The impetus to develop the REPAP protocol derives from the recognition CPAP failure often emerges because continuous pressurized air provokes expiratory pressure intolerance (EPI) when settings are raised to titrate out RERAs. In accordance with AASM standards, a sleep laboratory must attempt to titrate out RERAs, the most difficult to treat of the three main breathing events (apneas, hypopneas, RERAs). To solve this problem, we learned several years ago the sophisticated algorithms embedded within the auto-adjusting technology of ABPAP and ASV coupled with an assist through the manual override of the sleep technologist were sufficient meet AASM standards to eliminate RERAs without triggering EPI.
Although we alluded to this phenomenon in our initial PAP-NAP paper1 published in 2008, it was not until four years later we provided more definitive data2 and commentary3 on the topic to explicitly point out the failure of the CPAP mode of air delivery. Since then and more recently we published several papers describing the use of manual titrations for advanced auto-adjusting technology.
With that backdrop, we turn to the Results section of the REPAP article where we will delve into two components necessary to achieve these objectives: change the mode of PAP delivery and therefore change the pressure settings on the new mode. In addition, as implied by the REPAP concept, these mode and pressure setting changes can occur at any repeat titration, but the more common scenario is a patient arrives at their new and final mode early in the process, which means future retitrations focus on changes in pressure settings. Then again, due to specific insurance constraints, it is not unusual to encounter a patient who shows central apneas on successive retitrations spread out by intervals of months if not longer who only qualified for an ASV device at a much later point in the process. Without insurance constraints, many patients would have benefited from an earlier transition to ASV, and we know this point is valid anecdotally in light of a few patients who opted out of insurance coverage to buy an ASV device out-of-pocket, and all of whom reported immediate benefits unequivocally superior to any prior PAP technology used in the past.
Naturally, changing modes precedes changing pressures, so that topic comes next in the paper. In the first round of retitrations 227 of 273 patients exhibited intractable pressure intolerance, subjectively or objectively or both forms. Forty-five patients switched because of intractable residual breathing events. Only one patient in the entire chart review remained on their initial device of auto-CPAP (APAP). The pattern of new prescriptions included the following breakdown: ABPAP [48.9%], ASV [30.8%], and fixed BPAP [19.9%]. The latter proportion reflected our chart review dating back to 2006 when we had yet to start our more aggressive efforts to transition patients to auto-adjusting technology. The user rates in each of the three groups included: BPAP (35 of 53 [66.0%], ASV (65 of 82 [79.3%], and ABPAP (109 of 130 [83.8%].
Looking at the 158 patients in the sub-group who underwent more than one procedure, their final (most recent) retitrations demonstrated much greater proportions for the auto-adjusting technology: ASV [65.8%], ABPAP (42 [26.6%], BPAP [4.4%], and iVAPS [3.2%]. To better understand these percentages, it is important to recognize greater than 90% of these patients had been on ABPAP at some point before their last retitrations. Thus, the predominance of ASV in this sub-group is an overestimation. In other words, in our clinical practice, ABPAP almost always encompasses more than 50% and often as much as 80% of initial prescriptions when a mode is changed. ASV numbers pick up over time when ABPAP fails and a patient qualifies for complex sleep apnea (10 central apneas; CAI > 5; CAI/AHI ratio > 50%). In this sub-group, the proportion of users again showed relatively consistent numbers in all groups: ABPAP [92.9%], BPAP [85.7%], and ASV [77.6%].
Pressure setting changes are somewhat more difficult to describe because switching from CPAP to auto-adjusting modes means we are describing a system with one pressure setting changing to systems with 3 to 4 pressure settings. For ResMed devices, which were used almost exclusively in this research, ASV settings include Maximum and Minimum Pressure Support and Max and Min Expiratory Pressure while ABPAP uses Max Inspiratory Pressure, Minimum Expiratory Pressure, and Pressure Support. By focusing on changes in expiratory pressures there is some parallel between CPAP settings and the EPAP (expiratory) settings on the advanced devices. Both increases and decreases of EPAP were observed, the former when the original CPAP pressures were not effectively eliminating hypopneas and apneas, and the latter when EPI caused disruption to sleep quality. This point explains how tricky expiratory adjustments during titrations may become: too high might solve breathing problems but provoke EPI; too low might prevent EPI but breathing problems persist.
Initially, EPAP settings were decreased in 65% of the sample while 30% needed an increase in EPAP. Only a handful of patients needed no initial change in EPAP settings, yet nearly all patients ultimately received adjustments in their inspiratory settings in the fine-tuning effort to normalize (“round”) the airflow curve. Inspiratory pressure settings tended to be more straightforward in terms of eliminating the last vestiges of residual breathing events, usually RERAs (or flow limitation) and hypopneas of lesser severity.
The remainder of the results delved into various statistical analyses in an attempt to tease apart the reasons 72% of patients were able to transition from CPAP failure to PAP use. The bottom line appeared to be two simple pronouncements from the patients: they slept better and reported easier adaptability to the PAP device. From a research standpoint, the questions would be what exactly caused the patient to report sleeping better and anticipating easier adaptability. As you will see, the answer seems straightforward but proving the answer with the scientific method could not really be achieved in this type of research design.
Our take of course starts with the simple effects of ABPAP or ASV to eliminate the discomfort of expiratory pressure intolerance coupled with a normalization of the airflow signal never previously experienced by the patient while using CPAP. For these things to prove so important, however, we would like to see objective data to corroborate these changes. Not surprisingly, then, were several data points showing exactly this phenomenon. Among patients who eventually became users after their first retitrations the following improvements were observed: greater time spent in REM and less time spent in Stage 1 NREM (the most superficial stage of sleep); decreased sleep onset latency, and increased sleep efficiency (time asleep/time in bed). These changes were noted in comparison to those who remained non-users. Among the group undergoing multiple retitrations, similar analyses revealed these improvements in users: greater total sleep time, increased sleep efficiency, decreased sleep onset latency, less time awake after sleep onset, less Stage 1 NREM and more REM time. AHI was also significantly lower and there was a statistical trend for a lower RDI. Again, all these improvements were noted in comparison to those who remained non-users.
Two other factors associated with less use are worth mentioning because others have reported the same findings: married patients have higher rates of use than single patients; and individuals suffering from depression have lower rates than those without depression.
We now arrive at the final part of the paper in which we discuss (Discussion) several facets of the research with a special interest in how other sleep professionals could make use of our findings, the potential impact of the REPAP approach on current practices, and how to further research the concepts in the REPAP protocol.
One of the most obvious ways to take advantage of the REPAP protocol is to recognize its simplicity. To quote our paper, “Parsimoniously, discomfort (defined as physically distressing sensations and worse sleep) caused PAP failure. However, new technology enhanced comfort; and, greater comfort resulted in enhanced adaptability and use, which aligns with a rationale to make PAP more user-friendly to improve self-efficacy and ultimately increase adherence.” Said another way, it is obvious huge numbers of patients fail CPAP, and therefore it should not be a difficult approach to inquire of these individuals to what extent they are not achieving optimal results and whether they experience discomfort when breathing out against pressurized air. The former question will often imply RERAs may not have been effectively titrated away, and the latter question almost always signals expiratory pressure intolerance. Either problem or both is sufficient grounds to consider the value of the REPAP protocol.
