5 mg/kg rapacuronium group was shorter compared with the mivacurium group (15 vs. 21 min, respectively; P < 0.01). Heart rate changes were mild in the 1.5 mg/kg rapacuronium, succinylcholine, and mivacurium groups. The patients in the 2.5 mg/kg rapacuronium group had significantly higher heart rates compared with patients in the mivacurium group. No differences were found in blood pressure changes among patients in the four groups. CONCLUSIONS: Rapacuronium, 1.5 and 2.5 mg/kg, produced neuromuscular blockade as rapidly as succinylcholine and significantly faster than mivacurium. Although succinylcholine continued to show the shortest duration, 1.5 mg/kg rapacuronium used a rapid onset and a relatively short duration and may be considered an alternative to succinylcholine.     

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.     

Evaluation of Neuromuscular and Cardiovascular Effects of Two Doses of Rapacuronium (ORG 9487) versus Mivacurium and Succinylcholine

Background: This study compares the neuromuscular blocking and cardiovascular effects of rapacuronium (ORG 9487), a new aminosteroid nondepolarizing muscle relaxant, to recommended intubating doses of succinylcholine and mivacurium.

Methods: Adult patients were randomized in an open-label fashion to receive 1-5 [mu]g/kg fentanyl before 1.5 mg/kg propofol induction followed by 1.5 or 2.5 mg/kg rapacuronium, 1.0 mg/kg succinylcholine, or 0.25 mg/kg mivacurium (i.e., 0.15 mg/kg followed by 0.1 mg/kg 30 s later).

Results: Patient neuromuscular blockade status was monitored by measuring the train-of-four response to a supramaximal stimulus at the ulnar nerve every 12 s. Percentage of the first twitch of the train-of-four (T1) at 60 s was similar in patients receiving 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine and was significantly less than in patients in the mivacurium group (26, 16, and 18%, respectively, vs. 48%;P< 0.01). Times to 80% T1 depression were also similar among patients in the 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine groups and significantly longer in the mivacurium group (62, 54, and 54 s, respectively, vs. 112 s;P< 0.01). Clinical duration was longer in all groups compared with the succinylcholine group; however, clinical duration in the 1.5 mg/kg rapacuronium group was shorter compared with the mivacurium group (15 vs. 21 min, respectively;P< 0.01). Heart rate changes were mild in the 1.5 mg/kg rapacuronium, succinylcholine, and mivacurium groups. The patients in the 2.5mg/kg rapacuronium group had significantly higher heart rates compared with patients in the mivacurium group. No differences were found in blood pressure changes among patients in the four groups.     

预注不同剂量米库氯铵对肌松效应的影响

目的 观察预先注射(预注)不同剂量米库氯铵对肌松效应的影响. 方法 选择全身麻醉下行择期手术的患者40例,年龄18 ～60岁,ASA分级Ⅰ、Ⅱ级,按随机数字表法分为4组(每组10例):对照组(A组)、预注20％的95％有效药物剂量(95％ effective dose,ED95)米库氯铵组(B组)、预注30％ED95米库氯铵组(C组)、预注40％ED95米库氯铵组(D组).丙泊酚联合舒芬太尼麻醉诱导后,A组预注生理盐水,B组、C组和D组分别预注米库氯铵0.014 mg/kg(20％ED95)、0.021 mg/kg(30％ED95)和0.028 mg/kg(40％ED95),预注后2 min,给予剩余插管剂量(A组0.210 mg/kg、B组0.196 mg/kg、C组0.189 mg/kg、D组0.182 mg/kg).应用四个成串刺激(train of four stimulation,TOF)-Watch加速仪进行肌松监测.观察肌松起效时间、阻滞维持时间、临床作用时间、体内作用时间和恢复指数. 结果 与A组比较,B组、C组和D组米库氯铵起效时间显著缩短[(183±48)s比(141±18)、(132±30)、(117±21) s](P＜0.05);B组、C组和D组组间比较,起效时间差异无统计学意义(P＞0.05);4组间阻滞维持时间、临床作用时间、体内作用时间和恢复指数差异无统计学意义(P＞0.05). 结论 预注可显著缩短米库氯铵的起效时间,不影响肌松维持和恢复过程,但加大预注剂量未能明显缩短起效时间.     

