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.

Variations in pancuronium requirement, plasma concentration, and urinary excretion induced by cardiopulmonary bypass with hypothermia.

To determine the effects of cardiopulmonary bypass (CPB) and hypothermia on the neuromuscular blockade produced by pancuronium, this relaxant was infused intravenously into 10 anesthetized patients to produce and maintain 90% depression of the twitch tension of the adductor pollicis muscle following supramaximal ulnar nerve stimulation. Infusion rates, plasma concentration of pancuronium, and adductor pollicis temperature were measured every 15 min. During the normothermic period preceding the start of CPB, the pancuronium requirement, the pancuronium plasma concentration, and muscle temperature were mean (mean +/- SEM): 238 +/- 12 micrograms . m-2 . 15 min-1, 0.31 +/- 0.01 microgram/ml, and 33.9 +/- 0.1 degrees C, respectively. At the beginning of CPB, the pancuronium infusion rate increased to 362 +/- 32 micrograms . m-2 . 15 min-1 (P less than 0.001) despite a decrease in the muscle temperature to 29.2 +/- 0.9 degrees C (P less than 0.001) and in pancuronium plasma concentration to 0.22 +/- 0.02 microgram/ml. During sustained muscle hypothermia to 28.3 +/- 0.4 degrees C the pancuronium plasma concentration remained constant at 0.22 +/- 0.01 micrograms/ml (P less than 0.001) while the requirement decreased to 94 +/- 15 micrograms . m-2 . 15 min-1 (P less than 0.001). After the muscle temperature was returned to 34 +/- 0.6 degrees C, the plasma pancuronium concentration and requirements increased to 0.35 +/- 0.05 microgram/ml and 392 +/- 32 micrograms . m-2 . 15 min-1 (P less than 0.001), respectively. After CPB, these values were 0.39 +/- 0.04 microgram/ml and 239 +/- 25 microgram . m-2 . 15 min-1. These results demonstrate that pancuronium requirements are increased at the beginning of CPB because of circulatory volume changes and again during rewarming of the patient once muscle temperature reaches about 34 degrees C.

Is recovery of neuromuscular transmission complete after the use of neostigmine to antagonize block produced by rocuronium, vecuronium, atracurium and pancuronium?

To test if recovery of neuromuscular transmission is complete after the use of neostigmine under standardized conditions, we have measured adductor pollicis mechanical activity in response to 0.1 Hz (twitch height), train-of-four (TOF) and 100 Hz (RF 100 Hz) ulnar nerve stimulations. We studied 56 adult anaesthetized (thiopentone, fentanyl, nitrous oxide in oxygen) patients, allocated randomly to one of four groups (n = 14) to receive rocuronium (group Roc), vecuronium (group Vec), atracurium (group Atr) or pancuronium (group Pan). Recovery of neuromuscular transmission was studied for 15 min after neostigmine 40 micrograms kg-1 was given at 25% recovery of twitch height. Fifteen minutes after antagonism, the TOF ratio was 0.91 (SEM 0.01), 0.88 (0.02) and 0.92 (0.01) (ns), and RF 100 Hz was 0.78 (0.01), 0.79 (0.02) and 0.78 (0.01) (ns) respectively, in patients in groups Roc, Vec and Atr, respectively. In patients in group Pan, TOF ratio and RF 100 Hz were only 0.76 (0.01) and 0.33 (0.04) respectively (P < 0.01, one-way analysis of variance, Duncan's multiple classification range tests). In contrast with pancuronium, antagonism of rocuronium-, vecuronium- and atracurium-induced neuromuscular blocks produced a similar high degree of recovery of neuromuscular transmission.

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.

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.

Clinical and pharmacological actions of a bolus injection of suxamethonium: two phenomena of distinct duration.

Twenty-five healthy adult patients undergoing general anaesthesia for elective surgery were randomly allocated to five groups (n = 5) and their mechanical isometric adductor pollicis activity (twitch height (TH)), was monitored. The patients in groups I, II and III received suxamethonium 1 mg kg-1 followed by Org NC 45 40 micrograms kg-1 5 min (group I), 15 min (group II) or 30 min (group III) after complete recovery from muscle paralysis. The patients in groups IV and V received only Org NC 45 and 80 micrograms kg-1, respectively. Mean maximum TH depression (about 42% of initial value in group IV and 5% in group V) decreased to less than 4% in groups I, II and III regardless of the time interval between the injections of suxamethonium and Org NC 45. Mean duration to 90% recovery of Org NC 45-induced blockade was prolonged in patients in groups I, II and III when compared with the patients in group IV (28 min v. 12 min).

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)