However, this simplicity does not necessarily help to overcome three pernicious obstacles in the field of sleep medicine that will block efforts to encourage patients to enter a REPAP protocol. First, most sleep specialists are trained to believe in the “one-and-done” model of titrations as well as the “one-size-fits-all” mentality alleging CPAP works for all patients. Both conceptualizations are not only incomplete, but there is no evidence whatsoever to imagine they are genuinely valid ways of understanding OSA patients’ capacity to use PAP therapy. Second, sleep specialists are further constrained because of anxiety and fear in dealing with insurance carriers who tend to believe the same two points: a single titration and CPAP for all! (Let’s not forget though the foresight of Medicare when several years ago it mandated the necessity of retitrations in non-compliant patients, thus promulgating an exceptionally patient-centric model of care very much aligned with the REPAP protocol.) Last, insurance carrier obsessions with the HST model of care is already preventing sleep professionals from even attempting retitrations, because in the world of HST logic, data are interpreted to support the view APAP is all that will ever be needed. If a patient is not achieving optimal results, the only likely explanations are mask fit problems, mask leak, or mouth breathing, all of which require only adjustments to the mask or headgear and chinstraps. Even when residual breathing events and poor outcomes persist, insurance gatekeepers frequently fight with sleep professionals to thwart any opportunity to visit the sleep laboratory for a new evaluation, either for diagnostic data or a retitration or both.
Forging ahead I am very hopeful other sleep professionals will not only cite our work, but perhaps more practically, our efforts will encourage patients, other sleep professionals and insurance gatekeepers to actually read the ideas and details found in the article. If the information were to disseminate into our field through various means, it seems reasonable more patients would eventually be able to avail themselves of a REPAP protocol when they are not achieving optimal results or when they continue to report discomfort with single-level CPAP technology. And, let’s not forget that the AASM provides plenty of support for this approach in their current and past guidelines on the subject.4-5 Yet, as we mentioned in the paper, this area seems to be a blind spot among many sleep professionals who for the reasons stated above continue to discount or simply ignore the potential value of retitrations as well as advanced PAP technology.
Like all innovative studies, more research and replication of findings are crucial to expanding knowledge in the field. Our protocol reflects a lower level of evidence as it was a retrospective chart review comparing a non-random sample of users versus non-users. The essential research to confirm or reject the value of a REPAP protocol would be a prospective randomized controlled study to compare two groups: one receiving treatment as usual in which no retitrations would likely occur and the other a REPAP group where retitrations are the proposed practice pattern. In one sense, this research has already been done all over the universe of sleep centers and laboratories, because undoubtedly a fair number of patients having sought care for CPAP failure eventually made it back to the sleep lab. Nonetheless, prospectively investigating a well-defined group of CPAP failure cases and then randomly assigning them to REPAP or treatment as usual would go a very long way in explaining how retitrations might be especially beneficial to such cases, albeit one of the principal components of our model is the implementation of a manual titration of auto-adjusting technology in the sleep lab. Thus, another research experiment that would prove necessary will compare two groups of patients returning to the sleep lab due to CPAP failure, one randomized to repeat a CPAP titration and the other receiving advanced PAP devices, manually titrated, during the procedure.
Finally, one of the last points we wrote about in the paper is the critical distinction between patient education and patient experience. As we have long advised, no amount of education can overcome certain physiological problems such as residual breathing events and expiratory pressure intolerance. Ultimately, we consistently and repeatedly observe a sizeable proportion of patients need to experience the experience of successful use of PAP. By going through the laboratory experience to be titrated with a more advanced PAP device, we see close to an 80% chance or greater that individuals will feel and sense the auto-adjusting dual pressure device is easier to adapt to and more comfortable. In this process, it is very common for the individual to report the next morning having slept better, again another favorable and motivating experience the patient has now experienced. These events must be distinguished from the process of talking to a patient and educating him or her about PAP. Instead, the REPAP protocol offers patients the actual experience of a good response to PAP, and in our clinical care model we have not been surprised to witness that “actions” speak louder than “words.”
In the final post on the REPAP protocol, which will likely appear a few weeks hence, we will discuss some of the interesting commentary that emerged with the publication of the paper. To date there have been two main reviews or op-eds on the paper, one published in Respiratory Care alongside our paper and the other published in the Sleep Review trade magazine. We’ll discuss both pieces and the interesting points unique to each one.
- Krakow B, Ulibarri V, Melendrez D, Kikta S, Togami L, Haynes P. A daytime, abbreviated cardio-respiratory sleep study (CPT 95807-52) to acclimate insomnia patients with sleep disordered breathing to positive airway pressure (PAP-N AP). J Clin Sleep Med. 2008 Jun 15;4(3):212-22.
- Krakow B, Ulibarri VA, Romero E. 2012 Adaptive servo-ventilation therapy in a case series of patients with co-morbid insomnia and sleep apnea. Journal of Sleep Disorders: Treatment and Care
- Krakow B, Ulibarri VA, Sanchez JN, Kikta S, McIver N, Melendrez D. Driving on “auto”: hands-on is more effective than hands-free. J Clin Sleep Med. 2012 Jun 15;8(3):343-4. doi: 10.5664/jcsm.1934.
- Kushida CA, Chediak A, Berry RB, Brown LK, Gozal D, Iber C, et al. Clinical guidelines for the manual titration of positive airway pressure in patients with obstructive sleep apnea. J Clin Sleep Med 2008;4(2):157-171.
- Gay P, Weaver T, Loube D, Iber C. Evaluation of positive airway pressure treatment for sleep related breathing disorders in adults. Sleep 2006;29(3):381-401.
As we revisit the REPAP protocol, you will find a short summary of topics in the recently posted third installment that covers the two earlier REPAP posts I and II. REPAP III covered the interesting academic system through which the manuscript traversed in its various revisions in order to be accepted for publication. In this fourth installment, we now discuss the paper itself as well as details that are clinically relevant to patients seeking second opinions and to sleep professionals who provided help to these struggling individuals.
The REPAP paper has a lengthy introduction with much of the content already discussed in the other posts, and it refers to the background that led us to formulate a REPAP protocol (repeat, rescue, retitration). However, two points are worth mentioning again. First, we still must contend with the failure of the sleep medicine community to publish regularly on the topic of second opinions; and second, we should be aware of the failure of sleep researchers to recognize that several articles have already established the value of using retitrations to aid struggling patients.
In the introduction, we discussed four works, summarized here briefly, which had already demonstrated the obvious value in retitrations by showing the need to adjust pressure settings. Netzer et al re-titrated 905 cases, and more than half required pressure changes.1 Konermann et al studied 106 patients more than 6 months after starting PAP, and again more than half needed large PAP pressure increases due to their complaints of persisting symptoms.2 Mulgrew et al showed the apnea-hyponea index was greater than 10 events/hour in 25% of retitrated individuals.3 Last, in the most important study, Ballard et al prospectively investigated what he called “hard-core, non-compliers.” In one phase of the research the study compared CPAP to bilevel (BPAP) in 104 struggling patients; and, by comparison, compliance rates were significantly higher in the BPAP group (49%) than in the CPAP group (28%).4 This last study should have gained a lot more attention as it clearly demonstrated the advantage of BPAP over CPAP in reversing failure.
Regarding the absence of second opinion literature, our paper commented on how sleep professionals might perceive retitrations as cost-prohibitive whereas others proclaim the advantages of the expanding HST model of care that may eventually render the sleep laboratory obsolete. We felt it essential to address these issues in the introduction to clarify the potential value of a REPAP approach. Generally speaking, it is always more cost-effective to transform a CPAP failure case into someone regularly using PAP therapy for the obvious reason of healthcare cost-savings in sleep apnea patients who are no longer ravaged by the effects of sleep disruption on their physical and mental health. Regarding HST, we chose to frame the issue not as an either-or proposition, but rather to emphasize the strong probability that while some patients prove straightforward and can benefit from HST, others of greater complexity merit more precise attention in the sleep laboratory.
