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.     

Pharmacokinetics and pharmacodynamics of vecuronium and pancuronium in anesthetized children

The pharmacokinetics and pharmacodynamics of vecuronium and pancuronium were determined in 12 children (3-6 yr) undergoing minor surgery under 60% nitrous oxide, 1 MAC halothane anesthesia. When the level of anesthesia and the electromyograph (EMG) recording of the adductor pollicis were stable, an intravenous bolus of vecuronium (100 micrograms/kg) or pancuronium (100 micrograms/kg) was administered. Plasma concentrations of the two muscle relaxants were determined for 6 hr after the administration by means of a fluorimetric assay followed by a thin layer chromatography. Plasma concentrations of vecuronium and pancuronium declined biexponentially in children and no metabolites could be detected in plasma. The elimination half-lives of vecuronium and pancuronium did not differ significantly. The volume of distribution at steady state (Vdss) was greater (P less than 0.05) after vecuronium (320 +/- 181 ml/kg; mean +/- SD) than after pancuronium (203 +/- 36 ml/kg). Plasma clearance of vecuronium (2.8 +/- 0.9 ml X min-1 X kg-1) was greater than that of pancuronium (1.7 +/- 0.2 ml X min-1 X kg-1; P less than 0.05). Plasma concentrations measured at 10%, 50%, or 90% recovery of the EMG response did not differ significantly for vecuronium and pancuronium. Thus the shorter duration of action of vecuronium is probably due to its greater apparent volume of distribution, as well as to its higher plasma clearance. Thus although the elimination half-lives are comparable, the plasma disappearance of vecuronium is more rapid than that of pancuronium.     

Pharmacokinetics and pharmacodynamics of vecuronium (ORG NC45) and pancuronium in anesthetized humans

The pharmacokinetics and pharmacodynamics of vecuronium (25-50 micrograms/kg) and pancuronium (25-50 micrograms/kg) were determined in nine ASA class I or II patients anesthetized with nitrous oxide and halothane. Force of thumb adduction in response to supramaximal stimulation of the ulnar nerve was quantified and recorded. Serum concentrations of the muscle relaxants were determined for eight hours after their administration using a mass spectrometry assay. Data were analyzed by nonlinear regression and fit to a three-compartment pharmacokinetic model and a four-compartment pharmacodynamic model. Vecuronium had a more rapid clearance (5.2 +/- 0.7 ml X kg-1 X min-1; mean +/- SD) and a shorter elimination half-life (71 +/- 20 min) as compared with pancuronium (1.8 +/- 0.4 ml X kg-1 X min-1; 140 +/- 25 min). No other pharmacokinetic differences were found between the drugs. Pharmacodynamic analysis showed that the plasma concentration at steady state which produced a 50% neuromuscular blockade (Cpss 50) was similar for vecuronium and pancuronium. The authors conclude that the drugs are equivalent in their onset and potency; however, the more rapid clearance and shorter elimination half-life for vecuronium provides a kinetic basis for its shorter duration of neuromuscular blockade as compared with pancuronium.     

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.     

Pharmacokinetics of midazolam used as an intravenous induction agent for patients over 80 years of age

The pharmacokinetic profile of 0.2 mg kg-1 midazolam given i.v., for induction of anaesthesia, was compared in young subjects and in those who were over 80 years of age. Thirty-five patients were allocated into four groups according to their sex and age. Plasma samples were drawn before midazolam injection and at regular intervals over 24 h following injection. Plasma midazolam concentrations were measured by electron capture gas-liquid chromatography. Equilibrium dialysis was used to assess the plasma protein binding of midazolam. Distribution volume (Vdss) was significantly increased in elderly subjects when compared to young subjects of the same sex (young vs. elderly males, Vdss = 1.22 +/- 0.31 l kg-1 and 2.47 +/- 0.98 l kg-1 respectively; and young vs. elderly females, Vdss = 0.91 +/- 0.29 l kg-1 and 1.70 +/- 0.78 l kg-1 respectively). Total body clearance was significantly reduced in elderly males compared with young males (5.60 +/- 1.77 ml min-1 kg-1 vs. 8.10 +/- 3.58 ml min-1 kg-1). No significant difference in clearance was found between young and elderly females (6.08 +/- 2.04 ml min-1 kg-1 vs. 9.14 +/- 3.36 ml min-1 kg-1). As a consequence, elimination half-life (T1/2E) was significantly prolonged in elderly compared to young males (8.52 +/- 5.4 h vs. 2.77 +/- 0.80 h). In contrast, T1/2E was unchanged in elderly compared to young females (2.99 +/- 0.86 h vs. 2.86 +/- 1.04 h). Midazolam plasma protein binding was not influenced by age and sex.     

