Dose-response effect of serum butyrylcholinesterase activity after clinical doses of pancuronium.

INTRODUCTION: Low-dose pancuronium is known to affect serum cholinesterase activity (BChE); however, the dose-response effect of clinical doses of pancuronium on BChE has not been investigated. METHODS: Thirteen ASA I-II patients scheduled for elective surgery requiring muscle relaxation were enrolled in this study. All patients had normal BChE before surgery. Incremental doses of pancuronium (10, 20, 50, and 100 microg/kg) were injected in accordance with surgical needs every 45 min. BChE was measured 3 min after injection by an automatic colorimetric method. RESULTS: BChE decreased significantly in all except one patient in comparison to the baseline (P < 0.05). However all values remained within normal clinical range. A dose of 100 microg/kg yielded significant decrease in comparison to 10 microg/kg but not to other dosages. Linear regression was not significant for the dose-response relationship (P = 0.05). CONCLUSION: After clinical incremental doses of pancuronium, BChE remained within clinical range.

[French survey of neuromuscular relaxant use in anaesthetic practice in adults]. / Enquête de pratique sur l'utilisation en France des curares chez l'adulte en anesthésie.

Guidelines about the use of neuromuscular blocking agents based on a national consensus conference have been published in 2000. A survey was carried out to assess adherence to these guidelines. An online questionnaire was designed from the different guidelines concerning the use of muscle relaxant for tracheal intubation and surgery, monitoring and antagonism of neuromuscular blockade. In addition, question about the knowledge of the pharmacodynamics of neuromuscular blocking agents were asked. Analysis concerned 1230 answers from senior anaesthetists. Tracheal intubation is facilitated by the use of a competitive agent or by succinylcholine by 58 and 8% of responders respectively. Atracurium and cisatracurium were most frequently used (49 and 44%, respectively). The duration of effect of an intubating dose of atracurium, vecuronium or rocuronium was estimated equal or below 60 min by more than half of responders, whereas that of cisatracurium was longer. Fifty-two or 74% of responders used neuromuscular monitoring, whether a single or repeated dose of muscle relaxant was administered. Antagonism of neuromuscular blockade was systematic, frequent, and episodic or excluded by 6, 26, 55 and 13% of responders, respectively. Monitoring and antagonism of neuromuscular blockade are underused despite the guidelines. Underestimation of the risk of postoperative residual curarization is linked to the underestimation of the duration of competitive neuromuscular blocking agents.

Interaction between mivacurium and pancuronium: impact of the order of administration.

INTRODUCTION: Potentiation of mivacurium by low-dose pancuronium is mostly due to an inhibition of plasma butyryl cholinesterase (BchE) resulting in a decreased rate of hydrolysis of mivacurium. Nevertheless, an interaction at the receptor site could not be ruled out. By changing the order of the muscle relaxant injections, we may lessen the pharmacokinetic interaction and assess the impact at the acetylcholine receptor level. METHODS: Twenty patients scheduled for general anesthesia with propofol and fentanyl, and isoflurane were randomized into two groups receiving, mivacurium 100 microg kg-1 followed by pancuronium 15 microg kg-1 (group 1) or pancuronium 15 microg kg-1 followed by mivacurium 100 microg kg-1 (group 2). BchE before and after injection of each relaxant was measured. Neuromuscular block was assessed with a force transducer at the adductor pollicis measuring the elicited twitch to ulnar nerve stimulation. RESULTS: The neuromuscular block was greater when pancuronium was administered before mivacurium (100% versus 96+/-3%; P<0.05). Times to recovery of the elicited twitch response to 25% and 75% of control value were increased by 100% (P<0.05). After pancuronium, decreases in BchE of 11% and 14% in groups 1 and 2 were observed, respectively. CONCLUSION: Interaction between mivacurium and low dose pancuronium is significant only when mivacurium is injected after pancuronium.

The mechanism of pancuronium potentiation of mivacurium block: use of the isolated-arm technique.

