Early Signs of Success
We have been using adaptive servo-ventilation (ASV) with the ResMed VPAP Adapt SV’ (Adapt SV) since February of 2006 and have been quite impressed with our patient outcomes. ASV is a therapeutic modality for use in patients with Cheyne-Stokes respiration (CSR), central sleep apnea (CSA), and patients who experience centrally mediated events with the introduction of CPAP therapy (complex sleep apnea syndrome).1 Often our results have been impressive, and in some patients they have been almost spectacular. To date we have studied 25 patients, so you could say that our experience is still somewhat limited. Even in our first few patients, when we had little experience with the device, we still had mostly-gratifying responses
In one early patient, we were unable to get the apnea-hyponea index (AHI) below 120 events per hour with CPAP. With the Adapt SV, the AHI plummeted to nearly normal at 6 events per hour. In the next patient, who had had several previous non-stabilizing polysomnograms with CPAP, bilevel S and oxygen (and who had also had previous upper-airway surgery) we were able to decrease the AHI from about 40 events per hour with CPAP into the normal range with ASV. Hence, a clinical problem that had not been resolved previously despite multiple studies over a period of several years (and with the expenditure of substantial financial resources), was resolved in a single night. The patient continues to do well with ASV and is still grateful over a year later.
Adapt SV therapy seems to normalize or nearly normalize the AHI in about 75% to 80% of the patients we have studied. Dennis Nicholson, MD, a friend and colleague who is the medical director at Pomona Valley Hospital Sleep Disorders Center, has also had an early interest in the device and has had experience similar to ours. Several other local sleep disorders centers are also seeing early success with the device although their numbers are still small. We have all had failures to respond as well. Hence our experience in Long Beach appears to be fairly typical. One weakness of our experience is that we have typically not compared ASV with bilevel in the spontaneous-timed (bilevel ST) mode. Many investigators have noted better treatment of refractory CSA with bilevel ST than with bilevel in the spontaneous mode (bilevel S). Our experience with bilevel ST has not been so favorable, and we have, therefore, not used it very frequently. Rather, when patients have failed CPAP and/or bilevel S, we have favored go ing directly to ASV rather than first conducting a trial of bilevel ST.
To summarize, in our experience to date, the Adapt SV has the capability of stabilizing and often normalizing the AHI in the majority of patients whom we have been unable to stabilize with any other PAP modality. Hence, the Adapt SV seems to have the capability of making many ‘complex’ patients look ‘simple’.
Resolutions to Minor Difficulties
In the patients who have not stabilized with Adapt SV, the reason has typically been that the maximum end-expiratory pressure (EEP) of 10 centimeters of water provided by the device just has not been high enough. In a couple of patients, we also have had some difficulty with over- or under-titration, and there has not been a sharp improvement in event frequency between the different levels of EEP. Typically, however the titrations are quite simple and merely involve adjusting the EEP for residual obstructive events. Usually, all or most of the central events are automatically treated by fluctuations in the ‘adaptive’ inspiratory positive airway pressure (IPAP).
We have followed a small number of patients now for a year or more and have generally had good lasting treatment results, but the usual problems with PAP therapy, such as mask discomfort, nasal obstruction, leaks, compliance issues, patient reluctance to sleep every night with a mask, etcetera, still occur. The typical Adapt-treated complex patient feels better on ASV than he (approximately 85% of our patients are male) did either without treatment or with traditional PAP therapy
The manufacturer’s recommendation to start the titration for all patients with full-face masks adds a new level of interest and intrigue. We have had several patients who have not tolerated or who have not been stabilized with full-face masks. In some instances we have not been able to get an effective full-face mask seal despite the trial of masks from several manufacturers. These patients seem to have done just as well with a nasal mask, as long as a good seal was achieved and there was no unacceptable mouth leakage. We have yet to try the recently-released ResMed Quattro or Liberty full-face masks; although we hope the addition of these interfaces will add to the number of patients who can be stabilized using a full-face type of mask.
