Stabilizing ventilation in OSAHS with CPAP emergent periodic breathing through the use of dead space.

In this issue of the Journal, Gilmartin et al. present their retrospective experience with a novel therapy, “enhanced expiratory rebreathing space,” for CPAP emergent periodic breathing in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS).1 Using a tight-fitting, non-vented facemask and graduated additions of tubing to increase dead space on the patient side of the leak port of a conventional CPAP circuit, they significantly improved CPAP emergent central apnea/periodic breathing in the majority of 204 patients. While the clinician will be interested by the relative simplicity of this dead space circuit and the apparent long-term effectiveness it has on periodic breathing and clinical symptoms, as well as the tolerance and adherence to treatment shown by many patients, this study is also an exercise in applied physiology. Demonstrating in a clinical setting the ability to stabilize ventilatory pattern by adding dead space shows how physiological understanding can lead to new and rational forms of clinical therapy. It has long been known that control of breathing (particularly CO2) underlies periodic patterns of breathing.2,3 However, the recognition that central drive to the respiratory pump muscles plays an important role in the etiology of obstructive SAHS has had a checkered history. Originally, the “Pickwickian Syndrome” was thought to be entirely due to abnormal central respiratory drive.4 Recognition of OSAHS as a very common, but predominantly non-hypercapnic, entity re-directed interest towards control of the upper airway.5 Recently, however, there has been a resurgence of interest in the role ventilatory “instability,” a form of central control dysregulation, may play in OSAHS.2,6,7 Instability, we are now told, contributes importantly to the underlying pathophysiology of obstructive as well as central sleep apnea, at least in some patients. Nowhere is this better appreciated than in the conversion of what looked like pure obstructive sleep apnea to “central” periodic breathing with the application of CPAP. These are the patients described in the present report. “Ventilatory instability” in OSAHS can be understood as an intermittent “overshoot” of ventilation, thought to be due to two factors. At the end of apnea/hypopnea, there is a simultaneous relief of airway obstruction and a transient increase of ventilatory effort that is part of the arousal. Together, these produce a transient hyperventilation and consequent drop in alveolar and arterial PCO2. Perhaps due to excessive overshoot, mechanical reflexes or “chemosensitivity” to CO2, this transient fall in CO2 initiates repetitive cycles of “central” hypopneas/apneas and hyperventilatory intervals. While usually transient, these cycles of respiratory oscillations appear to persist in a subset of patients despite removal of the obstructive component. Clinical consequences and loss of benefit from CPAP may result as the obstructive cycles are replaced by central ones with similarly disrupted sleep, and poor CPAP compliance and clinical outcomes are not surprising. Many of the patients in the current report had this presentation. Appreciation of the role that “instability” may play in periodic breathing suggests that blunting respiratory “overshoot” should be helpful—even if the original pathology was predominantly obstructive and is now treated with CPAP. Two approaches have been taken to “stabilizing” ventilation: adaptive servoventilation provides a variable “boost” to ventilation in the form of pressure support, thus damping the expression of varying respiratory drive; adding dead space to the ventilator circuit blunts the effect of hyperventilation on CO2 and thus stabilizes ventilatory drive itself. Either approach effectively provides a “shock absorber” that reduces oscillations of effective ventilatory output and thus prevents the initiation of cycling. In the present paper, Gilmartin et al. report on the clinical utility of the dead space approach in 204 patients with initially primarily obstructive apnea/hypopnea but significant residual “central” events when placed on CPAP. Few patients had congestive heart failure and patients with overt hypercapnia at baseline were excluded. Interestingly, the rebreathing induced did not appear to produce a significant increase in end tidal PCO2 above that seen during sleep without EERS, suggesting that damping hypocapnia was more important than inducing hypercapnia. It is also significant that the EERS was apparently most necessary in NREM, consistent with the putative role of CO2 in periodicity, as REM is thought to be a state with diminished chemoresponsiveness. Despite its logic and efficacy, some caveats are in order before using EERS widely. The study had a reasonably large “n” but was retrospective. It thus suffers from the usual limitations: some patients will always improve when given “just one more try;” the authors themselves point out that much of CPAP emergent central apnea may disappear if patients are able to remain on CPAP,8 so the long term benefit may not have been entirely due to the novel therapy; and finally, in the present series EERS was applied in an algorithm that combined O2 and bilevel CPAP at times. Although tempting, the conclusion that the EERS was the critical intervention needs to be tested more carefully with a prospective trial of non-adherent patients with residual respiratory periodicity. The patients in whom poor sleep persisted despite control of the respiratory periodicity also are also of interest. The authors suggest that many in this group had primary sleep fragmentation, but it needs to be shown that some of sleep disruption was not a result of the dead space. Successful EERS also depended on a tight fit of the mask: as predicted, when there were significant leaks there was no increase in dead space and therapy was ineffective. While this occurred only in 11% to 24% of subjects acutely studied in the sleep laboratory, this may be an intermittent problem at home. Excellent stability is reported in the 88/204 patients able to achieve both a low leak and freedom from sleep fragmentation; while this limited overall success is a clinical problem, the relationship of efficacy to low leak does confirm the role of the dead space. It is clear that some patients with what appears to be garden variety obstructive sleep apnea cannot be treated with airway pressure alone. The algorithm of adding EERS in these patients merits further testing, and the present paper is an important proof of principle. However, caution is needed to distinguish (and not overtreat) patients with iatrogenic periodic breathing related to excessive CPAP.6 With this caveat, there appears to be a role for “stabilizing” respiration in some patients, as opposed to just maintaining an open airway, and the present report suggests one effective way to do so.