[Treatment] ASV settings for treatment of complex sleep apnea

[JoeyWallaby]

Went to bed earlier last night, trying to get a good sleep cycle. Seemed a bit more restless than usual on the camera. I looked on the camera if there was anything happening at the huge MV spike at about 1:00 but nothing interesting apart from moving around a bit.

Feel okay today...not well rested but not tired, just okay. Woke up and couldn't go back to sleep, probably due to the rapid pressure cycling at the end. Had aerophagia as well, not really bad but not nice.


The huge MV spike, breathing deeper and deeper despite no increase in PS


I'm thinking ASV could be aggravating CAs. Maybe I should try bilevel on the lowest possible setting and slowly titrate up the pressure by .2?

Some quotes from journal articles

TECSA = treatment-emergent central sleep apnea
TPCSA = treatment-persistant central sleep apnea

The physiological mechanism that leads to the occurrence of TECSA in OSA patients exposed to CPAP or other therapies is not well established. To date, several possible mechanisms including ventilatory control instability (high loop gain), low arousal threshold, activation of lung stretch receptors, and prolonged circulation time, have been suggested.

Medications could be selected to improve ventilatory control stability or elevate the arousal threshold for TECSA patients, which may be a supplement to PAP therapy. For example, acetazolamide, a carbonic anhydrase inhibitor, can modulate loop gain. Glidewell et al described a case of successful control of CompSAS with CPAP and acetazolamide in a 41-year-old white woman on long-term opioid therapy. This case suggested that acetazolamide may be an effective adjunct to PAP therapy for the treatment of TECSA in patients on long-term opioid therapy. Similarly, some studies reported that both trazodone and eszopiclone increased the respiratory arousal threshold of OSA patients with a low arousal threshold. Hence, these medications could possibly be a new method for the treatment of TECSA. It is necessary to conduct large sample clinical trials to confirm the effectiveness and safety of such therapeutic options.

The typical course of TECSA appears variable. The majority of patients with TECSA show resolution of central apneas over a few weeks to months. Although most cases of TECSA resolve over time, about one-third of such patients convert to TPCSA related to PAP therapy. Our systematic review noted that 0.9%-3.2% of all patients treated with PAP therapy for OSA will exhibit TPCSA on a long-term basis. They represent 14.3%-46.2% of TECSA patients, who continue to experience PAP therapy-related central sleep apnea over a protracted period after they were first diagnosed with TECSA. Javaheri et al, noted that the daily CPAP adherence tends to be lower in patients who eventually declare themselves as TPCSA on PAP-2 compared to patients who experience resolution of their TECSA.

The prevalence of TPCSA at 0.9%-3% in all patients with treated OSA may be an underrepresentation given some patients in the discussed studies were lost to follow-up after the first titration study. Cassel et al . reported a TPCSA prevalence of 3.2%, which was the highest of the five studies evaluating this phenomenon. Even this TPCSA prevalence figure could be an underestimation, as 28 out of the 82 patients with TECSA at PAP-1 were lost to follow-up and hence unavailable to undergo a PAP-2 study. Similarly, in the study by Dernaika et al, which reported the TPCSA prevalence at 1.7%, it was noted that seven out of 21 patients with TECSA at PAP-1 were lost to follow-up and also unavailable for a PAP-2 study. Selective exclusion of patients with preexisting central sleep apnea from the titration study can also lead to underestimation of overall prevalence.

[SarcasticDave94]

I'm not at all certain how the ASV is aggravating CA, that's the reason an ASV exists, its mission is to treat Central Apnea.

[Geer1]

I looked at the extra data you sent. It included last couple nights and then some old data from Jan-Apr last year (2020). On the vauto it is clear that even at a PS of 3 and min EPAP of 4 you were having noticeable central apnea and for significant periods where apnea is not present breathing is cyclical and showing evidence of central style breathing.

When looking at your ASV data now it makes it a little bit more clear that the ASV cycling is in fact the machine trying to compensate for central style breathing. I think there are only some periods where it is doing so to mitigate full on central apneas though. Resmed ASV makes corrections after every bad breath so all it takes is one half breath and it will try to pump you up the next one.

It is sort of interesting that you felt better on the 7th after increasing PS to 3 as the breathing looked slightly worse rather than better. I don't know that it was worse because of the increase to PS of 3 (can't draw that conclusion until multiple days of data to compare). I think it is pretty clear you probably felt better for some reason not related to your breathing.

