Barry Krakow MD
UARS: A Critical Link to Optimizing PAP Therapy Results
Having trained with the pioneer researcher Dr. Christian Guilleminault who discovered UARS, I wish to make a few comments that might help PAP therapy users optimize their responses to find high quality sleep.
A reminder that for all practical purposes, the following three terms are interchangeable:
· UARS (upper airway resistance)
· Flow limitation
· RERAs (respiratory effort-related arousals)
UARS as Mini-Suffocations
First and foremost, let's look at an analogy in cardiology to put to rest the nonsense that UARS does not exist or is somehow not important. We all know that asystole (heart stops) is bad, just as we know apnea (breathing stops) is bad. But, in cardiology, for decades we've known there are many other cardiac arrhythmias producing irregular heart rhythms, and we don't sit back and say, "well it's not asystole, so it must be OK." For decades, unfortunately, that practice is in fact what many physicians were taught or conditioned to believe, "it's not apnea, so it must be OK." Indeed, to this very day, I still see patients who have been to sleep doctors who told them their sleep study was OK because it didn't show apneas.
But, as we like to say, “a little choking is still choking,” therefore I think it is reasonable to state that each of the various forms of sleep-disordered breathing (apneas, hypopneas, UARS) reflects some degree of “suffocation.” Apnea is the most concrete form as the patient awakens choking or gasping, whereas UARS is probably equivalent to a “mini-suffocation,” which while asleep I imagine produces an unpleasant sensation but not choking.
UARS is not Mutually Exclusive of Hypopneas or Apneas
Please appreciate then that UARS is simply on the continuum of breathing events. To complete our analogy, UARS represents a more subtle form of breathing irregularity (or as some say pulmonary dysrhythmia). It is not mutually exclusive of apneas or hypopneas. You can have all three types of events when you are diagnosed with sleep-disordered breathing (SDB). In fact, the most common type of SDB shows all 3 components in varying proportions during the sleep study.
You would think though that apneas are more important than UARS events, right? Well, maybe. Don’t forget that UARS events, like apneas, are also frequently associated with sleep fragmentation and therefore unequivocally associated with daytime sleepiness and fatigue. We have seen patients with severe UARS (e.g. RDI > 40), who unequivocally have more sleepiness than say a patient with a moderate degree of apneas and hypopneas (AHI =20). That is why RDI (apneas + hypopneas + UARS) is more valuable when diagnosing and treating your condition than AHI.
To repeat, it is critical to realize that nearly all patients with OSA also have a UARS component on their diagnostic sleep studies, but if the sleep lab doesn’t use the proper respiratory sensors, they will not see it: "what you don't look for, you will not see!"
UARS Assessment and Treatment is Critical to Titration Success
Still more importantly, when a titration is conducted, UARS is invariably present, because the pressurized airflow doesn’t work like a magic wand to suddenly make apneas disappear. Apneas are often turned into hypopneas as the pressure is increased. Then hypopneas turn into UARS or as more commonly called in the lab nowadays “flow limitation.” Remarkably, many sleep lab techs do not push forward with the titration at this point, believing that their job is done. Even some proportion of sleep medicine physicians do not mandate that their sleep techs increase pressure for flow limitation.
“Consensus Medicine” Covered up The Science of UARS
How anyone would think UARS doesn't exist or isn\'t important probably relates to the sometimes misguided concepts of "conventional wisdom" and "consensus medicine" and how such processes frequently retard scientific discoveries from finding their way into community medical practices. In the early 1980s, papers were published about sleep apnea, then Medicare got on board to accept and cover the condition, after which a new CW was born that's taken quite awhile to revisit.
Once physicians and patients became accustomed to hearing the words "sleep apnea," it was only natural that people would block out any other pictures about the nature of a sleep breathing disorder. A consensus formed: either you stop breathing or you don't! Black and white, eliminate the gray! Which is why we always return to the heart rhythm analogy to help people understand the need to monitor different breathing irregularities, not just apneas.
I have treated thousands of patients with UARS who had either no apneas or hypopneas or an AHI less than 5. Nearly all these patients suffered sleepiness or fatigue from their conditions, and many suffered from insomnia and nocturia. Among those who were able to successfully use an appropriate SDB treatment (e.g PAP therapy, oral appliances, nasal strips, nasal surgery, nasal hygiene and so on.), virtually all achieved clear-cut improvements in their symptoms.
