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.     

Vecuronium infusion requirements in pediatric patients during fentanyl-N2O-O2 anesthesia

Eighty-one pediatric patients, ranging from neonates to adolescents, were studied during fentanyl-N2O-O2 anesthesia to determine for each of them the vecuronium infusion required to maintain 90-95% neuromuscular block (NMB). Electromyographic monitoring with train-of-four stimuli was used. The steady infusion rate was 62 +/- 15 (SD) micrograms.kg-1.hr-1 in neonates and infants. This rate was 40% of that required by children 3 to 10 years old (154 +/- 49 micrograms.kg-1.hr-1; P less than 0.05). In adolescents the vecuronium requirement was less than in children and was comparable to that reported in adults in other studies (89 +/- 13 micrograms.kg-1.hr-1). Despite considerable individual variation, the infusion rate could be reliably estimated on the basis of duration of greater than 90% NMB maintained by small doses of vecuronium given after intubation. Also, a close correlation existed between the duration of greater than 90% NMB maintained by 100 micrograms/kg of vecuronium and the individual infusion rate (r2 = 0.76).     

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

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

Vecuronium in pediatric anesthesia. Repeated bolus vs continuous infusion]

Vecuronium bromide was employed in 26 pediatric patients; 18 received vecuronium infusion and 11 intermittent bolus administration. The aim of the study was to evaluate the pharmacodynamics of the drug, the lack of cumulative properties, the best infusion rate, the possible advantage of the infusion technique. Neuromuscular blockade monitoring was performed in all patients. In the results, vecuronium shows lack of cumulative properties. The best infusion rate was 0.13 +/- 0.02 mg/kg/h. The continuous infusion allows the employment of lesser doses of the drug than the intermittent administration.     

Mivacurium infusion requirements in pediatric surgical patients during nitrous oxide-halothane and during nitrous oxide-narcotic anesthesia

We were interested in determining the infusion rate of mivacurium required to maintain approximately 95% neuromuscular blockade during nitrous oxide-halothane (0.8% end-tidal) or nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity (Datex NMT) of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Mivacurium steady-state infusion requirements averaged 315 +/- 26 micrograms.m-2.min-1 during nitrous oxide-halothane anesthesia and 375 +/- 19 micrograms.m-2.min-1 (mean +/- SEM) during nitrous oxide-narcotic anesthesia. Higher levels of pseudocholinesterase activity were generally associated with a higher mivacurium infusion requirement. During both anesthetics, younger age was associated with a higher infusion requirement when the infusion requirement was calculated in terms of micrograms.kg-1.min-1. This difference was not present when the infusion rate was calculated in terms of micrograms.m-2.m-1. There was no evidence of cumulation during prolonged mivacurium infusion. There was no difference in the rates of spontaneous or reversal-mediated recovery between anesthetic groups. After the termination of the infusion, spontaneous recovery to T4/T1 greater than or equal to 0.75 occurred in 9.8 +/- 0.4 min, with a recovery index, T25-75, of 4.0 +/- 0.2 min (mean +/- SEM). In summary, pseudocholinesterase activity is the major factor influencing mivacurium infusion rate in children during nitrous oxide-narcotic or nitrous oxide-halothane (0.8% end-tidal) anesthesia.     

The potency (ED50) and cardiovascular effects of rapacuronium (Org 9487) during narcotic-nitrous oxide-propofol anesthesia in neonates, infants, and children.

