Vecuronium pharmacokinetics in patients with major burns.

BACKGROUND: Burn patients develop resistance to non-depolarizing neuromuscular blocking agents (NDNMBAs) and require a significantly large dose to produce a desired clinical response. Pathophysiological changes related to burn injury may alter pharmacokinetics (PK) and pharmacodynamics of NDNMBAs. The purpose of this study was to compare vecuronium PK in burns vs non-burns. METHODS: Twenty adults, aged 23-58 yr, with 27-81% total body surface area (TBSA) burn, were studied at 4-57 post-burn days and compared with age- and sex-matched, non-burn controls. Vecuronium 0.12 mg kg(-1) was given i.v. as a single bolus within 10 s. Blood samples (n=20) were collected over 12 h at predetermined time points. NONMEM was used to describe plasma drug concentration-time profiles for burns and non-burns. RESULTS: A three-compartment model best described vecuronium concentration-time profiles. Burn patients showed enhanced distributional clearance at the terminal phase (0.12 vs 0.095 litre min(-1), P<0.0001), which yielded shorter elimination half-life for vecuronium (5.5 vs 6.6 h, P<0.001). BURN was the single most significant covariate that explained the altered vecuronium disposition in burns. CONCLUSIONS: The altered drug distribution between tissues may partially explain the known resistance to vecuronium in patients with major burns.

Effect of bolus injection of 20 ml saline with arm elevation on the onset time of vecuronium administered via a peripheral vein: a randomised controlled trial.

We investigated whether a bolus injection of 20 ml saline with arm elevation might shorten the onset time of vecuronium administered via a dorsal hand vein. Thirty patients were randomly allocated to the bolus saline group or control group. General anaesthesia was induced and maintained with remifentanil and propofol. Vecuronium 0.1 mg.kg(-1) was administered to all patients, followed in the treatment group by bolus injection of 20 ml saline and arm elevation. Response to train-of-four stimulation was measured by acceleromyography at the adductor pollicis muscle. The mean (SD) lag time was 47.2 (14.5) s in the bolus saline group and 67.9 (12.2) s in the control group (p = 0.0002). The time to 95% block of T1 was 104.6 (29.9) s in the bolus saline group and 128.3 (15.8) s in the control group (p = 0.011). Bolus saline injection results in shortened lag time and onset time of neuromuscular block with vecuronium.

The pharmacodynamics of vecuronium in chronic renal failure patients: the impact of different priming doses.

PURPOSE: The concept of priming was introduced to facilitate a faster onset of nondepolarizing neuromuscular blocker for endotracheal intubation. Vecuronium is still very much in use for most chronic renal failure patients posted for renal transplantation. The aim of this study was to examine the pharmacodynamics of vecuronium without and with preceding different small doses. METHODS: One hundred chronic renal failure patients were assigned into four groups according to the used vecuronium priming regimen. The first control group (V(0)-group), where no priming dose was given. The other three priming groups (V(10)- , V(15)- , and V(20)-groups), where 10%, 15%, and 20% of ED(95) of vecuronium were administrated 5 min prior to the remaining intubating dose (2 × ED(95)) of vecuronium. Neuromuscular blockade was measured via acceleromyographic response of the ulnar nerve. Train-of-four (TOF) ratio was measured every minute during priming interval. Any unpleasant symptoms during precurarization were recorded. Lag time and onset time (from injection of intubating dose) were recorded. Endotracheal intubation condition was scored blindly. The duration and recovery times were also recorded. RESULTS: The significant higher incidence of symptoms of paresis was encountered in V(20)-group in comparison with other two priming groups. TOF ratio started to decrease significantly at the first minute in V(20)-group, at the second minute in V(15)-group, and at the third minute in V(10)-group, till the fourth minute in the priming interval. Although TOF ratio was still above 0.90 in V(10)-group, it was below 0.80 in V(20)-group. Priming groups did not show significant intergroup difference in onset time. However, duration and recovery times were significantly longer in priming groups in comparison with V(0)-group without priming. CONCLUSION: Priming the chronic renal failure patients with 10% of ED(95) vecuronium dose acquit the best pharmacodynamics with the fewest signs of muscle weakness. Larger vecuronium priming doses are unfavorable and convey no more clinical utility.

