Anesthetics Drug Pharmacodynamics

Abstract

Anesthesia cannot be defined in an unambiguous manner. The essential components of general anesthesia are absence of consciousness and pain. This translates into two particular qualities: (1) sedation and hypnosis, i.e., mental blockade and (2) analgesia/antinociception, i.e., sensory blockade. Anesthetic actions on these two subcomponents are difficult to separate. On the one hand, very few anesthetics act exclusively on one of these components. On the other hand, these components are closely related to each other. Unconsciousness prevents (conscious) perception of pain, and nociception may serve as an arousal stimulus and change the level of sedation and hypnosis. The art of anesthesia lies in adequate dosing of drugs to reach both mental and sensory blockade. Drug administration can be based on pharmacokinetic considerations. Pharmacokinetic models allow an estimation of what happens to the administered drug in the body. Models with an effect site compartment may facilitate a tailored administration of anesthetic drugs. Finally, the quantification of pharmacodynamic effects allows a precise titration of drugs. Clinical assessment of mental blockade is often dichotomous, and therefore not very helpful to guide drug administration. Several scoring systems exist, but once consciousness is lost they become less reliable, in particular because reaction to stimuli is assessed, which mixes assessment of mental blockade with assessment of sensory blockade. Clinical assessment of analgesia requires a conscious patient, so antinociception is difficult to measure. Several methods of objective quantification on the basis of electrical brain activity are discussed including EEG and evoked potentials. Despite numerous indexes of the hypnotic component of anesthesia, there is no parameter that unambiguously quantifies the level of mental or sensory blockade.