UNLABELLED: The neuromuscular blocking effects of mivacurium are greatly enhanced when mivacurium is preceded by a subparalyzing dose of pancuronium. The mechanism of this potentiation has not been elucidated. This study investigated the effects of the anticholinesterase activity of a small dose of pancuronium on the neuromuscular blocking effects of mivacurium. Forty patients were enrolled in the study. The neuromuscular effects of 7.5 and 15 microg/kg pancuronium, followed by 50 and 100 microg/kg mivacurium, were assessed in Groups PM1 and PM2 (n = 20), respectively. The neuromuscular effects of 65 and 130 microg/kg mivacurium were assessed in Groups M1 and M2 (n = 20), respectively. One arm was excluded from circulation with a tourniquet, which was inflated before the injection of pancuronium and deflated 3 min after the injection of mivacurium. The plasma cholinesterase activity was measured before induction for all patients and 3 min after the injection of pancuronium for Groups PM1 and PM2. The plasma cholinesterase activity was decreased by 16% and 33% after pancuronium administration in Groups PM1 and PM2, respectively. In the nonexcluded arm, pancuronium significantly potentiated the effects of mivacurium. In the excluded arm, no significant block was detected for Groups M1 and M2, whereas the maximal degree of neuromuscular block was 79% and 100% for Groups PM1 and PM2, respectively. Using the isolated-arm technique, we suggest that pancuronium potentiation of the neuromuscular blocking effects of mivacurium is more likely attributable to an increase in the effective plasma concentration of mivacurium than to occupancy of postsynaptic acetylcholine receptors. IMPLICATIONS: Using the isolated-arm technique, we suggest that pancuronium potentiation of the neuromuscular blocking effects of mivacurium is more likely attributable to an increase in the effective plasma concentration of mivacurium than to occupancy of postsynaptic acetylcholine receptors.

Opposite changes in dopamine metabolites and met-enkephalin levels in the ventricular CSF of patients subjected to thalamic electrical stimulation.

High-frequency electrical stimulations of thalamic nuclei are currently used for the suppression of parkinsonian or essential tremor and for the relief of some types of intractable pain in man. However, the mechanisms by which such stimulations exert their therapeutic effects are essentially unknown. Attempts were made to provide some insight into these mechanisms by measuring the levels of the dopamine metabolites homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and met-enkephalin-like immunoreactivity in ventricular cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) or multiple sclerosis (MS) after a 30-minute therapeutic electrical stimulation of the ventralis intermedius nucleus of the thalamus. In nonstimulated control patients, the levels of these compounds did not significantly differ in two CSF samples taken 30 minutes apart. In stimulated patients, a decrease in dopamine metabolite levels associated with a relative increase in met-enkephalin-like immunoreactivity were observed in the CSF sample taken after the 30-minute stimulation as compared to the sample taken immediately before the stimulation. In contrast, the levels of 5-HIAA remained unaffected by the stimulation. These data confirmed the existence of negative interactions between dopaminergic and enkephalinergic systems in man similar to those previously demonstrated in rats. In addition, they suggest that alterations in dopaminergic or enkephalinergic neurotransmission might be involved in the therapeutic action of thalamic electrical stimulation in patients with parkinsonian symptoms and other patients.

[Tracheal intubation in prehospital resuscitation: importance of rapid-sequence induction anesthesia]. / Intubation [correction of Induction] trachéale en réanimation préhospitalière: intérêt de l'induction anesthésique à séquence rapide.

OBJECTIVE: To investigate complications of emergency endotracheal intubation (EEI), possibly facilitated by rapid-sequence induction, in the prehospital critical care setting: 1) the difficulty of intubation; 2) the cardiorespiratory consequences of intubation; 3) the relationship between the occurrence of complications and prognosis. STUDY DESIGN: Prospective non randomized, open study. PATIENTS: All patients treated over a 5-month period by a physician-manned ambulance service and requiring EEI. METHODS: Patients were allocated either in with cardiac arrest (CA) group or a group with maintained spontaneous circulation (SC). Difficulty of intubation was assessed by the number of attempts. RESULTS: Two hundred and twenty-four consecutive EEI were carried out by physicians (46%) and residents (38%) not trained in anaesthesia, anaesthetists (8%), or nurse anaesthetists (7%). Trachea was intubated after a maximum of three attempts in all patients. Success rate at the first attempt was 91%. It was 92% in CA patients (n = 76) and 90% in SC patients (P = 0.59). Anaesthetic induction, with (n = 112) or without (n = 12) succinylcholine, was used to facilitate 84% of intubations in SC patients. Complications occurred in 30 patients (20%). There was no relationship between the latter and hospital mortality, duration of ventilatory support, duration of stay in the intensive care unit. CONCLUSION: In this study, EEI in SC patients was frequently facilitated by rapid sequence induction and was associated with a high success rate at the first attempt, as in CA patients. Morbidity was low. All physicians involved in emergency airway management should be skilled in this technique.