Development and potential clinical impairment of ultra-short-acting neuromuscular blocking agents.

Developing a non-depolarizing neuromuscular blocking agent that, like succinylcholine, has a rapid onset and a short duration of effect remains a goal of ongoing research. While rocuronium fills a portion of this need, the large doses required for rapid intubation render it a much longer-acting neuromuscular blocking agent. Postoperative residual neuromuscular block (NMB) is an increasingly recognized complication of non-depolarizing neuromuscular blocking agents. This occurs because of dosing choices for neuromuscular blocking agents and anticholinesterases as well as insensitivity of typically used monitors of depth of NMB. While antagonism of NMB is necessary with partial recovery, it is unnecessary with more complete recovery. Even when monitoring with an accelerograph, reversal of NMB is complicated. In addition to the pharmacodynamics of the individual neuromuscular blocking agents, factors such as timing of anticholinesterase administration, dose of anticholinesterase, concomitant medications, electrolyte abnormalities, and hepatic or renal disease can influence the degree of reversal. Sugammadex works differently than anticholinesterases and, when administered in appropriate doses, can reverse even profound block induced with vecuronium or rocuronium. Two new fumarate neuromuscular blocking agents have a rapid onset of effect and can be reversed at any time by administration of cysteine, which could significantly reduce the risk of postoperative residual NMB.

[Comparison of atracurium, cisatracurium and vecuronium during anaesthesia for laparoscopic surgery]. / Ocena porównawcza atrakurium, cisatrakurium i wekuronium podczas znieczulenia ogólnego do operacji laparoskopowych.

BACKGROUND: The aim of the study was to compare the intubating conditions, onset time, and duration of action of atracurium, cisatracurium, and vecuronium, when used for muscle relaxation in laparoscopic surgery with carbon dioxide inflation. In trying to find an "ideal" relaxant we compared the relative potency of these drugs, and also measured pH, PaCO2 and skin temperature. METHODS: Ninety-five ASA I and II patients were randomly allocated to three groups, to receive atracurium (I), cisatracurium (II), or vecuronium (III), during propofol/fentanyl anaesthesia. Neuromuscular transmission was monitored using accelerography (TOF GUARD). Patients were intubated after the injection of 0.5 mg kg-1 atracurium (I), 0.1 mg kg(-1) cisatracurium (II), or 0.1 mg kg(-1) vecuronium (III). Muscle relaxation was maintained with incremental doses of 0.1 0.2 mg kg(-1) and 0.03 mg kg(-1) of the relaxants respectively, given after a second response to TOF stimulation was noted. Recovery time was defined as the time from a maximal block (TOF=0) to spontaneous recovery of TOF 75%. RESULTS: Conditions for performing tracheal intubation were noted to be excellent in groups I and III, and good in group II. The mean recovery time was significantly shorter in groups II and III, than in group I. No significant correlations were found between the duration of neuromuscular blockade and pH, PaCO2 or palm skin temperature. CONCLUSIONS: Vecuronium, besides providing excellent conditions for tracheal intubation, had the fastest onset time and optimal duration of action. We found the drug to be the most suitable for laparoscopic surgery.

Sedation after intubation using etomidate and a long-acting neuromuscular blocker.

