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Antinociceptive Agents as General Anesthetic Adjuncts: Supra-additive and Infra-additive Interactions.

Abstract
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.
AuthorsIgor Kissin
JournalAnesthesia and analgesia (Anesth Analg) Vol. 137 Issue 6 Pg. 1198-1207 (Dec 01 2023) ISSN: 1526-7598 [Electronic] United States
PMID37851902 (Publication Type: Review, Journal Article)
CopyrightCopyright © 2023 International Anesthesia Research Society.
Chemical References
  • Analgesics
  • Analgesics, Opioid
  • Anesthetics, General
  • Sodium Channel Blockers
  • Adrenergic Agonists
Topics
  • Analgesics (pharmacology)
  • Analgesics, Opioid (pharmacology)
  • Drug Interactions
  • Anesthetics, General
  • Sodium Channel Blockers
  • Adrenergic Agonists
  • Dose-Response Relationship, Drug

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