Neuromuscular and cardiovascular effects of pipecuronium

Pipecuronium bromide (Arduan) is a bisquaternary, steroid-type neuromuscular blocking agent in clinical use in Eastern Europe. Before its introduction into clinical practice in the USA, in the first phase of this study the neuromuscular potency of pipecuronium was determined under "balanced" and enflurance anaesthesia by the cumulative log dose-response method in 30 patients each. In the second phase the intubation and onset times, clinical duration of the first and repeated doses, spontaneous recovery index, reversibility of its residual neuromuscular effect by an anticholinesterase and its effect on heart rate and blood pressure was compared with the same variables observed in patients, anaesthetized with identical techniques but who had received vecuronium or pancuronium. The neuromuscular potency of pipecuronium was greater under enflurane (ED95 = 23.6 +/- 1.1 micrograms.kg-1 (mean +/- SEM)] than under balanced (ED95 = 35.1 +/- 17 micrograms.kg-1) anaesthesia. Pipecuronium was more potent than vecuronium under both balanced (ED95 = 45.8 micrograms.kg-1) and enflurane anaesthesia (ED95 = 27.4 micrograms.kg-1). Following the administration of 2 x ED95 doses there were no clinically significant differences in the intubation or onset times of pipecuronium, vecuronium and pancuronium. Under balanced anaesthesia the clinical duration of 2 x ED95 dose of pipecuronium (110.5 +/- 0.3 min) or pancuronium (115.8 +/- 8.1 min) were similar and about three times longer than that of vecuronium (36.3 +/- 2.1 min). The recovery indices of pipecuronium (44.5 +/- 8.2 min) and pancuronium (41.3 +/- 4.2 min) were also similar and about three times longer than that of vecuronium (14.3 +/- 1.4 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and disposition of pipecuronium bromide in the cat

The pharmacokinetics and hepatic disposition of pipecuronium have been investigated in cats with normal and absent renal function. A combined fluorimetric and chromatographic technique was used to determine the concentrations of pipecuronium and its metabolites in the samples. Following intravenous injection of 150 micrograms kg-1, pipecuronium disappeared from the plasma bi-exponentially with half-lives of 9.8 +/- 5.4, 77.7 +/- 9.7 min and 7.2 +/- 5.0, 100, 6 +/- 23.7 min; the Vd was 362.3 +/- 74.9 ml kg-1 and 123.7 +/- 14.6 ml kg-1 and the clearance was 5.0 +/- 0.9 ml min-1 kg-1 and 1.0 +/- 0.1 ml min-1 in the animals with and without renal function, respectively. In the animals with normal kidney function 53%, 12% and 8% of the administered dose of pipecuronium were recovered within 8 h in the urine, bile and liver, respectively. In 'nephrectomized' cats the lack of renal elimination was to a great extent compensated for by increased hepato-biliary elimination. Absence of renal function significantly altered the pharmacokinetic parameters and prolonged the time-course of the neuromuscular blocking effects of pipecuronium. Neither temporary hepatic exclusion nor intraportal administration of pipecuronium indicated any significant role of the liver in handling pipecuronium. Renal excretion seems to be the predominant route of elimination. No metabolites were found in this study.     

Comparative pharmacokinetics and dynamics of vecuronium and pancuronium in anesthetized patients

Plasma concentrations and the degree of neuromuscular blockade after a 2-min infusion of 0.1 mg/kg of vecuronium bromide or pancuronium bromide (equipotent doses) were studied in 12 gynecologic patients. The plasma concentrations of both drugs declined in a triphasic manner. The difference between the intercepts and rate constants of the two drugs was not significant. Vecuronium was removed faster from the plasma than pancuronium; this was reflected in a significantly larger plasma clearance rate for vecuronium (4 ml X min-1 X kg-1 vs 1.1 ml X min-1 X kg-1 for pancuronium). The effective plasma concentrations at 50% recovery of the twitch height were 0.11 +/- 0.02 (vecuronium) and 0.2 +/- 0.03 microgram/ml (pancuronium). The disposition kinetics were adequately described by a three-compartment model. An effect compartment was added to the model to correlate the neuromuscular effects and plasma concentrations of both drugs. The ratio between concentrations of vecuronium and pancuronium in the effect compartment at 50% twitch height was 0.83. In spite of its greater potency, vecuronium has a shorter duration of action than pancuronium.     

