曲马多对母婴乳酸盐和新生儿神经行为的影响

目的　研究曲马多对母婴血乳酸盐和新生儿神经行为与适应能力评分 (NACS)的影响。方法　 6 0例足月妊娠剖宫产产妇随机分三组 :T0 组 ,2 0例 ,肌注 0 9%氯化钠 2ml;T1组 2 0例 ,肌注曲马多 1 5mg/kg ;T2 组 ,2 0例 ,肌注曲马多 2mg/kg。各组肌注后开始麻醉 ,三组均采用脊麻与硬膜外联合阻滞。观察指标 :新生儿生后 15min的Apgar评分及新生儿生后 15min的NACS ;胎儿娩出时采脐动、静脉血和母体动脉血各 2ml,行血乳酸值测定及血气分析。结果　三组新生儿Apgar评分无明显差异 ,T0 组NACS明显高于T1组 (P <0 0 5 )和T2 组 (P <0 0 1) ;T2 组脐动、静脉血乳酸值明显高于T1组 (P <0 0 5 )和T0 组 (P <0 0 1) ;母体乳酸值三组间无明显差异 ;T2 组母体和脐动、静脉血PaCO2 明显高于T0 组 (P <0 0 1) ,T2 组脐动、静脉血SaO2 明显低于T0 组 (P <0 0 5 )。结论　剖宫产术前肌注曲马多 1 5mg/kg对新生儿无明显不良影响。但 2mg/kg曲马多肌注具有呼吸抑制作用 ,使脐动、静脉血乳酸盐增加 ,对新生儿NACS有一过性影响     

Refining the priming principle for vecuronium during rapid-sequence induction of anesthesia

Administration of a subparalyzing dose of a nondepolarizing muscle relaxant (priming dose) prior to its intubating dose hastens the onset time (time from muscle relaxant administration to 100% depression of twitch tension) of neuromuscular blockade. This study was undertaken to determine the optimal priming and intubating doses and time interval between these doses (priming interval) of vecuronium during rapid-sequence induction of anesthesia. The authors measured single-twitch tension in 79 healthy, awake, premedicated (fentanyl, 50-150 mu iv, and/or diazepam, 5-10 mg iv) patients. In Part A of the study, the priming dose was varied (0.0, 0.005, 0.01, 0.0015, or 0.02 mg/kg iv). Decrement of twitch tension and symptoms were recorded 3 min later. Four minutes after the priming dose, thiopental, 4-6 mg/kg iv, and vecuronium, 0.1 mg/kg iv, were given. Onset times for the 0.01, 0.015, and 0.02 mg/kg groups were significantly shorter than for 0.005 and 0.0 mg/kg groups. No breathing difficulties were encountered in any of the groups. Decrement of twitch tension greater than 25% of control only occurred in the 0.02 mg/kg group (4 of 11 patients). In Part B, the priming interval was varied (2, 4, or 6 min) after giving the optimal priming dose (0.01 mg/kg). Anesthesia was induced as in Part A. Onset times for the 4-min group were significantly faster than the 2- or 6-min groups. In Part C, the intubating dose was varied (0.07, 0.1, or 0.15 mg/kg iv) after the optimal priming dose and optimal priming interval (4 min). Onset times for the 0.1 mg/kg and 0.15 mg/kg groups were significantly faster than the 0.07 mg/kg group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vecuronium in infants and children: clinical and neuromuscular effects

The neuromuscular and cardiovascular effects of vecuronium (Norcuron, Organon Teknika) were studied in 58 infants (1 day-10 months) and 65 children (1-6 years) anaesthetized either with halothane or under balanced anaesthesia. After a bolus dose of 70 micrograms/kg vecuronium the time course of neuromuscular blockade was determined using an electromyographic equipment. Onset time (time to maximal effect) was significantly shorter in infants compared with children; 1.4 +/- 0.7 min (min +/- SD) and 2.7 +/- 0.8 min, respectively. In contrast the recovery index (time for 25% to 75% recovery) was longer in infants than in children 18 +/- 6.7 min and 10 +/- 2.3 min, respectively. Repetitive administration of vecuronium, up to five maintenance doses, did not show any cumulative effects in children under balanced anaesthesia. After repetitive administration the recovery index was 12 +/- 1.7 min. Vecuronium (a bolus dose of 80 or 100 micrograms/kg) did not cause any significant change of blood pressure in infants and children anaesthetized either with halothane or by balanced anaesthesia. Infants under balanced anaesthesia showed a significant decrease in heart rate 15 min after administration of vecuronium. In contrast an increase in heart rate could be observed in children under halothane anesthesia, which was not attributed to vecuronium.     

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.     

