[Course of the neuromuscular block under atracurium. Comparison with alcuronium]. / Evolution du bloc neuromusculaire sous atracurium. Comparaison avec l'alcuronium.

Using a standardized anaesthetic protocol, the continuous monitoring of the twitch height after a 0.1 Hz stimulus was used to follow the evolution of curarization following injection of either atracurium (0.6 mg . kg-1) or alcuronium (0.2 mg . kg-1). The maximum twitch height inhibition was always greater than 99% of the control value and occurred after 107 +/- 50 s with atracurium (n = 30) and 172 +/- 120 s for alcuronium (n = 30) (p less than 0.02). Although surgical stage of muscular relaxation (twitch height less than 25% of reference value) was the same for both drugs (55 +/- 15 min for alcuronium versus 52 +/- 10 min for atracurium; n = 30 for both groups), the clinical duration (spontaneous restoration of twitch height to 90% of the reference value) was significantly longer (p less than 0.005) for alcuronium: 89 +/- 20 min (n = 10) versus 62 +/- 9 min for atracurium (n = 10). The spontaneous return to normal of the train of four was also significantly longer (p less than 0.001) for alcuronium: 118 +/- 23 min (n = 10) versus 69 +/- 7 min for atracurium (n = 10). The recovery index (the time required for twitch height to rise from 25% to 75%) was three times quicker (p less than 0.01) for atracurium (10 +/- 3 min; n = 10) than for alcuronium (30 +/- 13 min; n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical research of muscular relaxation induced by alcuronium and pancuronium].

The clinical experiment was designed for observing effect of muscular relaxation induced by alcuronium and pancuronium. 40 patients were randomly divided into alcuronium group (A) and Pancuronium group (P). A group and P group were redivided into A1,A2 groups and P1,P2 groups according to differences of the initial doses of muscle relaxants. The results of neuromuscular monitoring indicate that onset time and main-tenance time of 0.3 mg/kg alcuronium were respectively 2.4 min and 63 min; 0.1 mg/kg pancuronium were 2.7 min and 70 min. The initial doses mentioned above are suitable to intubation of anesthesia and meet surgical need for muscular relaxation. The changes of MAP,HR,blood kalium and natrium were not evident in statistical significance before and after administration of relaxants.

Plasma proteins, packed-cell volume and requirements for alcuronium.

The relationship between alcuronium requirements and the plasma concentration of albumin and total globulin was investigated in 50 adult patients undergoing elective upper abdominal surgery. No significant correlation was obtained with the plasma proteins (g/100 ml plasma). A significant positive correlation between alcuronium requirements and plasma albumin X (1-PCV), especially in anaemic patients, was found. This relationship tended to decrease with time.

Clinical pharmacokinetics of alcuronium chloride in man.

The pharmacokinetic behaviour of alcuronium is described for nineteen patients undergoing anaesthesia for elective surgery. Eleven patients received a single bolus intravenous dose of 0.25 mg/kg, while 8 patients required additional doses of 0.125 mg/kg. A two-compartment open model was found to describe adequately both the single dose and multiple dose data for the majority of patients. No significant differences were found in the model-independent pharmacokinetic parameters between the single and multiple dose studies. Mean values for the pooled data for the half-life (t 1/2 beta), apparent volume of distribution (Vd beta), volume of distribution at steady-state (Vdss), volume of the central compartment (Vc) and plasma clearance (Clp) were 198.75 min, 24.261, 20.891, 8.181 and 90.22 ml/min respectively. Evoked muscle twitch response was monitored in 17 of the patients to assess the degree of relaxant blockade. The bolus dose of alcuronium produced complete block in 9 patients and between 95 and 99% block in the remainder. The time of onset to maximum block ranged from 3 to 30 min with the concurrently measured plasma levels of alcuronium being 0.79 to 2.25 microgram/ml. The time taken following bolus administration to 5% recovery (95% paralysis) was a mean of 42 min and the corresponding mean alcuronium plasma concentration was 0.78 microgram/ml.