From the introduction, we move next to the Methods as is standard research paper format, to provide the details on how we conducted this retrospective chart review of a large series of CPAP failure patients who sought second opinions at our sleep center. Our major premise of the investigation anticipated CPAP failure would often be related to the failure of technology to adequately treat sleep-disordered breathing or to the side-effects caused by PAP technology, which needed to be addressed to reverse failure.
First and foremost, the sample selected for a chart review must contain a well-defined group of individuals so that findings are congruent with the circumstances or situations of the patients selected in way that permits other clinics and researchers to generalize some of the findings to their own experiences. In this study, we wanted patients who unequivocally failed CPAP. In other words, although we had seen a few thousand patients who sought second opinions, this study only concentrated on the patients who tried and ultimately rejected CPAP, that is, they no longer used their devices, and many had returned them to the DME company. By gathering data on this extreme group, we felt we were making clear to the readers of the paper that the patients had given up on CPAP. On average, many of them were only returning for a second option several years after having failed CPAP.
Next, in Methods we detailed our retitration protocol, predicated on the AASM standard to eliminate all breathing events including apneas, hypopneas, and flow limitations (aka RERAs). We delved into our standard explanation of the need to raise pressures to eliminate flow limitation, which often triggers expiratory pressure intolerance (EPI). However, it has been our experience in general and in the specific cohort examined in this chart review to note that other sleep centers do not attend to this principle. As all the patients had previously visited another sleep center, we inquired about whether or not they had discussed the issue of eliminating all breathing events as well as the side-effect of EPI induced by higher pressures. For most patients, these discussion points were entirely new to them, but it was not difficult for them to picture the vicious cycle in play: pressure needs to be raised to treat flow limitation, but raising pressure causes EPI. At various points in their steps through the REPAP protocol, the patient learns how we manually titrated auto-adjusting technology (ABPAP, ASV), which through a fine-tuning process successfully treats RERAs while preventing EPI.
Last, in Methods we described a rationale for designating each patient as a user or a non-user. Ideally, we would have had objective data downloads on all the patients, but only about half of the charts contained this information. Usually, this problem arises, because as much as half of data downloads may occur through the DME company and may never make onto the patient’s chart at the sleep center. Instead, we used four criteria:
- prescription renewal for PAP supplies;
- clinic appointments regarding continued PAP use;
- re-titration and confirmation of use;
- contact with office staff, discussing continued PAP use.
As you can see, these types of encounters would strongly suggest a patient was currently using the device, and prior research studies have shown how some of these factors are reliable in predicting use.
Now, the next section is Results, where so much of the important details of the chart review are to be found. Our sample comprised mostly middle-aged men and women who were mildly obese and suffered moderate insomnia on average. Seventy percent reported one or more psychiatric symptoms or disorders, thus yielding a certain consistency to the sample. These patients had visited many different sleep centers in New Mexico, and about 10% had visited from locations out of state. These people had tried to use CPAP and averaged about 1.5 years of actual attempts, but it took roughly five years from the point of their original diagnosis of OSA to eventually turn up at our sleep center for a second opinion. More than 90% of the patients had tried CPAP or APAP (auto-CPAP) before giving up. Less than 5% tried other devices such as BPAP, ABPAP, or ASV. The largest complaints that led to their termination of therapy included pressure intolerance (24.5%), mask discomfort (20.1%), inability to adapt to PAP (10.6%), no appreciable benefits (10.6%), or no specific reason (8.8%). Another quarter of the group reported adverse effects from PAP use, other treatment efforts, or financial reasons. Seven out of 10 patients reported that these problematic factors had never been adequately addressed at the original sleep center they had visited.
In the study we next looked at the use patterns of these 273 individuals, and we examined the data in the context of the number of retitrations completed during the REPAP protocol. After undergoing their first retitrations and receiving a prescription for ABPAP or ASV, 210 patients were identified as Users and 63 as Non-Users. Over time, these numbers changed in various ways. For example, among the 210 patients who immediately achieved User status, 85 never underwent another retitrations; and their final status based on their most recent follow-up encounter showed 70 had remained Users but 15 ceased use. In the other 125 patients from this initial group of 210 Users, further retitrations were conducted, which resulted in 111 with a final status of Users and 14 Non-users. Among the 63 initial Non-users, 33 eventually went on to multiple retitrations and 18 achieved User status. In sum, by the end of the chart review period, 72% (196 out 273) patients were now using PAP therapy, compared to 0% at their point of entry into our facility.
One question that often arises in discussing the REPAP protocol is the interval between retitrations. In this study, the interval averaged between 9 and 11 months for the largest majority of cases, which is actually a wider span of time than described above in the four research studies that also retitrated their patients.1-4 However, in our day-to-day clinical practice, exceptions arise; for example, we have used the REPAP protocol on a few cases where the patient underwent a retitration weekly for 3 weeks; and, in a few other cases, retitrations have occurred monthly for two or three months. In these situations we do not hold the patient to this timetable; rather, their adaptability problems are so intense and disruptive to their efforts, we must expedite the REPAP protocol to overcome their inability to maintain use of the device. As you might imagine, these patients frequently suffer severe problems with depression, PTSD, anxiety, claustrophobia and sometimes suicidal ideation. And, in some cases, the individual suffers from a physical or mental disability that justifies the repetitive exposure in the sleep laboratory, because only the experience and then re-experience of using PAP all night seems to tip the scales in favor of compliance thereafter.
Regardless of the actual timing that sets the stage for REPAP in any given patient, the real drivers of the REPAP protocol are the subjective and objective barriers and side-effects that arise in the process of attempting PAP use, the most common of which in the study were based on the need to:
- reassess pressures
- reassess leg jerks
- evaluate the onset of central apneas
- treat residual breathing events, predominantly flow limitation
- address chronic complex mask issues that failed to resolve by DME or clinic appts
- assess sub-optimal treatment responses not otherwise perceived as related to another illness
- solve persistent physiological, tactile, or psychological adaptability issues
The next phase of the article drills down into the heart of the REPAP program where we focus on changes in masks, switching PAP modes, and adjusting pressure settings.
Mask changes seem straightforward, yet 249 of the 273 patients either needed a new type of mask (nasal pillows, over-the-nose, or full face mask), or they needed a new style (different brand) of the type used at the point of PAP cessation. Over the course of the interval studied, many patients progressed through different types of mask, but the predominant selection was the full face mask, followed by nasal pillows and with the standard nasal mask coming in last. This progression was also of interest because the nasal mask predominated for these patients at their original sleep centers. An unexpected finding for masks and headgear was that one-third of patients required a chinstrap irrespective of mask type. And, this combination was present in about 10% of patients, yet one can easily imagine that a psychiatric or PTSD patient might develop a claustrophobic response to so much headgear. In fact, when patients learned they breathed easier and more smoothly by various combinations of masks, headgear and chinstrap, including the bulky combo of FFM and chinstrap, their motivation was enhanced by their greater capacity for steady airflow, which in turn diminished their initial concerns about the constraining influences of all this stuff on the face and head.
As a final point for this post, it cannot go without saying how important masks are to the success of any patient’s efforts to use PAP therapy; yet, it is equally important to reiterate masks do not typically solve the problem of EPI, the condition we have written so much about because it is often the greatest single deal-breaker to many patients’ attempts to maintain PAP use. Remarkably, many sleep centers and researchers seem confused on this point, because they might have grown accustomed to the belief that fixing mask issues somehow indirectly or direct solves pressure adaptation issues. Our experience has informed us that resolving mask fit is critical and necessary but it is not sufficient to lead OSA/UARS patients toward optimal results with PAP therapy.
In the next post, we’ll pick up on the crucial aspect of switching PAP modes and adjusting PAP pressures, the ultimate core components of the REPAP protocol.