[Anesthesia for thalamic stimulations: value of flumazenil]. / Anesthésie pour stimulations thalamiques: intérêt du flumazénil.

Five cases are reported of peroperative awakening in order to obtain patient cooperation during stereotaxic procedures. General anaesthesia was induced with 0.25 mg.kg-1 midazolam, 1.5 to 2 micrograms.kg-1 fentanyl, and 0.1 mg.kg-1 vecuronium. Maintenance was obtained with isoflurane, nitrous oxide, and small doses of fentanyl. Isoflurane inhalation was discontinued 30 to 40 min before the time of awakening required by surgery. Once expiratory isoflurane concentration reached a level less than or equal to 0.1%, nitrous oxide administration was stopped, and 0.5 mg flumazenil administered. After surgical checking, on the fully awake patient of the efficiency of thalamic stimulation and the lack of any motor deficit, anaesthesia was deepened again, with either isoflurane or a non benzodiazepine intravenous agent. All five patients recovered rapidly and calmly.

Effects of a low dose of pancuronium on oxygen consumption during sustained muscular exercise.

The effects of a low dose of pancuronium on muscular performance were studied in six healthy volunteers. Three dynamic exercise tests at increasing levels of power were performed by each subject on two consecutive days using an ergometric bicycle. To assess muscular function, oxygen consumption was measured in a steady state at each level of power output. Pancuronium 6-8 micrograms kg-1 or placebo was administered i.v. in a double-blind fashion before the second test each day. Plasma pancuronium levels were measured 8 min after administration but even with pancuronium clearly detectable in the plasma no significant differences were found either in oxygen consumption or in the haemodynamic measurements made. The authors conclude that such doses of non-depolarizing neuromuscular blocking agents do not disturb oxygen consumption during dynamic muscular exercise and are therefore unlikely to have a significant effect on muscular function.

[Spontaneous development of paralysis induced by equipotent doses of vecuronium, atracurium, fazadinium, pancuronium, gallamine and d-tubocurarine]. / Evolution spontanée de la paralysie obtenue par des doses équipotentes de vécuronium, atracurium, fazadinium, pancuronium, gallamine et d-tubocurarine.

Thirty-six patients undergoing elective surgery were studied after obtaining their informed consent. They were randomly assigned to six series of six patients each. One hour before anaesthesia, all patients received 0.2 mg.kg-1 diazepam orally. After induction of anaesthesia with 1-1.5 mg.kg-1 methohexitone and 5 micrograms.kg-1 fentanyl, the patients were paralysed and ventilation was controlled manually (semi-open circuit; 50% N2O/50% O2). Each patient received a single dose of either 70 micrograms.kg-1 fazadinium, 70 micrograms.kg-1 pancuronium, 2,500 micrograms.kg-1 gallamine or 450 micrograms.kg-1 d-tubocurarine. Neuromuscular function was monitored by measuring the isometric contraction of the adductor pollicis muscle in response to supramaximal stimulations of the ulnar nerve at the wrist (square wave pulse of 0.2 ms duration at supramaximal intensity delivery at 0.1 Hz). Three parameters were measured: the time between the injection of the relaxant drug and recovery of the twitch height at 50% of its baseline (RT0-50); the time between the injection of the relaxant drug and recovery of the twitch height at 90% of its baseline (RT0-90); the time between the injection of the relaxant drug and recovery of the twitch height from 25 to 75% of its baseline (RT25-75). The values of the observed parameters were expressed in minutes (means +/- SEM).(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics and pharmacodynamics of vecuronium (ORG NC 45) in patients with cirrhosis.