BACKGROUND: Etomidate is an imidazole hypnotic which is commonly used by emergency medicine physicians during rapid sequence intubation. Etomidate's duration of action is significantly shorter than that of commonly used long-acting paralytic medications (3-12 minutes vs 25-73 minutes). If additional sedative medications are not administered in the paralyzed patient before the conclusion of etomidate's duration of action, patients are at risk for experiencing paralysis without adequate sedation. OBJECTIVE: To evaluate the frequency of the administration of additional sedation in pediatric emergency department patients undergoing endotracheal intubation with etomidate and a long-acting paralytic agent. METHODS: This study was a retrospective review of pediatric patients undergoing endotracheal intubation in a tertiary pediatric emergency department between July 2001 and December 2005. All patients intubated with etomidate and rocuronium or vecuronium were eligible for inclusion; patients with seizures were excluded. Data elements included the following: demographic variables, presenting complaint, intubation indication, medications used, time from etomidate administration to the administration of an additional sedative, Glasgow Coma Scale (GCS) score, and patient disposition. RESULTS: During the study period, 276 pediatric intubations were reviewed with 104 patients receiving etomidate and rocuronium or vecuronium. Twenty cases were excluded, 15 cases with documented seizures and 5 incomplete/missing charts. Eighty-four records were included in the final analysis. The mean age is 84 +/- 65 months; 62 (73.8%) patients were male; the mean GCS was 8.44 +/- 3.9, with a median GCS of 8 (interquartile range 6,11), and 41 (48.8%) of patients presented with blunt trauma. The mean time from etomidate to the administration of additional sedation was 46 +/- 49 minutes. Eleven (13.1%) patients received no additional sedative after etomidate administration, whereas only 20 (23.8%) patients were given a sedative within 15 minutes of the administration of etomidate. Fifty-three (63.1%) patients received an additional sedative more than 15 minutes after the administration of etomidate. CONCLUSIONS: A significant proportion of pediatric patients receiving etomidate and rocuronium or vecuronium during endotracheal intubation are likely experiencing ongoing paralysis without adequate sedation. Emergency medicine physicians should be cognizant of this when using these medications for facilitating intubation.

Neuromuscular blockade in cardiac surgery: an update for clinicians.

There have been great advancements in cardiac surgery over the last two decades; the widespread use of off-pump aortocoronary bypass surgery, minimally invasive cardiac surgery, and robotic surgery have also changed the face of cardiac anaesthesia. The concept of "Fast-track anaesthesia" demands the use of nondepolarising neuromuscular blocking drugs with short duration of action, combining the ability to provide (if necessary) sufficiently profound neuromuscular blockade during surgery and immediate re-establishment of normal neuromuscular transmission at the end of surgery. Postoperative residual muscle paralysis is one of the major hurdles for immediate or early extubation after cardiac surgery. Nondepolarising neuromuscular blocking drugs for cardiac surgery should therefore be easy to titrate, of rapid onset and short duration of action with a pathway of elimination independent from hepatic or renal dysfunction, and should equally not affect haemodynamic stability. The difference between repetitive bolus application and continuous infusion is outlined in this review, with the pharmacodynamic and pharmacokinetic characteristics of vecuronium, pancuronium, rocuronium, and cisatracurium. Kinemyography and acceleromyography are the most important currently used neuromuscular monitoring methods. Whereas monitoring at the adductor pollicis muscle is appropriate at the end of surgery, monitoring of the corrugator supercilii muscle better reflects neuromuscular blockade at more central, profound muscles, such as the diaphragm, larynx, or thoraco-abdominal muscles. In conclusion, cisatracurium or rocuronium is recommended for neuromuscular blockade in modern cardiac surgery.

Effects of different dose regimens of magnesium on pharmacodynamics and anesthetic requirements of balanced general anesthesia.