- Netzer NC, Juha´sz J, Hofmann M, Hohl K, Strohl KP, Ku¨pper TE. The need for pressure changes in CPAP therapy 2-3 months after initial treatment: a prospective trial in 905 patients with sleep-disordered breathing. Sleep Breath 2011;15(1):107-112.
- Konermann M, Sanner B, Burmann-Urbanek M, Ho¨rstensmeyer D, Laschewski F. [Constancy of the nCPAP pressure values in the long-term monitoring of patients with obstructive sleep apnea]. Dtsch Med Wochenschr 1995;120(5):125-129.
- Mulgrew AT, Lawati NA, Ayas NT, Fox N, Hamilton P, Cortes L, Ryan CF. Residual sleep apnea on polysomnography after 3 months of CPAP therapy: clinical implications, predictors and patterns. Sleep Med 2010;11(2):119-125.
- Ballard RD, Gay PC, Strollo PJ. Interventions to improve compliance n sleep apnea patients previously non-compliant with continuous positive airway pressure. J Clin Sleep Med 2007;3(7):706-712.
The popular trade magazine Sleep Review: The Journal for Sleep Specialists recentlypublished a story on the symposium last year in Bologna, Italy at the European Sleep Research Society meeting where Christian Guilleminault, Erla Björnsdóttir, Leon Lack and I each presented on the topic of comorbid insomnia and sleep-disordered breathing (aka “complex insomnia” or COMISA). The story was written by Alexander Sweetman, a graduate student working with Dr. Lack, and covers pragmatic issues regarding not only the connection between the two disorders, but also raises important questions on the ordering of treatment for these conditions.
Two key themes throughout Sweetman’s piece involved the extent to which PAP therapy might favorably influence different types of insomnia, and as a corollary, at what point in treatment should CBT-I (cognitive-behavioral therapy for insomnia) be offered to patients with co-morbid OSA/UARS. Some of the interesting points put forward in the presentations as well as during the Q & A following each speaker strongly indicated that CBT-I could almost always be offered early on in the treatment of a complex insomnia patient, the effects of which might actually improve the insomniac’s subsequent motivation to attempt PAP therapy. The research on this point was evident in showing that patients with severe OSA will experience clinically meaningful treatment gains for insomnia severity by applying CBT-I strategies prior to attempting treatment for sleep-disordered breathing. On the other side of the equation, the question was also raised as to how much more insomnia treatment (e.g. CBT-I, hypnotics) would be required for residual insomnia symptoms after successful application of PAP therapy.
Reading Sweetman’s article reminded me of several cases in the past few years where the timing of CBT-I implementation arose in complex insomnia patients and how circumstances and patient preferences often dictated the ordering of steps. To highlight the complexity of this issue, I will use a composite patient case description (i.e. merging details of several patients) to paint a comprehensive picture.
The patient is a middle-aged perimenopausal woman, who initially presented to us three years ago with complaints of severe insomnia, which manifested in classic ways with prolonged time in bed not sleeping, racing thoughts at bedtime, anxieties and fears about her sleep, hypnotic dependency, and excessive time monitoring behavior, the latter of which resulting in intense frustrations when lying awake in the middle of the night. She had been struggling with insomnia for nearly twenty years and once visited a sleep center that offered no CBT-I resources; instead, she was told to follow sleep hygiene instructions and was informed a sleep study would serve no purpose. For much of these 20 years, the patient was largely convinced her insomnia was a secondary effect of her anxiety and depressive disorders for which she used antidepressants and anxiolytic medications on a regular basis. Yet, neither these medications nor her benzodiazepine hypnotics solved the chronic bouts of sleeplessness often leading to more than 2 hours of wake time after initially going to sleep. In addition, the patient saw multiple therapists during this lengthy period, but while mental health gains were achieved, insomnia persisted and mild suicidal ideation was reported sporadically.
With some desperation the patient presented to our center, because her psychiatrist recently became aware of our work with severe insomnia cases and how we often found underlying pathophysiological problems that sometimes fueled the unwanted sleeplessness. The patient presented using two different benzodiazepines (Lorazepam, Clonazepam), both at low dosages at bedtime and reported being unable to fall asleep without the meds. She reported no symptoms of restless legs syndrome at bedtime or leg jerks during the night. Mild snoring was the only overt breathing symptom reported, but she occasionally to frequently complained of dry mouth in the morning and multiple episodes of nocturia each night.
With this background, we knew her risks were high for OSA/UARS, a finding we described in two papers published in 2010, both of which dealt with samples of insomniacs failing hypnotic meds at presentation to our center. The first paper appeared in the Journal of Nervous and Mental Disease and the second appeared in Primary Care Companion to the Journal of Clinical Psychiatry. Both articles demonstrated between 80 to 90% of these types of patients suffered underlying OSA/UARS, a condition that surprised nearly every patient in the samples studied. Moreover, one study specifically examined how insomnia was evaluated prior to referral to the sleep center. Again, the evidence was overwhelming that primary care physicians were not addressing insomnia problems with anything more than pharmacotherapy and rarely were discussions held regarding how to locate a CBT-I therapist or the necessity for polysomnography to assess for physical causes for insomnia.
We discussed our approach to insomnia with this patient and pointed out two pathways: the value in starting with CBT-I to overcome psychophysiological conditioning or PAP therapy to address the underlying nonrestorative component of her potential sleep-disordered breathing. Not only was the choice a slam dunk to rapidly target PAP, but the patient insisted she was not willing to stop her anxiolytic/hypnotics no matter what treatment she was provided. In her mind, PAP therapy sounded very expedient if in fact it was proven she suffered from a sleep breathing problem.
At this point the patient articulated a recurrent theme we had been noticing among COMISA patients dating back to the late 1990s. The perspective involved the strong belief that despite all the talk about psychological aspects of insomnia, many patients “felt” or “sensed” something physical was wrong with their bodies. In other words, in contrast to the obvious waking stress-related factors of anxiety or racing thoughts that plagued her along with nearly every other insomniac we encountered, a different insight was in play, though not readily accessible, indicating a belief in some other factor(s) as the destroyer of sleep quality. Now, this perspective is not necessarily a surprise in that virtually all these patients present with nonrestorative sleep or what we refer to as “bad and broken” sleep. And, therefore, it is also not a surprise when these patients express a strong feeling of resonance when they hear a sleep-breathing disorder might underlie their insomnia and an even stronger expression of relief once formally diagnosed.
As an aside, we ask a specific question on our online intake as to whether or not a person believes his or her sleep is broken, and among these types of patients greater than 90% respond affirmatively. It is true the wording of the question could simply indicate a patient’s perception of “sleep is broken up” during the night as an indicator of insomnia, but in our discussions we find the term also extends in some individuals to this concept of something feeling wrong or unhealthy with sleep itself.
The patient completed her overnight PSG and was diagnosed with a combination of moderate OSA and UARS events with only occasional oxygen desaturations during the minimal REM sleep she generated, probably due to her benzodiazepines or perhaps REM suppressant effects of her antidepressant. The study also showed a great deal of sleep fragmentation involving frequent bouts of wake time lasting 5 to 10 min or more, during which the patient showed some limb movements, perhaps suggestive of RLS since she was not sleeping at the time. The patient then returned for a retitration study, after which she was initiated on PAP therapy and was a regular user of the device for 3 years, during which she reported some benefits in both her insomnia and quality of sleep, but she was persuaded her results were not optimal.
The lack of optimal results led to subsequent follow-up clinic appointments and two additional retitration studies. At each encounter, the patient was encouraged to consider whether her continued use of benzodiazepines was interfering with the depth of her sleep and possibly decreasing the amount of time she spent in REM sleep. She was informed again that CBT-I might be a useful strategy if she elected to decrease or eliminate these hypnotic drugs. Instead, she focused on the retitrations, and with each tweak of her pressure settings coupled with aggressive attempts to manage persistent mask leak and mouth breathing issues further gains for insomnia and sleep quality were achieved, yet the patient continued to believe the response should have been better.