Pharmacokinetics, placental transfer, and neonatal effects of vecuronium and pancuronium administered during cesarean section

Vecuronium and pancuronium were compared for placental transfer, pharmacokinetic variables, and neonatal effects during cesarean section under general anesthesia. Eighteen women underwent rapid-sequence intravenous induction using d-tubocurarine, succinylcholine, thiopental, and oxygen. Immediately after tracheal intubation, an intravenous injection of vecuronium (n = 11) or pancuronium (n = 7), 0.04 mg/kg, was given. Maternal venous blood samples were obtained before induction and at frequent intervals for 4 h after administration of vecuronium or pancuronium. Also, maternal venous and umbilical-cord arterial and venous blood samples were obtained at delivery. To describe placental transfer and maternal pharmacokinetics of the drugs, serum drug concentrations were determined using single-ion-monitoring mass spectrometry. The Apgar score and Neurologic and Adaptive Capacity Score (NACS) were used to evaluate neonatal condition. Both drugs crossed the placenta, as demonstrated by low concentrations of vecuronium (8.5-26.4 ng/ml) or pancuronium (12.2-34.2 ng/ml) found in umbilical venous blood. At delivery, the ratio of the drug concentration in umbilical venous blood to that in maternal venous blood was 0.11 +/- 0.02 for vecuronium and 0.19 +/- 0.03 for pancuronium. Vecuronium had a more rapid clearance (6.4 +/- 0.4 ml X kg-1 X min-1, mean +/- SE) and a shorter elimination half-life (36 +/- 1.8 min) than pancuronium (3.0 +/- 0.1 ml X kg-1 X min-1 and 72 +/- 6 min, respectively). No other pharmacokinetic differences were found between the drugs. Neonatal outcome was not affected adversely by either muscle relaxant, as assessed by Apgar scores and NACSs . The short duration of action, the minimal placental transfer, and the apparent lack of clinical neuromuscular effects on the newborn suggest that vecuronium should be a useful muscle relaxant for cesarean section.     

Effects of residual concentrations of isoflurane on the reversal of vecuronium-induced neuromuscular blockade.

Thirty-six anesthetized patients (ASA physical status 1 or 2) undergoing elective surgery were monitored (isometric adductor pollicis mechanical activity) to detect the effects of discontinuing isoflurane anesthesia upon the reversal of vecuronium-induced neuromuscular blockade. Neuromuscular blockade was produced by vecuronium 100 micrograms/kg and additional doses of 20 micrograms/kg until completion of surgery. The patients were randomly divided into three groups: in the control group (n = 12), only fentanyl/N2O was given; in the "isostable" group (n = 12), isoflurane at an end-tidal concentration of 1.25% was maintained throughout anesthesia; in the "isostop" group (n = 12), isoflurane 1.25% was discontinued before neostigmine administration. In all groups, paralysis was antagonized with 15 micrograms/kg intravenous (iv) atropine and 40 micrograms/kg iv neostigmine when the twitch height (0.1 Hz) had regained 25% of its control value. The measured parameters were twitch height, train-of-four, and 50--100-Hz tetanic fade. No significant differences were found among the three groups with respect to the final twitch heights and tetanic fades at 50 Hz. In the isostable group, final mean train-of-four was significantly less (75%) than in the other patients (88%) (P less than 0.01). Mean tetanic fade at 100 Hz was significantly less in the isostable group (31%) than in the isostop group (57%) (P less than 0.01) and control group (84%) (P less than 0.01). We conclude that discontinuing isoflurane anesthesia for 15 min improves the reversal of a vecuronium paralysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of vecuronium by continuous infusion with either isoflurane or fentanyl-nitrous oxide anesthesia

The average infusion rate and efficacy of vecuronium bromide continuous infusions for surgical relaxation in human subjects was evaluated. Nineteen adult patients requiring more than 120 min of neuromuscular blockade for surgery were randomized to receive either fentanyl-nitrous oxide (Group 1) or isoflurane-fentanyl-nitrous oxide (Group 2). Neuromuscular function was monitored using train-of-four evoked electromyography (EMG). Following an intubating dose of 0.08 mg/kg of vecuronium bromide, the first twitch was allowed to return to 10% of its control value. An infusion of vecuronium at an initial rate of 60.0 micrograms/kg/h was then started and adjusted to maintain the first twitch at 10% of control. The average infusion rate (total infusion dose divided by the duration of the infusion) was 57.2 +/- 14 micrograms/kg/h in Group 1 (n = 10) and 42.4 +/- 12 micrograms/kg/h (n = 9) in Group 2, approximately 25% less (p = 0.02). There was a significant decrease in the infusion rate with time in Group 1 (p = 0.02), but this decrease was not observed in Group 2.     

Lack of interaction between propofol and vecuronium.