The present double- blind, randomized, placebo-controlled study was designed to assess the effect of two different dose regimens of magnesium sulphate (MgSO4) administration on intraoperative propofol and vecuronium requirements and postoperative fentanyl consumption in patients undergoing hernioraphy. Sixty patients were allocated to three equal groups; two magnesium groups and control group. Magnesium groups received 50 mg kg(-1) of magnesium preoperatively followed by intravenous infusion of magnesium 8 mg kg(-1) h(-1) (Mg1 G) or 16 mg kg(-1) h(-1) (Mg2 G). Patients in control group received the same volume of isotonic solution. Anesthesia was induced and maintained with propofol, fentanyl, and vecuronium. Magnesium Gs required significantly lower propofol (121.0 +/- 4.5, 117.4 +/- 6.3 microg kg(-1) min. (-1) in Mg1 & Mg2 Gs respectively vs. 153.8 +/- 8.4 microg kg(-1) min. (-1) in control G), and vecuronium requirements (0.097 +/- 0.008, 0.0921 +/- 0.006 mg kg(-1) h(-1) in Mg1 & Mg2 Gs respectively vs. 0.124 +/- 0.01 mg kg(-1) h(-1) in control G). Magnesium significantly shortened the onset time of vecuronium (154.0 +/- 25.9, 162.0 +/- 22.4 sec. in Mg1 & Mg2 Gs respectively vs. 227.4 +/- 10.9 sec. in control), prolonged its clinical duration (44.7 +/- 3.2, 46.4 +/- 5.1 min. in Mg1 & Mg2 Gs respectively vs. 26.0 +/- 3.9 min. in control) and prolonged its recovery index which was significantly longest in Mg2 G (25.4 +/- 1.9 min.) compared to Mg1 G (20.1 +/- 2.1 min.) and control (15.3 +/- 1.4 min.). Fentanyl consumption on the first postoperative day was significantly higher in control (1.52 +/- 0.08 microg kg(-1)) than in magnesium Gs (0.96 +/- 0.07, 0.91 +/- 0.08 microg kg(-1) in Mg1 & Mg2 Gs respectively). Postoperative sedation score showed significantly the highest value in Mg2 G compared to Mg1 and control Gs. Mean arterial blood pressure and heart rate were lower in magnesium groups with lowest value in Mg2 G. It is concluded that magnesium 50 mg kg(-1) bolus followed by 8 mg kg(-1) h(-1) leads to significant reductions in intraoperative propofol and vecuronium and postoperative fentanyl consumption. Doubling magnesium infusion rate added minimal benefits on the expense of haemodynamic consequences and delayed recovery.

Performance of an iterative two-stage bayesian technique for population pharmacokinetic analysis of rich data sets.

PURPOSE: To test the suitability of an Iterative Two-Stage Bayesian (ITSB) technique for population pharmacokinetic analysis of rich data sets, and to compare ITSB with Standard Two-Stage (STS) analysis and nonlinear Mixed Effect Modeling (MEM). MATERIALS AND METHODS: Data from a clinical study with rapacuronium and data generated by Monte Carlo simulation were analyzed by an ITSB technique described in literature, with some modifications, by STS, and by MEM (using NONMEM). The results were evaluated by comparing the mean error (accuracy) and root mean squared error (precision) of the estimated parameter values, their interindividual standard deviation, correlation coefficients, and residual standard deviation. In addition, the influence of initial estimates, number of subjects, number of measurements, and level of residual error on the performance of ITSB were investigated. RESULTS: ITSB yielded best results, and provided precise and virtually unbiased estimates of the population parameter means, interindividual variability, and residual standard deviation. The accuracy and precision of STS was poor, whereas ITSB performed better than MEM. CONCLUSIONS: ITSB is a suitable technique for population pharmacokinetic analysis of rich data sets, and in the presented data set it is superior to STS and MEM.

The efficacy of intratracheal administration of vecuronium in rats, compared with intravenous and intramuscular administration.

