Neuromuscular effects of pipecuronium bromide.

The neuromuscular effects of pipecuronium bromide have been evaluated in 90 adult patients anaesthetized with thiopentone, nitrous oxide in oxygen and intravenous fentanyl with or without halothane. Eighty patients received pipecuronium 45 micrograms kg-1 and the remaining ten 70 micrograms kg-1. A separate group of 10 patients received pancuronium in a dose of 60 micrograms kg-1 (equipotent to pipecuronium 45 micrograms kg-1). Neuromuscular block was measured using a single-twitch or train-of-four mode of stimulation. The time to onset of maximum block with pipecuronium 45 micrograms kg-1 varied between 3.5 and 5.7 min depending on the mode of stimulation and the anaesthetic technique used. The time to 25% recovery of this dose varied between 41 and 54 min. The recovery index (time from 25 to 75% recovery) averaged 29 min. These values were generally similar in the group receiving pancuronium 60 micrograms kg-1. The time to onset of complete block with 70 micrograms kg-1 of pipecuronium averaged 2.5 min and the duration to 25% recovery 95 min. There were no significant changes in heart rate and arterial pressure with the use of pipecuronium. The results show pipecuronium to be a drug resembling pancuronium in its neuromuscular effects when used in equipotent doses.     

阿曲库铵与哌库溴铵在预注法中的复合应用

目的 观察阿曲库铵和哌库溴铵在预注法中的复合应用。方法 选择平衡麻醉下择期手术病人70例。研究分两部分：第一部分，将30例病人随机均分为阿曲库铵组和哌库溴铵组，采用累计给药法建立两药量一效关系曲线，计算ED50和ED95；第二部分，根据两药ED95将另40例病人随机均分为单纯阿曲库铵预注组和复合哌库溴铵预注组。观察预注期间肌颤搐抑制值、起效时间和临床作用时间。结果 阿曲库铵ED50和ED95分别为117．5μg／kg和272．8μg／kg，哌库溴铵ED50和ED95分别为23．7μg／kg和42．6μg／kg；复合哌库溴铵预注组起效快于单纯阿曲库铵预注组；复合哌库溴铵预注组临床作用时间长于单纯阿曲库铵预注组。结论 在预注法中采用化学结构不同的肌松药可进一步加快起效，延长临床作用时间。     

Neuromuscular effects of pipecuronium during sevoflurane anesthesia compared with isoflurane and enflurane anesthesia

We evaluated the neuromuscular effects of pipecuronium during anesthesia with equipotent concentrations of either sevoflurane, isoflurane or enflurane.Twenty-seven patients scheduled for minor elective otolaryngeal or plastic surgery were studied and randomly assigned to 3 groups, one group per anesthetic agent. Anesthesia was induced with thiamylal 5mg·kg^–1 and the trachea was intubated with succinylcholine 1mg·kg^–1, then anesthesia was maintained with 60% nitrous oxide in oxygen and sevolfurane, isoflurane or enflurane, depending on the group. Neuromuscular blocking effects were monitored by recording the electromyographic activity of the adductor pollicis muscle from supramaximal stimulation of the ulnar nerve at 10-s intervals. Pipecuronium 40µg·kg^–1 was administered when electromyographic activity had reached a stable state, 30min after succinylcholine administration. The maximum effect (% block of control) and clinical duration (time to 25% recovery) of pipecuronium were 99.1 ± 1.4% and 63.7 ± 14.7min (mean ± S.D.) for sevoflurane, 99.0 ± 2.0% and 60.9 ± 20.5min for isoflurane, and 98.0 ± 2.5% and 62.8 ± 28.7min for enflurane, respectively. There were no significant differences in these values between the anesthetics. Cardiovascular stimulant effects were not observed in any of the groups.We conclude that the effect of pipecuronium under seveflurane anesthesia is similar to that under isoflurane and enflurane anesthesia.(Nakao Y, Ohno M, Imai M, et al.: Neuromuscular effects of pipecuronium during sevoflurane anesthesia compared with isoflurane and enflurane anesthesia. J Anesth 7: 405--410, 1993)     

