PHARMACOKINETIC-PHARMACODYNAMIC RELATIONSHIPS FOR OPIOIDS IN BALANCEDANESTHESIA

The pure mu-receptor opioid agonists fentanyl, sufentanil and alfentan il are commonly used to provide the specific anti-nociceptive componen t of a balanced anaesthesia technique. Trefentanil and remifentanil ar e new opioids with a very short duration of action. Remifentanil has a n ester structure and is very rapidly metabolised by blood and tissue esterases. Different perioperative stimuli require different plasma co ncentrations 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 p harmacodynamic variability. In addition, the combination of opioids an d other drugs used to produce the desired components of balanced anaes thesia may exert additive, synergistic or antagonistic effects. Knowle dge of factors influencing the pharmacokinetics and pharmacodynamics i s still fragmentary and often controversial. Consequently, the opioid dose needs to be adjusted according to the responses of the patient du ring surgery to ensure adequate anaesthesia and rapid recovery. The du ration of action is not predicted by the elimination half-life alone. The decline in effect-site concentration is dependent on the complex e ntity of infusion duration, and pharmacokinetic and pharmacodynamic pa rameters. Computer simulations of infusions of varying duration have b een extremely useful when selecting an opioid for a specific clinical scenario on a rational basis. Traditionally, opioids are still adminis tered by intermittent bolus injections. A disadvantage of this method of administration is that plasma concentrations fluctuate above and be low the level required for adequate anaesthesia. Computer-assisted inf usion pumps make it possible to target a particular drug concentration in plasma and to maintain or change this concentration as needed. Thi s technique provides more stable anaesthesia and a more rapid recovery of the patient.