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Biomedical subjects

W Buzello

Publications and source records attributed to W Buzello.

At least 37 records · Page 2Linked to original sources

Mivacurium chloride--a comparative profile.

Mivacurium is a new nondepolarizing muscle relaxant of the benzylisoquinoline type. Its short duration of action is due to rapid breakdown by plasma cholinesterase. The dose of mivacurium which produces 95% inhibition of twitch response (ED95) is between 60 and 80 micrograms/kg. Thus, mivacurium is 0.8 times and four times as potent as vecuronium and atracurium, respectively. With 2-3 x ED95, tracheal intubation can be accomplished within 2.5 min of intravenous injection. The ensuing DUR25% (time from injection to 25% recovery of control twitch tension) is twice as long as with suxamethonium and about half as long as with equipotent doses of atracurium or vecuronium. For muscle relaxation during long surgical procedures, mivacurium has been used as a continuous infusion. The average 6-min recovery index after infusion of mivacurium is particularly favourable for flexible control of muscle paralysis, whereas the recovery indices after infusion of atracurium or vecuronium are 15-30 min. In conclusion, mivacurium will close the pharmacodynamic gap between suxamethonium and the nondepolarizing muscle relaxants of intermediate duration of action. It will probably also be a suitable alternative to suxamethonium in elective cases.

Anesthesia Recovery Period↗

[Muscle relaxation in patients with neuromuscular diseases].

The classification of neuromuscular diseases with regard to the use of muscle relaxants is based on the localisation of the particular abnormality. Three types of syndromes can be differentiated: (1) denervation states; (2) disturbances of neuromuscular transmission; and (3) intracellular disease. Succinylcholine should be avoided in all types of denervation syndrome due to the possibility of life-threatening hyperkalaemia. The time frame during which succinylcholine must be avoided following a traumatic denervation or burn begins 24 h after the event. The exact period of risk is unknown, but a duration of 6 months can be considered the absolute minimum. Patients may display increased sensitivity to non-depolarising muscle relaxants following damage to the second motoneuron (e.g., amyotrophic lateral sclerosis), whereas in diseases of the first motoneuron (e.g., cerebral apoplexy), increased resistance to muscle relaxants may be observed in the affected parts of the body. In diseases of the neuromuscular junction (myasthenia gravis) there is increased sensitivity to non-depolarising muscle relaxants. No complications have been described following the use of succinylcholine in these patients, however, the use of reversal agents may lead to prolongation of the effect of succinylcholine. Patients with a primary myopathy may display increased sensitivity to non-depolarising muscle relaxants. The use of drugs with acetylcholine-like actions (succinylcholine, reversal agents) should be avoided due to the danger of triggering muscle spasms in patients with myotonic disease and the risk of rhabdomyolysis in patients with dystrophic muscle disease. Irrespective of the type of muscle disease present, titration of the dose of muscle relaxant should always be done using a nerve stimulator.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Dose-response relationship of rocuronium bromide during intravenous anaesthesia.

The dose-response relationship and time course of neuromuscular block following bolus injections of rocuronium was determined in four groups of nine patients each under nitrous oxide-narcotic anaesthesia. Each patient received a total of 800 micrograms kg-1 rocuronium in two divided doses, i.e. 120 and 680, 200 and 600, 250 and 550, or 300 and 500 micrograms kg-1. The respective second dose was injected when, following the first dose, the evoked twitch tension had recovered to 95% of its control value. The mean ED50 and ED95 values, calculated from the first doses, were 103 and 271 micrograms kg-1, respectively. The DUR25 ranged between 11 +/- 4 (200 micrograms kg-1) to 14 +/- 3 min (300 micrograms kg-1) following the first and from 30 +/- 6 (500 micrograms kg-1) to 43 +/- 11 min (680 micrograms kg-1) following the second doses. The recovery index following the second doses varied between 14 +/- 5 (500 micrograms kg-1) and 24 +/- 20 min (600 micrograms kg-1), more than twice as long as following the first doses. We conclude that rocuronium is a muscle relaxant of low potency with an intermediate duration of action.

Adult↗

Variability of pipecuronium neuromuscular blockade.

