Second Opinions and the Rise of REPAP: Part IV

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:

  1. prescription renewal for PAP supplies; 
  2. clinic appointments regarding continued PAP use; 
  3. re-titration and confirmation of use;
  4. 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.


  1. 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.
  2. 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.
  3. 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.
  4. 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.


Barry Krakow MD


Dr Krakow’s 27 years of sleep research have focused on the complex relationship between physiological and psychological sleep disorders. Dr Krakow currently operates private sleep medical center, Maimonides Sleep Arts & Sciences, Ltd., and serves as Classic SleepCare’s paid Medical Director.

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