To investigate the suitability of the intratracheal (IT) route as an alternative route for the administration of vecuronium, we compared the pharmacodynamic parameters for neuromuscular block in three groups of rats given vecuronium via the IT, IM, and IV routes. We also examined the pharmacokinetics of vecuronium in the three groups. The doses for the IT, IV, and IM groups were set at 1.50, 0.300, and 2.25 mg/kg, respectively. The onset of action in the IT group (127 +/- 17 s) was significantly earlier than that in the IM group (267 +/- 62 s), and significantly later than that in the IV group (18 +/- 7 s) (P < 0.05 by analysis of variance and the Tukey-Kramer analysis). The duration of action in the IT group (794 +/- 162 s) was significantly longer than that in the IV group (93 +/- 30 s) but not significantly different from that in the IM group (743 +/- 131 s). The recovery index in the IT group (134 +/- 30 s) was significantly shorter than that in the IM group (222 +/- 47 s) and significantly longer than that in the IV group (32 +/- 12 s). Although IT administration of vecuronium is still slower than IV administration, it appears to be more advantageous as compared with IM administration, given the more rapid absorption and faster onset of action.

Reversión del bloqueo neuromuscular residual por atracurio y vecuronio con dosis bajas de neostigmina / Reversion of atracurium and vecuronium residual nondepolarising neuromuscular blockade with low doses of neostigmine

Objetivos. Comprobar la eficacia de dosis bajas deneostigmina en la reversión del bloqueo neuromuscularno despolarizante residual (BNM-R).Material y Métodos. Se realizó el trabajo con 119pacientes adultos, ASA I-III, anestesiados con tiopental,fentanilo, O2-N2O-isoflurano y atracurio (n=62) o vecuronio(n=57). Se monitorizó el BNM-R mediante registroelectromiográfico del adductor pollicis ante estímuloulnar tipo tren de cuatro (TOF), considerando recuperaciónespontánea un TOF-Ratio > 75%. En caso contrariose revertía el BNM-R en función del grado de bloqueo(0-1, 2, 3 ó 4 respuestas al TOF) con neostigmina (0,035;0,03; 0,025 ó 0,02 mg/kg) y atropina (0,0175; 0,015; 0,0125ó 0,01 mg/kg) respectivamente. Se registró el tiempo dedecurarización y los efectos secundarios.Resultados. Los grupos resultaron demográficamentehomogéneos, con TOF-Ratio>75% el 25,8 (atracurio)y 21,1% (vecuronio), mostrando el resto 0-1 respuestasal TOF (11,3 y 19,2%), 2 (6,5 y 11,5%), 3 (4,8 y7,6%) ó 4 respuestas (51,6 y 50%) respectivamente,decurarizándose en 10,5±7 (atracurio) y 10,3±6,4 min(vecuronio). Hubo predominio de efectos secundariosen el grupo del atracurio (p=0,027) a expensas de sialorrea,naúseas y vómitos. No se registró ningún casode recurarización.Conclusiones. La reversión del BNM-R con dosisbajas de neostigmina y atropina ajustadas al grado debloqueo es efectiva incluso en bloqueos profundos yreduce el riesgo de efectos secundarios de estos fármacos

Objectives. To assess the effectiveness of low doses of neostigmine in the reversion of residual nonpolarising neuromuscular blockade (RNMB). Material and methods. The work involved one hundred and nineteen adult patients, ASA I-III, anaesthetised with fentanyl, thiopental, O2-N2O-isoflurane and atracurium (n=62) or vecuronium (n=57). RNMB was monitored with continuous electromyography of adductor pollicis with TOF stimulation. When TOF-Ratio (TR) 75% and secondary effects. Results. Both groups were homogeneous. Twentyfive point eight percent (25.8%) (group A) and 21.1% (group V) presented TR>75% at the end of surgery, while 11.3% and 19.2% showed TR 75% in 10.5±7 (group A) and 10.3±6.4 min. (group V). A predominance of secondary effects in the atracurium group was observed (p=0.027), basically due to excessive salivation, nausea and vomiting. There were no cases of RNMB. Conclusions. The reversion of the residual neuromuscular blockade of atracurium or vecuronium with low doses of neostigmine and atropine adjusted to the degree of RNMB is effective even in deep blockades, reducing the risk of secondary effects

Morphine metabolite pharmacokinetics during venoarterial extra corporeal membrane oxygenation in neonates.

