Tubocurarine Administration Based Upon Its Disappearance and Accumulation Curves in Anaesthetized Man

Abstract

A method is described which results in smooth curarization and prompt recovery using minimal amounts of tubocurarine. Following an initial dose, usually 15 mg, paralysis is maintained by a continuous infusion delivering an amount per hour about equal to the initial dose. From a mathematical interpretation of this statement an equation for the exponential disappearance of tubocurarine from the extracellular water can be obtained. Controlled ventilation is used with a light level of halothane anaesthesia. No supplementary injections of anaesthetic or analgesic are necessary. Reversal with neostigmine is prompt and complete. The accumulation curve of tubocurarine has been described and its applications stated. The time required for it to reach equilibrium between the plasma and interstitial fluid has been calculated At any time following single or multiple doses of tubocurarine, the quantity remaining in the extracellular water may be determined from the equations; this also applies to tubocurarine delivered by infusion.

Application of the relationship between pharmacokinetics and pharmacodynamics in drug development and therapeutic equivalence: a PEARRL review

“…Already in the early 1960s, the first attempts to simultaneously model pharmacokinetics and pharmacodynamics, based on the available plasma concentration and effect data for d‐tubocurarine, were made. In 1964, Levy implemented a log‐linear model to describe the time course of d‐tubocurarine response, assuming one‐compartment pharmacokinetics following intravenous bolus administration, based on the results of Ryan et al . The log‐linear model assumed that the effect of muscular relaxation is a linear function of the logarithm of the amount of d‐tubocurarine present in the plasma, while elimination of the amount of d‐tubocurarine in the body occurs exponentially with time.…”

Inadvertent Administration of 100% Oxygen During Anaesthesia

“…Sir,-When referring to my use of tubocurarine to maintain neuromuscular blockade (Ryan, 1964), Drs Somogyi, Shanks and Triggs (1978) stated that I employed this drug in a manner similar to that of Evans and Spencer Gray (1953) who allowed their patients to breathe spontaneously. By 1964 most anaesthetists were using controlled ventilation and this was also my technique.…”

Pharmacokinetics of Tubocurarine Administered by Combined I.V. Bolus and Infusion

“…Sustained muscular relaxation has been produced by continuous administration of tubocurarine (dtc) based on the rate of disappearance and accumulation of the drug in anaesthetized man (Ryan, 1964). The degree of relaxation was judged clinically, and from mathematical interpretation of the dtc requirements Ryan derived an equation for the exponential disappearance of dtc from the plasma and interstitial fluid.…”