Two additional key observations manifested in this patient’s case. First, in her follow-up retitrations she continued to show scattered leg movements, but again only while awake, and still the patient continued to deny RLS or PLMD; her husband also reported no awareness of unusual leg activity during the night. Second, as noted, at no time during this three year interval was the patient motivated to consider CBT-I or the possibility of tapering off her bedtime benzodiazepines.
A change of circumstances serendipitously led to a change in the patient’s perspective about these bedtime medications. A change of jobs and a new psychotherapist apparently were critical factors in the patient developing a less rigid attitude about her meds, and in discussing things with her primary care physician (the current prescribing doctor), they developed a plan for tapering, which she completed during a two month period, all without her ever attempting CBT-I.
Due to the change in circumstances and the patient’s report of mild deterioration of sleep quality since successfully tapering off the benzodiazepines, the patient was eager return for a retitration to determine whether or not she could in fact obtain a deeper quality of sleep in the form of longer REM periods and more total REM sleep. Instead, the next study in fact revealed what we had been missing all along. The patient showed marked problems with periodic limb movements, now for the first time showing up frequently while asleep and clearly with disruption to sleep quality in the form of both arousals and frank awakenings.
While more REM sleep emerged due to the absence of the benzos, the findings also helped us understand the greater complexity of her case. All this time, including before she visited any sleep center and during her visits with us, everyone had missed the diagnosis of RLS/PLMD. Instead, somewhere at the outset, a prescribing doctor diagnosed anxiety and insomnia and placed the patient on benzodiazepines. Because they were marginally effective for insomnia and leg jerks, the patient maintained use for 3 years. Once the medications were removed from the treatment regimen, the leg jerks were unmasked, and the patient experienced more REM sleep.
Clinically, the patient reported sleeping better on this study, perhaps due to greater REM sleep, but she was not persuaded things were suddenly optimal. When she learned about the leg jerks, she was very interested in proceeding with treatment to clarify whether or not this movement problem was indeed the missing link.
In similar cases, a patient starts a leg jerk med and finally achieves the near optimal to fully optimal response he or she had so long had hoped for. One clinical take home message here is that if we had been able to persuade the patient to go directly into CBT-I as her first treatment, there’s a possibility she would have tapered off the medications sooner, which then would have unmasked the leg jerk problem much sooner. We anticipate that future research studies will be heavily focused on these complex insomnia cases, because it is so apparent these individuals have an assortment of pathways to choose from in starting their care. Hopefully, research will guides on predicting the paths to match each type of complex patient.
- Start with SR review of ESRS to segue into the complexities of starting with CBT I or PAP and describe the hegemony case as extending over 2 to 3 years.
As the REPAP paper has just been published, now is a good time to finish up our earlier series on this innovative protocol. Briefly to summarize key points from the earlier works: 1) second opinion research is rare to non-existent in the sleep literature; 2) the use of retitrations to reverse CPAP failure is only slightly more evident in research publications; 3) the nature of CPAP failure is mostly defined by non-technological factors; whereas the notion of a technological solution for CPAP rejection is rarely considered in the literature or sleep medicine practice; 4) the key objective finding in second opinion patients is known as expiratory pressure intolerance (EPI), the problematic and uncomfortable sensation of breathing out against fixed (CPAP) pressure coming in; 5) sleep medicine professionals in general and reviewers of sleep research papers in particular show a lack of awareness or simply do not consider the potential for advanced PAP algorithms in newer pressurized air technology to solve the problem of EPI.
In working with the reviewers who critiqued our paper for Respiratory Care, we found much greater receptivity to discussions on all of the above points, and through the process of revise and resubmission we were able to make the recommended changes and finalize the manuscript into a publishable form. However, an early sticking had to be resolved, because we once again realized that reviewers here and before were concerned the REPAP protocol was promoted too rapidly for too many patients. To clarify this specific complaint, in our final submission we included the following information:
We strictly follow AASM guidelines and conventional wisdom in our patient management approach. We developed an intensive and extensive follow-up program involving patient encounters in the clinic as well as through telephone and email communications. At no point will a patient end up in the REPAP protocol unless and until he or she has gone through all other standard steps in the management of PAP therapy patients. We vigorously attempt to solve all mask issues in the clinical environment using extensive mask fittings and a highly accessible, patient-friendly mask loaner program. All mask problem-solving is coupled either with assessment of leak data from objective downloads or the use of our own in-lab technology to directly monitor leak while the patient tries a new mask. Patients are repeatedly encouraged to contact our center for any issues, complaints, or concerns about using PAP therapy. Outcomes data are used to determine level of responsiveness to treatment, but we also place great emphasis on patients’ subjective reports about their progress and their perspective on whether the treatment response has achieved an optimal level to the best of their ability to interpret this standard. Before a patient would even be considered for the REPAP protocol, they would have experienced multiple encounters with the sleep physician, the Results Coordinator, the Follow-up Coordinator, the Clinical Manager, or one or more sleep technologists. These encounters, as above occur in person, by phone or by email. Some of the encounters are indirect through our collaboration with DME companies.
Then, to follow-up our introduction in the revised submission, we provided interesting background information to indicate why we were surprised about the eventual development of a retitration protocol to rescue CPAP failure patients:
Specific to the topic of the REPAP protocol, we would never have imagined the need for a retitrations approach to patient care in 2003 when we opened our private, community-based sleep center. Instead, based on our earlier research in the field, which eventually led to the formulation of the Sleep Dynamic Therapy™ model (tested on trauma survivors from the Cerro Grand Fire in Los Alamos, NM, 2000 Journal of Clinical Psychiatry, 2002),(1) we had already begun using cognitive-imagery distraction techniques and sleep-related emotional processing strategies in our PAP patients to ease their adaptation to pressurized airflow. Despite the clear value of these techniques, which are used every single day at our sleep center, we were perplexed during the period of 2003 to 2005 to learn that the physiological barrier of expiratory pressure intolerance (EPI) was frequently triggered when attempting to titrate respiratory effort-related arousals (RERAs: discrete breathing events of UARS). Soon thereafter, we recognized this barrier was a crucial element in CPAP failure. And, as much as we were able to lessen subjective EPI in some patients with imagery distraction techniques and emotion-focused therapies, objective EPI often re-emerged once the patient was asleep.
In sum, we have gone down the path of focusing on the need for a physiological intervention to solve this particular side-effect that may occur in many (but certainly not all) patients who require PAP therapy. We have described an extraordinarily high rate of this problem set in psychiatric patients, mostly due to their anxiety in trying to use pressurized air. Overall, our psychiatric patients receive a great deal of standard care as well as specialized care before they are scheduled for retitrations in the REPAP protocol.
Several additional points from the review process were quite illuminating and will be discussed in the remainder of this post.
The issue of CPAP failure as we described in the earlier post can be noted in different ways. Thus, when the reviewer asked about patients who were still using CPAP but responding poorly, the question arose as to why we did not include them in the protocol. We responded:
We began our chart review and analysis with nearly 1500 2nd opinion patients seen in a 7-year period (2006 – 2013) and eventually found 900+ who met various criteria for CPAP failure irrespective of current use. Then, we further explained the same information posted earlier and why we wanted to include only a “pure” sample of current non-users and then we followed with four rationales for approaching the problem in this manner. First, there is no generally accepted definition of CPAP failure in the literature or from the insurance carriers who greatly influence this area of care. Second, as we looked over current CPAP users suffering from low levels of use, we perceived distinctive features between these users with low hours and a poor response and those not using CPAP at all. Third, we intend to examine low hours/poor response patients in another manuscript on the REPAP protocol, because these patients require different approaches and pathways compared to CPAP rejectors. Last, by focusing on patients who have unequivocally rejected PAP therapy, we believe we have removed any doubt about categorizing them as CPAP failure.
