Principles of intravenous drug infusion
The most efficient way of maintaining a desired drug effect is by continuous infusion to attain constant blood concentrations. Dose regimens that compensate for drug distribution as well as for excretion, can achieve and maintain targeted concentrations by using pharmacokinetic simulations. These target-controlled infusions (TCI) can be administered by computer control using syringe pumps that have inbuilt TCI software, or by manual control, using simulation software that calculates and displays expected drug concentrations. Clinicians now need to associate blood concentrations with expected effects, but fortunately, this is familiar to anaesthetists who relate alveolar partial pressures of inhaled anaesthetic to drug effect. TCI facilitates fine-tuning of drug concentrations according to patient requirements in similar fashion to a vaporizer. The speed with which patients recover after intravenous infusions is influenced by the duration of the infusion as well as by the concentrations achieved, and this is best described by the concept of context-sensitive decrement times. Recovery after an infusion has little relevance to the elimination half-life of a drug because the latter does not take drug distribution into account. Pharmacokinetic simulations continuously calculate and display expected recovery times, should the infusion be stopped, assisting clinicians to ascertain when to reduce or terminate an infusion. For example, correct administration of fentanyl allows for a rapid recovery to spontaneous respiration if the initial decrement to that concentration is small (20-30%). Thereafter the decrement rates are slow, allowing for extended analgesic effects after surgery. © 2005 Elsevier Ltd. All rights reserved.