Dosage patterns of non-depolarizing neuromuscular blockers in the sheep.

Eighty per cent paralysis was induced and maintained for 90 minute in the sheep by computer-controlled injection of gallamine, pancuronium, alcuronium or d-tubocurarine, using the integrated electromyogram as a measure of neuromuscular transmission. The dosage pattern consisted of a loading phase before any IEMG depression was detected, an onset phase during which a moderate amount of drug was required to achieve increasing paralysis, and a maintenance phase during which a substantially constant and relatively low infusion rate was required. The steady state rates of infusion in microgram/kg/min during "maintenance" was found to be 6.0 for gallamine, 0.15 for pancuronium, 0.2 for alcuronium and 0.5 for d-tubocurarine.

Caesarean section and placental transfer of alcuronium.

The placental transfer of alcuronium was studied in twelve patients undergoing elective or emergency caesarean section. Umbilical cord vein and maternal plasma was analysed for alcuronium at dose-delivery time intervals ranging from 5 to 10.5 minutes. The mean umbilical vein concentration of the relaxant was 0.41 +/- 0.18 (SD) microgram/ml, and the mean foetal/maternal concentration ratio was 0.26 +/- 0.11. A positive correlation between foetal and maternal concentrations of alcuronium was demonstrated. Although alcuronium appears to cross the placenta rapidly and in reasonably high concentration, no apparent adverse effects on the neonates was evident as judged by measurement of Apgar scores.

Recurarisation following a suxamethonium-alcuronium sequence in patients with atypical cholinesterase.

Alcuronium 10 mg was administered to maintain muscle relaxation in two patients before recovery from suxamethonium neuromuscular blockade to facilitate tracheal intubation. This sequence resulted in a markedly prolonged block which could not be antagonised adequately by neostigmine 0.05 mg/kg; initial antagonism was followed rapidly by prolonged recurarisation. Estimation of plasma cholinesterase activity revealed that the two patients were homozygous for the atypical and silent genes. respectively.

Alcuronium kinetics in patients undergoing cardiopulmonary bypass surgery.

1 The disposition of alcuronium was investigated in 10 patients undergoing surgery involving cardiopulmonary bypass (CPB) and compared with results from a group of non-cardiac patients studied previously. 2 After intravenous administration of a combined bolus and infusion dosage regimen, plasma concentrations fell in a bi-exponential fashion to a mean value of 0.55 micrograms/ml immediately before the start of extracorporeal circulation. 3 During CPB an apparent steady-state of alcuronium was reached immediately after commencement of CPB, however plasma concentrations were some 50% higher than those noted prior to commencement of CPB and those predicted using previous pharmacokinetic data from normal surgical patients. 4 Once CPB was completed and the alcuronium infusion terminated, post-infusion alcuronium plasma concentrations again appeared to decline bi-exponentially with time. 5 Of the pharmacokinetic parameters which were calculated model-independently, the apparent volume of distribution (Vss) was unchanged (329 vs 313 ml/kg) and the elimination half-life (t1/2,z) (532 vs 199 min) was prolonged and the plasma clearance (CL) (0.8 vs 1.34 ml min-1kg-1) markedly reduced in these patients compared to non-cardiac surgical patients. 6 As a result of these changes in alcuronium concentration during CPB and the diminished elimination of alcuronium following CPB, a closer monitoring of neuromuscular function may be necessary in cardiac patients undergoing CPB.

[Increased requirement of alcuronium in burned patients]. / Erhöhter Bedarf an Alloferin Bei Verbrennungspatienten.