Another very clinically relevant point was offered by one of the reviewers to suggest that the intensive model of care we were pursuing with the REPAP protocol “was” or “should be” standard of care at the majority of sleep centers. The reviewer then asked the pivotal question of what is different about the REPAP protocol other than using precise pressure changes during the retitration? To which, we replied:
If we are correctly interpreting the reviewer’s comment/question, it seems the REPAP protocol is something that would or should already be in use at all accredited sleep centers. Our struggle with this specific interpretation is that most of the 2nd opinion patients we treated had originally been diagnosed and treated at accredited sleep centers (>90% in New Mexico). As the best example, the vast majority of patients were never offered a trial of bilevel devices not to mention ABPAP or ASV after reporting difficulty or failure with CPAP. Nearly all these patients reported no discussions occurred on the problems of subjective pressure intolerance at any point in their care, and greater than 90% reported that the concept of residual breathing events such as RERAs were never broached. Many were never offered new mask choices from the sleep centers or their DMEs. While we are reporting information alleged by the patients, we hear these comments repeatedly among 2nd opinion patients, expressed succinctly by the phrase: ‘I was not informed of these other options.’
Regarding the rounding of the airflow curve, we published a paper describing exactly this protocol in our clinical practice whereby we titrate in small increments, and we cite Condos et al 1994 paper (2) that to our knowledge first described the clinical relevance of rounding the airflow curve. Their work showed rounding the airflow curve led to further reductions in daytime sleepiness in their research sample. To reiterate, the delicate nature of raising and lowering pressures also is required to prevent expiratory pressure intolerance, which appeared as a central factor in preventing patients from using CPAP devices and appears to have contributed to their CPAP failure.
Another salient comment asked whether or not patients would constantly need to change their pressures modes after each titration, necessitating far too much transitioning from one device to another, to which we replied:
There is the possibility that a new device would be needed after every titration, but we conduct our titrations similar to Kuzniar et al’s protocol (2007)(3) to avoid this issue from arising in the majority of cases. Using the multi-modal protocol, we progress through a sequence that might include CPAP, APAP, CPAP w/EPR, APAP w/EPR, BPAP, ABPAP on the very first titration as indicated in any given patient. Thus, the most common scenario is that a patient fails the other modes by persistent RERAs or EPI or both and initiates treatment with ABPAP. In the smaller proportion of cases that ultimately need ASV, they usually are switched to this mode after having used ABPAP and then returning for a retitration due to poor outcomes and low use.
There was a concern about whether patients had the opportunity to try less sophisticated modes of PAP prior to advancing to ABPAP or ASV, despite the fact that all these patients were currently failing modes, most typically CPAP. Nonetheless, this point is a valid one, and we responded as follows:
We followed AASM guidelines for titrations in all patients. Thus, all patients always attempted CPAP at some point in their care at our center. The two most common places where CPAP was re-attempted occurred during the desensitization period of the retitration or in the early period of the retitration itself. Once objective findings of residual breathing events or expiratory pressure intolerance or both could not be resolved, then a switch to a dual pressure device would be initiated. APAP was used rarely because it suffers the same problem as fixed CPAP, since APAP is fixed CPAP at any given point in time and space. To resolve expiratory pressure intolerance, we discovered dual pressures provide much less stress on the patient while preventing the emergence of RERA breathing events.
During the time of our work on the revisions, a paper was published raising questions about the value of full face masks (FFM), and this issue may have prompted the reviewer to ask why we showed the tendency for even greater use of FFM. In responding to this comment, we took the opportunity to also note our surprisingly greater use of FFM in psychiatric patients who would have presumably suffered a higher likelihood for claustrophobic responses. Our response was as follows:
Regarding FFM, we find the recent evidence weighing against the full face mask to be confounded, because nearly all this research involves patients using fixed CPAP. In other words, regardless of mask type, when pressures are raised with a CPAP device, there is likely to be a triggering or exacerbation of expiratory pressure intolerance, which in practice should lead to lower levels of adherence. In contrast, this mask issue did not carry over in our sample when they used the combination of FFM with dual pressure auto-adjusting devices, perhaps because these modes allow for raising inspiratory pressures to eliminate RERAs while maintaining lower expiratory pressures to prevent or minimize expiratory pressure intolerance.
In a related issue, it might be anticipated that our predominant sample of psychiatric patients would suffer greater claustrophobia or claustrophobic-like responses to FFM. Ironically, we find the exact opposite. Many of these patients, who need considerable coaxing to try FFM, reported FFM relieves their anxieties, because they know and feel they can breathe through their mouths if a panicky feeling emerges. Since acute mouth opening and mouth breathing are classic responses in claustrophobic patients trying to gain more air, these patients realized FFM is actually a more natural fit, especially compared to the use of a chinstrap, which in many cases adds to the restrictive nature of feeling foreign objects on one’s face. The majority of psychiatric patients do not start with FFMs for the obvious reason it looks like a guaranteed trigger for claustrophobia, but as patients learn more about and adapt to PAP therapy, we have been surprised how many eventually chose FFM. Remarkably, we saw the combo of FFM and chinstrap in 39 patients.
A great question was raised on how we were able to precisely sort out the problem of expiratory pressure intolerance, to which we replied:
In our 2013 paper,(4) we published a graph showing how we observe objective EPI in the sleep lab, which may arise with any mode of PAP but especially with fixed pressure devices such as CPAP or APAP; even BPAP is technically fixed at given points in time and space for inspiratory and expiratory settings. The irregularities we see on the expiratory limb of the airflow curve have been the most consistent objective indicator of EPI in our clinical practice. But, as part of our protocol, the technologist is required to insure other factors such as nasal congestion, mask leak, mask flutter, mouth breathing, mouth sputtering, and dropped jaw displacement are not causing an artefact in the tracing. Switching to ABPAP or ASV and then switching back to standard PAP modes has also been a reliable indicator of objective EPI. Subjective EPI requires a much more simplistic approach, because we rely on the patient to communicate specific discomfort when breathing out against pressurized air coming in. During the desensitization period, patients are instructed on imagery distraction techniques to avoid focusing on breathing as well as receiving a “control of breathing” educational session to prepare them to not try to synchronize (usually over-control) their breathing with the PAP device. Together, these two instructions, delivered to all patients, lead to some diminishment of subjective EPI in many patients, yet once asleep many individuals still demonstrate objective EPI.”
In a related technology question, a reviewer noted that “better sleep” the morning after and patient reports of “easier adaptability” were crucial factors in the statistical analysis regarding what predicted the patient’s likelihood of transitioning from non-user to user. This point came up several times, and we felt obliged to explain it from the point of view of what makes for better sleep and easier adaptability:
These questions are crucial to understanding our manuscript and teasing apart the clinically relevant practice points. That statistical analysis demonstrated consistent findings of better sleep ratings in the morning and greater capacity to use PAP raises the larger question of what actually caused the better sleep and what caused the greater sense of adaptability. We believe it is of clinical interest that our patients consistently reported sleeping better with the advanced PAP devices (ABPAP, ASV) and also found these modes easier to use than standard CPAP. Moreover, these same patients reported greater than 70% of adverse factors attributed to CPAP failure were due to related technological barriers (e.g. pressure intolerance, unable to adapt to PAP, mask issues, and PAP side-effects), thus further aligning with the association between use of advanced technology and better sleep or easier adaptability. That Users also show a significantly lower AHI and a trend for a lower RDI also aligns with the association between use and advanced technology.
