The development of ultrashort acting neuromuscular relaxant tropane derivatives.

There is a need for neuromuscular relaxant (NMR) agents that are of the "nondepolarizing type" and produce rapidly developing and short-lasting skeletal muscle relaxation in anesthesiology. Many efforts have been directed to produce such agents. Our research focused on the design, synthesis, and evaluation of numerous "bisquaternary" derivatives of the cyclic aminoalkanes: tropane and granatane. Through systematic "steric structure-activity relationship" studies, we arrived at some new bisquaternary tropine and granatanol diesters, which in laboratory studies appeared to be the fastest and shortest acting NMRs recognized so far. Their ultrashort duration action-mechanism was, however, linked to the formation of nephrotoxic metabolites, precluding further development. Even so, we believe that the scientific information gained from more than a thousand such agents, will be useful toward developing the "ideal," ultrashort-acting NMR that could be clinically successful without the use of "reversing" agents, at least until "new biotechnology" may solve all problematic aspects of "transient" muscle relaxation.

Fast-track method in cardiac surgery: evaluation of risks and benefits of continuous administration technique.

INTRODUCTION: Fast-track is a method proposed to decrease medical costs through the reduction of patients' length of stay in the hospital. This study was carried out to assess the risks and benefits of conducting the fast-track method in cardiac anaesthesia and to evaluate the role of continuous infusion of short-acting anaesthetics in a successful fast-track protocol. METHODS: 100 cases were divided into two groups. In the fast-track group, fentanyl and propofol infusions were started at induction time and atracurium one hour later. No bolus drug was administered during the operation. Fentanyl infusion was continued up to 12 hours after surgery. The conventional extubation group received fentanyl and pancuronium as bolus doses. The two groups were evaluated for time of alertness and extubation in the intensive care unit, total analgesic dosage administered during the 24 hours after operation, arterial blood gas and peripheral saturation of oxygen before and after extubation. RESULTS: Time period between intensive care unit admission and alertness was significantly different in the fast-track (1.3 hours) and control (3.3 hours) groups (p-value is less than 0.001) as well as total time of intubation in the intensive care unit (4.3 hours vs. 7 hours) (p-value is less than 0.001). No patient of the fast-track group experienced low pressure of arterial oxygen, low saturation of arterial oxygen, high pressure of arterial carbon dioxide or need for reintubation in the first 24 hours after surgery. CONCLUSION: Continuous infusion of drugs in the fast-track method facilitates earlier extubation. It maintains continuous sedation and analgesia without increasing respiratory complications.

Uso de bloqueantes neuromusculares y su monitoreo en pediatría / Use of neuromuscular blocking agents and its monitoring in pediatrics

El actual arsenal farmacológico, en cuanto a relajantes musculares ha hecho necesario la constante actualización y desarrollo de técnicas para las indicaciones adecuadas y el correcto control de los mismos. El aumento de la utilización de estos fármacos en pediatría, sobre todo los relajantes musculares no despolarizantes ha facilitado la tarea médica del anestesiólogo, obligándolo a una constante actualización en el conocimiento sobre el desarrollo de estos fármacos y el monitoreo clínico e instrumental sobre el paciente.

Uso de bloqueantes neuromusculares y su monitoreo en pediatría / Use of neuromuscular blocking agents and its monitoring in pediatrics

El actual arsenal farmacológico, en cuanto a relajantes musculares ha hecho necesario la constante actualización y desarrollo de técnicas para las indicaciones adecuadas y el correcto control de los mismos. El aumento de la utilización de estos fármacos en pediatría, sobre todo los relajantes musculares no despolarizantes ha facilitado la tarea médica del anestesiólogo, obligándolo a una constante actualización en el conocimiento sobre el desarrollo de estos fármacos y el monitoreo clínico e instrumental sobre el paciente. (AU)

The future of the benzylisoquinolinium relaxants.

The benzylisoquinolinium relaxants currently include the intermediate-acting agent, atracurium, and the short-acting agent, mivacurium. This class of relaxants has always retained the distinct advantages of rapid degradation, enzymatic metabolism, or both in the plasma, resulting in short half-lives and fast, complete recovery, unrelated to dose or duration of administration. Any improvements in this class of relaxants must focus on retaining this property at the same time as decreasing or eliminating histamine release, which has always been the major disadvantage of the benzylisoquinoliniums. The introduction of 51W89, an isomer of atracurium, may represent an advance in the development of this class of relaxants.

Muscle relaxants in renal disease.

The use of neuromuscular blocking drugs during anaesthesia for patients with chronic renal failure is discussed. The disadvantages of the older non-depolarizing agents, such as tubocurarine, alcuronium, and pancuronium are outlined, as are the significant benefits of the use of atracurium or vecuronium in these patients. Preliminary reports on the new non-depolarizing drugs, pipecuronium, mivacurium, doxacurium, and rocuronium are also noted.