Central sleep apnea: Pathophysiology and treatment

Abstract

Central sleep apnea (CSA) is characterized by a lack of drive to breathe during sleep, resulting in repetitive periods of insufficient ventilation and compromised gas exchange. These nighttime breathing disturbances can lead to important comorbidity and increased risk of adverse cardiovascular outcomes. There are several manifestations of CSA, including high altitude-induced periodic breathing, idiopathic CSA, narcotic-induced central apnea, obesity hypoventilation syndrome, and Cheyne-Stokes breathing. While unstable ventilatory control during sleep is the hallmark of CSA, the pathophysiology and the prevalence of the various forms of CSA vary greatly. This brief review summarizes the underlying physiology and modulating components influencing ventilatory control in CSA, describes the etiology of each of the various forms of CSA, and examines the key factors that may exacerbate apnea severity. The clinical implications of improved CSA pathophysiology knowledge and the potential for novel therapeutic treatment approaches are also discussed.

Figure 1

An example of experimentally induced arousal leading to central apnea. During stable stage 2 sleep, a 55-decibel (db) tone was played to induce an arousal from sleep (shown by solid line under EEG) in a 33-year-old woman (follicular menstrual phase) with severe OSA who was receiving CPAP (14 cm H₂O). A brisk ventilatory response ensues driving end-tidal Pco₂ (PETCO₂) from 44 mm Hg during stable sleep (first arrow, note there is an approximate 3-s sampling delay between ventilation and end-tidal Pco₂) to 38 mm Hg by the return to sleep (second arrow) and was accompanied by an approximate 10-s central apnea as documented by no change in epiglottic pressure (Pepi). VT = tidal volume. PMASK = pressure at the mask.

Figure 2

Top, A: An example of a patient receiving high-dose opioid medication for back pain experiencing repetitive central apneas as demonstrated by a lack of movement of respiratory effort bands (both abdominal and thoracic) with associated oxygen desaturations. Bottom, B: Marked improvement in SDB following gradual dose reduction of opioid medication. Sao₂ = arterial oxygen saturation

Figure 3

An example of a patient with CSB. Note the characteristic crescendo/decrescendo pattern of breathing, long circulation time (each oxygen desaturation corresponds to the previous apnea), and arousal occurring at the peak of respiratory effort. See Figure 2 legend for expansion of abbreviation.

Figure 4

An example of ICSA. Note the shortened cycle time (approximately 25 s in this example) compared to CSB and that arousal (arrow) occurs at the cessation of apnea. See Figure 2 legend for expansion of abbreviation. Adapted from Malhotra et al with permission.

Figure 5

Schematic of the many potential mechanisms contributing to CSA/hypopnea. The gray boxes and largest solid arrows represent the key components contributing to unstable breathing and central apnea/hypopnea during sleep. The smaller solid arrows denote the main factors that lead to or modulate unstable breathing during sleep. Dashed arrows highlight the potential interactive links between obstructive and central apnea/hypopnea and for hypercapnia to cause arousal. Some arrows have been omitted to simplify the Figure. Refer to the text for further detail.