Impact of Sleeping Angle on the Upper Airway and Pathogenesis of Cheyne Stokes Respiration

Dr. Hanly has indicated no financial conflicts of interest. CHEYNE-STOKES RESPIRATION (CSR), FIRST DESCRIBED ALMOST 200 YEARS AGO, IS A FORM OF CENTRAL SLEEP APNEA THAT CONTINUES TO BE FOUND in 21% to 31% of patients with congestive heart failure despite conventional medical therapy.1,2 Its pathogenesis is complex and multifactorial, but a critical and consistent requirement is the development of hypocapnia3 associated with hyperventilation, which has been attributed to stimulation from pulmonary mechanoreceptors associated with pulmonary congestion.4 If PaCO2 falls below the level required to stimulate breathing (apnea threshold) apnea will ensue. During apnea, PaCO2 rises above the apnea threshold with resumption of breathing, which is amplified in patients with CSR due to increased sensitivity of the peripheral and central chemoreceptors.5 The resulting ventilatory overshoot lowers PaCO2, thereby setting the stage for the next apnea. These destabilizing influences are particularly important in NREM sleep, during which stable breathing is almost exclusively dependent upon the metabolic system, and are further facilitated by hypoxia, prolonged circulation time, compromised cerebral blood flow responsiveness to carbon dioxide, arousals from sleep, metabolic alkalosis, and possibly upper airway instability.4 The indications for treatment of CSR in heart failure remain somewhat of a dilemma for the practicing sleep physician. Some patients do have nocturnal symptoms such as recurrent awakenings associated with the hyperpneic phase of the periodic breathing cycle that are relieved by treatment of CSR.6 Furthermore, objective daytime sleepiness associated with CSR has been reported.7 However, many patients with CSR do not report specific sleep symptoms, and subjective daytime sleepiness has been absent in large cohorts of heart failure patients.8 The impact of CSR on long-term cardiovascular outcomes is also unclear. Observational studies have reported an association between CSR and increased mortality9,10 which suggests that CSR either reflects the severity of heart failure or that it accelerates its progression. However, a large, randomized, controlled study (CANPAP trial) failed to show that treatment of CSR with CPAP improved transplant-free survival.11 It is worth noting that CPAP did not suppress CSR in all patients, and a subsequent post hoc analysis showed that patients whose AHI fell below 15 (57% of patients) did have an improved transplant free survival.12 The challenge for the clinician is further increased by the fact that there is no single, uniformly effective treatment for CSR. Several therapeutic modalities have been reported with variable success. CPAP and supplemental oxygen are effective in approximately 50% of patients.6,11 Inhaled carbon dioxide suppresses CSR,13 but a safe and practical method of delivery is not readily available. Pharmacologic therapy with sedative hypnotics, acetazolamide, and theophylline is limited by variable efficacy and the potential for unwanted side effects. Although more sophisticated ventilatory support such as that provided by adaptive servoventilation holds the promise of greater efficacy than CPAP,14 these units are too costly for many patients and health care systems at the present time. Consequently, clinicians need to consider whether treatment of CSR is indicated and what treatment is most appropriate in each individual patient. In this issue of SLEEP, Soll and colleagues report on the impact of sleeping position on CSR in 25 patients with stable heart failure.15 They monitored AHI at 4 different sleeping angles (0, 15, 30, and 45 degrees) that were chosen randomly throughout the night. They found that AHI fell from 34.7±30 to 23.2±23.7 as sleeping angle increased from 0 to 45 degrees. Although this was not statistically significant, the apnea index did fall significantly as the sleeping angle increased, but only during NREM sleep and in the supine position. The investigators also continuously monitored indices of both left ventricular hemodynamics and “thoracic fluid content” by impedance cardiography. They found no change in either of these parameters as sleeping angle was altered. Although previous publications have documented that CSR is partly posture dependent,16–18 the current study differs from them in two important ways. First, the sleeping angle was modified in a standardized fashion to look for a “dose-response” relationship between sleeping position and CSR, whereas previous studies have simply compared CSR between the supine and non-supine positions which occurred spontaneously during sleep. Second, continuous monitoring of ventricular hemodynamics and thoracic fluid content was added to investigate potential mechanisms for this phenomenon. Notwithstanding that the study did not identify an underlying mechanism, it is the first one to go beyond a descriptive report. Which of the predominant pathophysiologic mechanisms outlined above are most likely to be influenced by a change in the sleeping angle? The reduction in central apnea frequency was noted to occur “immediately after the adjustment of the sleeping angle”. Interestingly, this observation was also specifically illustrated by Sahlin et al.17 It is unlikely that such a rapid change was due to alteration in pulmonary congestion or circulation time, which is supported by the authors' negative impedance cardiography results, nor by changes in the sensitivity of the chemoreceptors and cerebral vasculature. Lung volume is likely to change with sleeping angle and, if this were associated with correction of hypoxia, it could help to stabilize breathing during sleep. However, hypoxia was minimal and did not change with sleeping angle.15 Consequently, we are left to consider the potential impact of posture on the upper airway. Although characteristically associated with obstructive sleep apnea, upper airway instability has been reported in CSR19 and spontaneously occurring central sleep apnea.20 It is postulated to contribute to destabilization of breathing during sleep by increasing the ventilatory overshoot that has been previously described. Alternatively, upper airway reflexes that have a more direct effect on the control of breathing21 could be impacted by a change in sleeping position. Although the authors comment that inspiratory airflow limitation was seen in many patients and that it did not appear to be related to the sleeping angle, changes in upper airway structure and function need to be monitored more comprehensively in order to address this question. What are the implications of these findings for the sleep community? For the clinician, alteration of sleeping position may offer an alternative therapy for CSR that is practical and noninvasive. This may be particularly helpful for those with nocturnal symptoms, and it is interesting to note that most patients were able to sleep at 45 degrees.15 Researchers who are engaged in the evaluation of new therapies for CSR may want to consider controlling for sleeping position in their experimental designs. In summary, the findings of Soll and colleagues15 have high-lighted the relationship between sleeping position and CSR and the potential contribution of the upper airway to the pathogenesis of this common breathing disorder. Future research is required to determine the underlying physiologic mechanisms for this relationship and whether their modification can lead to alternative or adjunct therapy for CSR.

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