Pharmacokinetics and disposition of pipecuronium bromide in dogs with and without ligated renal pedicles

The pharmacokinetics of pipecuronium bromide have been studied in anesthetized beagle dogs with and without ligated renal pedicles. A gas chromatographic assay was used to measure the plasma, urine, bile concentrations, and liver content of pipecuronium, the later of which was obtained 8 h after injection. Following an iv bolus injection of 0.1 mg/kg, pipecuronium disappeared from the plasma exponentially with distribution half-lives of 3.9 +/- 1.1 min and 12.7 +/- 9.5 min (mean +/- SD), and elimination half-lives of 44.8 +/- 2.6 min and 196.7 +/- 102.0 min in animals with and without renal pedicle ligation, respectively. Except for the volume of central compartment, all other pharmacokinetic variables differed significantly between the two experimental groups. The elimination half-life was longer (196.7 +/- 102 (SD) vs. 44.8 +/- 2.6 min), plasma clearance slower (5.9 +/- 0.8 ml.kg-1.min-1 vs. 0.9 +/- 0.1 ml.kg-1.min-1) and mean residence time longer (221 +/- 73 vs. 51.1 +/- 1.8 min) in dogs with ligated renal pedicles. Eight hours after injection, the recovery of the parent form of pipecuronium approximated 77% of the administered dose in the urine, 4.5% in the bile, and 3.3% in the liver of normal animals. In animals with ligated renal pedicles 16% of the unchanged pipecuronium was excreted into the bile and 10% of the administered dose was recovered from the liver. Since the total recovery of unaltered pipecuronium approximated 85% of the administered dose in the intact animals, biotransformation seems to play an insignificant role in disposition of this new neuromuscular blocking drug.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of renal failure on the pharmacokinetics and duration of action of pipecuronium bromide in patients anesthetized with halothane and nitrous oxide

The authors determined the pharmacokinetics and duration of action of a bolus dose of pipecuronium bromide (0.07 mg.kg-1) in 40 patients anesthetized with halothane and nitrous oxide. Twenty were patients with normal renal function, undergoing a variety of surgical procedures, and 20 were undergoing cadaver renal transplantation because of end-stage renal disease. Plasma concentrations of pipecuronium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay. Plasma concentration versus time data were analyzed by nonlinear regression and fit to a two-compartment or three-compartment model; in addition, the data were analyzed by a non-compartmental method based on statistical moments. Neuromuscular blockade was assessed by measuring the mechanical evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The pharmacokinetic parameters derived by compartmental modelling were (normal vs. renal failure, respectively): volume of distribution at steady state (309 +/- 103 vs. 442 +/- 158 ml.kg-1, mean +/- SD), plasma clearance, (2.4 +/- 0.6 vs. 1.6 +/- 0.6 ml.kg-1.min-1), mean residence time (140 +/- 63 vs. 329 +/- 198 min), and elimination half-life (137 +/- 68 vs. 263 +/- 168 min). The same parameters as derived by the non-compartmental method were (normal vs. renal failure, respectively): volume of distribution at steady state (307 +/- 80 vs. 426 +/- 119 ml.kg-1, mean +/- SD), plasma clearance (2.4 +/- 0.6 vs. 1.6 +/- 0.6 ml.kg-1.min-1), mean residence time (134 +/- 41 vs. 323 +/- 228 min), and elimination half-life (118 +/- 35 vs. 247 +/- 168 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of intravenously administered meptazinol during general anaesthesia in man

