Sleep specialists prescribe bilevel PAP in hopes of increased efficacy and adherence in patients who don’t tolerate CPAP well. But could it instead be exacerbating therapy problems in some obstructive sleep apnea patients?
By Chaunie Brusie, RN, BSN
The invention of bilevel positive airway pressure (bilevel PAP) revolutionized the science of noninvasive ventilation and added an important home-based therapy to the sleep medicine armamentarium, says sleep specialist William H. Noah, MD, medical director of Sleep Centers of Middle Tennessee PLLC and CEO of SleepRes. Bilevel PAP is effective for obstructive sleep apnea (OSA), and a minority of patients require it for OSA therapy efficacy.
But bilevel PAP’s status as a second-line option for people with OSA who fail CPAP has been grossly overused, especially when considering its high price tag, Noah says. He argues that billions of dollars have been wasted switching patients to bilevel PAP therapy when, for most patients, peer-reviewed research suggests that continuing CPAP would result in the same outcomes.1 Even an American Academy of Sleep Medicine systematic review of bilevel PAP showed no adherence benefit,2 he notes.
“The physics and the physiology behind using higher inspiratory pressures don’t make sense,” Noah says. “You effectively increase airway obstruction by reducing expiratory pressure, and then you increase inspiratory pressure to increase air velocity over the obstruction you just caused.”
History of Bilevel
The first commercial CPAP devices had inspiratory pressures almost a third lower than expiratory pressures because of blowers that adjusted slowly.3 Some patients complained of difficulty exhaling, so as blower technology improved, CPAP devices were designed with inspiration and expiratory pressures either the same or with inspiratory pressures a little greater.
In 1990, Mark H. Sanders, MD, FCCP, and Nancy Kern, CRTT, RPSGT, published a research article detailing the implications of a device that allowed for independent adjustment of expiratory and inspiratory pressures. “Obstructive sleep-disordered breathing can be eliminated at lower levels of expiratory airway pressure compared with conventional nasal CPAP therapy. This may reduce the adverse effects associated with nasal CPAP therapy and improve long-term therapeutic compliance,” they wrote.4
And so bilevel was born. However, setting expiratory pressure lower than inspiratory pressure did not lead to the reduction in adverse effects they predicted. The opposite scenario instead arose, Noah says.
“If this reverse approach increased adherence, then it could have some merit,” Noah says. “But it didn’t.”
Physics and Physiology of the Upper Airway
Making inspiratory pressure greater than expiratory not only failed to improve efficacy or adherence but led to a myth that inspiratory positive airway pressure (IPAP) is a superior treatment for hypopneas, Noah says, adding that higher IPAP cannot increase upper airway diameter but merely increases flow across the obstruction. Optimal expiratory positive airway pressure (EPAP) best stabilizes the airway and prevents hypopneas.
In fact, lowering EPAP increases flow limitation,5 meaning IPAP must be increased above the CPAP level to compensate, generating a higher peak pressure in the system and decreasing overall upper airway stability.6
Bilevel treats people with OSA, Noah continues, but he says it also causes unnecessary side effects, such as aerophagia and leaks, while not improving adherence problems for people with normal or near-normal lung mechanics (which most OSA patients have).
Patients with complicated sleep apnea phenotypes, such as those with comorbid chronic obstructive pulmonary disease, benefit from the augmented ventilation of bilevel PAP because it results in decreased work of breathing for people with poor lung mechanics. But these results “may not be generalized to uncomplicated OSA in non-obese individuals,” wrote sleep specialists Olabimpe Omobomi, MD, MPH, and Stuart F. Quan, MD, in a 2019 editorial.7
The opposite is likely true, Noah argues. For people with healthy lung mechanics, reducing EPAP and pharyngeal cross-sectional area increases inspiratory resistance and effort, which increases the work of breathing. It’s like trying to wean a ventilator patient with a small endotracheal tube, Noah says. The patient may fail weaning because of increased work of breathing.
