Cheyne-Stokes respiration


 * Associate Editor-In-Chief:

Overview
Cheyne-Stokes respiration (also known as periodic breathing) is an abnormal pattern of breathing characterized by periods of breathing with gradually increasing and decreasing tidal volume interspersed with the brain to compensate quickly for changing serum partial pressure of oxygen and carbon dioxide.

Sleep disordered breathing was first described by Cheyne in 1818 in a 60 year old obese man with heart failure. In 1854, Stokes described a similar pattern of breathing that eventually culminated in apnea. The term Cheyne-Stokes respiration (CSR) describes a pattern of breathing with a crescendo – decrescendo variation in tidal volume separated by periods of central apnea or hypopnea.

It is seen primarily in patients with congestive heart failure, and in those who have suffered a stroke, but is also seen in patients with other CNS processes such as tumors, meningitis, encephalitis and trauma, as well as patients exposed to high altitudes. Patients with CSR have fragmented sleep with frequent arousals and desaturations. These cause problems with quality of life, as well as cardiopulmonary physiology.

Association with Congestive Heart Failure (CHF)
Although the incidence of CSR is unknown, it seems to be fairly common in patients with New York Heart Association (NYHA) class III and IV disease.
 * One study found that 45% of patients with moderate, stable, optimally treated CHF had CSR with an apnea – hypopnea index (AHI) >20. These episodes were associated with a SaO2 < 90% for ¼ - ½ of total sleep time. The patients were also found to have a significant increase in the number of episodes of nocturnal ventricular arrhythmias.
 * Another study found that although the cardiac parameters did not differ between patients, those with CHF and CSR has reduced total sleep time, reduced sleep efficiency, increased proportion of stages I, II, and NREM sleep and reduced REM sleep. By definition, they had higher AHIs, however the degree of hypoxemia during desaturation did not differ between the groups.
 * The recurrent desaturations and arousals experienced by patients with CHF and CSR have been associated with an increase in nocturnal angina and ventricular arrhythmias. It has also been shown that these patients have higher circulating plasma norepinephrine levels, which can obviously worsen afterload and heart failure.

Association with Stroke
CSR was once thought only to occur with bilateral or large deeper strokes, however is now recognized to be much more common, and can be seen in patients with ischemic stroke in any location.
 * One study identified CSR in 59% of patients with supratentorial stroke, and in 40% with infratentorial stroke. The patients with CSR had a significant decrease in SaO2 as compared to those without CSR, and the authors raised the concern for potential worsening of ischemia in the peri-infarct zone, due to low sats in these patients.

Pathophysiology in Patients with CHF
The exact mechanisms responsible for the development of CSR are unknown. Among the more important factors are hyperventilation, and a prolonged circulatory time.
 * Hyperventilation and resultant hypocapnia, is thought to occur in patients with CHF due to stimulation of pulmonary mechanoreceptors by interstitial edema.
 * Patients with CHF and CSR have been found to have lower awake and sleep PaCO2 levels, and increased minute ventilation as compared to patients with CHF without CSR.
 * In addition, the apnea threshold (the PaCO2 below which apnea occurs) also seems to be increased in patients with CHF and CSR.
 * Furthermore, hypoxemia shifts the ventilatory response curve for CO2 up and to the left (higher ventilation at any given CO2). This reduces the stability of the ventilatory control system.
 * Thus, hyperventilation reduces the PaCO2 below the apnea threshold, and as PaCO2 rises, an exaggerated ventilatory response causes the PaCO2 to fall below the apnea threshold, and a vicious cycle ensued.
 * Prolonged circulatory time, as a marker of severity of CHF, is directly correlated to the duration of sleep spent in CSR, as well as the cycle length of each episode.
 * This is due to an increase in the oscillation around a set point PaO2 and PaCO2. As circulatory time increases, the PaO2 and PaOC2 become more out of phase with the respiratory pattern set by the ventilatory control centers (carotid body and medulla).
 * It also seems that patients with CHF have less ability to buffer changes in PaCO2, i.e. the system is underdamped. This results from the fact that CHF causes a decrease in FRC, which reduces total body stores of CO2 and O2. It has been shown that, as total body stores of CO2 decrease, the body is not able to buffer the transient changes in PaCO2 as well.