Just looked at your sleep study data again and I think I previously just assumed your hypopneas were obstructive. I assumed your centrals were treatment emergent because they clearly are worsened by treatment. Now after seeing how your bilevel data shows significant central apnea related breathing it makes me think your hypopneas in sleep study were probably central in nature as well. One other thing I noticed that seemed a bit weird to me is that they only reported 4 central apnea but graph shows what looks like closer to 9 ticks. Some of the hypopneas seem to be around those central apnea ticks as well.

My recommendation is to get doctors involved to investigate this issue further and I think a titration study could be very helpful. If you explain your history so far it will make it easier to recommend how to try to get help from your doctors in obtaining such a study. Which doctors have you seen and when? What tests have been done (just that one PSG?)? Who prescribed CPAP (or did you self treat from the beginning)? What follow ups have been done? Any relevant data like that will help.

As for self treatment going forward I believe ASV is notably better than vauto and I wouldn't go over a psmin of 3. I think higher psmax causes more aerophagia, potentially disturbs your sleep and I don't see anything in your data that makes me think it is necessary or beneficial so I would leave it handcuffed at 5 over psmin.

Imo your main self treatment option right now is maintaining the current settings and hopefully your body adapts over time. Your sleep has been disturbed for a long time now, it is going to take weeks to adjust even if we find the right settings. One more change worth considering would be turning the auto EPAP feature off (think it is called asvauto mode). This is meant for treating obstructive apneas and your main issue appears to be central in nature (if some obstructive issues are present I believe they are treated at pretty much any setting). Turning this off will further reduce pressure fluctuations and overall pressure.

[JoeyWallaby]

SarcasticDave94, maybe not specifically aggravating CA, but the pressure cycling might be causing arousals/fragmented sleep and making it harder to acclimatize to CPAP.

Geer1, I've set it to fixed EPAP 4 and PS 2.6-7.6.

I've only had that one sleep test in 2017. No titration study. Self-treatment from the beginning with no follow-ups. I'll insist on another sleep study when I visit my doctor.

The PPIs have helped the LPR, some of my events on BiLevel could have been related to that too.

In regards to long-term acetazolamide use, I found some studies...

This one (https://pubmed.ncbi.nlm.nih.gov/33538687/), however I can't access the full-text.

Results: Fifteen trials with a total of 256 patients were pooled in our systematic review. Acetazolamide reduced the overall AHI in CSA, but not in OSA. Acetazolamide reduced the respiratory related arousal index, improved partial arterial of oxygen, mean oxygen saturation, total sleep time, N2 sleep and sleep efficiency.

Conclusions: Acetazolamide improves the AHI and several sleep metrics in CSA. The drug may be of clinical benefit in patients with high loop gain apnea of various etiologies and patterns. The existence of high heterogeneity is an important limitation in applicability of our analysis.

And this (https://pubmed.ncbi.nlm.nih.gov/32502849/), which I can access the full-text.

It's a case study of a 69-year old male with OSA, CSA and periodic breathing. Dose was 250mg acetazolamide 1-hour before bed, studied for 10 months.



This was the conclusion.

Acetazolamide can reduce loop gain by approximately 40% in individuals with OSA. Due to a diuretic effect, it could facilitate the fluid clearance from the neck area/lung and improve ventilation/perfusion ratios. Moreover, the hypoxic ventilatory response can be reduced possibly by inhibiting the carotid bodies and the interaction of O2–H+.

Renal/metabolic acidosis effects or even speculatively neuroplasticity of carotid body function may exist and contributes to long term effects of acetazolamide.

In conclusion, chronic acetazolamide treatment could be a useful adjunct to CPAP therapy when high loop gain is present in patients with OSA.

Here is better quality images from the pressure cycling study I posted before (Estimation of adaptive ventilation success and failure using polysomnogram and outpatient therapy biomarkers).



Some of notable excerpts from the pressure cycling study...

These complex algorithms also interact with numerous other factors to generate a pressure cycling response—including arousals from other etiologies, mask leak, sleep–wake transitions, and phasic REM sleep. Thus, not all what is noted as pressure cycling is harmful or generated solely by the ASV device. Patients with periodic breathing or central sleep apnea have a high propensity for arousals and sleep fragmentation, which likely contributed to some of the pressure cycling seen.

Improvements in AHI and normalization of airflow have commonly been accepted as surrogate markers of improvement in sleep quality, but if those improvements come at the cost of inducing patient-device desynchrony, with associated microarousals and surges in autonomic activity, the trade-off is suboptimal.

The ASV algorithm may in some instances contribute to disruption of sleep, but numerous reasons for persistent and excessive pressure cycling exist.

The subset of patients found to have severe pressure cycling and desynchrony can then undergo further titration or evaluation of adjunctive therapies such as acetazolamide, oxygen, sedatives, or hypocapnia minimization, to attempt to identify pressure settings that allow improvements in sleep quality and hemodynamics.