OBJECTIVE: To examine morphine metabolite serum concentrations in neonates undergoing venoarterial extra corporeal membrane oxygenation (ECMO) and to quantify clearance differences between these neonates and those subjected to noncardiac major surgery. PATIENTS AND METHODS: This was an observational study in level III referral centre. Fourteen neonates (< 7 days old) undergoing ECMO were included. Morphine and concomitant medications were given by protocol, adapted to the clinical conditions of the neonates. Pharmacokinetic findings were compared with those from a previous study in infants after noncardiac major surgery. Nonlinear mixed-effect modelling was used. Parameter estimates were standardised to a 70 kg person using allometric modeling RESULTS: Morphine-3-glucuronide (M3G) was the predominant metabolite. Formation clearance to M3G at the start of ECMO on day 1 was lower than those in postoperative children, but matured more rapidly. After 10 days formation clearances of M3G in neonates on ECMO equalled those of postoperative children. Higher ECMO flows were associated with reduced formation clearances. Elimination clearances of M3G, but not morphine-6-glucuronide (M6G), were lower in the ECMO neonates; this was attributable to reduced renal clearance. These elimination clearances were correlated positively with ECMO flow and negatively with dopamine dose. Haemofiltration cleared M3G and M6G, but not morphine. CONCLUSION: Formation clearance to M3G, the predominant metabolite, is reduced during the first 10 days of ECMO. Elimination clearance of M3G and M6G is related to creatinine clearance. ECMO flow had a small effect on metabolite clearance. Higher flows were associated with decreased formation clearances, possibly reflecting illness severity. Dopamine dose reflected decreased renal clearance.

Meta-analysis of the differences in the time to onset of action between rocuronium and vecuronium.

1. The aim of the present study was to conduct a meta-analysis of the magnitude of differences in the onset of action (T(max)) between rocuronium and vecuronium. 2. A search was made in PubMed, EMBASE Drugs and Pharmacology, Cochrane Controlled Trials Register and Cochrane Database on Systematic Reviews. Studies comparing the T(max) at the adductor policies between rocuronium and vecuronium administered as an intravenous bolus were included in the study. Twenty-nine effect sizes obtained from 21 studies were included. 3. The result of the meta-analysis of differences was -57.9 s (95% confidence interval -71.4 to -44.3 s), favouring rocuronium over vecuronium. The smallest difference in T(max) between these neuromuscular-blocking agents was observed in children (-19.1 s). The difference in T(max) between rocuronium and vecuronium in female patients was -38.7 s. The difference in T(max) between rocuronium and vecuronium measured by electromyography was approximately 50% shorter than that determined by acceleromyography or mechanomyography. In a subanalysis between rocuronium 600 mg/kg versus vecuronium 100 mg/kg, the difference in T(max) between them was very similar to that obtained in the general meta-analysis. 4. According to subanalyses of patient age and sex, drug dose and neuromuscular monitoring systems, the T(max) of rocuronium was approximately 20-70 s faster than that of vecuronium.

Randomised controlled trial comparing cisatracurium and vecuronium infusions in a paediatric intensive care unit.

