Pharmacokinetic-pharmacodynamic relationships for opioids in balanced anaesthesia

Abstract

The pure mu-receptor opioid agonists fentanyl, sufentanil and alfentanil are commonly used to provide the specific anti-nociceptive component of a balanced anaesthesia technique. Trefentanil and remifentanil are new opioids with a very short duration of action. Remifentanil has an ester structure and is very rapidly metabolised by blood and tissue esterases. Different perioperative stimuli require different plasma concentrations to suppress responses of the patient. The ability of the anaesthesiologist to select a precise dosage scheme for the individual patient is impeded by the large interindividual pharmacokinetic and pharmacodynamic variability. In addition, the combination of opioids and other drugs used to produce the desired components of balanced anaesthesia may exert additive, synergistic or antagonistic effects. Knowledge of factors influencing the pharmacokinetics and pharmacodynamics is still fragmentary and often controversial. Consequently, the opioid dose needs to be adjusted according to the responses of the patient during surgery to ensure adequate anaesthesia and rapid recovery. The duration of action is not predicted by the elimination half-life alone. The decline in effect-site concentration is dependent on the complex entity of infusion duration, and pharmacokinetic and pharmacodynamic parameters. Computer simulations of infusions of varying duration have been extremely useful when selecting an opioid for a specific clinical scenario on a rational basis. Traditionally, opioids are still administered by intermittent bolus injections. A disadvantage of this method of administration is that plasma concentrations fluctuate above and below the level required for adequate anaesthesia. Computer-assisted infusion pumps make it possible to target a particular drug concentration in plasma and to maintain or change this concentration as needed. This technique provides more stable anaesthesia and a more rapid recovery of the patient.