We studied the neuromuscular blocking effects of rapacuronium (Org 9487) (dose-response curve, onset, and 50% effective dose [ED50] value), and changes in heart rate and blood pressure, as well as evidence of histamine release in neonates, infants, and children in an open-label, randomized, two-center study. Fifteen neonates, 30 infants, and 30 children were studied. Anesthesia was induced and maintained with propofol, nitrous oxide:oxygen (60:40), and fentanyl. Mechanomyographic monitoring of neuromuscular function was performed at the thumb. The potency (ED50) for neonates, infants, and children were 0.32 (95% confidence interval [CI] 0.15-0.61), 0.28 (95% CI 0.11-0.61), and 0.39 (95% CI 0.17-0.85) mg/kg, respectively. Neonates who received 0.3, 0.6, or 0.9 mg/kg Org 9487 developed a maximum T1 twitch depression of 34 +/-28%, 98 +/- 3%, and 99 +/- 2%, respectively. Time-to-peak effect (onset time) for 0.9 mg/kg Org 9487 was 57 +/- 20 s. Maximum percent T1 twitch depression (+/-SD) in infants who received 0.3, 0.6, or 0.9 mg/kg rapacuronium was 41 +/- 34%, 96 +/- 7%, and 100 +/- 1%, respectively. Time-to-peak effect for 0.9 mg/kg Org 9487 was 62 +/- 29 s. In children 0.3, 0.6, and 0.9 mg/kg rapacuronium resulted in an average percent T1 twitch suppression of 29 +/- 23, 83 +/- 11, and 90 +/- 16, respectively. Time-to-peak effect of 0.9 mg/kg Org 9487 was 96 +/- 33 s, respectively. There was no evidence of histamine release or significant changes in heart rate or blood pressure in either group at any dose. Rapacuronium is a low-potency nondepolarizing muscle relaxant with a fast onset of relaxation and minimal cardiovascular effects. Its potency (ED50) is similar in neonates (0.32 mg/kg), infants (0.28 mg/kg), and children (0.39 mg/kg). T1 suppression (90% +/- 16) is less and time to peak effect (96 +/- 33 s) is greater (0.9 mg/kg rapacuronium) in children, compared with the combined group of infants and neonates. IMPLICATIONS: This study assesses the potency of rapacuronium (Org 9487) in pediatric patients. The potency of rapacuronium is similar in neonates (0.32 mg/kg), infants (0.28 mg/kg), and children (0.39 mg/kg).     

Vecuronium requirement during liver transplantation under sevoflurane anesthesia

Purpose  

In liver transplantation patients under intravenous anesthesia, the vecuronium dose is known to be reduced, especially during the anhepatic phase. Volatile anesthetics potentiate a muscle relaxation effect of neuromuscular blocking agents, so the vecuronium dose is supposed to further decrease if sevoflurane is used during liver transplantation. The purpose of this study was to determine the appropriate dose of vecuronium at each phase of liver transplantation under sevoflurane anesthesia.     

安氟醚,七氟醚对维库溴铵肌松作用的影响

目的：观察１．０ＭＡＣ的安氟醚或七氟醚对０．０５ｍｇ·ｋｇ－１的维库溴铵临床药效的影响。方法：选择３０例择期手术病人随机分为３组，异丙酚组以异丙酚６～８ｍｇ·ｋｇ－１·ｈ－１及间断追加芬太尼维持麻醉，安氟醚组和七氟醚组分别吸入１．０ＭＡＣ的安氟醚和七氟醚维持麻醉。监测起效时间、最大抑制程度、维持时间、维持剂量。结果：安氟醚组、七氟醚组与对照组在起效时间、最大抑制程度方面的差异无显著性，而在维持时间、维持剂量上的差异则有显著性，分别是对照组的１．９倍、１．８倍和４６．２％、４８．７％。结论：安氟醚和七氟醚能明显延长维库溴铵的维持时间并减少其维持剂量，但对起效时间和最大抑制程度则无明显影响。     

Vecuronium infusion requirements in paediatric patients in intensive care units: the use of acceleromyography

Neuromuscular blocking drugs in intensive care units (ICU) may cause complications, including prolonged neuromuscular block as a result of overdosage and post-ventilation muscle weakness. These may be increased by using inappropriately high infusion rates for infants, in whom published studies are scarce, and by failure to monitor neuromuscular block. There is little ICU experience of acceleromyography, which may permit more reliable monitoring. To determine appropriate vecuronium infusion rates, 12 neonates/infants (median age 4 (interquartile range (IQR) 2-5) months) and 18 children (median age 3.07 (2-10 yr) were studied. The vecuronium infusion rate was adjusted to maintain train-of- four (TOF) at 1 response using the TOF guard accelerometer. Recovery time was measured from cessation of infusion until spontaneous TOF ratio recovery of 0.7. Neonates and infants required 45% less vecuronium (mean infusion rate 54.7 (SEM 4.23) micrograms kg-1 h-1) than older children (98.7 (7.07) micrograms kg-1 h-1) and had faster recovery to 70% T4/T1 (45 (IQR 20-51) min vs 65 (55-103) min), with no evidence of prolonged weakness. Routine monitoring of neuromuscular block in ICU is essential; acceleromyography is convenient and reliable.      

Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children

PURPOSE: To determine the effect of moderate and deep hypothermic cardiopulmonary bypass (CPB) on the pharmacokinetic and pharmacodynamic behaviour of vecuronium in infants and children. METHODS: We studied 12 patients undergoing surgery for congenital heart disease under narcotic-nitrous oxide anesthesia. Neuromuscular blockade was maintained constant (TI 4-10% by Datex electromyograph) by adjusting a vecuronium infusion. Plasma vecuronium concentrations (Cpss) were analysed by HPLC to describe a pseudosteady-state during each of the pre-CPB, CPB and post-CPB phases. Paired arterial blood samples were taken 20 min apart after at least 20 min of constant infusion. RESULTS: Nine cases were analysed, mean age 20 mo, mean weight 9 kg. Three patients had deep and six moderate hypothermia. In the pre-CPB phase Cpss fell into two groups (mean +/- SD: 330 +/- 42 ng x ml(-1); 127 +/- 27 ng x ml(-1); P < 0.001); similarly the clearances showed a bimodal distribution (mean +/- SD: 5.08 +/- 0.94; 11.51 +/- 0.2 ml x min(-1) x kg(-1) P < 0.001), although in different patients. During CPB this bimodal distribution disappeared. Vecuronium infusion rate (VIR) decreased by 84% and 92% from pre-CPB to CPB phase in deep and moderate hypothermia groups respectively (P < 0.05), paralleled by decreases in Cpss of 36% (P > 0.05) and 52% (P < 0.05). CONCLUSION: Changes in vecuronium requirements and plasma concentrations during CPB demonstrate that vecuronium pharmacokinetics and pharmacodynamics are both affected by hypothermic CPB in infants. The finding of bimodal distributions for plasma vecuronium and vecuronium clearance highlights the need for individual monitoring of neuromuscular blockade in this age group.     

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.     

Perioperative opiate requirements in children with previous opiate infusion

Background: Critically ill children often require continuous opiate infusions. Tolerance may develop requiring a weaning strategy to prevent withdrawal symptoms. These children may also require subsequent surgical procedures. This is the first study to investigate whether previously opiate‐tolerant patients require higher doses of opiates for adequate pain management perioperatively. Methods: A retrospective study was conducted at a tertiary children’s hospital to investigate whether children previously exposed to continuous opiates for 10 or more days with subsequent weaning from those opiates will have similar or increased perioperative opiate requirements when compared to opioid‐naïve controls. Study patients included 31 children with previous continuous opiate exposure for 10 or more days followed by weaning and without signs of withdrawal for at least 72 h prior to the surgical procedure. Excluded were patients over 18 years of age, those whose surgical procedures would be unlikely to require perioperative opiates, oncological patients, burn patients, neurologically devastated patients, and patients who received regional anesthesia in addition to perioperative narcotics. The control group consisted of 31 age‐ and case‐matched opiate‐naïve patients who underwent a surgical procedure during a similar time frame as the study patient. The medication administration record was reviewed for the length of continuous opiate exposure, date of last opiate use prior to a subsequent surgical procedure, and opiate use during the perioperative period. Opiate use was calculated as morphine equivalents per kilogram body weight (MSEQ·kg^?1). The Wilcoxon rank sum test was used for univariate comparisons between matched pairs, and P‐values <0.05 were considered statistically significant. Results: The perioperative opiate requirements in opiate‐exposed patients (median, interquartile range: 0.14, 0.08–0.25 MSEQ·kg^?1) were not significantly different from opiate‐naïve patients (median, interquartile range 0.10, 0.05–0.2 MSEQ·kg^?1, P = 0.19). Pain scores indicated that patients were generally comfortable in the perioperative period. Conclusions: The perioperative opiate requirements of pediatric patients who were successfully weaned after prolonged opiate use were similar to opiate‐naïve patients. A history of prolonged opiate use alone does not necessitate special pain management for future procedures.     

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.     