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.     

Onset of the effect and intubation conditions following atracurium, verocuronium and suxamethonium

1. The onset of neuromuscular blockade following i.v. injection of atracurium 0.3, 0.4, or 0.5 mg/kg; vecuronium 0.08 or 0.1 mg/kg; and succinylcholine 1.0 mg/kg was studied in 205 adult patients during induction of anesthesia by means of the compound action potential (EMG) of the hypothenar muscle, which was indirectly stimulated via the ulnar nerve above the wrist, using the Datex Relaxograph. At the same time, the intubation conditions at 0.5, 1, 2, or 3 min after injection were assessed using a scoring system (Crul 1983) related to ease of laryngoscopy, movement of vocal cords and coughing, and reflex movements of the extremities. 2. Neuromuscular blockade and intubation conditions 2 min after administration of atracurium 0.3 mg/kg were 60 +/- 10% and 8.7 +/- 0.3; after 0.4 mg/kg 74 +/- 4% and 10.3 +/- 0.3; and after 0.5 mg/kg 86 +/- 5% and 11.8 +/- 0.2. After 0.08 mg/kg vecuronium 76 +/- 3% and 7.4 +/- 0.5 were recorded and after 0.1 mg/kg 85 +/- 6% and 10.5 +/- 0.4. Motor blockade 1 min after succinylcholine was 98 +/- 2% and intubation conditions scored 11.3 +/- 0.3. Relating intubation conditions to neuromuscular blockade yielded a close correlation and surprisingly good or very good intubation conditions (score more than 10) at a motor blockade of 80% (resp. 20% transmission). 3. Although succinylcholine is still the muscle relaxant with the most rapid onset of action, the new drug atracurium seems to satisfactorily facilitate tracheal intubation within an acceptably short time interval of 2 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

The "intubating dose" of succinylcholine: the effect of decreasing doses on recovery time

BACKGROUND: The usually cited "intubation dose" of succinylcholine is 1.0 mg/kg. In the majority of patients, this dose will produce apnea of sufficient duration that significant hemoglobin desaturation may occur before neuromuscular recovery takes place in those whose ventilation is not assisted. This study was undertaken to examine the extent to which reducing this dose would decrease the duration of action of succinylcholine. METHODS: During stable desflurane/oxygen/opioid anesthesia and after adequate twitch stabilization, neuromuscular function was recorded with an acceleromyographic monitor. Supramaximal stimuli were delivered at 0.10 Hz. Patients received 0.40, 0.60, or 1.0 mg/kg succinylcholine, and twitch height was monitored for at least 20 min thereafter. RESULTS: The onset times to maximal effect were 105 +/- 23 s, 81 +/- 19 s, and 71 +/- 22 s, respectively. The lowest dose (0.40 mg/kg) did not reliably produce 100% twitch depression. The times to 90% twitch recovery at the adductor pollicis in the three groups were 6.6 +/- 1.5 min, 7.6 +/- 1.6 min, and 9.3 +/- 1.2 min, respectively. CONCLUSIONS: Reducing the dose of succinylcholine from 1.0 mg/kg to 0.60 mg/kg shortens the duration of effect at the adductor pollicis by more than 90 s. The authors believe that even this modest decrease in the duration of drug-induced paralysis is often worth pursuing.     

