Treatment of Positive Airway Pressure Treatment-Associated Respiratory Instability with Enhanced Expiratory Rebreathing Space (EERS)

Central sleep apnea and Cheyne-Stokes breathing pattern (periodic breathing) are manifestations, in part, of increased respiratory control chemosensitivity during sleep. Complex sleep apnea is characterized by predominantly obstructive sleep apnea on a diagnostic polysomnogram with central sleep apnea or periodic breathing that emerges during positive airway pressure titration.1–3 These patients may have underlying alterations in chemoreflex sensitivity, which only come to prominence when the clinically significant obstructive sleep apnea has been relieved. This concept expands the role of respiratory control dysfunction in clinical practice, previously restricted to those with overt central sleep apnea or Cheyne-Stokes respiration during diagnostic polysomnography.4 This group of disorders might best be considered “chemoreflex modulated sleep apnea.” An incomplete polysomnographic and clinical response to conventional positive airway pressure may be the hallmark of strong chemoreflex modulation of sleep apnea.2,5 Recent attempts to treat these chemoreflex-modulated sleep apnea syndromes include novel applications of positive airway pressure. For example, adaptive servo-ventilation is a newly approved concept in the therapy for central and complex sleep apnea.6–10 Two devices are already available in clinical practice, using different algorithms to vary pressure support in order to stabilize ventilation, and others are likely to follow. BRIEF SUMMARY Current Knowledge/Study Rationale: Ventilatory instability during sleep, including that associated with positive airway pressure titration, is induced or worsened by hypocapnia. Methods that can minimize hypocapnia during pressure titration for sleep apnea have the potential to improve the effective CO2 reserve and improve the quality of sleep and breathing. Study Impact: The authors describe a simple and practical way to minimize hypocapnia during positive pressure treatment. This method may be of special benefit to those demonstrating central apneas or periodic breathing on diagnostic polysomnograms, or those who have emergence of these same phenomena during positive pressure treatment. Improved clinical outcomes seem possible in a subset of positive pressure treatment failures. We hypothesized that manipulation of arterial carbon dioxide levels might provide an alternative treatment strategy. Specifically, keeping PCO2 just over the apnea threshold would be predicted to buffer chemoreflex influences and make the disease more purely obstructive in physiology, thus remaining responsive to positive airway pressure treatment. Central apneas and periodic breathing can be generated when the arterial PCO2 level falls below that required to stimulate respiration, a set-point that is unmasked during sleep.11 Preventing hypocapnia is a powerful stabilizing influence on sleep respiratory control.12 Hypocapnia is critical in the genesis of altitude-induced periodic breathing,13 idiopathic central sleep apnea syndrome,4 heart failure-related periodic breathing and Cheyne-Stokes respiration,4,14 and stroke-related mixed forms of sleep apnea.15 CO2 can be introduced into the circuit, using dead space,16–18 bleed-in, or by a more precisely controlled flow-independent method that is currently investigational.12 There are, however, several problems with the use of dead space alone: (1) Pure central sleep apnea is rare, and even in these instances, collapse of the upper airway can be demonstrated.19 (2) “Mixed” patterns of disease are typical in clinical practice20 and require simultaneous upper airway support.5 (3) Tidal volume increases are necessary to effectively use the volumes of dead space that appear effective (500-600 mL).17 Consequences of this include respiratory discomfort, increased work of breathing, and the need to inhale the equivalent of 3% to 4% CO2. We hypothesized that adding dead space to positive airway pressure therapy would be effective in the treatment of central apneas and periodic breathing that emerged or persisted on positive airway pressure therapy, and that sub-tidal volume dead space would be adequate when the upper airway was also supported.21 As dead space is a volume ventilation concept, and our technique was meant to complement positive pressure application, the term enhanced expiratory rebreathing space or EERS was coined. We present a retrospective analysis of our experience with this technique for improved management of positive pressure treatment-associated ventilatory instability.