We determined using the visual semi-quantitative method (train of four; Myotest) the initial dose of Alloferin (alcuronium) needed for complete neuromuscular relaxation during nitrous oxide/oxygen anaesthesia with fentanyl and diazepam in 12 burned patients operated for excision of necrotic skin and skin-graft on the 7th to 21th day following thermal injury. In a control group of 20 general surgery patients the initial dose of Alloferin was determined in the same way. The requirements of Alloferin was in the control group 15 mg (0.21 mg/kg) and in the group of burned patients 23.75 mg (0.35 mg/kg). The difference of the requirement of Alloferin was statistical significant between the two groups (p: 0.1%). The total protein and the beta globulin were significant higher in the control group. A extrajunctional spread of acetylcholine receptors might explain the increased requirement of Alloferin in burned patients.

Priming and the onset of neuromuscular blockade with alcuronium.

"Priming" with alcuronium has been studied in 72 female patients. Blockade of single twitch responses of the adductor pollicis by alcuronium 0.15, 0.2 or 0.3 mg kg-1 could be accelerated by priming with a suitable priming portion of the total dose. Giving alcuronium 0.04 mg kg-1 30 s after the induction of anaesthesia, followed by the balance 4 min later, resulted in more rapid neuromuscular blockade than giving the total dose at 4.5 min after induction. There was some suggestion of an increase in maximal twitch depression, but this could not be demonstrated confidently. The effect of increasing the priming portion was tested for the 0.3 mg kg-1 total dose, but any priming effect was attenuated. The mechanism of priming is not obvious. Occupation of "spare receptors" does not explain all of the features of priming.

[Anesthsiological experiences in experimental surgery]. / Anaesthesiologische Erfahrungen in der experimentellen Chirurgie.

The paper reports experience with methods of anaesthesia in rabbits, rats, mice, guinea-pigs, pigs, sheep, baboons, dogs and cats. Special problems of handling, mode of injection and intubation are discussed. A comprehensive survey of literature provides further information about the proposed patterns of anaesthesia and informs about other anaesthetic methods, not practised by the authors.

The elimination of pollution by a non inhalational technique.

A method is described whereby major surgery can be accomplished without inhalational anaesthtic agents, thus completely eliminating operating room pollution. The method is based on the balanced use of three intravenous agents--morphine, alcuronium and gamma-hydroxybutyrate (GHB). In the dose chosen for GHB, reliable unconsciousness can be produced for surgery of any length, and using physostigmine as an antidote, patients can be wakened within ten minutes. The advantages are convenience, simplicity of equipment, low cost, absence of pollution and good patient acceptance. The disadvantages are a certain incidence of hypertension and in this series, a small failure rate with the antidote.

Intubating conditions following pre-induction priming with alcuronium.

Three priming doses of alcuronium have been investigated and, using a logistic transformation technique, the priming dose required to produce adequate intubating conditions in 99% of patients at 60 seconds following the second dose of alcuronium has been deduced. This dose, 106.5 micrograms/kg is extremely high and may be unsafe if used, since 30% of our patients complained of side effects when given a priming dose of only 50 micrograms/kg.

Adverse reactions to atracurium and alcuronium. A prospective surveillance study.

A multicentre prospective surveillance study was undertaken to compare the incidence and severity of adverse reactions attributed to atracurium and alcuronium. Clinical manifestations were used by the anaesthetist to diagnose an adverse reaction (a cutaneous reaction, a greater than 20% change in arterial pressure or heart rate, and bronchospasm). Of the 1956 patients receiving atracurium, 10.1% had adverse reactions compared with 17.9% of the 1425 patients receiving alcuronium (P less than 0.001). There were no longterm sequelae. The atracurium group had a markedly lower incidence of hypotension (3.4% v. 13.7%; P less than 0.0001), but a higher incidence of cutaneous reactions (4.6% v. 2.3%; P less than 0.005) which were not associated with other adverse reactions. There was a low incidence of bronchospasm in both groups (0.2% v. 0.1%).

[The dose-response relationship and time course of the neuromuscular blockade by alcuronium]. / Dosis-Wirkungs-Beziehung und Zeitverlauf der neuromuskulären Blockade von Alcuronium.

