Central sleep apnea: misunderstood and mistreated!

Abstract

Central sleep apnea is prevalent in patients with heart failure, healthy individuals at high altitudes, and chronic opiate users and in the initiation of "mixed" (that is, central plus obstructive apneas). This brief review focuses on (a) the causes of repetitive, cyclical central apneas as mediated primarily through enhanced sensitivities in the respiratory control system and (b) treatment of central sleep apnea through modification of key components of neurochemical control as opposed to the current universal use of positive airway pressure.

Keywords: Heart failure; hypoxic exposure; loop gain; opioid use; positive airway pressure.

Figure 1.. Three common types of cyclical central sleep apneas.

The three types are congestive heart failure (CHF), high-altitude/chronic opioid use, and mixed-central followed by obstructive apneas. See text for detailed descriptions. EEG, electroencephalography; P _es, esophageal pressure; SaO ₂, arterial oxygenated hemoglobin saturation; Vt, tidal volume. Adapted from .

Figure 2.. Diagram of alveolar gas equation to illustrate the effects of loop gain components on the propensity for central and cyclical central sleep apnea.

The equation is PaCO ₂ = V̇CO ₂/V̇A·K, where V̇CO ₂ = 250 mL/min. Each example shown is from an experimental study in sleeping humans or canines in which the apneic threshold and the slope of the carbon dioxide (CO ₂) response below eupnea were measured during non-rapid eye movement (NREM) sleep by using a mechanical ventilator in the assist-control mode to gradually raise tidal volume (Vt) and lower partial pressure of end-tidal carbon dioxide (PetCO ₂) until apnea occurred. The top panel shows effects of changing “plant” gain (ΔPaCO ₂/ΔV̇A) with steady-state hyper- or hypo-ventilation along the iso-metabolic hyperbola. The red filled-in areas indicate the magnitude of increase in alveolar ventilation needed to reduce PaCO ₂ sufficiently to reach the apneic threshold. For example, under control conditions in NREM sleep (eupneic PaCO ₂ ~ 45 mm Hg, denoted by X), a transient ventilatory overshoot of about 1 L/min is required to reduce PaCO ₂ ~ 5 mm Hg to the apneic threshold of 40 mm Hg. With steady-state hyperventilation (for example, oral acetazolamide; PaCO ₂ 30 mm Hg), the required ventilatory overshoot to achieve apnea (PaCO ₂ 23 mm Hg) is about twice that of the control; conversely, with steady-state hypoventilation (for example, metabolic alkalosis, opiate use; PaCO ₂ ~ 55 mm Hg), the required ventilatory overshoot to achieve apnea (PaCO ₂ ~ 51 mm Hg) is about one third that of control. Not illustrated here are ( a) the effects of transient arousal from sleep, which will increase the magnitude of the ventilatory overshoot above eupnea, and ( b) the dynamic effects of lung volume on plant gain. For example, at low lung volumes, plant gain is raised; thus, the CO ₂ washout from the alveoli will occur more quickly and will require smaller transient increments in ventilation to reach the apneic threshold . The lower panel shows effects of changing “controller” gain or chemoreceptor sensitivity to PCO ₂ (ΔV̇A/ΔPaCO ₂) above eupnea (which affects the magnitude of the ventilatory overshoot) and below eupnea (which affects the CO ₂ “reserve” or difference in PaCO ₂ between eupneic breathing and the apneic threshold). Note the increased chemosensitivities of the CO ₂ response slopes above and below eupnea in congestive heart failure (CHF) and hypoxic environments and the reduced CO ₂ sensitivity in hyperoxia which is further reduced with carotid chemoreceptor denervation (see text). CBX, Carotid Body Denervation; K, constant .863; PaCO ₂, mmHg arterial PCO2; PCO ₂, partial pressure CO2; V̇A, alveolar ventilation ; V̇CO ₂ ventilation to CO2 production; VE, ventilation.