Dose-response relationship and infusion requirement of cisatracurium besylate in infants and children during nitrous oxide-narcotic anesthesia

BACKGROUND: To determine the effect of age on the dose-response relation and infusion requirement of cisatracurium besylate in pediatric patients, 32 infants (mean age, 0.7 yr; range, 0.3-1.0 yr) and 32 children (mean age, 4.9 yr; range, 3.1-9.6 yr) were studied during thiopentone-nitrous oxideoxygen-narcotic anesthesia. METHODS: Potency was determined using a single-dose (20, 26, 33, or 40 microg/kg) technique. Neuromuscular block was assessed by monitoring the electromyographic response of the adductor pollicis to supramaximal train-of-four stimulation of the ulnar nerve at 2 Hz. RESULTS: Least-squares linear regression analysis of the log-probit transformation of dose and maximal response yielded median effective dose (ED50) and 95% effective dose (ED95) values for infants (29+/-3 microg/kg and 43+/-9 microg/kg, respectively) that were similar to those for children (29+/-2 microg/kg and 47+/-7 microg/kg, respectively). The mean infusion rate necessary to maintain 90-99% neuromuscular block during the first hour in infants (1.9+/-0.4 microg x kg(-1) x min(-1); range: 1.3-2.5 microg x kg(-1) x min(-1)) was similar to that in children (2.0+/-0.5 microg x kg(-1) x min(-1); range: 1.3-2.9 microg x kg(-1) x min(-1)). CONCLUSION: The authors conclude that cisatracurium is equipotent in infants and children when dose is referenced to body weight during balanced anesthesia.     

Music decreases sedative requirements during spinal anesthesia

Ambulatory surgery can create significant anxiety. This prospective study measured whether music can influence anxiety and perioperative sedative requirements in outpatients undergoing surgery with spinal anesthesia. We also evaluated the correlation between two anxiety measures, the State-Trait Anxiety Inventory test (STAI) and the 0- to 10-cm visual analog scale (VAS 0-10), with 0 meaning complete relaxation and 10 the worst feeling of anxiety possible. Fifty unpremedicated patients were randomly assigned to listen to music of their choice via headset during the perioperative period (Group I) or to have no music (Group II). All participants used patient-controlled IV midazolam sedation and underwent repeated evaluations of their anxiety level with the STAI and the VAS 0-10. Midazolam requirements during surgery (Group I, 0.6 +/- 0.7 versus Group II, 1.3 +/- 1.1 mg; P < 0.05) and for the whole perioperative period (Group I, 1.2 +/- 1.3 versus Group II, 2.5 +/- 2.0 mg; P < 0.05) were smaller in patients listening to music. Anxiety levels, measured with STAI or VAS 0-10, were similar in both groups. The Spearman's coefficient values between STAI and VAS 0-10 ranged from 0.532 to 0.687. We conclude that patients listening to music require less midazolam to achieve a similar degree of relaxation as controls and that measures of anxiety obtained from the STAI and the VAS 0-10 are positively, but only moderately, correlated. IMPLICATIONS: It is possible to decrease sedative requirements during surgery under spinal anesthesia by allowing patients to listen to music to reduce their anxiety.     

Propofol requirements for induction of anesthesia in children of different age groups.

To demonstrate any age-related differences in propofol requirements for induction of anesthesia, 150 healthy children aged 3-5 yr (n = 50), 6-9 yr (n = 50), and 10-15 yr (n = 50) scheduled for outpatient surgery were randomly assigned to receive an induction dose of propofol of 1.5, 2.0, 2.5, 3.0, or 3.5 mg/kg. To limit pain during injection, alfentanil (5 micrograms/kg) was administered before the propofol. Patients were classified as asleep or not asleep 30 s after the propofol. Incidence of excitation, injection pain, and apnea during induction of anesthesia were noted; arterial blood pressure and heart rate were recorded for 5 min after induction. More than 95% of the children were asleep in the dose groups receiving > or = 2.5 mg/kg. The number of patients falling asleep after receiving 1.5 mg/kg of propofol increased significantly with increasing age (P < 0.05); the difference between the oldest and the youngest age groups was the most significant (P < 0.05). Significant decreases in mean arterial blood pressure and heart rate occurred after induction in all dose and age groups without any systematic intergroup differences. Apnea occurred more frequently in older children (P < 0.01) and with larger doses (P < 0.01). The most frequent side effect was erythema near the site of injection, and its occurrence was dose dependent. The authors conclude that 2.5 mg/kg of propofol, if preceded by 5 micrograms/kg of alfentanil, is an appropriate induction dose for children aged 3-15 yr and that the sleep response to 1.5 mg/kg is more in older children.     

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

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