Comparative use of muscle relaxants and their reversal in three European countries: a survey in France, Germany and Great Britain.

A survey was conducted among British, French and German anaesthetists to evaluate possible national differences in the peri-operative use of muscle relaxants and their reversal agents. The same non-depolarizing relaxants are used in all three countries, with the exception of d-tubocurarine, which is only available in Great Britain, and alcuronium which is mainly used in Germany. The French anaesthetists seem to use significantly less succinylcholine than their peers in Great Britain or Germany for both elective and emergency intubation. Monitoring of neuromuscular blockade still relies mainly on "clinical judgement'. Reversal of non-depolarizing muscle relaxants is performed routinely in Great Britain, while a substantial number of French anaesthetists avoid the use of a reversal. Dose regimes for neostigmine vary largely, with German anaesthetists administering the lowest, and British anaesthetists administering the highest doses. Side effects of reversal agents are reported by colleagues from all three countries in too high a percentage to justify uncritical administration of these drugs. In Germany there seems to be a noteworthy lack of recovery facilities.

[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.

Atracurio mas alcuronio en anestesia / Atracurio and alcuronio in anesthesia

Con el presente trabajo se busca demostrar los beneficios del ejemplo alternado en un mismo paciente de dos relajantes musculares no despolarizantes, en este caso atracurio y alcuronio, obteniendose condiciones optimas mas o menos rapidas de intubacion endo-traqueal, adecuada relajacion quirurgica, sin la necesidad de revertir a estos relajantes al finalizar el acto quirurgico. Disminuyendo de esta forma la dosis total de ambos relajantes, probabilidad de depresion respiratoria por relajacion residual post anestesica.

Intubating conditions and haemodynamic changes following thiopentone or propofol for early tracheal intubation.

Intubating conditions and haemodynamic changes were studied 30 sec after a fixed induction dose of thiopentone or propofol in patients scheduled for elective surgery. The hypnotic agent was preceded by the administration of papaveretum 10 mg three minutes before induction and alcuronium 0.2 mg.kg-1 at induction. Ease of intubation was graded and the study conducted in a randomised double-blind fashion. In the thiopentone group (n = 30) intubation was very easy in 73% compared with 79% in the propofol group (n = 29). In two patients in the propofol group the tracheas were moderately difficult to intubate but there were no failed intubations in either group. No patients recalled the intubation period on subsequent postoperative questioning. The immediate post-induction average systolic pressure in the thiopentone group decreased by 0.7% (range 15.9% increase to 25.3% decrease) whilst the post-intubation systolic pressure increased by 6.3% (range - 31.5% increase to 24.2% decrease). In the propofol group there was a decrease in systolic pressure after induction (average 14.4%; range 15.5% increase to 41.4% decrease, P < 0.05) but the subsequent pressor response to intubation was markedly attenuated compared with baseline (average systolic pressure decreased 15.5% (range 22.4% increase to 42.7% decrease)). Following intubation and maintenance, ventilation with nitrous oxide 70% and halothane 1% the systolic pressure decreased markedly in both groups with a greater reduction in the propofol group (P < 0.05). Compared with baseline there were increases (P < 0.0001) in heart rate in both groups from induction of anaesthesia to the end of study.(ABSTRACT TRUNCATED AT 250 WORDS)

The onset of alcuronium and tubocurarine: alone and in combination.

The rates of onset of neuromuscular blockade have been measured following 0.25 mg.kg-1 alcuronium (ED95), 0.51 mg.kg-1 tubocurarine (ED95), a combination of 50% of the ED95 of each and a combination of 33% of the ED95 of each. Train-of-four stimulation of the ulnar nerve was used with recording of the amplitude of the evoked compound electromyogram from the thenar prominence. The rate of increase in blockade in patients receiving the 50% combination was significantly greater than for either agent given alone, or than for the 33% combination. The mean time to 75% block of the first contraction of the train (T1) with the 50% mixture was 90 s, significantly faster than alcuronium alone (132 s), tubocurarine alone (174 s) or the 33% mixture (127 s). These latter three groups did not differ significantly. In conclusion, the rate of onset of the 50% combination resulted in a more rapid onset of neuromuscular blockade, whereas the rate of onset of the 33% combination was no different to that of either drug alone. This small degree of acceleration with agents which are known to be markedly synergistic makes it unlikely that this technique will prove to be of clinical importance.

Dose response of alcuronium and d-tubocurarine in infants, children and adolescents.