To evaluate the effect of liver cirrhosis on the pharmacokinetics and the pharmacodynamics of vecuronium, 12 patients with cirrhosis, aged (mean +/- SD) 52 +/- 12 yr, and 14 control patients, 42 +/- 15 yr, undergoing elective surgery under general anesthesia were studied. The simultaneous time courses of the plasma concentration of vecuronium and of the neuromuscular blockade were studied after the administration of a bolus dose of 0.2 mg X kg-1. Vecuronium plasma concentration declined biexponentially in both groups. Vecuronium plasma clearance was reduced significantly (P less than 0.01) from 4.26 +/- 1.38 ml X min-1 X kg-1 in the controls to 2.73 +/- 1.19 ml X min-1 X kg-1 in the patients with cirrhosis. The elimination half-life was 58 +/- 19 min in the controls and was prolonged significantly to 84 +/- 23 min (P less than 0.01) in the patients with cirrhosis. The total apparent volume of distribution was unchanged in patients with cirrhosis (0.253 +/- 0.086 1 X kg-1 vs. 0.246 +/- 0.092 1 X kg-1 in the controls). Cirrhosis caused a prolongation of the neuromuscular blockade induced by vecuronium: the duration of effect from injection to 50% recovery of the twitch height was prolonged by 100% (P less than 0.01) from 62 +/- 16 min in the controls to 130 +/- 52 min in patients with cirrhosis. The recovery rate (TH 25-75) also was prolonged (P less than 0.05) from 21 +/- 7 min in the controls to 44 +/- 18 min in patients with cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Induced normovolemic hemodilution associated with autotransfusion in orthopedic surgery in children]. / Hémodilution normovolémique intentionnelle associée à l'autotransfusion en chirurgie orthopédique infantile.

One hundred provoked normovolemic hemodilutions, which were associated with autotransfusion, have been performed in ninety-three children during a period of sixteen months. This study shows a significant saving of homologous blood (thirteen children, only had to be transfused). The mean difference in the hemoglobin level before and after surgery was of 2.1 g/100 ml. This technic did not result in any complication.

[Comparative study of ORG NC 45 and pancuronium during anesthesia]. / Etude comparative de l'ORG NC 45 et du pancuronium en pratique anesthésique.

The muscle relaxant effects of ORG NC 45 and pancuronium were compared in anesthetized patients with normal liver and renal functions. In all patients, the muscle relaxant effect was monitored by measuring the strength of the adductor pollicis muscle elicited by supramaximal stimulation of the ulnar nerve at the wrist. Different modes of administration of the muscle relaxants were used. In order to facilitate tracheal intubation, a dose of 100 mu X kg-1 of ORG NC 45 or pancuronium was administered. This dose was followed or not according to the type of surgery by repeated doses of 25 micrograms X kg-1. The results of this study indicate that ORG NC 45 is much shorter acting than pancuronium, and non cumulative. The dose of 100 micrograms X kg-1 produced adequate conditions for tracheal intubation 3 to 4 min after the administration of the muscle relaxant. The recovery of the muscle strength to 75% of control value was achieved 46 min and 100 min after a single dose of 100 micrograms X kg-1 of ORG NC 45 and pancuronium respectively. The interval of time between repeat injections averaged 20 min for ORG NC 45 and 40 min for pancuronium.

Pharmacokinetics of pancuronium in man: a linear system.

Pancuronium in bolus doses of 40 to 350 microgram/kg was administered to surgical patients in order to evaluate the linearity of its pharmacokinetics. The profile of the plasma decay curve and of its urinary elimination were compared with reference to the administered dose. It was possible to superimpose the dose-normalized plasma decay-curves. The parameters of the two compartment-open model used to describe the pharmacokinetics of pancuronium were not influenced by the dose. The elimination half-life was 89 +/- 20 min and the plasma clearance was 1.84 +/- 0.38 ml/min/kg. The profiles of cumulative urinary excretion were also dose-independent. After 6 and 24 h, 57% and 69% of the administered dose, respectively, had been excreted in the urine. The results indicate that the pharmacokinetics of pancuronium is linear.

Pancuronium pharmacokinetics in patients with liver cirrhosis.

The serum and urinary concentrations of pancuronium were measured in 14 surgical patients with cirrhosis and 12 patients free from liver disease undergoing abdominal surgery. A two-compartment open model was used in the pharmacokinetic analysis of the data. A two-fold increase in both the distribution half-life (T 1/2 alpha) from 11 min to 24 min and in the elimination half-life (T 1/2 beta) from 114 min to 208 min was observed in patients with cirrhosis. In these individuals, the total apparent volume of distribution of pancuronium was increased by 50%. Plasma clearance of pancuronium was decreased by 22%. No significant difference was found in the urinary excretion and biotransformation pattern of pancuronium. These results suggest that there is a risk of prolonged duration of action of pancuronium in patients with cirrhosis. In these patients, the initial dose to achieve adequate muscle relaxation is high and simultaneously there is slow disappearance of pancuronium from plasma. These alterations are mainly a consequence of the increase in the distribution volume of pancuronium in patients with cirrhosis.