Complex Sleep Apnea Frustrates Everyone
Let me tell you what complex sleep apnea means to me clinically. Complex apnea is, very simply, the apnea that you cannot fix with either CPAP or traditional bilevel therapy. Complex sleep apnea is the apnea that frustrates everyone. It frustrates the night recording technologist in the sleep disorders center (SDC) because he/she is unable to stabilize the patient regardless of what positive airway pressure modality is used. It frustrates the scoring technologist because the studies are difficult and time-consuming to score and reviewing treatment records with so many residual apneas and arousals is discouraging. It frustrates the interpreting sleep physician because the sleep doctor does not like to admit that the sleep center was not able to stabilize the patient or provide effective treatment. It frustrates the sleep center technical director because the patients keep getting referred back to the lab for additional attempts at successful treatment, with physician requests to that the SDC try bilevel S, bilevel ST, entrainment of oxygen into the breathing circuit during titration, and/or the addition of drugs in attempt to decrease respiratory drive, etcetera.
It frustrates the home medical equipment (HME) company because complex patients on traditional treatment have many complaints and problems, make frequent calls for help or service, and are more likely to throw up their hands and dump their equipment on the HME’s doorstep after a period of non-satisfactory positive airway pressure use. Since PAP does not make them feel any better, they often see little reason to continue therapy.
It has, or should at least should have, frustrated the device manufacturers that their equipment has not been able to help complex patients. It frustrates the sleep researcher or physiologist who has difficulty understanding and explaining the intricacies of the mechanism of the syndrome to others. Most importantly, it frustrates the patients who have it, as their valiant efforts to make PAP treatment to work for them are usually unrewarded. When it comes to complex sleep apnea, ‘giving up’ by either patient or physician is an all too common outcome. Hence many patients remain symptomatic and at risk.
The Mechanisms of Complex Sleep Apnea
I would like to talk about the description, mechanisms, and common risk factors for complex sleep apnea. Complex sleep apnea has been defined as a subtype of central sleep apnea in which central apnea either emerges or worsens when positive pressure is applied.
Hence a complex patient may or may not have frequent central events during a diagnostic study. The events may only become evident when treatment has begun. Often the central events are intermingled with mixed and obstructive events. Apneas are erratic or irregular in timing and also vary in duration. This is in contrast to the Cheyne-Stokes respiration type of central apnea where all events are central, have a common length and frequency, and tend to wax and wane with a regular predictable pattern.
With complex sleep apnea, there seems to be no such pattern or predictability, as the events occur in a chaotic fashion. Mechanisms responsible for the syndrome are still being debated, but instability in respiratory drive (abnormal CO2 homeostasis) seems to be a key feature that results in an under damped CO2 feedback loop.
Patients with complex disease appear to have an increased sensitivity to CO2 during sleep, with CO2 ‘overshoots’ on both the high and the low side. The frequent EEG arousals that occur at the end of the apneas and result in sleep fragmentation seem to cause rapid on/off cycling of the waking neural drive, resulting in oscillations in the pattern of ventilation that develop into a self-perpetuating cycle of chaotic events. This may be thought of as something like rapidly turning the thermostat on your furnace at home, on and off. The thermostat then has difficulty figuring out what temperature you want it to “defend”. In a similar matter, the body’s CO2 homeostatic mechanism has difficulty figuring out what PCO2 to “defend”.
Common risk factors for this disorder seem to be stroke or other central nervous system injury, atrial fibrillation and chronic use of long-acting opioid medications for pain management; although some authorities like to consider the long-acting opioid subset as a separate entity. Some patients with heart failure may also have complex disease instead of the ordinary Cheyne-Stokes respiration. In a number of our patients, especially those with very high body mass indexes (BMI), the central events almost seem to be superimposed on a foundation of obstructive sleep apnea. One of our youngest patients has myotonic dystrophy. In contrast, a small number of our complex patients seem to be healthy without any other known risk factors.