Pharmacodynamics and safety of mivacurium in infants and children under halothane-nitrous oxide anesthesia

OBJECTIVES: To determine pharmacodynamic effects and safety of mivacurium in paediatric patients. STUDY DESIGN: Multicentric, prospective, open, non-randomized study. PATIENTS: Forty-eight three-month-old to eight-year-old physical class ASA I or II children. METHOD: Anaesthesia was induced and maintained with halothane and nitrous oxide. Tracheal intubation was performed without a neuromuscular blocking agent. Neuromuscular blockade was measured with a strain force transducer after train-of-four stimulation of the ulnar nerve at the wrist every ten seconds. A single bolus dose of mivacurium (0.2 mg.kg-1) was injected during 15 seconds in patients allocated into three groups. Group 1: three to 12-month-old infants (n = 15), group 2: one- to three-year-old children (n = 16) and group 3: three- to eight-year-old children (n = 17). Onset and recovery parameters were measured in each patient. Heart rate and noninvasive arterial blood pressure were recorded every minute for five minutes after mivacurium injection. RESULTS: Following halothane administration for 29 and 32 min, and a FEThalothane = 1 vol%, mivacurium (0.2 mg.kg-1) determined a 100% neuromusmcular blockade in all patients. The onset time was 71 +/- 34 s (mean +/- SD) in all patients and did not differ between groups. Time to 25% and 95% recovery of the first twitch and recovery index for all the patients were 12 +/- 3 min, 19 +/- 5 min and 4 +/- 2 min respectively and did not differ between groups. No prolonged paralysis was observed. No significant changes of HR and BP occurred. CONCLUSIONS: Following 0.2 mg.kg-1 of mivacurium in patients aged between three months to eight years, a complete blockade occurs with a rapid onset time and a short duration of action, without significant cardiovascular effect.     

Comparison of the intubation conditions provided by rapacuronium (ORG 9487) or succinylcholine in humans during anesthesia with fentanyl and propofol.

BACKGROUND: Currently, the only approved muscle relaxant with a rapid onset and short duration of action is succinylcholine, a drug with some undesirable effects. Rapacuronium is an investigational nondepolarizing relaxant that also has a rapid onset and short duration and consequently should be compared with succinylcholine in its ability to facilitate rapid tracheal intubation. METHODS: This prospective, randomized clinical trial involved 336 patients. Anesthesia was induced with fentanyl and propofol and either 1.5 mg/kg rapacuronium or 1.0 mg/kg succinylcholine. The goal was to accomplish tracheal intubation by 60 s after administration of the neuromuscular blocking drug. Endotracheal intubation was performed, and conditions were graded by a blinded investigator. Recovery of neuromuscular function was assessed by electromyography. RESULTS: Intubation conditions were evaluated in 236 patients. Intubation by 60 s after drug administration occurred in 100% of patients with rapacuronium and in 98% with succinylcholine. Intubation conditions were excellent or good in 87% of patients with rapacuronium and in 95% with succinylcholine (P < 0.05). The time (median and range) to the first recovery of the train-of-four response was 8.0 (2.8-20.0) min with rapacuronium and 5.7 (1.8-17.7) min with succinylcholine (P < 0.05). The overall incidence of adverse effects was similar with both drugs. CONCLUSIONS: A 1.5-mg/kg dose of rapacuronium effectively facilitates rapid tracheal intubation. It can be considered a valid alternative to 1.0 mg/kg succinylcholine for this purpose.     

Mivacurium-induced neuromuscular blockade following single bolus doses and with continuous infusion during either balanced or enflurane anesthesia