Neuromuscular and cardiovascular effects of high-dose vecuronium

The effects of bolus administration of large doses of vecuronium on the onset and duration of neuromuscular blockade and histamine release were studied during fentanyl-nitrous oxide anesthesia. Forty adults were randomly assigned to receive a bolus injection of either 0.1, 0.2, 0.3, or 0.4 mg/kg of vecuronium. The evoked electromyogram of thumb adduction to train-of-four stimulation was monitored. The time of onset and clinical duration (mean +/- SEM) after each dose were as follows: 0.1 mg/kg, 164 +/- 27 s and 42 +/- 5 min; 0.2 mg/kg, 120 +/- 17 s and 68 +/- 8 min; 0.3 mg/kg, 88 +/- 17 s and 111 +/- 19 min; 0.4 mg/kg, 78 +/- 19 s and 115 +/- 19 min. Both time of onset and duration after doses of 0.3 or 0.4 mg/kg were significantly different from values after the lower doses. No dose-related changes in blood pressure, heart rate, or histamine release were observed. The authors conclude that large bolus doses of vecuronium can be safely used to speed the onset of blockade, but with a significantly prolonged duration of action.     

Neuromuscular and cardiovascular effects of mivacurium in children

The neuromuscular and cardiovascular effects of mivacurium chloride (BW B1090U) were evaluated in 90 children (2-12 yr) during N2O:O2 halothane or N2O:O2 narcotic anesthesia. Neuromuscular response was evaluated by recording the force of contraction of the adductor of the thumb during train-of-four stimulation at 0.1 Hz. The children were divided into two groups. Patients in group A (n = 45) were anesthetized with N2O:O2 and halothane (1% inspired) and patients in group B (n = 45) were anesthetized with N2O:O2 and fentanyl or morphine. Each group was further divided into five subgroups of nine children. Children in the first three sets of subgroups (A1-A3, B1-B3) received an initial dose of 0.02, 0.04, 0.05, 0.06 or 0.07 mg/kg mivacurium to determine dose response relationships under the different anesthetic regimens. The ED50 and ED95 neuromuscular blocking doses calculated from this single dose technique were 0.051 mg/kg and 0.095 mg/kg, respectively, in children anesthetized with halothane N2O:O2, and 0.059 mg/kg and 0.11 mg/kg in children anesthetized with N2O:O2 narcotic. The fourth subset of each group (A4 and B4) received 0.09 mg/kg and 0.11 mg/kg mivacurium, the estimated ED95 for each respectively. The last subsets (A5 and B5) received 0.2 mg/kg. This dose induced 100% depression of the twitch response in all 18 patients in 1.8 +/- 0.1 min, with recovery to 5%, 25%, and 95% of control occurring in 8.4 +/- 0.5, 11.2 +/- 0.6 and 18.4 +/- 1.6 min, respectively. The recovery indices for all patients were 4.6 +/- 0.6 min for 25-75% recovery and 9.7 +/- 1.3 min for 5-95% recovery.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Pharmacokinetics and cardiovascular dynamics of pipecuronium bromide during coronary artery surgery

The haemodynamic effects of 200 micrograms.kg-1 pipecuronium and pancuronium were compared under etomidate/piritramide anaesthesia in 20 patients scheduled for elective coronary artery surgery. Following the completion of the haemodynamic measurements (ten minutes), anaesthesia was maintained by etomidate/sufentanil infusion. The mean changes in cardiac output were approximately -19 and -2 per cent and in heart rate -1 and +26 per cent for pipecuronium and pancuronium respectively. Plasma and urine concentrations of pipecuronium were also measured and the pharmacokinetic variables obtained indicated rapid initial decrease in plasma concentration (t1/2 = 7.6 minutes) followed by a longer terminal phase (t1/2 = 161 minutes). The central compartment volume was 102 +/- 24 ml.kg-1 and plasma clearance was 1.8 +/- 0.4 ml.kg-1 min-1. Approximately 56 per cent of the dose was recovered from the urine within 24 hours of administration and about 25 per cent of this was the metabolite, 3-desacetyl pipecuronium. High-dose pipecuronium administration under the anaesthetic regimen employed did not produce deleterious haemodynamic effects. The pharmacokinetic variables after bolus injection of pipecuronium did not deviate from those reported under normothermic conditions.     

Comparison of cardiovascular effects of pipecuronium versus vecuronium in patients receiving sufentanil anesthesia for myocardial revascularization.