The dose-response relationship and the variability of the time variables in pipercuronium neuromuscular blockade were studied in 29 patients (ASA physical status 3) during halothane anaesthesia. The ED95 (twitch tension) was determined in 9 patients using the cumulative dose response technique. Another 20 patients received the resulting ED95 as a single bolus. The mean ED95 was 35 micrograms.kg-1 (95% confidence interval: 29-41 micrograms.kg-1). Following bolus injection of 1.ED95, an 80-100% twitch depression was achieved within 4.6 +/- 1.3 min (mean +/- s.d.). The duration from end of injection of pipecuronium to 25% twitch recovery, the time from 25% to 75% twitch recovery, and the time from 25% twitch recovery to the train-of-four ratio (TOF) returning to 0.7 was 35 +/- 14, 37 +/- 26, and 63 +/- 27 min, respectively. The time from end of injection to TOF = 0.7 varied within a 2-h range (54-160 min). Thus, the time variables in pipecuronium neuromuscular blockade were as poorly predictable as those reported in the literature on pancuronium, alcuronium and doxacurium.

Adult↗

[Curare and its successors. A 50-year's evolution].

The introduction of curare into clinical anaesthesia by Griffith and Johnson in 1942 contributed to the termination of the era where anaesthesia was a reversible intoxication rather than the result of controlled drug action. Curare allowed general anaesthesia to be reduced to a lighter level, thereby conferring a significant safety factor to the patient. Both the shortage in supply of crude curare and its variable composition led the search for synthetic curare analogues conferring well defined pharmacodynamic and pharmacokinetic properties. Based on the chemical structure of tubocurarine which has been known since 1935 the efforts concentrated on bisquaternary ammonium compounds. Gallamine was the only synthetic curare analogue to contain three quaternary ammonium groups. This drug had significant undesired vagolytic effects. In 1951 succinylbischoline appeared to be the ideal muscle relaxant, particularly with respect to its fast onset and short duration of action. The disadvantages of its depolarising mechanism of action which were appreciated during the years to follow prevented the concept of depolarising neuromuscular blockade to be pursued further. With other muscle relaxants, including curare itself, histamine release, vagal blockade and ganglionic blockade were undesired effects to be eliminated in future compounds. Improved understanding of structure-activity relationships turned out to be an indispensable tool for future research. This in turn required more elaborate methods in chemical analysis, in electrophysiology of the motor endplate, and in ultrastructural research. As a result, alcuronium and pancuronium became available in the late sixties and early seventies. Both muscle relaxants had a non-depolarising mechanism of action with reduced side effects relative to curare. From now on better techniques for pharmacodynamic and pharmacokinetic research became available resulting in research activity with particular emphasis in this field. Researchers became aware that new muscle relaxants should be designed for larger volumes of distribution and more rapid biodegradation than those currently available. Concurrently, anaesthesia techniques had changed in a way to use intubation and mechanical ventilation as a routine procedure. The risk of intraoperative hypoventilation and hypoxemia was eliminated, yet, due to the lack of adequate monitoring techniques the slow recovery from curare, alcuronium or pancuronium neuromuscular blockade was hardly appreciated.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesiology↗

Mivacurium: dose-response relationship and administration by repeated injection or infusion.

The dose-response relationship and neuromuscular blockade after infusion or repeated injection of mivacurium were studied in 65 patients in nitrous oxide-narcotic anesthesia. The ED95 (twitch tension) was determined in 45 patients by intravenous injection of a single bolus of 30, 39, 47, 54, or 60 micrograms/kg (9 patients per dose). Another 20 patients received an initial bolus of 2 x ED95 followed either by an infusion started at 5% twitch recovery (i.e., 95% depression) and adjusted to sustain 95% twitch depression (n = 10) or by repeated injection of 0.6 x ED95 whenever twitch tension had recovered to 25% of control (n = 10). Five patients in each of these two groups received 7 micrograms/kg of neostigmine at 25% twitch recovery, and the others recovered twitch tension spontaneously. The mean ED95 was 73 micrograms/kg. A 2 x ED95 bolus was followed by complete twitch depression within 2.2 +/- 0.7 min. The mean infusion rate resulted in 6 +/- 2 micrograms.kg-1.min-1. The ensuing recovery index was 6 +/- 3 min. A 6 +/- 2 min recovery index was found after up to 10 repeat injections given every 9 +/- 3 min. There was no significant effect of neostigmine in both groups. In conclusion, the recovery indices after the infusion or repeat injection of near-equal doses of mivacurium were identical.

Adolescent↗

Atracurium and vecuronium: repeated bolus injection versus infusion.