Mivacurium chloride (BW B1090U) was administered to 72 patients during their elective surgery. The eight groups (nine subjects per cell) in the 2 x 2 x 2 study design differed in three factors: the size of the mivacurium bolus dose administered, whether or not this dose was followed by an infusion of mivacurium, and in the technique used for the maintenance of anesthesia. Four groups received a single bolus dose of mivacurium, 0.15 mg/kg, and the remaining four groups received mivacurium, 0.25 mg/kg, administered iv in 15 s. Precisely 2 min later, tracheal intubation was attempted. Conditions were judged to be good or excellent on most occasions, but intubation was not possible for two of the patients in the low-dose and one in the high-dose groups. Four groups, two at each bolus dose, received no additional mivacurium: there was a dose-dependent decrease in the rate of spontaneous recovery following the bolus dose. The other subdivision of groups was the use of either barbiturate-nitrous oxide-narcotic (balanced) anesthesia, or enflurane-nitrous oxide anesthesia; the anesthetic technique did not affect the pattern of spontaneous recovery from either bolus dose. Four groups, again two at each bolus dose, subsequently received an infusion of mivacurium, adjusted to depress the twitch response by approximately 95%. Infusion rates averaged 6.0 micrograms.kg-1.min-1 in the groups receiving balanced anesthesia and 4.2 micrograms.kg-1.min-1 for those receiving enflurane anesthesia. Recovery following administration by infusion was slower than that observed following a bolus dose of mivacurium, 0.15 mg/kg but did not differ between the anesthetic groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical pharmacology of mivacurium chloride: a review.

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

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.     

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)     

Dose-related effects of succinylcholine on the adductor pollicis and masséter muscles in children

This study was performed to determine the effects of various doses of succinylcholine on resting tension and evoked twitch height at the masseter and adductor pollicis muscles in children. Twenty patients, aged 3-10 yr, ASA physical status I or II, were randomly assigned to receive succinylcholine 0.15, 0.25, 0.50 or 1.00 mg.kg-1, during halothane-nitrous oxide anaesthesia. Supramaximal train-of-four stimulation was applied simultaneously to the ulnar nerve and the nerve to the masseter. Transducers recorded force at the jaw and the thumb. Maximum blockade of the first twitch (T1) and maximum resting tension change were measured. Potency of succinylcholine at the two muscles was estimated by linear regression of the logit transformation of T1 versus log dose. The relationship between resting tension change and log dose was established by linear regression. The masseter muscle was more sensitive to succinylcholine than the adductor pollicis with an ED95 of 0.28 +/- 0.02 (mean +/- SEM) vs 0.44 +/- 0.05 mg.kg-1 (P less than 0.05). Onset of neuromuscular blockade was faster at the masseter, and recovery occurred simultaneously in both muscles. A dose-related increase in resting tension was observed in both muscles, but its magnitude was five times greater at the masseter. With succinylcholine, 1 mg.kg-1, this increase was 51.6 +/- 16.8 g at the masseter and 9.1 +/- 2.3 g at the adductor pollicis. Tension returned to baseline within 1-2 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mivacurium chloride (BW B1090U)-induced neuromuscular blockade during nitrous oxide-isoflurane and nitrous oxide-narcotic anesthesia in adult surgical patients

The neuromuscular and cardiovascular effects of mivacurium were studied in 90 adult patients during nitrous oxide-oxygen-isoflurane (n = 45, ISO group) and nitrous oxide-oxygen-narcotic (n = 45, BAL group) anesthesia. Neuromuscular blockade was measured using electromyographic activity of the adductor pollicis muscle after supramaximal stimulation of the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate dose-response relations, three subgroups of nine patients in the ISO group received mivacurium doses of 0.025, 0.03, and 0.04 mg/kg, respectively. Similarly, three subgroups of nine patients in the BAL group received mivacurium doses of 0.03, 0.04, and 0.05 mg/kg, respectively. The ED50 and ED95 of mivacurium in each group were estimated from linear regression plots of log dose vs probit of maximum percentage depression of neuromuscular function. The estimated ED50 values for the ISO and BAL groups were 0.029 and 0.041 mg/kg, respectively. The estimated ED95 values for the ISO and BAL groups were 0.045 and 0.058 mg/kg, respectively. Recovery indexes were measured in 26 patients who received ED95 or greater doses of mivacurium in either the ISO or BAL groups. The recovery index was shorter in the BAL group (5.5 +/- 1.6 minutes [n = 10]), than in the ISO group (7.4 +/- 3.0 minutes [n = 16]). The addition of isoflurane (0.5-0.75% end-tidal concentration) to nitrous oxide-narcotic anesthesia augments the degree of neuromuscular blockade from a given dose of mivacurium and also prolongs the recovery index.     

