Central Sleep Apnea in Adults: Diagnosis and Treatment
Background: While the literature has demonstrated a higher prevalence of moderate-to-severe obstructive sleep apnea (OSA) in the general population compared with central sleep apnea (CSA), more evidence is needed on the long-term clinical impact of and optimal treatment strategies for CSA.
Observations: CSA is overrepresented among certain clinical populations, such as those with heart failure, stroke, neuromuscular disorders, and opioid use. The clinical concerns with CSA parallel those of OSA. The absence of respiration (apneas and hypopneas due to lack of effort) results in sympathetic surge, compromise of oxygenation and ventilation, sleep fragmentation, and elevation in blood pressure. Symptoms such as excessive daytime sleepiness, morning headaches, witnessed apneas, and nocturnal arrhythmias are shared between the 2 disorders. A systematic clinical approach should be used to identify and treat CSA.
Conclusions: The purpose of this review is to familiarize the primary care community with CSA to aid in the identification and management of this breathing disturbance.
CSA-HAPB is defined by the following ICSD-3 criteria: (1) Recent ascent to a high altitude (typically ≥ 2500 m, although some individuals may exhibit the disorder at altitudes as low as 1500 m); (2) the patient reports sleepiness, awakening with shortness of breath, snoring, witnessed apneas, or insomnia; (3) symptoms are clinically attributable to HAPB, or PSG, if performed, reveals recurrent CSAs or hypopneas primarily during non-REM sleep at a frequency of ≥ 5 events per hour; (4) the disorder is not better explained by another current sleep disorder, medical or neurological disorder, medication use (eg, narcotics), or SUD.8
Treatment options to improve nocturnal oxygen saturation and reduce or eliminate CSA-HAPB in nonacclimatized individuals include oxygen-enriched air, acetazolamide, or combination treatment with acetazolamide and automatic PAP (APAP).22 A meta-analysis looking at the effectiveness of acetazolamide in 8 different randomized controlled trials demonstrated that a dose of 250 mg per day was effective in improving sleep apnea at altitude as measured by a decrease in AHI, decrease in percentage of periodic breathing, and increasing oxygenation during sleep.15 The question of superiority of combined acetazolamide with APAP to placebo with APAP in treatment of high-altitude OSA was addressed in a randomized double-blind, placebo-controlled trial. The results showed that combined APAP (5-15 cm of water pressure) and acetazolamide (250 mg morning, 500 mg evening) decreased the AHI to normal range, whereas central events persisted in the APAP and placebo group.23 In addition, Latshang and colleagues have demonstrated that ASV may not be as efficacious for controlling CSA-HAPB in nonacclimatized individuals compared with oxygen therapy and suggested that further research is warranted examining if ASV device algorithm adjustment improves efficacy of this therapeutic option.24
Comorbidity-Induced CSA
Several medical conditions may be associated with CSA, including chronic kidney disease (CKD), pulmonary hypertension, acromegaly, and hypothyroidism. The common pathophysiologic link is that these disorders may result in alteration of ventilatory responses to CO2, ultimately resulting in CSA.
As many as 10% of patients with CKD may experience CSA.25,26 The complications encountered in CKD include fluid overload with pulmonary edema, chronic metabolic acidosis, and anemia. These can provoke hyperventilation in addition to poor sleep quality, triggering arousals that further drive CSA in these patients. Additional risk factors for CSA in this population include atrial fibrillation and cardiac dysfunction. Clinical interventions that have demonstrated reduction in CSA include hemodialysis at night vs daytime and using bicarbonate buffer vs acetate for hemodialysis 22-24,26-29
Hypersecretion of growth hormone in acromegaly also results in hyperventilation contributing to CSA. While medical and surgical management of acromegaly results in a reduction in OSA, there is limited evidence on the outcome of the CSA after these interventions.
Hypothyroidism and CSA both present with similar symptoms of fatigue, daytime sleepiness, depression, and headaches. Studies suggest that respiratory muscle fatigue and decreased ventilatory response to hypercapnia and hypoxia contribute to apnea in this population. In one study, 27% of hypothyroid patients had a blunted response to hypercapnia, and 34% suffered from a blunted response to hypoxia. The same study showed universal reversal of the impairment following thyroid replacement therapy and return to euthyroid state.30 Similarly, multiple studies have shown reversal of respiratory muscle fatigue after initiation of thyroid replacement.30-32 Assessing thyroid function is an appropriate initial step during any sleep-disordered breathing workup, as it is a reversible cause of apnea. Up to 2.4% of patients presenting for PSG (and diagnosed with OSA) are found to have undiagnosed hypothyroidism.32,33 In a military population, treatment of a secondary cause of CSA, such as hypothyroidism, could remove some administrative burden as well as improve service members’ quality of life.
If CSA persists despite previous treatment strategies, then clinicians should focus on the optimization of treatment for comorbid conditions. If that does not resolve CSA, CPAP should be used when AHI remains above 15 events per hour or ASV can be used.