One of the final concerns for one reviewer was how much the role of education might have played in these patients ultimately achieving user status, especially given all the complexities in attempting to help PAP patients to overcome barriers and gain compliance. Our response was as follows:
We could not agree more with the reviewer on the complexities involved in CPAP rejection and non-adherence, albeit recent data suggests education may not play as large a role as once thought, and certainly follow-up efforts depend a great deal on who is providing the follow-up and what issues are being addressed. As far as data downloads, it remains concerning that so many sleep centers are apparently ignoring the AASM mandated obligation to address the problem of residual RERAs. Unfortunately, RERAs are only indirectly measured if at all on many device data downloads. Thus, RERA-induced sleep fragmentation is a likely cause of poor subjective outcomes that may go unnoticed despite PAP use, and in our experience downloads that show residual “flattening” are very helpful in our decision-making to consider a retitration in the sleep lab.
Further, a key distinction in our theory about rejection and non-adherence is that “experience” appears to be significantly more important than “education” in resolving a great many adaptation issues with PAP therapy. As our first major step in developing an experiential model, we formally organized the PAP-NAP procedure to give reluctant and otherwise complex patients the opportunity to “test-drive” PAP therapy. As we fine-tuned this experiential model, we realized how crucial retitrations were for some (but not all) of these complex patients.
As you can see, reviewers often ask very probing and challenging questions to insure that a research paper is not only clear but arguably more importantly that all dimensions of the research including all the strengths and weaknesses are discussed at length to insure the manuscript does not attempt to claim more than what was achieved in the study. The process of revise and resubmission therefore is a very intense and rewarding experience.
- Krakow BJ, Melendrez DC, Johnston LG, Clark JO, Santana EM, Warner TD, Hollifield MA, Schrader R, Sisley BN, Lee SA. Sleep Dynamic Therapy for Cerro Grande Fire evacuees with posttraumatic stress symptoms: a preliminary report. J Clin Psychiatry. 2002 Aug;63(8):673-84.
- Condos R, Norman RG, Krishnasamy I, Peduzzi N, Goldring RM,Rapoport DM. Flow limitation as a noninvasive assessment of residual upper-airway resistance during continuous positive airway pressure therapy of obstructive sleep apnea. Am J Respir Crit Care Med 1994;150(2):475-480.
- Kuzniar TJ, Golbin JM, Morgenthaler TI. Moving beyond empiric continuous positive airway pressure (CPAP) trials for central sleep apnea: a multi-modality titration study. Sleep Breath. 2007 Dec;11(4):259-66.
- Krakow B, Ulibarri VA, Romero EA, Thomas RJ, McIver ND. Adaptive servo-ventilation therapy in a case series of patients with comorbid insomnia and sleep apnea. J Sleep Disord Treat Care 2013. doi: 10.4172/2325-9639.1000107.
In the prior post on the Respiratory Threat Matrix Model, we delved into many facets of this theory, which you can read about here. In this post, we will focus on a few key points about this theory especially is it relates to the concept of threat.
Not being able to breath or suffering through a temporary episode of struggling to breathe is a mind-boggling event like very few other experiences in one’s life. Instantaneously, the potential for the loss of your life can overwhelm your consciousness inducing a state of panic and abject fear. There is no way to overestimate how emotionally painful and physically frightening you would feel in the instant you might believe you cannot re-establish your breathing. As described in the earlier posts on racing thoughts and ruminations, these events are arguably the most terrifying experiences you might suffer, because you actually feel or believe you are about to die.
Most people probably know what these episodes feel like, because most people experience rare episodes of choking on something while eating, or swallowing too much water while swimming, or getting the wind knocked out playing sports. Another common one is roughhousing as kids and ending up on the bottom of the pile. Any of these episodes and more could lead to the sensation of being unable to breathe properly. Therefore, virtually everyone knows how horrific the sensation feels while awake.
In sleep-disordered breathing, you could argue we have the advantage of being asleep at the time, so perhaps the traumatizing nature of the experience is much less severe. That theory is a reasonable one, but I wonder if an opposing point of view is more valid. That is, because you are asleep and do not gain much awareness or memory of these events (except for the occasional waking with the feeling of choking, gasping, or frank apneas), perhaps you are in such a highly vulnerable state on an unconscious level that the experience may prove more traumatizing to you than if you were awake. While awake the semblance of control is real; while asleep you would feel no sense of control.
In my opinion, one of the reasons OSA/UARS patients awaken most mornings feeling awful may not simply be due to the chronic sleep fragmentation and subsequent nonrestorative sleep caused by sleep breathing events. In addition, the individual suffering through hundreds of these events each night is literally, not figuratively, being assaulted minute after minute with episodes of apneas, mini-suffocations, or other feelings of constrained breathing. In other words, the main issue regarding threat is not just a diminution of the volume of each breath. It is the all-out assault on your respiratory system’s primary function to breathe in and breathe out. The sleeper arising in the morning has been attacked nonstop in most cases throughout the night, during which he or she was defenseless against the assaults.
Imagine suffering the same experiences of sleep-disordered breathing events but now in the hypothetical circumstances of being awake. In fact, individuals with severe lung diseases such as asthma or emphysema periodically encounter circumstances in which they cannot draw in a full breath; and, in extreme cases, these patients must be hospitalized and sometimes intubated with mechanical ventilation because the respiratory system has become severely compromised. Yet, even these diseases might pale in comparison to the theoretical scenario of your actually suffering sleep breathing events while awake. In such a circumstance, you would be constantly fighting through airway collapse, at whatever severity level, every single minute of your waking experience, hour after hour. It would prove impossible to function, let alone accomplish anything of value or meaning in your daily existence. Your entire life would be consumed with efforts to breathe, just as if you were walking around all day long with a wet washcloth draped over your nose and mouth through which it would be impossible to inhale or exhale a full breath.
It is useful to consider sleep breathing events in this light, because you will more accurately comprehend how problematic these sleep breathing episodes must be for any OSA/UARS patient in general as well as for those individuals who are the topic of this discussion, namely, insomniacs. Indeed, this theoretical concept may also help other people understand the disease from which their friends and family members suffer. Just consider the look on someone else’s face when you would say: “Each night when I sleep, my breathing is so disrupted from these attacks that were you to see me suffering in this same way while awake, you would presume I were some sort of respiratory cripple.”
Ironically, however, the human body adapts in ways that typically do not manifest outwardly regarding this respiratory compromise unless one suffers the most severe forms of OSA, where the bed partner watches first-hand these frequent ghastly episodes of choking or stoppage of breath. It is unclear whether or not this adaptation is related to the fact that a human suffers these events during the “luxury” of sleeping, that is lying down, and not while trying to function. However, internally, the individual suffers in this horrific way to some degree in virtually all cases of sleep-disordered breathing, because disturbed and restricted breathing is too threatening of an experience not to induce some reaction to attempt to overcome the problem. And, the feeling of distress is a highly effective and common way to achieve vigilance; and, in the case of more prolonged or intense breathing events, this severity of distress may be a factor in why or how one awakens from any particular episode.
All these points persuade me the actual intensity and frequency of breathing attacks occurring during sleeping hours must play a critical if not primary role in the development of the insomnia condition, the most obvious manifestation of which would be the racing thoughts and ruminations that emerge within the individual in the attempt to prevent sleep from happening. If sleep is prevented, then sleep breathing events are prevented.
Furthermore, I cannot help but wonder whether the problem goes deeper. What happens to a person’s psyche when he or she is constantly attacked in this life-threatening physical way during sleep by an unknown assailant? What perspective on life does the insomniac bring into waking hours after so many hours of these assaults? How likely is the night time threat going to carry over into the person’s waking hours as a sense of doom and gloom as he or she would always know on a subconscious level that in so many hours hence, the attacks will begin again without respite and without any predictive knowledge of the severity of the assaults? This latter point is one I have used to explain to night owls how their subconscious thoughts and feelings may promote later and later bedtimes. Why not delay your entry into the bedroom and into bed if only terror awaits you?