In addition to that increased resistive work of breathing, obese patients with decreased lung volumes and reduced lung mechanics also have increased elastic work of breathing (the work needed to overcome elastic recoil of the lung and to displace the chest wall and abdomen),8 Noah adds. EPAP increases end-expiratory lung volume and improves lung mechanics with decreased work of breathing in many obese patients—why CPAP is just as effective as bilevel PAP in a majority of patients with obesity hypoventilation,9 he says.
The erroneous focus on inspiratory pressure as therapy fails to account for the viscoelastic nature of the airway and the accompanying time delay with changes in pharyngeal cross-sectional area, he adds. The airway is a flexible tube, so its wall compliance changes. Its walls are stiffest during inspiration and floppiest at end-expiration (when lung volume is the lowest and the airway is most vulnerable). So sufficient EPAP is required not only to maintain the pharyngeal cross-sectional area and minimize inspiratory upper airway resistance but also to increase end-expiratory lung volume to stiffen the airway against collapse.
Being flexible, the airway likely requires time to change shape and obstruct due to the viscous portion of the viscoelastic property, Noah says.10 But the Starling resistor model, on which CPAP devices were tested, uses a purely elastic material, which insinuates an immediate change in pharyngeal cross-sectional area as intraluminal pressure changes, thus not simulating the time delay. In reality, the reduced pharyngeal cross-sectional area and increased resistance that begins during expiration leading to obstruction develops over several breaths, Noah says.11 He, along with several engineers, derived an equation for this time constant.
He says reducing EPAP also increases the risk of rebreathing carbon dioxide, and higher IPAP possibly increases treatment-emergent central sleep apnea (TECSA), aerophagia, leaks, and mouth openings.
“People think the IPAP is fixing the cross-sectional change, but it’s not; the airway is still destabilized,” Noah says.
“If we are honest with ourselves, based on the literature in the 1990s, we should have moved away from bilevel PAP for uncomplicated OSA back then, and expiratory pressure reduction algorithms should have never been added to devices. It is a little embarrassing that the payors finally restricted [bilevel] use, not our guidelines.”
He even suspects that increased IPAP is linked to TECSA—the first paper to mention the sleep disorder was published two years after expiratory pressure reduction algorithms were introduced into CPAP devices.12 Noah, in conjunction with colleagues at the University of Utah Sleep/Wake Center, will soon submit for peer review their findings of TECSA resolving with lower inspiratory pressures.
Industry Support for Bilevel PAP Alternative
Sleep specialist David P. White, MD, a part-time professor of medicine at Harvard Medical School, also sees potential risks in current pressure settings as a precursor to TECSA. He cites the loop gain theory, noting that in lowering expiratory pressure relative to inspiratory pressure, the device is breathing for a patient, lowering carbon dioxide levels and thus lowering the natural drive to breathe on their own. “With IPAP less than EPAP, you’re not ventilating them at all, which will reduce that risk,” White says.
But White took time to arrive here. At first, “I was unimpressed that it would make much difference one way or the other,” White says. But after testing CPAP with lowered inspiratory pressure himself, White changed his tune.
“It’s not generally a terribly comfortable sensation,” White describes of his previous experiences trying to breathe through elevated inspiratory pressure on CPAP. “Some people get to where they’re 100% comfortable with it, but a lot of people struggle with it.”
White adds that a lowering IPAP below EPAP is “much better” and theorizes that the increased comfort could be due to how it more naturally mirrors breathing instead of forcing a patient to inspire through elevated pressure. “The way this is delivered, it feels very natural for you while you’re inspiring,” he says.
Like White, Robert Miller, RPSGT, RST, vice president of sleep business of home medical equipment company Apria, was also “skeptical.” However, Miller says, after testing CPAP with lowered inspiratory pressure, he was “amazed” at how much easier it was to breathe with IPAP lower than EPAP, even at higher expiratory pressures.
Initially, White and Miller tested a positive airway pressure device in which IPAP was set less than EPAP via a CPAP comfort accessory commercially released in 2022 that Noah invented for this purpose.13 That’s because today’s CPAP and bilevel devices are not designed to allow inspiratory pressures to be set less than expiratory ones.
Recently, both experts breathed on a prototype CPAP that features an algorithm developed by Noah and his team to reduce IPAP below EPAP. This CPAP algorithm could become commercially available in the future.
