Central Sleep Apnea at High Altitude

Adv Exp Med Biol. 2016:903:275-83. doi: 10.1007/978-1-4899-7678-9_19.


The discovery of central sleep apnea (CSA) at high altitude is usually attributed to Angelo Mosso who published in 1898. It can occur in susceptible individuals at altitude above 2000 m, but at very high altitude, say above 5000 m, it will occur in most subjects. Severity is correlated with ventilatory responsiveness, particularly to hypoxia. Theoretically, it should spontaneously improve with time and acclimatization. Although the time course of resolution is not well described, it appears to persist for more than a month at 5000 m.It occurs due to the interaction of hypocapnia with stages 1 and 2 NREM sleep, in the presence of increased loop-gain. The hypocapnia is secondary to hypoxic ventilatory drive. With acclimatization, one might expect that the increase in PaO2 and cerebral blood flow (CBF) would mitigate the CSA. However, over time, both the hypoxic and hypercapnic ventilatory responses increase, causing an increase in loop gain which is a counteracting force.The severity of the CSA can be reduced by descent, supplemental oxygen therapy, oral or intravenous acetazolamide. Recent studies suggest that acute further increases in cerebral blood flow will substantially, but temporarily, reduce central sleep apnea, without altering acid based balance. Very recently, bi-level noninvasive ventilation has also been shown to help (mechanism unknown). Sleep quality can be improved independent of the presence of CSA by the use of benzodiazepine sedation.

Keywords: Central sleep apnea; Cerebral blood flow; Loop gain; Sleep quality.

Publication types

  • Review

MeSH terms

  • Altitude*
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / physiology
  • Humans
  • Hypnotics and Sedatives / pharmacology
  • Hypnotics and Sedatives / therapeutic use
  • Oxygen / metabolism
  • Sleep / drug effects
  • Sleep Apnea, Central / drug therapy
  • Sleep Apnea, Central / pathology*
  • Sleep Apnea, Central / physiopathology


  • Hypnotics and Sedatives
  • Oxygen