This study was designed to compare the cardiovascular effects of pipecuronium bromide (PIP) to vecuronium (V) when combined with sufentanil (SF) in patients undergoing coronary artery bypass surgery. Eighty-two patients were studied; 40 were normotensive and 42 had hypertension currently controlled by pharmacological therapy. All patients were randomly assigned to receive either intravenous V, 0.12 mg/kg, or PIP, 0.10 mg/kg. Anesthesia was induced with SF, 6 micrograms/kg, while breathing 100% oxygen. Hemodynamic data including heart rate, mean arterial pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac index, systemic vascular resistance, pulmonary vascular resistance, and left ventricular stroke work index were collected at five points: prior to induction, 3 and 6 minutes after the complete administration of PIP or V, and 3 and 6 minutes after intubation. There were no statistical differences in hemodynamic changes associated with either PIP or V. In addition, there were no statistical differences in the hemodynamic parameters measured at the five time points between the normotensive and hypertensive patient groups. This study demonstrates that there are no significant hemodynamic changes between SF/PIP and SF/V when used during coronary artery surgery. Due to its associated stable hemodynamics, as well as its long duration of action, PIP could become a commonly used muscle relaxant for anesthesia for cardiac surgery.     

Comparison of the haemodynamic effects of pipecuronium and pancuronium during fentanyl anaesthesia

Haemodynamic variables were measured following administration of pipecuronium 70 micrograms.kg-1 and pancuronium 90 micrograms.kg-1 (approximately equivalent to 1.5 x ED95) in patients anaesthetised with fentanyl 50 micrograms.kg-1 and scheduled to undergo coronary artery bypass grafting. There were significant increases in heart rate (22%), mean arterial pressure (10%), cardiac index (16%), and the rate pressure product (35%) following administration of pancuronium. The absolute values of these parameters were, however, within acceptable clinical limits. Administration of pipecuronium produced minimal and insignificant changes in these parameters. Other measured or derived indices showed only small changes with both agents and these were generally insignificant. There were no incidences of significant bradycardia following pipecuronium administration. The results from the present study suggest that pipecuronium would have advantages for use in patients with significant cardiovascular disease.     

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 effects of pipecuronium bromide on intracranial pressure and cerebral perfusion pressure

Twenty patients with expansive pathologic intracranial lesions, who were anesthetized with thiopental, nitrous oxide in oxygen, and fentanyl and mechanically ventilated to ensure normocarbia, received pipecuronium bromide 70 microg/kg i.v. Intracranial pressure (ICP), heart rate, arterial pressure, central venous pressure (CVP), EKG, and end-tidal CO2 were simultaneously recorded for 5 min before and for 15 min after administration of the muscle relaxant. No statistically significant changes in ICP and cerebral perfusion pressure were observed after administration of pipecuronium bromide. Cardiovascular stability was maintained during the study period except for a small, although significant, decrease of the CVP from 5.7 +/- 2.5 (SEM) to 5.0 +/- 2.5 mm Hg. These results, together with the long-lasting muscular effect of pipecuronium bromide, suggest that this new neuromuscular blocking agent may be used for muscle relaxation during neurosurgical operations in patients who have normal intracranial pressure at the time of administration of the drug.     

Evaluation of the action of pipecuronium bromide in patients under halothane anesthesia--a comparison with pancuronium bromide regarding their neuromuscular blocking and cardiovascular effects

Neuromuscular blocking and circulatory actions of pipecuronium bromide (PPB) were evaluated in patients under halothane-nitrous oxide-oxygen anesthesia in comparison with those of pancuronium bromide (PCB) in a multi-center cooperative study. Twitch tension of the adductor pollicis muscle was elicited by supramaximal stimulation of the ulnar nerve every 10 seconds. The study was performed according to the following 4 steps and the results were obtained. 1) Cumulative administration of 0.01 mg.kg-1 of PPB or PCB resulted in the potency ratio of 1.3:1.0 and the dose response curves of the two agents paralleled with each other. 2) With PPB 0.05 mg.kg-1 or 0.1 mg.kg-1, almost 100% block of the twitch was obtained. Both duration of action and the recovery time were shorter with 0.05 mg.kg-1 group. 3) After the first dose of 0.04 mg.kg-1 when the twitch recovered to 25% of the initial height 0.02 mg.kg-1 was given and this was repeated. Intervals between the doses showed large individual differences and no significant change was observed with repeated doses. 4) Safety of the drug. No significant change in heart rate or blood pressure was observed with PPB but with PCB a significant increase in heart rate was observed. The study revealed that PPB is slightly more potent than PCB and the duration of action is longer, but it has no untoward cardiovascular action in man under halothane anesthesia.     