The pharmacokinetics of meptazinol (3 mg kg-1 i.v.), a centrally acting opioid agonist-antagonist, were studied in six male and six female patients during anaesthesia with 1-3 vol.% enflurane and an infusion of 10-30 micrograms kg-1 min-1 etomidate. Arterial blood samples were taken up to 300 min postinjection. The plasma meptazinol concentrations, determined by HPLC, best fitted to a three-compartment open mamillary model with central elimination using a non-linear extended least-squares regression analysis. Derived pharmacokinetic parameters indicated a rapid distribution (T1/2 pi = 1.24 +/- 0.83 min, T1/2 alpha = 7.55 +/- 3.97 min), a short elimination half-life (T1/2 beta = 86.9 +/- 15.6 min), a volume of the central compartment twice as large in females (Vc = 0.557 +/- 0.237 l kg-1) as in males (Vc = 0.274 +/- 0.144 l kg-1), a small distribution volume at steady state (Vss = 2.52 +/- 0.66 l kg-1) and a high total plasma clearance (ClP = 1547 +/- 385 ml min-1). The elimination rate microconstant in females (k10 = 0.0577 +/- 0.0337 min-1) was significantly lower than in males (k10 = 0.1093 +/- 0.0437 min-1 with a lower drug fraction in the central compartment in the post-distributive phase (Fc = males: 0.08 +/- 0.02, females 0.19 +/- 0.11). As Vss and ClP were similar in both groups, sex-related differences were only observed in the dynamics of distribution of the drug. From a pharmacokinetic point of view we suspect that meptazinol shows very little cumulation on repeated i.v. administration as necessary during anaesthesia.     

Adenosine potentiation of neuromuscular blocking agents in guinea-pigs

We have investigated the effects of adenosine i.v. on neuromuscular block induced by rocuronium, vecuronium and pipecuronium in an in vivo guinea-pig sciatic nerve-tibialis anterior preparation. The ED50 of each neuromuscular blocker was determined from cumulative log dose- response regression lines (n = 14). In separate experiments, adenosine 0.1 mg kg-1 min-1 or the same volume of 0.9% NaCl was given i.v. via a constant infusion and the ED50 of each neuromuscular blocking agent was then administered (n = 24). Adenosine 0.1 mg kg-1 min-1 increased significantly maximal block induced by the ED50 of these neuromuscular blockers (55-72%, 49-73% and 60-96%, respectively, for rocuronium, vecuronium and pipecuronium; P < 0.05). Time to maximal block after rocuronium was significantly prolonged by adenosine (1.4-2.1 min; P < 0.05) and time to maximal block after vecuronium and pipecuronium was unchanged by adenosine. Time to maximal recovery of twitch tension after administration of the ED50 of all neuromuscular blocking agents was prolonged significantly by adenosine (4.5-10.7 min, 8.2-15.8 min and 47.0-128.7 min, respectively, for rocuronium, vecuronium and pipecuronium; P < 0.05). We conclude that continuous infusion of adenosine 0.1 mg kg-1 min-1 potentiated the effects of neuromuscular blocking agents in this in vivo guinea-pig preparation.      

The incidence of myocardial ischemia during anesthesia for coronary artery bypass surgery in patients receiving pancuronium or vecuronium

This study was performed to compare the incidence of prebypass myocardial ischemia in patients receiving fentanyl and enflurane for anesthesia along with either pancuronium or vecuronium. Ninety-eight patients with normal left ventricular function were randomly allocated to receive either pancuronium 0.15 mg.kg-1 or vecuronium 0.15 mg.kg-1 in a double-blind manner after fentanyl 40 micrograms.kg-1 for induction of anesthesia for elective coronary artery bypass grafting (CABG). Premedication included diazepam 0.15 mg.kg-1 po, morphine 0.10 mg.kg-1, and scopolamine 0.005 mg.kg-1 im. Two lead Holter monitor recordings (leads V6 and V9) from the time of arrival in the operating suite to institution of cardiopulmonary bypass were analyzed for ischemia by a cardiologist blinded to the choice of muscle relaxant. Intraoperatively, heart rates greater than 90 beats.min-1 and systolic blood pressure +/- 20% of ward values were treated with propranolol, enflurane, or phenylephrine. Nitroglycerin was infused for ECG signs of ischemia or pulmonary hypertension. After induction of anesthesia the heart rate and cardiac index were consistently decreased in patients receiving vecuronium and also lower in these patients compared with those receiving pancuronium. Thirty-two per cent of patients receiving pancuronium received propranolol for heart rates greater than 90 beats.min-1 versus 7% of those who received vecuronium (P approximately 0.01). Eight patients developed 13 episodes of ischemia after administration of the muscle relaxant: four who received pancuronium (n = 44; 9%) and four receiving vecuronium (n = 54; 7%). Four episodes occurred at induction or tracheal intubation, two in each group. There were four perioperative myocardial infarctions as determined by ECG and CPK-MB levels, two in each group.(ABSTRACT TRUNCATED AT 250 WORDS)     

The pharmacokinetics, urinary and biliary excretion of pipecuronium bromide.