The following potential mechanisms of patient-ventilator desynchrony and persistent pressure cycling are speculative, but biologically plausible. Loop gain may be too high for the device algorithm to compensate or correct. Variable obstructive features may add to variability of tidal or flow volumes sensed by these devices and trigger or sustain pressure cycling. Induction of hypocapnia can worsen respiratory  control  instability. Arousals associated with pressure cycling can amplify loop gain and desynchrony effects. Analogous to pacemaker-loop arrhythmias, it is possible that the ventilator’s oscillatory output algorithm loops with circulation time and controller gain to cause a perpetual cycle during periods of unstable NREM sleep. Some patients find the sensation of ASV-related pressure oscillations uncomfortable, which may prolong sleep–wake transitional instability and enhance pressure cycling. Some of these challenges, though unlikely all, can be addressed in principle with improved machine algorithms. Reduced pressure cycling in users of acetazolamide (itself started likely for excessive pressure cycling) suggests that persistent and unresolved high loop gain effects drive at least some of the pressure cycling.

Here's three days from when I used bilevel at a low pressure.



And, with ASV, two most recent days and the one night (2nd April) when I took 500mg acetazolamide long-release. As you can see, there is minimal difference.



In conclusion, I'm going to try to get another sleep study. With my LPR mostly controlled by PPIs and a camera setup now, it'd be interesting to see (at a very low pressure) if CAs are present when using BiLevel, and to check on the camera when they're occurring (holding breath when rolling over or just laying still). I wonder what's worse for sleep, CAs or pressure cycling?

[Geer1]

Yeah I don't see any evidence that the Acetazolamide makes significant improvement. Not like the studies on it are talking about (drastic drops in AHI numbers etc).

Since you have always done self treatment that makes it a bit harder. Does your doctor not believe that you have sleep issues?

I would put together a package to try and convince your doctor (or a new one if necessary). I would have the sleep study and show that there was no obstructive apnea but there were central apnea and hypopneas that may have been central in nature. I would say I disagree with conclusion of mild sleep fragmentation and that no sleep study only a few hours long should be used as a sole definitive proof of minor to mild sleep issues especially when it doesn't encompass all aspects of required sleep (rem sleep was not present).

Then I would explain that you decided to try self treating with CPAP (if he isn't already aware of this). I assume you started out with a basic CPAP, tell him that. Print some of your OSCAR data showing high numbers of centrals on CPAP and BiPAP (overview tab can be helpful for that as well). Cherry pick low pressure/PS data with high centrals to show him, if you show high PS he will blame it on that (if he knows anything about it).

Then explain that under guidance of online forum you figured you need ASV to treat the central apneas. That you have tried self titrating but feel you have done all you can. That your central apneas and AHI are improved but that your sleep is still fragmented and you still feel unrefreshed in morning and tired through the day.

Then I would say you think you need a follow up PSG/titration study done to confirm central apneas, sleep fragmentation, see what breathing looks like in rem sleep (or if you struggle to get into/stay in rem sleep and double check that there are no other settings etc that might help.

[Geer1]

I was looking through some uptodate (a doctors resource) items and found the following on treating central apnea. It agrees with what we are doing now.

Central Apnea Due to Hyperventilation (most common and likely your issue)

- Central apnea best conceptualized as sequence of events
- First any variety of stimuli induces hyperpnea (deep breathing)
- Hyperpnea causes ventilatory overshoot and hypocapnia (low CO2) inducing a central apnea
- Central apnea causes CO2 levels to rise until mild hypercapnia (high CO2) restores respiration at which point there may or may not be an arousal.
- Cyclical repeating nature of this hyperpnea, hypocapnia, central apnea, hypercapnia.

Usually occurs mostly during NREM sleep, rarely during REM. What I find interesting about your data is that a lot of your central like breathing is later in morning. That doesn't mean it is in REM but probably more likely means fragmented REM and apneas during transitions/arousal.

There is a section on treating centrals with PAP and specifically ASV titration.

The goal of PAP titration is to determine minimal pressure required to resolve all apneas, hypopneas and other sleep related respiratory events, in all stages of sleep and in all sleep positions (you don't even have a sleep study yet in all stages of sleep).

Caveats of PAP titration in CSA - In contrast with patients who have OSA, PAP therapy may not eliminate all sleep disordered breathing events in those with CSA. In addition, ventilatory instability can lead to overventilation and hypocapnia which can worsen central apnea (as you, we have noted with your treatment), particularly when PAP is administered at higher pressures a phenomenon termed pressure toxicity. Worsening CSA due to this can lead to an increase in sleep fragmentation.

