News

HISTORY AND EVOLUTION OF INTRAVENOUS ANAESTHESIA

Intravenous administration of drugs dates back to the seventeenth century when Christopher Wren injected opium into a dog using a goose quill and pig bladder and the dog becomes ‘stupefied’.  In the 1930s hexobarbital and pentothal were introduced into clinical practice.

It was in the 1960s Pharmacokinetic that models and equations for IV infusions were formed and in the 1980s, computer controlled IV infusion systems were introduced. In 1996 the first target controlled infusion system (the ‘Diprufusor’) was introduced.

DEFINITION

A target controlled infusion is an infusion controlled in such manner as to attempt to achieve a user defined drug concentration in a body compartment of interest or tissue of interest. This concept was first suggested by Kruger Thiemer in 1968.

PHARMACOKINETICS

Volume of distribution.

This is the apparent volume in which the drug is distributed.  It is calculated by the formula: Vd = dose/concentration of drug.  Its value depends on whether it is calculated at time zero – after a bolus (Vc) or at steady state after an infusion (Vss).

Clearance.

Clearance represents the volume of plasma (Vp) from which the drug is eliminated per unit time to account for its elimination from the body.  Clearance = Elimination X Vp.

As clearance increases the half-life reduces, and as the volume of distribution increases so does the half-life.  Clearance can also be used to describe how quickly the drug moves between compartments.  The drug is initially distributed into the central compartment before distribution to peripheral compartments. If the initial volume of distribution (Vc) and the desired concentration for therapeutic effect (Cp) are known, it is possible to calculate the loading dose to achieve that concentration:

Loading dose = Cp x Vc

It can also be used to calculate the bolus dose required to rapidly increase the concentration during a continuous infusion: Bolus dose = (Cnew – Cactual) X  Vc. The rate of infusion to maintain steady state = Cp X Clearance.

Simple infusion regimens do not achieve a steady state plasma concentration until at least five multiples of the elimination half life.  The desired concentration can be achieved more quickly if a bolus dose is followed by an infusion rate.