Seventy neonatal to adolescent general surgical patients were studied to create an individual dose-response curve for the long-acting neuromuscular blocking agents, alcuronium and d-tubocurarine. The mean (SEM) ED95 of alcuronium was 196 (9), 271 (13) and 243 (8) micrograms/kg in infants, children and adolescents, respectively (P less than 0.01). d-tubocurarine showed a similar age dependent dose-response relationship. ED95 doses were 414 (40), 499 (41) and 445 (31) micrograms/kg, respectively. The onset time (time from intravenous administration to maximal effect) following equipotent dosages was 40-50% shorter in infants than in children or adolescents (1.5 vs 2.7 minutes, P less than 0.05).

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.

Does suxamethonium influence the subsequent dose requirements of alcuronium and its reversibility in children?

Suxamethonium is often used for intubation prior to the use of a nondepolarizing muscle relaxant. This study was performed to determine whether suxamethonium altered the dose of alcuronium required to produce neuromuscular block. The findings were that suxamethonium 1.0 mg/kg did not alter the depth, duration or reversibility of block if given before alcuronium 0.3 mg/kg. Reversal with neostigmine was more rapid following 50 micrograms/kg than after 25 micrograms/kg. If recovery from neuromuscular block was greater than 25 per cent, the lower dose produced satisfactory reversal, whether or not suxamethonium had been given previously.

Response to nondepolarizing muscle relaxants in children with tumours.

The rate of onset of action of d-tubocurarine (64 patients) or alcuronium (36 patients) was studied electromyographically in 100 children who had abdominal, bone or cerebral tumours. It was found that there was a significantly delayed onset (over three times longer than controls) or additional doses were required in patients with malignant liver, renal and bone tumours who received d-tubocurarine. The onset of alcuronium blockade was also prolonged but to a lesser extent. When tumours with an abnormal prolongation of onset of relaxation were successfully treated by chemotherapy and/or surgery, the response reverted to normal. Children with benign tumours or masses had normal responses. In contrast, neuroblastomas were associated with little prolongation of onset. Cerebral tumours showed a variable response, with the observed changes being unreliable indicators of degree of malignancy.

[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.

[Atracurium--increased duration of its effect following alcuronium]. / Atracurium--Verlängerte Wirkdauer nach Alcuronium.

The duration of action of a supplementary dose of Atracurium 0.125 mg/kg after an initial dose of Atracurium 0.5 mg/kg respectively Alcuronium 0.25 mg/kg was investigated in 2 groups of 7 patients each. The average duration of action of Atracurium after Alcuronium (44.62 +/- 9.95 min) was 1.75 times longer than that of Atracurium after Atracurium (25.49 +/- 4.08 min). The difference is statistically significant (p = 0.05). For the clinical application of a combination of Atracurium with Alcuronium, 2 conclusions which might appear contradictory can be considered: 1. the pretreatment with Alcuronium can enhance intentionally the duration of action of Atracurium and spare total dosage of muscle relaxants at the same time. Prompt antagonism of muscle blockade of Atracurium remains unchanged according to our experience. 2. the pretreatment with Alcuronium may be dangerous whenever Atracurium is administered close to the end of the operation because of the possibility of prolonged postoperative muscle relaxation.

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.

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%).

Optimal time interval between pretreatment with alcuronium and suxamethonium during anaesthetic induction.

Alcuronium 0.03 mg/kg was studied in a double-blind randomized fashion as a pretreatment before suxamethonium using different time intervals between the administration of the drugs in 78 patients (ASA I-II) undergoing otolaryngological surgery. Alcuronium was given 1, 2 or 3 min before suxamethonium 1.5 mg/kg. The control group received saline as a pretreatment and suxamethonium 1 mg/kg. Anaesthesia was induced with thiopental 5.5 mg/kg over 60 s. Muscle fasciculations, intubating conditions, cardiovascular responses to endotracheal intubation and duration of neuromuscular block were assessed. Muscle fasciculations were statistically and similarly inhibited (P less than 0.01) at all time intervals between alcuronium and suxamethonium. Intubating conditions were worse (P less than 0.05) in the 3-min group than in the other groups. Cardiovascular responses to endotracheal intubation were similar in all groups. The neuromuscular block after suxamethonium was significantly shorter (P less than 0.05) in the 2- and 3-min groups than in the other groups. In conclusion, from the clinical point of view the 1-min time interval between alcuronium and suxamethonium is optimal since muscle fasciculations are inhibited and intubating conditions are satisfactory.

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.