These questions are not merely speculative. I believe these theories raise relevant clinical questions germane to most insomniacs. Again, as in the starting point of this discussion on racing thoughts, I remain persuaded this inability to turn off one’s mind is frequently related to the threat of the unsuspected breathing events. But, in digging deeper, we need to ask whether or not sleep-disordered breathing by its mechanisms plays a substantial role in the development of anxiety in a large proportion of insomniacs. The clinical relevance of this theory is enormous, because for at least 100 years if not longer the theory would be the reverse: anxiety symptoms arise due to mental issues and over time anxious patients show irregularities in their waking breathing patterns. Here, we hypothesize the reverse, wherein irregular sleep breathing patterns habituate individuals to unknowingly lose confidence in their respiratory system. Over time, acutely and chronically, the unpleasant and disturbing feelings associated with this pathophysiological breathing pattern leads to anxiety, not the other way around.
If this theory is accurate, it will cause a radical paradigm shift in how mental health patients are treated in general and insomnia patients in particular. The conventional model of therapy for many of these conditions revolves around “abnormal brain chemistry.” Drugs then must be the answer. And, with the bombardment of advertisements in all sorts of media on the psychotropic/sedative medication approach, this conventional wisdom leads a huge proportion of patients to believe drugs must either be the best option or perhaps the only option. And it follows that among patients currently on medications yet reporting sub-optimal responses, often their most immediate question arising out of their continued misery is: “well, what drug do I try next?” not “what other treatment options should I consider?”
To learn more, insomniacs and mental health patients must receive more frequent evaluations for OSA/UARS and subsequently more evidence-based therapies such as PAP, OAT or site-specific ENT surgeries. When large cohorts of these patients are routinely treated in primary care clinics or mental health facilities as if sleep-disordered breathing were of the utmost importance, then and only then will we discover the true impact of these breathing events on the individual’s sleep, mood, and personality. Regrettably, with the current and ongoing disruptions to the healthcare systems and the expanding denigration of the field of sleep medicine, particularly sleep centers and labs, we are many years away from gathering this essential data.
However, regardless of the absence of treatment data in large sample, we are beginning to see some interesting information emerge about the treatment of insomnia in patients with untreated OSA/UARS. Thought it might seem surprising, given the so-called potency of this respiratory threat, it is of considerable clinical interest that cognitive-behavioral therapy for insomnia (CBT-I) still may prove effective in treating insomnia even when the patient suffers from co-occurring sleep-disordered breathing. Unfortunately, the small number of studies covering this topic has shown mixed results, so the jury may be out, but anecdotally many insomnia treatment experts report they have treated numerous patients with co-morbid OSA/UARS, wittingly or unwittingly, and have observed marked decreases in insomnia severity. This perspective is very good news in light of how many insomnia patients will go undiagnosed in the years ahead with their unsuspected OSA/UARS.
Nevertheless, this research area is ripe for vigorous attention, because we now recognize that a huge proportion of these patients are presenting to sleep centers; and, they are presenting with both complaints regardless of whether they emphasize the sleeplessness or the sleep breathing symptoms. Several recent research studies and review articles (1-13) are examining this comorbidity, and eventually clarity should be forthcoming on how the threat of sleep breathing events impacts the insomnia condition in the conventional circumstances in which only non-breathing interventions treat the sleeplessness, such as sedatives or CBT-I. Would the untreated sleep breathing events still impact the quality of sleep, prolonged awakenings or daytime fatigue and sleepiness? Or, would enhanced sleep consolidation that often follows the use of stimulus control and sleep restriction therapy (standard CBT-I tools) lead to deeper sleep, fewer awakenings and improvement in daytime energy levels? Furthermore, would this improved sleep consolidation create more stable sleep architecture, which in turn might diminish sleep breathing events? We published a few papers more than a decade ago raising some of these questions (14-16).
Other symptoms as research variables will also prove informative in how these patients respond to either single or combined treatment programs. Looking at the residual OSA/UARS symptoms in patients receiving only CBT-I or sedatives, we will learn a great deal from patients’ changes or lack thereof for nocturia, morning headaches, fatigue, and hypertension. All four conditions, with the possible exception of fatigue, have fairly clear-cut mechanisms to explain the symptoms. Nocturia is caused by the SDB-induced expansion of blood flow into the right atrium and subsequent release of the body’s natural diuretic, atrial natriuretic peptide. Morning headache is thought to arise when excess CO2 in the blood from untreated OSA causes a dilation of blood flow in the cerebral arteries. Hypertension seems to result from damaged to the inner lining of blood vessels, rapidly fluctuating levels of oxygenation, and the elimination of the normal “dipping” or lowering of the blood pressure during the sleep period. If patients were only treated with CBT-I, we might expect some of these physiological symptoms to persist because the sleep breathing events were not eliminated?
Last, fatigue is a more mysterious symptom, one that circles us back to the whole discussion of threat, because threat in general is a very draining experience for anyone to suffer through. As mentioned above, vigilance or hypervigilance is a natural result of suffering too many threats, real or imagined. If a person experienced the respiratory threat while asleep, there is no obvious way to measure its impact or to even gauge how it might have affected daytime energy levels. Of course, it would not be surprising to observe that nonrestorative sleep was the major cause of fatigue in patients who otherwise do not seem to develop sleepiness. And, there are many such OSA/UARS patients who present without sleepiness and only with fatigue. On the other hand, we have always surmised that the combination of anxiety plus sleepiness leads to the feeling of fatigue by somehow obliterating the sensation of sleepiness. If so, then parsimoniously, the respiratory threat matrix model may help us understand more than just the racing thoughts of insomniacs; it may shed light on why so many insomniacs are more likely to report the symptom of fatigue.
- Lack L, Sweetman A. Diagnosis and Treatment of Insomnia Comorbid with Obstructive Sleep Apnea. Sleep Med Clin. 2016 Sep;11(3):379-88. doi: 10.1016/j.jsmc.2016.05.006. Epub 2016 Jul 21.
- Sweetman AM, Lack LC, Catcheside PG, Antic NA, Chai-Coetzer CL, Smith SS, Douglas JA, McEvoy RD. Developing a successful treatment for co-morbid insomnia and sleep apnoea. Sleep Med Rev. 2016 May 6. pii: S1087-0792(16)30010-7. doi: 10.1016/j.smrv.2016.04.004. [Epub ahead of print] Review.
- Luyster FS, Buysse DJ, Strollo PJ Jr. Comorbid insomnia and obstructive sleep apnea: challenges for clinical practice and research. J Clin Sleep Med. 2010 Apr 15;6(2):196-204. Review.
- Crawford MR, Turner AD, Wyatt JK, Fogg LF, Ong JC. Evaluating the treatment of obstructive sleep apnea comorbid with insomnia disorder using an incomplete factorial design. Contemp Clin Trials. 2016 Mar;47:146-52. doi: 10.1016/j.cct.2015.12.017.
- Ong JC, Crisostomo MI. The more the merrier? Working towards multidisciplinary management of obstructive sleep apnea and comorbid insomnia. J Clin Psychol. 2013 Oct;69(10):1066-77. doi: 10.1002/jclp.21958. Review.
- Benetó A, Gomez-Siurana E, Rubio-Sanchez P. Comorbidity between sleep apnea and insomnia. Sleep Med Rev. 2009 Aug;13(4):287-93. doi: 10.1016/j.smrv.2008.09.006. Review.
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