Low and high frequency stimulation tests to characterize the effects of edrophonium on vecuronium-induced neuromuscular block.

We recorded adductor pollicis mechanical activity in response to low (0.1 and 2 Hz) and high (50 and 100 Hz) frequency stimulation 15 min after edrophonium 250, 500 and 1000 micrograms kg-1, given to antagonize vecuronium-induced block at 10, 25 and 50% pre-reversal twitch height. We studied 54 ASA class I and II anaesthetized (methohexitone, fentanyl, nitrous oxide) young adult patients allocated randomly to nine groups of six patients each. The greater sensitivity of train-of four (TOF) ratio and residual force after 100-Hz, 5-s tetanic stimulation (RF100) to residual deficit allowed discrimination more readily between the effects of edrophonium dose and pre-reversal twitch height (P < 0.001, two-way analysis of variance). The highest reversal scores (approximately 0.9 TOF ratio and 0.6 RF100) were obtained when edrophonium 500-1000 mg kg-1 was given at 50% twitch height (P < 0.05, Duncan's test).

[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)

Effect of age on the establishment of muscle paralysis induced in anaesthetized adult subjects by ORG NC 45.

The establishment of muscle paralysis produced by a single dose of 70 micrograms . kg-1 of ORG NC 45 was studied in 30 healthy anaesthetized patients, aged 15-85 years, by recording adductor pollicis isometric mechanical activity-twitch height (TH). Significant correlations were observed between age and the latency of ORG NC 45 action, defined as the reduction of TH to 95% of its initial value (r:0.315, P less than 0.05) and between age and the onset time, defined as the time elapsing between ORG NC 45 administration and maximum TH depression observed (r:0.454, P less than 0.005). Correlation between age and maximum TH depression was not significant. These results show that if the maximum TH depression observed after a standard dose of ORG NC 45 is not altered by the age of the patient, the establishment of the paralysis is delayed by ageing.

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.

Age-dependent dose-response relationship of ORG NC 45 in anaesthetized patients.

The effects of age on the dose of Org NC 45 were studied in 24 healthy, anaesthetized patients using an on-demand infusion of the drug which produced a stable twitch height of 10% of its initial value. The patients were allocated as follows: group I = age less than 40 yr; group II = 40-60 yr and group III = age greater than 60 yr. A steady-state dose measured every 10 min, was achieved in all the patients 30 min after the start of the administration of Org NC 45. Significant decreases of steady-state dosage requirement (P = 0.01) and rate of recovery from blockade (P less than 0.01) were observed between group III and the other two groups.

Stable muscle relaxation during abdominal surgery using combined intravenous bolus and demand infusion: clinical appraisal with ORG NC45.

In order to obtain stable muscle relaxation for intra-abdominal operation, a continuous demand perfusion of ORG NC45 was administered following a loading dose of 0.07 mg . kg-1. The patients had previously been anaesthetized with methohexitone, fentanyl and nitrous oxide. The perfusion rate of ORG NC45 was regulated so that the mechanical muscular response of the adductor pollicis following a supra-maximal stimulation of the ulnar nerve was maintained at 10 per cent of its initial value. The level of relaxation thus obtained was always adequate for the surgeons. During the course of the operation the requirement for more relaxant decreased progressively, becoming stable after one half hour. Nevertheless, during stable administration, individual variations were quite marked, being 44 to 483 micrograms/M2 BSA/10 min (average 225 micrograms/M2 BSA/10 min). The duration of the infusion varied from 60 to 107 minutes (average 103 minutes). After its termination the time taken from recovery varied between 3 and 82 minutes (average 27 minutes). Having regained a single twitch height of 75 per cent patients awoke rapidly after the administration of nitrous oxide was terminated. No signs of recurarization were noticed in any of the patients. In conclusion, this method of administration of ORG NC45 assures a stable level of curarization without side-effects. However, because of the different individual levels of sensitivity which were noted, this mode of administration requires careful monitoring to avoid inappropriate dosage.

Comparative evaluation of neuro-muscular blockade after pancuronium administration in patients with and without renal failure.

Objective studies about the duration of action pancuronium (PCM) in renal failure patients are scarce. This study was undertaken to obtain more complete information on spontaneous reversal from PCM-induced neuromuscular block by monitoring the twitch height to full recovery in the absence of any potentiating agent. Thumb abduction was monitored by a deplacement transducer in end-stage renal failure (ESRF) and in control patients without renal failure (RF) during neuroleptanalgesia after 0.04 mg/kg and 0.08 mg/kg PCM administration. In the small dosage series, the prologation of action in ESRF becomes significant for the 75% recovery level (mean values +/- s.e.mean:control: 42 +/- 7 min, ESRF: 71 +/- 10 min, P less than or equal to 0.05). In the second series (0.08 mg/kg), the 50% recovery level is already significantly delayed in ESRF patients (control: 91 +/- 7 min, ESRF: 163 +/- 27 min, P less than or equal to 0.05). The 100% twitch height recovery is obtained with 0.04 mg/kg PCM within 65+/- 7 min for patients without RF and within 103 +/- 9 min in ESRF patients (P less than or equal to 0.01). For the 0.08 mg/kg PCM dose, these figures are, respectively, 139 +/- 9 min and 214 +/- 20 min (P less than or equal to 0.01). The prolongation of PCM action in ESRF is in agreement with the pharmaco-kinetics of the drug. Large dosages of PCM must be avoided in ESRF patients because it delays spontaneous full recovery for too long.