The pharmacodynamics and -kinetics of pipecuronium were studied in 12 patients, six of whom received 100 micrograms kg-1 for laryngectomy (Group L), and six who underwent choledochotomy after insertion of the T-drain and were given 50 micrograms kg-1 (Group C). Onset time and clinical duration were 2.3 and 109 min and 2.8 and 39 min in Groups L and C, respectively. All patients could be sufficiently reversed with neostigmine. Terminal half-lives were 101.5 min (Group L) and 179 min (Group C) in a three-exponent decay; the distribution volumes at steady state 0.339 l kg-1 (Group L) and 0.506 l kg-1 (Group C); the plasma clearance 3.4 ml kg-1 min-1 (Group L) and 2.5 ml kg-1 min-1 (Group C). Within 24 h, 38.6% and 37% were excreted unchanged in the urine and 4.4% and 1% as 3-desacetyl pipecuronium in Groups L and C, respectively. Within 24 h only 2% was excreted into the bile in Group C. Distribution volume and terminal half-life in Group C were positively correlated with pre-operative serum aminotransferase levels (P less than 0.005).     

Accelerated onset of non-depolarizing neuromuscular blocking drugs: pancuronium, atracurium and vecuronium. A comparison with succinylcholine

The time of onset and degree of neuromuscular blockade (NMB) in 80 anaesthetized patients, following either a single bolus injection of pancuronium 0.95 mg kg-1, atracurium 0.53 mg kg-1 or vecuronium 0.07 mg kg-1, or divided doses of pancuronium 0.15 mg kg-1, atracurium 0.07 mg kg-1 or vecuronium 0.01 mg kg-1 administered 3 min or 5 min before the second dose of pancuronium 0.08 mg kg-1, atracurium 0.46 mg kg-1 or vecuronium 0.06 mg kg-1, were determined and compared to the same parameters measured following succinylcholine administration (1 mg kg-1). The time to maximum NMB (100%) following the administration of succinylcholine was 58.1 +/- 5.3 s, whereas the time to maximum NMB (100%) following a single bolus injection of either pancuronium, atracurium or vecuronium was 130.6 +/- 22.2, 93.0 +/- 6.4, 127.5 +/- 13.0 s, respectively. These values for time to maximum NMB are significantly longer than the time required for succinylcholine to achieve maximal blockade. The time to attain maximum NMB following divided doses of pancuronium, atracurium or vecuronium separated by 3 min decreased significantly to 77.9 +/- 4.3, 77.5 +/- 7.6, 89.0 +/- 8.6 s, respectively. However, when the two doses of drug were separated by 5 min, only small, non-significant further decreases occurred in the time required to achieve maximum blockade. Although the time to maximum NMB following divided doses of pancuronium, atracurium or vecuronium is significantly longer than that for succinylcholine, divided dosing significantly decreases the time required to reach maximal NMB.     

Effects of prostaglandin E1 on vecuronium and fentanyl pharmacokinetics in humans]

The effects of prostaglandin E1 (PGE1) on pharmacokinetics of vecuronium and fentanyl were studied during anesthesia. Pharmacokinetic parameters of these drugs were obtained by using two-compartment open model and population pharmacokinetics. Significant increases of Vdss, Vp, and k12 in the pharmacokinetic parameters of vecuronium were observed with 0.024-0.025 microgram.kg-1.min-1 of PGE1. The results demonstrate that PGE1 accelerates the drug transport to peripheral tissues. However, there are no significant changes in the pharmacokinetic parameters of fentanyl with the same dose of PGE1. This difference in the effect of PGE1 on the drug transport to peripheral compartment between vecuronium and fentanyl may be due to the essential large peripheral distribution of fentanyl.     

Comparative potency of steroidal neuromuscular blocking drugs and isobolographic analysis of the interaction between rocuronium and other aminosteroids