Unique Features of ASV
There are several unique features that seem to work together seamlessly and/or synergistically in the Adapt SV. The design and concept of the device have fascinated me ever since I read the first paper published by Teschler et al. in 2001 that reported the results of ASV in patients with congestive heart failure and Cheyne-Stokes respiration.2
At its core, the Adapt SV is a highly evolved bilevel device. The IPAP is variable and responds rapidly within 2 or 3 breaths to significant changes in patient tidal volume. When patient tidal volume increases, the device IPAP decreases. When patient tidal volume decreases, the device IPAP increases. Thus the marked fluctuations in patient tidal volume that characterize complex sleep apnea are attenuated and usually the tidal volume is stabilized by the device.
A longer-term correction is effected by the trailing 3-minute memory of minute ventilation and pattern of breathing. After a 3-minute initial collection period, the Adapt SV then sets a minute-ventilation target that is 90% of the previous minute volume. Hence there is a weak downward force on total minute-ventilation that nudges the PCO2 upward 2 or 3 millimeters of mercury, decreasing or eliminating the frequent CO2 dips below the apnea threshold that drives the central events. Because of this 90% target, the manufacturer cautions that the device should not be used in patients who have a condition that might result in hypoventilation (severe COPD, neuromuscular disorders, etcetera). At least theoretically, the downward force on minute ventilation could worsen hypercapnia in this patient group and perhaps even precipitate respiratory failure. We have not seen this potential complication, even though several patients we have studied have had PaCO2 values at, or a little above, the upper limit of normal.
In the background lurks a subtle backup rate that is actuated only when needed. This feature might be considered similar to the synchronized IMV feature of a hospital ventilator.
Finally, the Adapt SV waveform has a soft ‘shark-fin’ or ‘ocean-wave’ profile instead of the nearly square-wave profile of traditional bilevel devices. Some patients report that this slower graded increase and decrease in pressure is more comfortable.
Making Waves in the Sleep Market
I think the Adapt SV device is effective because it interacts with the patient in a way that no PAP device previously has ever done. The rapid adjustment to changes in patient minute ventilation, respiratory rate, and tidal volume is an unprecedented feature in my opinion. No other PAP device in the past has had this ability.
The interaction of the different features on this device seems to be smooth and seamless in a way that makes the job it usually does look quite easy. The algorithms that were created to accomplish this are very sophisticated and are a real tribute to the creative genius of Michael Berthon-Jones who developed them.2
I expect that the market for flow generators will expand somewhat with this new technology as many of the previously-untreatable patients can now be effectively stabilized with ASV. By the same token, the current and future versions of Adapt SV and ASV devices made by other manufacturers could in some way erode the market for traditional bilevel devices. If there were the ability to adjust or turn off the 90% target ventilation on the Adapt SV, I could conceive of ASV devices taking significant market share from traditional bilevel platforms, if the ASV devices are not too much more expensive. With the ability to adjust or eliminate the 90% target, I expect the device could be safely used in patients who might be at risk for hypoventilation, which would expand the utility of the device and increase its potential market.
ASV might also then expand into the hospital environment where more acutely ill patients could be stabilized without intubation and traditional ventilation therapy. Theoretically a very small decrease in demand for CPAP (as ASV steals market share) might occur. However, with the increase in awareness of the importance of sleep-disordered breathing, the overall growth of the market for PAP will probably more than compensate for any such small losses.
Stephen Brown, MD,
Medical Director, Memorial Care,
Sleep Disorders Centers, Long Beach, CA
Associate Clinical Professor of Medicine,
University of California, Irvine, CA
References
1. Morgenthaler TI, Kagramanov V, Hanak V, Decker PA. Complex sleep apnea syndrome: Is it a unique clinical syndrome? Sleep 2006;29:1203-1209.
2. Teschler H, Dohring J, Wang YM, Berthon-Jones M. Adaptive pressure support servo-ventilation: A novel treatment for Cheyne-Stokes respiration in heart failure. Am J Respir Crit Care Med 2001;164:614-619.