We estimated the potency of vecuronium and measured the onset and duration of its action during total intravenous anesthesia with propofol to examine the possibility of any interaction between these two drugs. Propofol infusion was administered according to a three-step dosage scheme, and neuromuscular block was monitored by measuring the force of contraction of the adductor pollicis muscle after single-twitch stimulation of the ulnar nerve at 0.1 Hz. A control group of patients were similarly studied during anesthesia with thiopental, nitrous oxide, oxygen, and fentanyl. The ED50 and ED95 (dose required to produce a 50% and 95% depression of twitch tension, respectively) of vecuronium in patients given total intravenous anesthesia (n = 24) were 24 (22-27, 95% confidence limits) and 41 (37-48, 95% confidence limits) micrograms/kg, respectively, and in the control group (n = 24), 20 (17-24) and 39 (34-37) micrograms/kg, respectively. The onset of action of an 80-micrograms/kg dose (2 x ED95) of vecuronium was 3.6 +/- 1.2 and 4.1 +/- 1.7 min (mean +/- SD), in the propofol (n = 10) and control (n = 10) groups, respectively. The respective times to recovery of the twitch height to 25% of control and the recovery indices (25%-75% recovery of twitch height) in the propofol versus control groups were 28.3 +/- 6.6 and 28.0 +/- 1.7 min and 13.3 +/- 6.8 and 15.4 +/- 11.9 min, respectively. There were no significant differences in any of the measured variables between the propofol and control groups, indicating the lack of any interaction between propofol and vecuronium.     

Evolution of vecuronium requirements for stable mechanical effect: comparison with or without previous succinylcholine administration

To evaluate possible interactions between residual succinylcholine and vecuronium, the amount of vecuronium required to maintain the twitch height (TH) at 10% of its initial value was measured over a 90-min period by the on-demand infusion method in two series of 15 adult patients (ASA class I-II). One group, the vecuronium treatment (V) group, received 70 micrograms X kg-1 of vecuronium and the on-demand infusion. The second group, the succinylcholine-vecuronium treatment group (SV), was given 30 micrograms X kg-1 of vecuronium and on-demand infusion 5 min after the complete recovery of TH after administration of 1 mg X kg-1 of succinylcholine. During the first 10 min, the amount of vecuronium required to maintain TH at 10% of its control was significantly greater in the group given V than in the group given SV, 15122 +/- 856 (mean +/- SEM) vs 9851 +/- 486 micrograms X m-2 X hr-1 (P less than 0.001). Thereafter, the amount of vecuronium required to maintain TH at 10% of control was similar: 2808 +/- 275 and 3068 +/- 206 micrograms X m-2 X hr-1. When the infusion of vecuronium was stopped after 90 min, the time required for spontaneous recovery from 25 to 75% of control TH levels was similar: 20.1 +/- 3.3 min in the group given V and 18.9 +/- 2.5 min in the group given SV (not significant). We conclude that after a vecuronium on-demand infusion of long duration (lasting more than 90 min), previous succinylcholine administration does not interfere with late vecuronium requirements and the spontaneous rate of recovery of TH.     

Lidocaine hydrocarbonate and lidocaine hydrochloride for cesarean section: transplacental passage and neonatal effects

Twenty-six patients, ASA physical status 1, scheduled for elective cesarean section, were divided at random into two groups and received via an epidural catheter 20 ml of 2.2% lidocaine hydrocarbonate (17.3 mg.ml-1 lidocaine base) with 5 micrograms.ml-1 epinephrine freshly added (Group CO2 = 13 patients) or 20 ml of 2% lidocaine hydrochloride (17.3 mg.ml-1 lidocaine base) also with 5 micrograms.ml-1 epinephrine freshly added. Following clampage of the umbilical cord (at 40.1 +/- 4.9 min after the injection of lidocaine for the CO2 group and at 41.0 +/- 5.4 min for the HCl group), serum concentrations of lidocaine were measured both in the mother and in the umbilical vein. All newborns were examined by the same blinded pediatrician with Apgar scores at 1, 5 and 10 min and with Neurobehavioral Adaptive Capacity Scores (NACS) at 15 min, 2 h and 24 h. The concentrations of lidocaine in the serum were comparable in both groups: in the mothers 8.61 +/- 1.48 mumol.l-1 for the CO2 group vs 8.04 +/- 2.36 mumol.l-1 for the HCl group and in the newborns 3.86 +/- 0.84 mumol.l-1 for the CO2 group vs 3.92 +/- 0.95 mumol.l-1 for the HCl group. The ratio of umbilical vein to maternal vein concentrations of lidocaine was also similar in both groups: 0.45 +/- 0.07 for the CO2 group vs 0.54 +/- 0.24 for the HCl group. The percentage of newborns with a normal NACS (score > or = 35/40) was equal in both groups, i.e. 91% at 15 min and 2 h of life and 100% at 24 h of life.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

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 ([latin capital V with dot above]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 [latin capital V with dot above]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 <= 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 II: 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.     