The purpose of this study was to compare the characteristics of recovery from neuromuscular blockade after either atracurium or vecuronium given by intravenous infusion or by repeated injection. Four groups of 10 patients each were studied during nitrous oxide narcotic anesthesia. An initial intravenous dose of 2 x ED95 of either muscle relaxant was followed by an intravenous infusion started at 5% recovery of control twitch tension and adjusted for 95% block or by repeated injection of 0.6 x ED95 administered whenever twitch tension had returned to 25% of control. There were no significant differences between the maintenance doses required based on method of administration: atracurium repeated injection, 1.6 +/- 0.3 x ED95 h-1; atracurium infusion, 1.7 +/- 0.3 x ED95 h-1; vecuronium repeated injection, 1.8 +/- 0.5 x ED95 h-1; and vecuronium infusion, 1.6 +/- 0.4 x ED95 h-1. Nevertheless, differences of up to 20 min were noted in the recovery indices in the following order: atracurium repeated injection = atracurium infusion less than vecuronium repeated injection less than vecuronium infusion. A single dose of neostigmine (7 micrograms/kg) significantly reduced the recovery indices, thereby eliminating their differences.

Adult↗

Greater neuromuscular blocking potency of atracurium during hypothermic than during normothermic cardiopulmonary bypass.

Previous studies drew attention to the greater neuromuscular blocking potency of atracurium during, than before or after, hypothermic cardiopulmonary bypass (CPB) while disregarding the periods of normothermic perfusion. We recorded the evoked twitch tension in 15 patients during nitrous oxide/narcotic anesthesia who were undergoing open heart surgery. Atracurium was injected as an initial bolus dose of 460 micrograms/kg. Waning neuromuscular blockade was enhanced by repeat injections of 138 micrograms/kg whenever the twitch tension attained 25% of control. During hypothermic (< 32 degrees C) and normothermic (> 34 degrees C) CPB, the times of onset of the maintenance doses were 57% and 18% longer, respectively, than before CPB (P < 0.05). Maintenance doses of atracurium were required every 24 +/- 4 min (mean +/- SD) before CPB, every 45 +/- 8 min (P < 0.05) during hypothermia, every 22 +/- 3 min during normothermic perfusion, and every 23 +/- 3 min after CPB. In conclusion, the patients' changing demand of atracurium paralleled the changes of temperature rather than the institution and cessation of CPB.

Aged↗

[Mechanomyography and electromyography--2 competing methods of relaxometry using vecuronium].

The recording of the evoked twitch tension has been the established reference method to quantitate neuromuscular blockade. The evoked compound electromyogram has been introduced later as a clinically more convenient alternative. We compared both methods in 20 patients in whom cumulative dose response curves of vecuronium and the time constants of weaning neuromuscular blockade were determined. The evoked twitch tension was slightly more sensitive in detecting residual neuromuscular blockade than the EMG. No significant differences between the two methods were found in the cumulative 90% blocking dose, the duration of block and the recovery time (25%-75%). These results are in agreement with communications of previous authors using different nondepolarizing muscle relaxants. In the absence of abnormal conditions such as neuromuscular disorders and hypothermia, recording of evoked electromyography is a clinically satisfactory method to quantitate neuromuscular blockade.

Adult↗

Muscle relaxation in patients with Duchenne's muscular dystrophy. Use of vecuronium in two patients.

Cumulative 50% and 90% neuromuscular blocking doses of vecuronium were determined in two 4-yr-old boys with Duchenne's muscular dystrophy. Vecuronium 20 micrograms kg-1 was required for 50% twitch depression in both patients. The 90% blocking doses were 43 and 57 micrograms kg-1. Although these data do not indicate a greater than normal sensitivity to vecuronium, the recovery time (75-25% block) of twitch tension was three to almost six times as long as in normal children. The evoked compound EMG, additionally recorded in one patient, reflected almost the same dose-response relationship as twitch tension, yet the EMG recovered faster than the twitch. The present findings do not exclude an increased sensitivity to neuromuscular blocking drugs in a larger population of patients with muscular dystrophy. Thus, the titration of the individual neuromuscular blocking dose with the aid of a nerve stimulator is mandatory. During a previous anaesthetic, cardiac arrest and acute rhabdomyolysis had occurred in one patient. The substitution of suxamethonium by vecuronium, or probably any other non-depolarizing myoneural blocking drug of intermediate or short duration of action, may help to avoid this complication.

Child, Preschool↗