What’s in a Name?
In most of my UARS cases, the patients would almost invariably start the discussion with, “so, you don’t mean I have sleep apnea do you?” Which is interesting, because if you follow the workings of the American Academy of Sleep Medicine, you’ll notice their strategy is to abandon the word UARS, and simply declare that UARS equals sleep apnea. In their lexicon, they would answer the UARS patient as follows, “yes, you have sleep apnea, oh but by the way, you don’t stop breathing.” See the problem? That’s why I continue to use the term UARS to make it clearer to the patient.
As an aside, I’ve seen cases where the UARS was ridiculously subtle (I was almost too embarrassed to call it UARS) or it only appeared in REM sleep. I had to inform these patients that I was skeptical about whether PAP therapy would make any difference. Although I still encouraged this particular subset of patients to give PAP therapy a chance, no more than 50% were willing to try it. Yet, in several cases, some of these patients reported dramatic and sustained (as in years) improvements in fatigue or sleepiness with PAP therapy. Undoubtedly, we find these events very perplexing, but the upshot appears to be that sleep assessment technology for measuring respiration and arousals has a long way to go….but then most of you knew that already!
Start Connecting Some Zzzzzots
Along these lines, let me mention a working theory we have developed about UARS and why bilevel might be the best option for its treatment.
The most salient factor during most titrations is how well the patient responds during expiration. Think about it: it sure feels a lot easier if not pleasurable to breathe in with pressurized airflow coming into your lungs. Many SDB patients are immediately hooked on PAP therapy because of this singular experience.
But breathing out against pressurized airflow is a completely different experience for a very large proportion of patients. After all, it’s downright weird to breathe out when pressurized air is coming in. And, that’s exactly how many people describe it and worse. It’s weird, anxiety-producing, claustrophobic, and triggers a sense of panic. Now, the biggest question is who are the types of UARS patients that would feel so negatively about exhaling on PAP therapy?
In our clinical and research experience, it would be someone who already has some degree of anxiety, a lot or a little, it may not matter, because once they try to use fixed CPAP in particular, they quickly report that it’s very uncomfortable or worse, they report feeling more anxious.
In a large proportion of these patients, we switch them to bilevel during the pre-sleep desensitization/adaptation period, and remarkably, we have found that 90% of these patients report immediate relief by virtue of the lower expiratory pressure.
Note: Bilevel combines IPAP (pressure on Inhalation) and EPAP (pressure dropping on Exhalation).
Can You Feel Anxiety in your Sleep?
Although we have more recently discovered that most patients want to switch to bilevel during the desensitization, that is, before the formal titration begins, we didn’t really figure out this point until we watched UARS patients while asleep. That’s when we saw that they did not like CPAP, that is, a fixed pressure on exhalation. That’s when we saw the ratty looking signal suggesting they were having some kind of anxiety or otherwise unpleasant response to air coming in while they were trying to breathe out.
In my opinion, which I don’t think is shared by the majority of sleep docs, anxiety is experienced while you sleep. If you can experience anxiety in dreams, I don’t see why you can’t experience anxiety to pressurized airflow in your sleep. So, in a nutshell, I think that’s why CPAP doesn’t work well in UARS patients and for that matter, I don’t think it works well in most SDB patients except for truly classic hypersomnolent, anxiety-free, sleep apnea cases.
I think anxiety is already present in the majority of SDB cases, because it is an anxiety-producing experience to breath abnormally all night long. That is, anxiety and breathing are intimately connected, so most SDB patients are more or less conditioned to be more nervous in general by having spent the night not breathing well. Now, introduce a foreign stimulus, CPAP, which then triggers or worsens anxiety by the introduction of an extremely foreign sensation: pressurized airflow forced inward during exhalation.
Is Bilevel the Answer?
Why bilevel works so well is still a puzzle. But, what’s so intriguing is that the subjective and objective findings match. That is, nearly all patients who switch from CPAP to bilevel state that it is easier (subjectively) to breathe out with bilevel. And, during their titrations, the ratty airflow signal disappears on expiration (objectively) and is replaced by a smooth and rounded curve indicating normal expiration.
Should you be able to produce the same results with CFLEX, APAP, etc? Presumably so, except for one “large” difference. You cannot generate the same gradient or gap between IPAP and EPAP with any of the other devices. And, in our clinical and research experience, we are using gaps of 4 to 12 cm of water in our patients. My personal bilevel settings are 21/12.5 for a gap of 8.5.