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)     

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.     

Antagonism of vecuronium paralysis: comparison between edrophonium and neostigmine.

The reversal of vecuronium paralysis was studied in three series of anesthetized (methohexital, fentanyl, N2O/O2) informed adult patients receiving either 40 micrograms/kg neostigmine (NEO40) (n = 6), either 500 micrograms/kg edrophonium (EDRO500) (n = 6) or 1000 micrograms/kg edrophonium (EDRO1000) (n = 6). These drugs were given randomly once the adductor pollicis twitch height regained 10% of its initial value. The neuromuscular transmission recovery was assessed during 15 minutes after the antagonist administration, by recording twitch height (TH), train of four--2 Hz--every 3 minutes (TOF Ratio) and finally tetanic fade--50 Herz (TET50) and 100 Hz (TET100), 5 seconds duration, one minute apart--. At 15 minutes, the TH values (mean +/- SEM) were for EDRO500 92% +/- 7, for EDRO1000 93% +/- 3 and for NEO40 100% +/- 4 percent (n.s.). For the TOF Ratio, a statistical difference (p less than 0.05) was found between NEO40 86% +/- 4 and the two other groups: EDRO500 73% +/- 3, EDRO1000 69% +/- 4. For the TET50, the values were: EDRO500 93% +/- 3, EDRO1000 86% +/- 5 and NEO40 94% +/- 2 (n.s.). At 100 Hz, the values were: NEO40 61% +/- 8, EDRO500 43 +/- 151 and EDRO1000 31 +/- 12 (p less than 0.01). In conclusion, in the conditions studied, 40 micrograms/kg neostigmine restores the neuromuscular transmission of the adductor pollicis at a higher level than edrophonium 500 micrograms/kg does. Edrophonium, 1000 micrograms/kg instead of 500 micrograms/kg does not change the neuromuscular transmission recovery.     

Benzodiazepines and neuromuscular blocking drugs in patients

The interaction between four benzodiazepines (diazepam, lorazepam, lormetazepam and midazolam) and two nondepolarizing neuromuscular blocking drugs (vecuronium and atracurium) was investigated in 113 patients during general anaesthesia. Neuromuscular function was monitored by recording the mechanical twitch tension of the adductor pollicis muscle of the thumb in response to ulnar nerve stimulation with single supramaximal stimuli of 0.2 ms at 0.1 Hz. In the first group of patients a benzodiazepine (diazepam 20 mg, lorazepam 5 mg, lormetazepam 2 mg or midazolam 15 mg), was injected i.v. 15 min before a single bolus of vecuronium 45 micrograms kg-1. In the second group of patients suxamethonium 1 mg kg-1 was given for endotracheal intubation, and 30 min later the patients received atracurium 200 micrograms kg-1. Fifteen min before injection of atracurium one of the same benzodiazepines as in the first group was injected i.v. Comparisons were made with control patients receiving thiopentone. Neither benzodiazepine caused significant potentiation of neuromuscular blocking agents in comparison with control. With midazolam, however, the duration to 25% and to 75% recovery of the twitch height after vecuronium was significantly longer than with diazepam. The time to 25% recovery of the twitch height after atracurium was significantly longer in patients receiving midazolam than in those receiving diazepam. The recovery index was not influenced by the four benzodiazepines.     

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)     

Characterization of the train-of-four response in fast and slow muscles: effect of d-tubocurarine, pancuronium, and vecuronium

The in vivo cat soleus and gastrocnemius muscles were used to compare isometric contraction strength and the train-of-four (T4) response (2 Hz for 2 s) of two muscle types (fast and slow) during onset of competitive neuromuscular blockade in order to determine the extent of the correlation between twitch depression and T4 fade. Prior to drug administration the muscles that were studied differed significantly in that the T4 ratio was 1.0 in the gastrocnemius and only 0.87 in the soleus. Three competitive neuromuscular-blocking agents were compared: d-tubocurarine, pancuronium, and vecuronium. d-Tubocurarine was found to produce a close correlation between the degrees of twitch strength depression and T4 for both muscles. However, these muscles demonstrated significantly different ED50 values (105 micrograms/kg for gastrocnemius, 150 micrograms/kg for soleus). Pancuronium also produced a similar relationship between twitch strength depression and T4 decrement for each muscle. In this case, however, there was little difference in their ED50 values for twitch depression (11.5 micrograms/kg for gastrocnemius, 13 micrograms/kg for soleus). The effects of vecuronium were quite different from the other two muscle relaxants. Although vecuronium produced a comparable correlation between twitch tension and T4 fade in fast muscle, no such relationship was found to exist in slow muscle. Even when the twitch strength was blocked to 18% of control, the soleus T4 response was depressed to only 75% of control. These results highlight major differences among competitive neuromuscular-blocking agents and suggest multiple sites of action.