Evaluation of the endotracheal intubating conditions of rocuronium (ORG 9426) and succinylcholine in outpatient surgery.

The time-course of action and tracheal intubating conditions of rocuronium and succinylcholine under intravenous anesthesia with propofol, alfentanil, and nitrous oxide were studied in 30 patients undergoing outpatient surgery. The neuromuscular effects of both drugs were quantified by recording the indirectly evoked twitch response of the adductor pollicis muscle after ulnar nerve stimulation (0.1 Hz, 0.2 ms supramaximal stimuli). Patients were given either 0.6 mg/kg rocuronium (n = 20) or 1 mg/kg succinylcholine (n = 10) intravenously. Sixty seconds after the administration of the muscle relaxant, the trachea was intubated and the intubating conditions were scored by a "blinded" assessor. Intubating conditions were not different (P = 0.34) between the rocuronium and succinylcholine groups. The onset and duration of neuromuscular blockade were shorter with succinylcholine than with rocuronium. The depression of the twitch response to 5% of control value occurred in 0.8 +/- 0.1 min with 1 mg/kg succinylcholine and 1.2 +/- 0.5 min with 0.6 mg/kg rocuronium (P less than 0.01). The recovery of the twitch response to 25%, 75%, and 90% of its control value was shorter after succinylcholine (P less than 0.001) and occurred at 8.1 +/- 2.6, 10.3 +/- 3.9, 11.3 +/- 4.6 and 25.3 +/- 5.0, 33.1 +/- 5.9, 36.1 +/- 6.3 min after succinylcholine and rocuronium, respectively. Also the time required for spontaneous recovery from 25% to 75% of the control twitch response was significantly shorter (P less than 0.001) after succinylcholine (2.2 +/- 1.4 min) than after rocuronium (7.8 +/- 2.1 min). It is concluded that in spite of the pharmacodynamic differences between succinylcholine and rocuronium, the intubating conditions after administration of both compounds are similar and develop at the same rate.     

Effect of d-tubocurarine pretreatment on succinylcholine twitch augmentation and neuromuscular blockade

Subparalyzing doses of d-tubocurarine (dTC) given before succinylcholine decrease the duration of neuromuscular blockade. In animal preparations, they also abolish succinylcholine-induced twitch augmentation, defined as a greater-than-maximal contraction in response to a single stimulus. To determine quantitatively the effect of dTC on succinylcholine potency and on twitch augmentation in humans, 60 adult patients, ASA physical status I or II, were assigned randomly to receive either 0.05 mg/kg of dTC or saline 2 min before induction of anesthesia with fentanyl and thiopental. Train-of-four stimulation was applied every 12 s to the ulnar nerve and the force of contraction of the adductor pollicis muscle was measured. One minute after induction of anesthesia, 0.15, 0.20, 0.25, 0.35, or 0.50 mg/kg of succinylcholine was given. The height of the first twitch (T1) reached 121% +/- 6% (mean +/- SEM) of control without dTC, and was virtually abolished by dTC pretreatment (105% +/- 1%, P less than 0.01). Twitch augmentation was more noticeable with lower doses of succinylcholine, and was not observed in the response to the fourth stimulus of the train of four (T4). The potency of succinylcholine was decreased by approximately one-half in the dTC-pretreated groups. The ED50 was 0.27 +/- 0.04 mg/kg without dTC and 0.50 +/- 0.06 mg/kg with dTC (P less than 0.002). The corresponding values for ED90 were 0.51 +/- 0.07 and 1.02 +/- 0.12 mg/kg, respectively (P less than 0.02). The ED95 values were 0.63 +/- 0.09 and 1.28 +/- 0.15 mg/kg, respectively (P less than 0.02). The slopes of the regression lines did not deviate significantly from parallelism.(ABSTRACT TRUNCATED AT 250 WORDS)