In our prescriptions for bilevel, I would venture that the average gap is in the 5 to 6 range with tremendous variation, including some with a gap of only 2 or 3. Those with a lower gap requirement would likely do as well on FLEX or APAP, but to repeat, the large majority of our patients have a gap of 4 or greater.
Still, it would be nice to have a respiratory physiologist explain to us why the larger gap is so effective. As an internist and sleep medicine physician, there are only two obvious theories that stand out. First, what if we’ve always assumed, mistakenly, that airway pressure had to be constant for both inspiration and expiration? I think it has already been proven by other researchers that you actually need higher pressure to keep the airway pinned open on inspiration and a lower pressure on expiration. If that’s so, then is bilevel the best system because it provides the exact pressure you need (not too much and not too little) during expiration.
The second idea relates more to the psychophysiological response to PAP therapy. Maybe the larger gradient simply gives the patient a distinctly more comfortable feeling, because the lower pressure creates a feeling so much closer to breathing normally (without PAP). If this theory were accurate, though, it would imply that over time as you get used to any sort of PAP therapy, then perhaps the gap would narrow and eventually you could use fixed CPAP again. If this were true, I would expect more people to eventually adapt to fixed CPAP pressure, and I don’t believe that’s occurring.
UARS Diagnosis and Medicare
Last, insurance coverage for UARS is always a hot topic. This section is not relevant to titrations, because nearly everyone manifests UARS on the titration. Insurance questions revolve around the diagnostic study: does the patient “only” have UARS?
In Albuquerque, I have pushed back on this issue for more than a decade, and the results have been tangible and somewhat satisfying. At this point, there are only 3 insurance carriers in New Mexico who do not cover treatment (specifically, PAP therapy or oral appliances) for UARS. Even among these 3 carriers, we can always make an appeal on very specific comorbidities (e.g. a UARS patient who has had 2 car accidents in the last year), then Medicare might decide to cover such a UARS patient.
In the beginning of this particular journey, I found it frustrating at first, but it was also an opportunity to educate medical directors at insurance companies. We would routinely call these individuals, send them research publications, and explain how UARS was going to cost them more money in the long-run if they didn't cover it.
As an aside, I have to mention how frustrating and disappointing it is to hear about sleep physicians who might make their decisions about UARS based on insurance considerations. I was never trained to think that way in medical school, and it approaches unethical behavior in my opinion. If a patient is diagnosed with UARS, that's the diagnosis whether it's covered by insurance or not. Insurance companies don't tell me what I can diagnose and they don't tell me how to treat my patients!
Financial considerations are relevant and important, but they have nothing to do with my patient advocacy and my duty to inform the sleep patient of the diagnosis and treatment plan we recommend.
I am deeply perplexed by the notion that a sleep physician would withhold this information from a UARS patient because the insurance company wasn't going to cover it. As before, it borders on unethical behavior, in my opinion.
Last and not least, UARS is one of the primary reasons that many SDB patients do not achieve an optimal response. As I describe at length in my book, it is a human tendency to "normalize" behaviors, which over time prevents us from obtaining the best possible response to PAP Therapy. If you are so used to fatigue and sleepiness, having suffered for so many years, then how could you possibly discern what a normal level of sleepiness and fatigue should be? Instead, (and I know this from my own trials from CPAP to APAP and finally bilevel), when you experience some improvement, the tendency is to create a new "normal" and wrongly assume that this is "as good as it gets."
Well, it's not as good as it gets if the UARS component of the SDB hasn't been treated, because there is still more to treat. Undoubtedly, most of the members of this forum recognize the fine-tuning and tweaking that's needed to manage mask leaks, mask comfort, mouth breathing, humidifier settings, and nasal congestion, just to name a few of the issues that must be regularly attended to enhance the PAP response.
Notwithstanding, in my clinical experience, I have found that resolving the UARS component of SDB is in the top tier of factors that frequently must be addressed to achieve optimal results, especially so among patients whose regular use of PAP therapy has not yielded the desired effects.
I\'ve lived through this problem and I've breathed through it, and no other single factor enhanced my sleep quality to the level I currently enjoy and am eternally grateful for experiencing.
Surely, this is something to sleep on. I do, night after night.