The CPAP Algorithm of the Future?
Pierrick Haan, president and founder of French CPAP manufacturer SEFAM, says he was initially “skeptical” about the theory that decreasing inspiratory pressure could improve comfort while maintaining efficacy but now says the “physiology is hard to argue with.”
So Haan and his company have started trials with Noah to validate the concept with additional data. SEFAM is not using an add-on comfort accessory for these trials; instead, the tests are being conducted with the new CPAP algorithm.
Haan notes that multi-centric clinical testing protocols have been developed to validate the algorithm. “For a company like SEFAM, which manufactured the first CPAP in the world in 1984 and whose strategy is founded on innovation and differentiation, it’s very interesting to consider that there are still ways of improvement, opportunities for innovation, and even potential disruptions 40 years after the first CPAP,” he says.
Haan says preliminary tests are “positive” with the new algorithm improving breathing comfort, and the decreased pressure during inhalation showing promise in reducing risks of leaks and aerophagia and in increasing lung volume—all aspects it had been hoped bilevel PAP would accomplish.
White also hopes that a lowered inspiratory pressure algorithm could benefit future patients. “In theory, if the expiratory pressure was brought back too slowly, it could be less effective than CPAP at a constant pressure,” White says. “But [Noah] has reasonable evidence showing that’s not true, and the apnea-hypopnea index is the same. I don’t see any downside.”
So many people have sleep apnea and aren’t getting treated because they can’t tolerate the treatment, so making it more comfortable leads to more people improving their quality of life, sleep, and health, says White, adding: “That’s a big deal.”
References
1. Mansukhani MP, Kolla BP, Olson EJ, et al. Bilevel positive airway pressure for obstructive sleep apnea. Expert Rev Med Dev. 2014;11(3):283-94.
2. Patil SP, Ayappa IA, Caples SM, et al. Treatment of adult obstructive sleep apnea with positive airway pressure: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2019;15(2):301–34.
3. Brusie C. A potentially huge CPAP pressure mistake. Sleep Review. 2022;23(9):10-3.
4. Sanders MH, Kern N. Obstructive sleep apnea treated by independently adjusted inspiratory and expiratory positive airway pressures via nasal mask. Physiologic and clinical implications. Chest. 1990 Aug;98(2):317-24.
5. Sériès F, Marc I. Effects of inspiratory and expiratory positive pressure difference on
airflow dynamics during sleep. J Applied Physiology. 1998;85(5):1855-62.
6. Lévy P, Pépin JL, Ferretti G. Pharyngeal dynamics in obstructive sleep apnea syndrome. Clinical Neurophysiology. 1994;24(3):227-48.
7. Omobomi O, Quan SF. BPAP for CPAP failures: For the many or the few. Respirology. 2020 Apr;25(4):358-9.
8. Lee MY, Lin CC, Shen SY, et al. Work of breathing in eucapnic and hypercapnic sleep apnea syndrome. Respiration. 2009;77(2):146-53.
9. Masa JF, Mokhlesi B, Benítez I, et al; Spanish Sleep Network. Long-term clinical effectiveness of continuous positive airway pressure therapy versus non-invasive ventilation therapy in patients with obesity hypoventilation syndrome: a multicentre, open-label, randomised controlled trial. Lancet. 2019 Apr 27;393(10182):1721-32.
10. Tamisier R, Pepin JL, Wuyam B, et al. 2004. Expiratory changes in pressure: Flow ratio during sleep in patients with sleep-disordered breathing. Sleep. 27(2), 240-8.
11. Morrell MJ, Arabi Y, Zahn B, Badr MS. Progressive retropalatal narrowing preceding obstructive apnea. Am J Respir Crit Care Med. 1998;158(6):1974-81.
12. Zhang J, Wang L, Guo HJ, et al. Treatment-emergent central sleep apnea: a unique sleep-disordered breathing. Chin Med J (Engl). 2020 Nov 20;133(22):2721-30.
13. SleepRes introduces V-Com, a comfort accessory to soften CPAP peak inspiratory flow. Sleep Review. Published online 8 Jun 2022.
Photo 64251236 © Nomadsoul1 | Dreamstime.com
