The hypothesis "
General anesthesia consists of producing both
loss of consciousness and the inhibition of noxious stimuli reaching the brain and causing arousal" was used as a basis for the review of published data on
general anesthetic interactions with
antinociceptive agents:
opioids, α 2
adrenergic agonists, and systemic
sodium channel blockers. This review is focused on a specific type of
anesthetic interaction-the transformation of
antinociceptive agents into
general anesthetic adjuncts. The primary aim is to answer 2 questions. First, how does an antinociceptive agent transform the effect of an
anesthetic in providing a certain component of
anesthesia-
hypnosis, immobility, or hemodynamic response to noxious stimulation? Second, does a combination of an
anesthetic with an adjunct result in a simple summation of their respective effects or in a supra-additive or infra-additive interaction? The Medline database was searched for data describing the interactions of
antinociceptive agents and
general anesthetics. The following classes of
antinociceptive agents were considered:
opioids, α 2
adrenergic agonists, and systemic
sodium channel blockers. Drugs used in combination with
antinociceptive agents were
general anesthetics and
benzodiazepines. The following terms related to drug interactions were used:
anesthetic interactions, synergy, antagonism, isobolographic analysis, response surface analysis, and fractional analysis. The interactions of
antinociceptive agents with
general anesthetics result in a decrease of
general anesthetic requirements, which differ for each of the components of
general anesthesia:
hypnosis, immobility, and hemodynamic response to noxious stimulation. Most studies of the nature of
anesthetic interactions are related to
opioid-
general anesthetic combinations, and their conclusions usually confirm supra-additivity.