Although alcuronium has been in clinical use for almost 40 years, there is still considerable controversy in the literature regarding its neuromuscular blocking potency, the time course of the drug action and the side effects. The aim of this study was to investigate the dose-response relationship of alcuronium and to compare the time course of its neuromuscular effects with vecuronium following intubation doses of both compounds. METHODS. The study was carried out in two parts. In the first part 60 patients and in the second part 30 consenting ASA class I or II patients 20-60 years of age were included. The patients were undergoing elective gynecological or intra-abdominal operations. In the first part the patients received six different doses of alcuronium (60, 90, 120, 150, 180 or 210 micrograms/kg) in order to establish its dose-response relationship. Each dose was administered to ten patients. In the second part patients received either 300 micrograms/kg alcuronium (n = 15) or 100 micrograms/kg vecuronium (n = 15), and the time course of these two compounds (onset time, duration 25%, duration 75% and the recovery index) were compared. To test the reversibility, ten patients in each group received 30 micrograms/kg neostigmine at 25% recovery of T1. The neuromuscular effects of alcuronium and vecuronium were quantitated by EMG using the DATEX relaxograph. RESULTS. The log-logit analysis of the dose response data revealed an ED50 of 111 micrograms/kg and an ED95 of 250 micrograms/kg, which is in reasonable agreement with the measured effects following 120 micrograms/kg and 210 micrograms/kg alcuronium, resulting in 52 +/- 21% and 96 +/- 4% T1 depression, respectively. The onset time, duration 25%, duration 75% and spontaneous recovery index following 300 micrograms/kg alcuronium (5.0 +/- 3.4 min, 62 +/- 25 min, 119 +/- 38 min and 58 +/- 34 min) appeared to be significantly longer (P less than 0.05) than those observed after 100 micrograms/kg vecuronium (3.2 +/- 1.2 min, 33 +/- 7 min, 49 +/- 9 min and 18 +/- 7 min), respectively. The most striking finding of this study is the enormous individual variations observed in both neuromuscular potency and the time course of action of alcuronium. Following 150 micrograms/kg (routinely employed in daily clinical practice), the magnitude of T1 depression ranged between 19% and 100%. The same vast individual variations were observed in the time course of action following 300 micrograms/kg of alcuronium. The onset time, duration 25%, duration 75% and spontaneous recovery index ranged between 1.3 and 14 min, 22 and 110 min, 93 and 186 min and 32 and 116 min, respectively. CONCLUSIONS. The ED50 and ED95 values for alcuronium found in this study are in the same order of magnitude as 106.8 micrograms/kg and 135 micrograms/kg for ED50 and with 280 micrograms/kg for ED95, respectively, as reported by others. The long duration with slow recovery and the wide individual variation in the neuromuscular effects observed in our study have been reported earlier. Based on the above observations and because of the availability of better alternatives with fewer side effects, we conclude that alcuronium should be added to the list of obsolete neuromuscular blocking agents, together with gallamine and d-tubocurarine.

Maintenance requirement of alcuronium in paediatric patients.

Seventeen paediatric patients from 0.3 to 19 years old were studied to determine the individual dose-response curves and the maintenance requirements of alcuronium during N2O-O2-opioid anaesthesia. Alcuronium 300 micrograms/kg maintained the mean (SD) neuromuscular block at 90-95% for 62 34 min). This time was longest in patients of less than 1 year of age (92 min). The hourly maintenance requirement of alcuronium was 0.41 (0.12) times the individual ED95 dose. This value was comparable in infants, children and adolescents and indicates similar duration of effect of alcuronium in all paediatric age groups.

Priming with alcuronium and tubocurarine accelerates the onset of neuromuscular block.

The individual rate of onset of action of tubocurarine and alcuronium has been examined with and without a priming dose of the same agent or the other agent, by measurement of changes in the evoked compound electromyogram of the adductor pollicis muscle. Priming was associated with acceleration of the onset of neuromuscular block.