Pathophysiology in Patients with Stroke
There is a lot less data on the mechanisms of CSR in patients with CNS disease, than in patients with CHF. Some potential mechanisms include a delay in afferent, efferent neural transmission, delays in central processing of afferent signals, slowed brain blood flow, and altered chemoresponsiveness with a heightened ventilatory responsiveness.

Differential Diagnosis

 * Stroke
 * Drugs
 * Heart Failure
 * Hypoxia
 * Subdural hematoma
 * Uremic coma

Chest X Ray
Congestive heart failure maybe present

Treatment
Obviously, CHF is associated with an increased mortality. The data concerning CSR and mortality is equivocal. It is unclear if CSR actually increases mortality from CHF (which would make physiologic sense), or is just a marker of more severe disease. It has been shown that CSR can resolve in a majority of patients with adequate treatment of the underlying CHF.
 * ACE inhibitors have been associated with a 50% reduction in the frequency of apnea and desaturation in patients with class II – III CHF. The exact mechanism remains unknown, but improved circulatory time is a leading contender.
 * Nocturnal oxygen (2-3 L/min) has been shown to reduce the duration of CSR, improve hypoxemia, sleep, and daytime cognitive function patients with severe CHF. The long term effects of nocturnal oxygen in these patients, however, remain unproven.
 * Low-flow oxygen was also found to reverse both CSR and desaturations in patients with acute strokes.
 * It is felt that eliminating hypoxemia reduces the gain of the respiratory control system. It also reduces respiratory drive, thus resulting in an increase in PaCO2 as well.
 * One study showed that 3.3 mg/kg of theophylline bid reduced the AHI (from 37 to 18), and duration of sleep with SaO2 < 90% (23% vs. 6%) in patients with CHF / obstructive sleep apnea (OSA).
 * Theophylline has also been shown to reverse CSR and desaturation in patients with acute stroke.
 * Another study found that administering 3% CO2 to 6 patients with CHF and CSR reduced the duration of CSR from 62% to 2.2% of sleep time.
 * The mechanisms by which continuous positive airway pressure (CPAP) improves central sleep apnea (CSA) in patients with CHF are likely multifactorial.
 * By increasing functional residual capacity (FRC), and therefore intrathoracic pressure, afterload and preload are reduced, and cardiac output increases. This results in a shorter circulation time. In patients with low filling pressures, however, the decrease in preload can reduce cardiac output.
 * Several studies have shown improvement in [NYHA classification]] in patients with CHF/CSR, and with CHF alone, who were treated with CPAP.
 * Additionally, Naughton et.al. showed that nasal CPAP caused an increase in left ventricular ejection fraction (LVEF), a decrease in heart rate (HR), and an increase in quality of life, as measured by dyspnea, fatigue, emotional well being and disease mastery.
 * CPAP, usually in pressures of 8 – 12 cm H20, can also eliminate apneas (and therefore arousals), as well as desaturations. The reduction in sympathetic tone may be another mechanism for improved CHF.
 * By increasing PaO2, the gain of the system is reduced (as above).
 * CPAP can also increase the PaCO2. The mechanism of this is likely multifactorial, and includes a reduction in ventilatory effort caused by improvement in pulmonary edema, a reduction in arousal mediated hyperventilation, and by reducing the gain of the ventilatory system by increasing PaO2.
 * This may drive the PaCO2 over the apnea threshold. Additionally, increased body CO2 stores can help buffer transient changes in PaCO2.
 * Unfortunately, there are no good studies that recommend using sleep studies in the routine evaluation of CHF. However, if a patients CHF is maximally treated, preliminary data would suggest performing sleep studies in patients with signs and symptoms of obstructive sleep apnea (OSA), CSR and possibly in patients with nocturnal angina or arrhythmia.