Sources of Inspiration: A Neurophysiologic Framework for Understanding Anesthetic Effects on Ventilatory Control

Abstract

Almost every medication that is presently available to provide sedation, analgesia, or general anesthesia significantly depresses one or more ventilatory control mechanisms. This places patients at risk of developing hypoventilation and hypoxemia during moderate or deep sedation as well as general anesthesia. As the neurophysiologic processes underlying normal ventilatory drive are discovered, new insights into the influence of anesthetics on ventilation have been recognized. More importantly, research into ways to circumvent these effects is underway. For example, drugs such as serotonin agonists and ampakines have been shown to counteract opioidinduced ventilatory depression without reversing the analgesic effect. On the other hand, efforts to identify agents that reverse the respiratory depression associated with propofol and the inhalation anesthetics have been less promising. Until reliable means for reversing drug-induced ventilatory depression are developed, prompt recognition of ventilatory insufficiency and initiation of resuscitative measures remain the keys to patient safety.

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“…67 The carotid bodies (neural crest-derived structures located at the carotid bifurcations), are the peripheral chemoreceptors, regulating the ventilatory response to hypoxia. 69 Carotid body glomus cells scan their extensive blood supply for adequacy of oxygenation: 69,70 if arterial partial pressure (PaO 2 ) falls below approximately 60 mmHg, potassium background leak channels close, halting K + exit and depolarizing the glomus cells. 69 Next, calcium influx through voltage-gated channels triggers the release of glomus cell neurotransmitters which initiate firing of action potentials by adjacent afferent terminals of the carotid sinus branch of cranial nerve IX.…”

“…69 Carotid body glomus cells scan their extensive blood supply for adequacy of oxygenation: 69,70 if arterial partial pressure (PaO 2 ) falls below approximately 60 mmHg, potassium background leak channels close, halting K + exit and depolarizing the glomus cells. 69 Next, calcium influx through voltage-gated channels triggers the release of glomus cell neurotransmitters which initiate firing of action potentials by adjacent afferent terminals of the carotid sinus branch of cranial nerve IX. 69,70 The action potentials travel first to the nucleus tractus solitarius (NTS), and then to the Prebotzinger complex in the medulla, augmenting respiratory drive as an attempt to correct the oxygen shortfall, 68,69 (Figure 4) and simultaneously invoking the reflex pathways that mediate air hunger.…”

“…69 Next, calcium influx through voltage-gated channels triggers the release of glomus cell neurotransmitters which initiate firing of action potentials by adjacent afferent terminals of the carotid sinus branch of cranial nerve IX. 69,70 The action potentials travel first to the nucleus tractus solitarius (NTS), and then to the Prebotzinger complex in the medulla, augmenting respiratory drive as an attempt to correct the oxygen shortfall, 68,69 (Figure 4) and simultaneously invoking the reflex pathways that mediate air hunger.…”

“…The oxygen sensor which initiates glomus depolarization is still debated, but it may be ROS-producing NADPH oxidase, 69 which also happens to participate in AT1 receptor signaling. Whether or not AT1 and NADPH oxidase are involved in hypoxia sensing, RAS is definitively activated during the hypoxic response.…”

“…Glomus cells, located within the carotid body, are neural crest-derived, and they exhibit voltage-dependent neurotransmitter release upon detection of hypoxemia. 69,70 Glomus cells detect hypoxemia by an as-yet undefined sensor, which is thought to close K+ channels, halting K+ exit and thereby depolarizing the Glomus cell. 69,70,241,242 Depolarization leads to opening of voltage-gated Ca2+ channels and neurotransmitter release, which triggers action potential firing in nearby cranial nerve IX.…”