OBJECTIVE: To evaluate and compare the efficacy, infusion rate and recovery profile of vecuronium and cisatracurium continuous infusion in critically ill children requiring mechanical ventilation. DESIGN AND SETTING: Prospective, randomised, double-blind, single-centre study in critically ill children in a paediatric intensive care unit in a tertiary children's hospital. METHODS: Thirty-seven children from 3 months to 16 years old (median 4.1 year) were randomised to receive either drug; those already receiving more than 6 h of neuromuscular blocking drugs were excluded. The Train-of-Four (TOF) Watch maintained neuromuscular blockade to at least one twitch in the TOF response. Recovery time was measured from cessation of infusion until spontaneous TOF ratio recovery of 70%. RESULTS: The cisatracurium infusion rate in nineteen children averaged 3.9+/-1.3 microg kg(-1) min(-1) with a median duration of 63 h (IQR 23-88). The vecuronium infusion rate in 18 children averaged mean 2.6+/-1.3 microg kg(-1) min(-1) with a median duration of 40 h (IQR 27-72). Median time to recovery was significantly shorter with cisatracurium (52 min, 35-73) than with vecuronium (123 min, 80-480). Prolonged recovery of neuromuscular function (>24 h) occurred in one child (6%) on vecuronium. CONCLUSIONS: Recovery of neuromuscular function after discontinuation of neuromuscular blocking drug infusion in children is significantly faster with cisatracurium than vecuronium. Neuromuscular monitoring was not sufficient to eliminate prolonged recovery in children on vecuronium infusions.

Comparison of cisatracurium and vecuronium by infusion in neonates and small infants after congenital heart surgery.

BACKGROUND: Neonates and infants often require extended periods of mechanical ventilation facilitated by sedation and neuromuscular blockade. METHODS: Twenty-three patients aged younger than 2 yr were randomly assigned to receive either cisatracurium or vecuronium infusions postoperatively in a double-blinded fashion after undergoing congenital heart surgery. The infusion was titrated to maintain one twitch of a train-of-four. The times to full spontaneous recovery of train-of-four without fade, extubation, intensive care unit discharge, and hospital discharge were documented after drug discontinuation. Sparse sampling after termination of the infusion and a one-compartment model were used for pharmacokinetic analysis. The Mann-Whitney U test and Student t test were used to compare data between groups. RESULTS: There were no significant differences between groups with respect to demographic data or duration of postoperative neuromuscular blockade infusion. The median recovery time for train-of-four for cisatracurium (30 min) was less than that for vecuronium (180 min) (P < 0.05). Three patients in the vecuronium group had prolonged train-of-four recovery: Two had long elimination half-lives for vecuronium, and one had a high concentration of 3-OH vecuronium. There were no differences in extubation times, intensive care unit stays, or hospital stays between groups. CONCLUSIONS: Our results parallel data from adults demonstrating a markedly shorter recovery of neuromuscular transmission after cisatracurium compared with vecuronium. Decreased clearance of vecuronium and the accumulation of 3-OH vecuronium may contribute to prolonged spontaneous recovery times. Cisatracurium is associated with faster spontaneous recovery of neuromuscular function compared with vecuronium but not with any differences in intermediate outcome measures in neonates and infants.

Influence of chronic phenytoin administration on the pharmacokinetics and pharmacodynamics of vecuronium.

BACKGROUND: The duration of action of vecuronium is reduced in patients receiving phenytoin. In this study, the authors examined, simultaneously, the influence of phenytoin on both the pharmacokinetics and the pharmacodynamics of vecuronium. METHODS: This study was approved by the institutional review board of the University of California, San Francisco, and patients gave written informed consent. Twenty-two patients, 11 taking phenytoin and all scheduled to undergo prolonged neurosurgical procedures with general anesthesia, participated in the study. In 12 patients (6 phenytoin, 6 control), vecuronium was infused at 7.5 microg x kg(-1) x min(-1) until the first response (T1) of each train-of-four decreased by 50%; in the remaining 10 patients (5 phenytoin, 5 control), 200 microg/kg vecuronium was infused over 10 min. Arterial blood samples were drawn at intervals over the next 5-7 h. Plasma concentrations of vecuronium and 3-desacetylvecuronium were measured by capillary gas chromatography. Pharmacokinetic and pharmacodynamic modeling was used to characterize the disposition of vecuronium and patient responses to it in the two groups. RESULTS: Clearance was typically increased by 138% (95% confidence interval, 93-183%) in patients taking phenytoin. The effect of vecuronium was well described using a sigmoid Emax model. The concentration of vecuronium giving 50% twitch depression was increased 124% (45-202%) in patients taking phenytoin. CONCLUSIONS: Chronic phenytoin therapy reduces the effect of vecuronium by mechanisms that include both increased vecuronium metabolism and reduced sensitivity of the patient to circulating concentrations of vecuronium.