We have determined the relative potency of rocuronium, pancuronium, pipecuronium and vecuronium, and examined the nature of the interaction of rocuronium with the other three steroidal neuromuscular blocking drugs. We studied the dose-response relationships of each drug and their combination with rocuronium in 200 ASA I or II patients during propofol-fentanyl-nitrous oxide-oxygen anaesthesia. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to single twitch stimulation of the ulnar nerve at 10-s intervals. The dose- response curves were determined by probit analysis. Isobolographic and algebraic (fractional) analyses were used to assess the combined effect of equipotent doses of rocuronium and vecuronium, pipecuronium or pancuronium and to define the type of interaction between these drugs. The isobolograms were constructed by plotting single-drug ED50 points on the dose co-ordinates, and a combined ED50 point in the dose field. The calculated doses producing 50% depression (ED50) of the twitch height for rocuronium, pancuronium, pipecuronium and vecuronium were 144.8 (95% confidence intervals 140.4-149.3), 32.4 (31.7-32.9), 27.1 (26.5-27.6) and 23.7 (22.7-24.8) micrograms kg-1, respectively. Corresponding doses producing 95% depression (ED95) of twitch height were, respectively, 322.1 (307.5-337.3), 58.1 (56.2-60.1), 48.7 (46.9- 50.5) and 39.9 (38.4-41.4) micrograms kg-1. Based on the estimate of ED50, the relative potency was 1:4.5:5.4:6, respectively. The interaction between rocuronium and vecuronium, pipecuronium or pancuronium was found to be additive.      

Pharmacokinetics of bupivacaine following intraoperative intercostal nerve block in neonates and in infants aged less than 6 months

Pharmacokinetics and blood concentrations of bupivacaine were studied after intercostal nerve blocks were performed intraoperatively using 1.5 mg.kg-1 in 11 neonates (age 0-28 days) and 11 infants between age 1 and 6 months. The study aimed to provide pharmacokinetic data that are limited in these age groups, and to identify any adverse effects of intercostal nerve block in infancy. Arterial blood samples were taken at 0, 5, 10, 15, 20, 30, 60, 120, 240, and 360 min. Whole blood bupivacaine was assayed by high-performance liquid chromatography. Peak blood concentrations were attained within 10 min in 18 of 22 subjects, and were 087 micrograms.ml-1 [corrected] +/- 0.56 micrograms.ml-1 (mean and SD) and 0.91 +/- 0.27 micrograms.ml-1 in neonates and infants, respectively. Pharmacokinetic variables in the two groups included elimination half-life (t1/2 beta): 132 +/- 59 min and 102 +/- 39 min; steady-state volume of distribution (Vdss): 2.56 +/- 0.76 l.kg-1 and 2.17 +/- 0.17 l.kg-1; and total body clearance (Clt): 16.93 +/- 9.32 ml.min-1.kg-1 and 15.71 +/- 6.99 ml.min-1.kg-1. There was no statistically significant difference between neonates and infants with regard to any of these parameters. Patients were further divided into those with acyanotic and cyanotic disease. Cyanotic infants were significantly heavier than acyanotic infants (P less than 0.05), but no other differences were demonstrated. No adverse effects resulting from the technique were identified.(ABSTRACT TRUNCATED AT 250 WORDS)     

Continuous infusions of atracurium and vecuronium,compared with intermittent boluses of pancuronium: dose requirements and reversal

This study was designed to determine the effect of prolonged infusion on the ease of reversal of atracurium and vecuronium, and whether factors which potentiate the block delayed reversal. In phase one, 40 patients were randomized (double blind) to determine the steady state conditions for atracurium and vecuronium. Fourteen atracurium patients and 17 vecuronium patients were evaluable. The unblinded second phase involved the steady state conditions using halothane or isoflurane and atracurium infusions. The infusion required for 95% twitch depression (TD95) for atracurium was 7.6 +/- 1.1 micrograms.kg-1 x min-1. The requirement for vecuronium changes with time: TD95 at 30 min was 1.01 +/- 0.16, at 60 min 0.89 +/- 0.12 and after 90 min 0.85 +/- 0.17 micrograms.kg-1 x min-1 (P < 0.05). The mean TD95 was 0.94 +/- 0.23 micrograms.kg-1 x min-1. Multivariate regression analysis of the infusion data revealed a vecuronium model predicting TD95 by the duration of infusion (P < 0.05) and weight (P = 0.05). Atracurium TD95 was predicted by age (P = 0.05). The addition of an inhalation agent to atracurium reduced the infusion rate by 2.01 +/- 0.28 micrograms.kg-1 x min-1 (P = 0.0001) for each increase in MAC. The mean reversal times for atracurium with three different anaesthetics and for vecuronium were not different. Reversal of pancuronium blockade, from less profound twitch depression (86.4 vs 95%) took twice as long as for atracurium and vecuronium for which the following predictors were identified: age, weight, duration of infusion, level of blockade, and type of anaesthetic, using a stepwise regression model.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.