TOC | Pulm

Sleep Apnea Syndrome  
Sleep Apnea CPAP Rx 1999        

Apnea and Periodic Breathing during Sleep
The New England Journal of Medicine -- September 23, 1999 -- Vol. 341, No. 13 (Editorial)    

Clinical Practice:  Obstructive Sleep Apnea - W.W. Flemons     (See Local Full Text of Sleep Apnea )
NEJM August 15, 2002 - Vol. 347:498-504  

Since breathing is usually regular, periodic breathing, with its clusters of breaths separated by intervals of apnea or near-apnea, has fascinated physicians for years. (2,3) The pattern of periodic breathing can vary considerably. Cheyne-Stokes respiration is characterized by rhythmic rises and falls in tidal volume and breathing frequency and is usually observed in patients with congestive heart failure.

At first, periodic breathing, regardless of the type, was thought to indicate a poor prognosis and to arise from serious neurologic or cardiovascular disease. It is now known that periodic breathing generally occurs during sleep, that it may occur in healthy persons, and that the apnea is usually central (i.e., without respiratory movements) rather than obstructive (i.e., caused by upper-airway blockage). However, periodic breathing can also be associated with obstructive or mixed (central followed by obstructive) apnea. The cyclic changes in ventilation and in the partial pressures of carbon dioxide and oxygen in blood that occur during periodic breathing are often associated with oscillations in heart rate, blood pressure, and autonomic nervous system activity. They can also trigger changes in upper-airway resistance and in the sleep-wake cycle, which can in turn affect ventilation and the symmetry and length of periodic-breathing cycles.

The idea that periodic breathing might result from instability of the feedback system that regulates breathing provided an explanation for the way in which neural and circulatory interactions could cause this phenomenon. (4,5)   In the respiratory control system, the chemoreceptors and the brain are the controllers, the lungs with the blood and respiratory muscles are the plant, and the circulation is the communication channel. The system operates to keep the arterial partial pressures of carbon dioxide and oxygen within a restricted, "normal" range by regulating the level of ventilation.

Since the sensitivity of the peripheral chemoreceptors to oxygen increases as hypoxia becomes more severe, and since changes in ventilation produce large changes in the partial pressure of oxygen, the occurrence of hypoxia increases the likelihood of periodic breathing. When the central chemoreceptors are active, the more gradual changes in the partial pressure of carbon dioxide in the brain, where the central chemoreceptors reside, and the lesser effects of ventilation on the partial pressure of carbon dioxide tend to stabilize breathing. The respiratory control models predict that periodic breathing will follow disturbances that enhance the sensitivity of the peripheral chemoreceptors and weaken the activity of the central chemoreceptors. (2,3,4,5,6)

Interest in breathing disturbances during sleep has led to an increasing number of studies of periodic breathing in humans. (11,12,13) These studies have shown that central apnea occurs commonly with periodic breathing, especially during the non-rapid-eye-movement stages of sleep, and support the idea that the underlying mechanism of periodic breathing is unstable feedback control. Javaheri, for example, reports that in patients with congestive heart failure, the ventilatory response to carbon dioxide increased in those who had periodic breathing and central sleep apnea. (1) These patients also tended to have hypocapnia. Javaheri also found a significant positive correlation between the ventilatory response to carbon dioxide and the number of episodes of apnea or hypopnea per hour during sleep. These results are consistent with those of Xie et al. (12) and Naughton et al., (13) who also reported hypocapnia in patients with periodic breathing and central sleep apnea. Xie and coworkers observed periodic breathing in persons who had central sleep apnea but no obvious neurologic or cardiac abnormalities (i.e., idiopathic central sleep apnea). (12) Those with idiopathic central sleep apnea, like those with Cheyne-Stokes respiration, had hypocapnia and increased ventilatory sensitivity to carbon dioxide. (1,12,13) In idiopathic central sleep apnea, the increased sensitivity to carbon dioxide may have a genetic origin, but in Cheyne-Stokes respiration it could be caused by lung edema, which can excite carbon dioxide responses through vagal reflexes.

Although we have a fairly good understanding of how chemoreflexes produce periodic breathing, we know much less about the role of sleep in this phenomenon. Some things we do know.

Although periodic breathing can occur in healthy persons, in patients with congestive heart failure its presence has been associated with a worse prognosis in most studies. (1,11,12,13) It is reasonable to conclude that the intermittent hypoxia, bursts of discharge from the autonomic nervous system, and wide fluctuations of intrathoracic pressure that can occur with periodic breathing diminish cardiac function. Fortunately, periodic breathing is easily diagnosed and treated with oxygen or continuous positive airway pressure, with resulting increases in survival. (1,15)

Neil S. Cherniack, M.D.   University of Medicine and Dentistry of New Jersey, Newark, NJ 07103-2714

Association of Sleep-Disordered Breathing (SDB), Sleep Apnea, and Hypertension in a Large Community-Based Study
  F. Javier Nieto - JAMA. April 12, 2000;283:1829-1836 |   Editorial  
Our findings from the largest cross-sectional study to date indicate that SDB is associated with systemic hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds.

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