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Nondepolarizing relaxants: new concepts and new drugs.

Less than a decade ago, the only nondepolarizing neuromuscular blocking drugs available to the anesthetist were traditional long-acting drugs such as pancuronium and d-tubocurarine. The revolution that began 10 years ago in our use of relaxants promises to continue unabated into the next decade. Changes in our clinical use of these drugs will be sparked not just by the introduction of new drugs but also by a greater understanding of the pharmacokinetic/pharmacodynamic principles that govern onset and recovery.

Androstanols↗

The isolated heart-lung preparation in the cat. An in situ model to study the role of the lungs in the disposition of drugs.

In the search for drugs with an extreme short time course of action, compounds should be developed that are rapidly distributed to and temporarily stored in well-perfused organs. Since the lungs receive the complete cardiac output and have the ability to temporarily store drugs, we have developed an in situ, isolated lung preparation in the cat to study the contribution of the lungs to the disposition of drugs. The cat's own heart perfuses the lung in situ with autologous blood. The circulation between the left ventricle and the right atrium is short-circuited via an aorta-caval shunt. The right forelimb is added to study pharmacodynamics simultaneously (only for muscle relaxants). Validation of the model for 180 min of perfusion showed complete isolation of the organs without major biochemical changes or edema and a stable muscle response. In pilot experiments with two structurally related muscle relaxants, initial muscle relaxation was followed by spontaneous recovery of neuromuscular function and a gradually decreasing plasma concentration, indicating partial disposition by the lungs. This was confirmed by direct concentration measurements in the lung. The present model may provide a powerful experimental tool to elucidate the role of the lungs in the disposition of drugs.

Albumins↗

Anesthetic management of a patient with asystolic spells.

Breathholding spells are common in infancy. In a subset of patients they may be associated with bradycardia and asystole. Management of these children necessitates placement of a permanent pacemaker. We discuss the anesthetic management of one such case.

Androstanols↗

Modulation of breathing by phasic pulmonary stretch receptor feedback in an amphibian, Bufo marinus.

This study examined the role of phasic pulmonary stretch receptor (PSR) feedback in ventilatory control, breath clustering and breath timing in decerebrate, paralysed and artificially-ventilated cane toads (Bufo marinus) under conditions designed to minimise tonic PSR feedback. Fictive breathing was recorded as trigeminal motor output to the buccal musculature. Artificial tidal ventilation, with hypercarbic gas mixtures, was either continuous or activated by the fictive breaths and was manipulated to provide differing amounts/patterns of phasic PSR feedback. The results demonstrate that increased amounts of phasic PSR feedback increase overall breathing frequency. Within multi-breath episodes there was an increase in the instantaneous breathing frequency during the later stages of the episode. The temporal relationship between a fictive breath and lung inflation influenced the duration of the pause between fictive breaths. The data indicate that phasic PSR feedback stimulates breathing by enhancing the occurrence of breathing episodes in this species but does not appear to modify the instantaneous breathing frequency during an episode.

Action Potentials↗

Advances in airway pharmacology. Emerging trends and evolving controversy.

The practice of emergency medicine is a constant onslaught of decision making and challenges and the issues of airway management are no exception. Obtaining proper airway control requires thoughtful organization and planning, and necessitates a thorough working knowledge of the drugs or medications employed. Because there are so many agents available, expertise in airway pharmacology has become essential. The emergency physician who is well versed in the uses, and the physiologic effects, contraindications, and alternatives of drugs administered is both providing immediate intervention and positively affecting patient outcome, which is certainly a goal worth achieving.

Adrenergic beta-Antagonists↗

The impact of price labeling of muscle relaxants on cost consciousness among anesthesiologists.

STUDY OBJECTIVE: To determine whether placing price labels on the vial caps of muscle relaxants increases cost consciousness among anesthesiologists. DESIGN: Retrospective study. SETTING: University hospital departments of anesthesia and pharmacy. MEASUREMENTS AND MAIN RESULTS: We placed price labels on the vial caps of all muscle relaxants for a study period of 1 year. At the beginning of the investigation, we informed the anesthesiologists of the study, discussed the prices for different muscle relaxants, and encouraged utilizing less expensive muscle relaxants whenever possible without compromising patient care. The price labels on the vial caps served as visual reminders of the various costs of muscle relaxants during daily practice. We compared the total amount spent on each muscle relaxant during the period from October 1993 to September 1994 with the period from October 1994 to September 1995. The total number of surgical cases from October 1993 to September 1994 and from October 1994 to September 1995 was unchanged and equaled 20,389 and 20,358 cases, respectively. Expenditures for pancuronium increased 104.1%. Total expenditure decreased by 12.5%, with a net savings of $47,111. CONCLUSION: Expenditures for the less costly pancuronium increased while expenditures for vecuronium and atracurium decreased. Price labeling of muscle relaxants in conjunction with education reduces total pharmacy expenditure on muscle relaxants.

Androstanols↗

Pharmacology of G-1-64, a new nondepolarizing neuromuscular blocking agent with rapid onset and short duration of action.

BACKGROUND: Chances are slim that a clinically useful ultra-short-acting neuromuscular blocking agent of rapid onset will emerge from the benzylisoquinolinium or the aminosteroid series to which all currently popular relaxants belong. G-1-64 is a promising prototype of a new series of bis-quaternary ammonium salt of bistropinyl diester derivatives we have synthesized and studied in the laboratory. METHODS: Neuromuscular block (NMB) and autonomic and cardiovascular side effects were studied on appropriate preparations of anesthetized rats, rabbits, cats, ferrets, pigs and monkeys. Neuromuscular blocking characteristics, cumulativeness, and pharmacological reversibility were determined. Cardiac vagal block was evaluated by the inhibition of the bradycardic response to stimulation of the vagus in the cat, rat, ferret, and pig. Sympathetic ganglion block was evaluated on the cat's superior cervical ganglion/nictitating membrane preparation. Arterial blood pressure and heart rate were determined in all species. RESULTS: G-1-64 produced nondepolarizing NMB with train-of-four (TOF) and tetanic fades, and reversible with anticholinesterases. Its ED50 ranged between 60 and 800 microg/kg in these species. It showed a significantly faster onset (0.9-2.1 min) and/or shorter duration of action (5-12 min) than either atracurium or mivacurium. It did not show cumulativeness on repeated doses or infusion. A varying degree of cardiac vagal block was present, dependent on the species at doses exceeding the ED80 for NMB. Cardiovascular changes, ganglion block or signs suggesting histamine release were absent. CONCLUSION: With favorable neuromuscular blocking characteristics and modest side effects, G-1-64 and similar derivatives may have clinical potential.

Androstanols↗

Anaesthetic management of an adolescent for scoliosis surgery with a Fontan circulation.

Advances in the treatment of congenital heart disease have led to a new group of adolescents or adults patients with cardiac anomalies. The anaesthetic management of these patients can be challenging especially when they are scheduled for major noncardiac surgery inducing haemodynamic instability. We report the case of a 14-year-old boy scheduled for posterior spinal fusion for idiopathic scoliosis who underwent a Fontan operation in infancy for pulmonary atresia with right ventricle hypoplasia. The preoperative investigations and the anaesthetic management are described.

Adolescent↗

Anaesthetic implications of Robinow syndrome.

Robinow (fetal face) syndrome is a rare inherited multisystem disorder featuring mesomelic or acromesomelic limb shortening, facial and spinal deformities, hypoplastic genitalia, kidney disease and congenital heart defects. We report the anaesthetic management of a patient with Robinow syndrome presenting for elective surgery and review specific issues of interest in the perioperative workup.

Abnormalities, Multiple↗