Evaluation of infusion regimens for thiopentone as a primary anaesthetic agent

Abstract

Several multi-stage infusion regimens and a computer controlled exponentially decreasing infusion regimen were evaluated in twelve patients undergoing head and neck surgery or neurosurgery. Thiopentone dosage was based on the mean of pharmacokinetic parameter values from the literature and adjusted for each patient's lean body mass in order to rapidly achieve a predetermined plasma thiopentone concentration of 15 or 20 micrograms/ml in the period following the initial bolus dose to induce anaesthesia. Anaesthesia was satisfactory in all cases. Plasma thiopentone concentrations were maintained between 10-20 micrograms/ml during infusion in the five patients who received either a four or five stage infusion and in the six patients who received the exponential infusion, but not in the single patient who received a two-stage infusion. The mean recovery time was 111 min. The plasma concentrations of total and unbound thiopentone at awakening showed little intersubject variability, despite considerable differences in total dose and duration of infusion, suggesting the absence of acute tolerance to the drug. Plasma clearance of total thiopentone correlated strongly with calculated lean body mass and to a lesser extent with total body weight suggesting that lean body mass, in particular, should be an accurate predictor of thiopentone maintenance dose requirements. This study shows that it is feasible to use thiopentone as a primary anaesthetic agent during surgery by administering the drug either as an exponentially decreasing infusion or as an infusion comprising 4 or 5 stepwise decreasing rates.

Production of Laudanosine Following Infusion of Atracurium in Man and Its Effects on Awakening

“…The intensity of effect corresponds to the 20-30 % increase in the MAC of halothane found in rabbits with similar plasma concentrations of laudanosine [7]. Using opening of eyes on command as a criterion, awakening from anaesthesia has previously been found to occur at a relatively constant alveolar concentration for several of the volatile anaesthetic agents [15] and of thiopentone following infusion anaesthesia [16]. Eye opening on command may be considered an all-or-none response and does not require a blind observer for accurate assessment.…”

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Clinical Pharmacokinetic Considerations in the Treatment of Increased Intracranial Pressure

“…Crankshaw et al (1985) showed that at the time of surgery thiopentone concentrations can be predicted quite accurately because total plasma clearance strongly correlates with lean body mass. A mean elimination half-life of 15 ± 7.32 hours was calculated, which is slightly longer than following single injections.…”