Title:The Modulation by Anesthetics and Analgesics of Respiratory Rhythm in
the Nervous System
Volume: 22
Issue: 2
Author(s): Xuechao Hao, Yaoxin Yang, Jin Liu, Donghang Zhang, Mengchan Ou, Bowen Ke, Tao Zhu*Cheng Zhou*
Affiliation:
- Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, 610041, China
- Laboratory of
Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of
Anesthesiology, West China Hospital of Sichuan University, Chengdu, 610041, China
Keywords:
General anesthetics, analgesics, respiratory rhythm, synaptic transmission, neurotransmitter, ion channels.
Abstract: Rhythmic eupneic breathing in mammals depends on the coordinated activities of the neural
system that sends cranial and spinal motor outputs to respiratory muscles. These outputs modulate
lung ventilation and adjust respiratory airflow, which depends on the upper airway patency and ventilatory
musculature. Anesthetics are widely used in clinical practice worldwide. In addition to clinically
necessary pharmacological effects, respiratory depression is a critical side effect induced by most general
anesthetics. Therefore, understanding how general anesthetics modulate the respiratory system is
important for the development of safer general anesthetics. Currently used volatile anesthetics and
most intravenous anesthetics induce inhibitory effects on respiratory outputs. Various general anesthetics
produce differential effects on respiratory characteristics, including the respiratory rate, tidal
volume, airway resistance, and ventilatory response. At the cellular and molecular levels, the mechanisms
underlying anesthetic-induced breathing depression mainly include modulation of synaptic
transmission of ligand-gated ionotropic receptors (e.g., γ-aminobutyric acid, N-methyl-D-aspartate,
and nicotinic acetylcholine receptors) and ion channels (e.g., voltage-gated sodium, calcium, and potassium
channels, two-pore domain potassium channels, and sodium leak channels), which affect neuronal
firing in brainstem respiratory and peripheral chemoreceptor areas. The present review comprehensively
summarizes the modulation of the respiratory system by clinically used general anesthetics,
including the effects at the molecular, cellular, anatomic, and behavioral levels. Specifically, analgesics,
such as opioids, which cause respiratory depression and the “opioid crisis”, are discussed. Finally,
underlying strategies of respiratory stimulation that target general anesthetics and/or analgesics are
summarized.