Atracurium, cisatracurium, vecuronium and rocuronium in patients with renal failure.

AIM: The cumulative index, the recovery, the onset and the duration of action, of atracurium, cisatracurium, vecuronium and rocuronium in uremic patients undergoing kidney transplantation compared to healthy patients undergoing general surgery were studied. METHODS: In all patients (64 uremic vs 62 "healthy" patients) after anesthesia induction, atracurium 0.5 mgxkg(-1) or cisatracurium 0.15 mgxkg(-1) or vecuronium 0.1 mgxkg(-1) or rocuronium 0.6 mgxkg(-1) were administered, and at the end of surgery when T1 reached 25% neostigmine 0.05 mgxkg(-1) was given. Neuro-muscu-lar transmission was monitored by accelerometry (TOF-GUARD, Organon). RESULTS: Cumulative index of vecuronium (1.3+/-0.1 vs 1.06+/-0.11, p<0.001) and rocuronium (1.45+/-0.18 vs 1.04+/-0.16, p<0.001), recovery index (time of T1 25-75) of atracurium (14.2+/-5 vs 9+/-4, p<0.005), cisatracurium (18.7+/-3 vs 9.1, p<0.001), vecuronium (18.5+/-3 vs 12.5+/-3, p<0.001) and rocuronium (18+/-6 vs 11+/-4, p<0.001) and interval T1 25% to TOF 0.8 of cisatracurium (20.5+/-1.2 vs 16+/-2.1, p<0.001) and vecuronium (27+/-6.3 vs 20+/-3.3, p<0.001) were longer in uremic patients. The onset time and the duration of action of atracurium, cisatracurium, vecuronium and rocuronium were similar in all groups compared to controls one. CONCLUSION: In patients with renal failure the use of atracurium, cisatracurium, vecuronium and rocuronium is suitable and predictable in terms of onset, and duration of action. Care has to be taken to vecuronium and rocuronium cumulative index. Neuromuscular trasmission has to be always monitored.

The effect of vecuronium is enhanced by a large rather than a modest dose of gentamicin as compared with no preoperative gentamicin.

UNLABELLED: We compared the effect of two doses of gentamicin versus no gentamicin (NG) given before surgery on the neuromuscular relaxant effect of vecuronium. Seventy patients (intraabdominal procedures) were randomly allocated to receive preoperative large-dose (4 mg/kg) gentamicin (LD), a modest dose (1.2 mg/kg) of gentamicin (MD), or NG. No more than one dose of gentamicin was given before the vecuronium administration. Serum gentamicin levels, the time for 25% recovery of the first twitch in the train-of-four after a bolus of vecuronium, and the time from cessation of the vecuronium infusion to extubation of the trachea were estimated. Serum gentamicin levels were higher (P < 0.001) for LD than MD. The time for 25% recovery of the first twitch after the vecuronium bolus was slightly longer with LD than MD (P = 0.06) and longer in LD than NG (P = 0.001) (42.9 +/- 23.6 min versus 36.2 +/- 17 min and 27.4 +/- 9 min, respectively). The time to extubation was similar with LD and MD and longer for LD than NG (P = 0.008) (34.7 +/- 19.2 min versus 27.4 +/- 19.3 min and 19.4 +/- 10.1 min, respectively). The differences in these times were insignificant between MD and NG. Gentamicin administered as a LD rather than MD enhanced the neuromuscular blockade of vecuronium as compared with NG given before surgery. IMPLICATIONS: We demonstrated that the neuromuscular relaxant effect of vecuronium is enhanced by a large (4 mg/kg) rather than a modest (1.2 mg/kg) dose of gentamicin as compared with no gentamicin given before surgery.