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)     

Neuromuscular effects of stun device discharges

BACKGROUND: Stun guns or electromuscular incapacitation devices (EMIs) generate between 25,000 and 250,000 V and can be discharged continuously for as long as 5 to 10 min. In the United States, over 200,000 individuals have been exposed to discharges from the most common type of device used. EMI devices are being used increasingly despite a lack of objective laboratory data describing the physiological effects and safety of these devices. An increasing amount of morbidity, and even death, is associated with EMI device use. To examine this type of electrical injury, we hypothesized that EMI discharges will induce acute or delayed cardiac arrhythmia and neuromuscular injury in an animal model. METHODS: Using an IACUC approved protocol, from May 2005 through June 2006 in a teaching hospital research setting, 30 Yucatan mini-pigs (24 experimentals and 6 sham controls) were deeply anesthetized with ketamine and xylazine without paralytics. Experimentals were exposed to discharges from an EID (MK63; Aegis Industries, Bellevue, ID) over the femoral nerve on the anterior left hind limb for an 80 s exposure delivered as two 40 s discharges. EKGs, EMGs, troponin I, CK-MB, potassium, and myoglobin levels were obtained pre-discharge and post-discharge at 5, 15, 30, and 60 min, 24, 48, and 72 h (n = 6 animals) and 5, 15, and 30 d post-discharge (n = 6 animals at each time point). Skin, skeletal muscle, and peripheral nerve biopsies were studied bilaterally. Data were compared using one-way analysis of variance and paired t-tests. P-values <0.05 were considered significant. RESULTS: No cardiac arrhythmias or sudden deaths were seen in any animals at any time point. No evidence of skeletal muscle damage was detected. No significant changes were seen in troponin I, myoglobin, CK-MB, potassium, or creatinine levels. There were no significant changes in compound muscle action potentials (CMAP). No evidence of conduction block, conduction slowing, or axonal loss were detected on EMG. M-wave latency (M(lat), ms), amplitude (M(amp), mV), area (M(area), mV-ms), and duration (M(dur), ms) were not significantly affected by MK63 discharge compared with contralateral or sham controls. F-wave latency (F(lat), ms), a sensitive indicator of retrograde nerve conduction and function, was not significantly affected by MK63 discharge compared with contralateral or sham controls. No significant histological changes were seen at any time point in skeletal muscle or peripheral nerve biopsies although mild skin inflammation was evident. CONCLUSIONS: There was no evidence of acute arrhythmia from MK63 discharges. No clinically significant changes were seen in any of the physiological parameters measured here at any time point. Neuromuscular function was not significantly altered by the MK63 discharge. In this animal model, even lengthy MK63 discharges did not induce muscle or nerve injury as seen using EMG, blood chemistry, or histology.     

Neuromuscular effects of atracurium in man

The neuromuscular effects of atracurium were studied in 25 A.S.A. class I or II patients anesthetized by a N2O-O2 narcotic technique. In five patients incremental doses of 0.05 to 0.1 mg/kg of atracurium were given intravenously every 3 minutes until approximately 95% depression of the evoked electromyographic (EMG) response of the adductor policus muscle was produced. This required 0.25 to 0.35 mg/kg of atracurium. The duration of block (return to 95% of control) was 25 to 50 minutes. In addition, four groups of five patients each received 0.15, 0.25, 0.375, or 0.6mg/kg of atracurium. The block produced by 0.15 mg/kg was 10% to 92% and lasted 8 to 55 minutes. The block produced by 0.25, 0.375, and 0.6 mg/kg was 95% or greater with a duration of action of 30 to 68 minutes, 52 to 70 minutes, and 65 to 95 minutes, respectively. Tracheal intubation was easily carried out in all patients in whom there was a block of 90% or greater. The block could be antagonized by the common clinical combination of atropine and neostigmine. Changes in heart rate and blood pressure following atracurium were less than 5%.