EPAP - Expiratory pressure needed to overcome obstruction. When moving to ASV some places use EPAP determine from CPAP trials, some use EPAP 2 cm below. If pressure needed to overcome obstruction or no obstructive apnea is present (your case) then EPAP is initiated at the lowest setting (4 cm) and increased gradually to eliminate obstructive apneas (you have none so no reason to increase EPAP).

PS - Level of PS is unclear, some disagreement among experts. The author and many experts support all breaths by setting a minimal pressure support in 2-3 cm range. Maximum PS is typically set between 8 and 15, some experts limit PS range to 5 cm (as we just did). Hoewever supporting each breath during ASV treatment is controversial since PS during periods of hyperpnea may lead to worsening hypocapnea further enhancing central apnea activity thus some experts set minimal PS at 0 cm (this falls in line with us recently lowering PSmin due to belief that it causes excessive pressure cycling and hyperventilation ultimately ending in Resmed ASV targeting too high of MV and depressing respiratory drive).

This to me confirms my thoughts that we have done pretty much all we can do with our recent actions to maximize self treatment. Turning off auto EPAP might be advantageous since there is no reason to believe you have obstructive apnea. Definitely shouldn't increase PS min over 3 and if anything could try even lower levels to try and see if it makes any improvement (I think key is just finding what seems most comfortable and minimizes pressure cycling).

[sheepless]

before you give up on the vauto, have you tried very high trigger? again, I've been using vauto more than asv solely to avoid the asv ps cycling that seems to create problems for you (and me). trigger set at very high keeps my ca down to barely any and the fixed epap and ipap is much less disturbing than asv's minimum ps range of 5 cmw.

[JoeyWallaby]

Thanks Geer1, no the sleep doctor I saw wasn't very good. He didn't listen to me at all. 

My grandpa was on ASV for complex SA (OSA and CSA), his sleep doctor didn't care that his data was abysmal (taking off mask multiple times a night, obvious flow limitations, severe pressure cycling)... because his AHI was low

There aren't many sleep doctors here where I live, I'll have a look at who else is available.


I want to get another sleep study and maybe titration but I don't know how helpful discussing things with them would be. 

sheepless, I want to try BiLevel again sometime and look at the camera recording to see when the CAs are occurring. And see if taking PPIs for LPR has improved anything regarding CAs.

This last night of sleep data may not be very useful due to multiple compounding factors. I went out and had a couple drinks, I took 50mcg (microgram) clonidine and also changed the settings as described above (change to fixed EPAP from auto, slightly lowered PS).

I feel just okay today and the clonidine definitely makes it easier to fall asleep. No aerophagia.

[JoeyWallaby]

Changed the settings back to Auto EPAP (4-7) and lowered PS back to 2 (2-7).

Took clonidine 50mcg, also an antihistamine and a nasal spray to help clear up any congestion. Nasal spray definitely helps. Feel decent today.

Stability of minute vent and insp/exp time seems a bit better. Pressure cycling also seems slightly improved.

First two events occurred when I was on my back and the last two when I was on my side and had my chin tucked towards my chest.

[Geer1]

None of those are real apnea/hypopnea. See the spikes/disturbed breathing prior (in some cases one breath prior, in other times for a while)? Those are arousal related breaths/breathing. In the cases where apnea occurs directly after the arousal breath your body is taking a break from breathing while transitioning out/in of sleep or you are holding breath while changing position. In the cases where it is a while after the arousal breathing it is a transition back to sleep. These are all normal and the issue(if it even is an issue) is the arousal, not the breathing after the arousal.

Sleep doctors and respiratory therapists are annoying and it seems hard to find a good one. It will also be tough for you because you don't have obvious breathing issues (other than self induced excessive centrals when treating with CPAP/BiPAP). On the obstructive side the worst you could have is UARS but you don't have the obvious flow limitations, RERA's etc to support it and even if you do ASV is effectively treating it. If you have SDB it appears to be central in nature and the ASV at these settings seems to treat it pretty reasonably (can't confirm how well without PSG). New PSG data whether or not it comes from a good sleep doctor or not is helpful in determining if your data has changed since first sleep study, seeing if there are any signs of obstructive breathing, seeing if centrals are an issue, if possible trying to get the clinic to determine if hypopneas are central in nature, collecting data for rem sleep and most importantly seeing if ASV treatment is actually improving your sleep quality (reducing hypopneas, arousals etc) in the eyes of a trained sleep technologist with PSG data.

Imo you seriously need to change your handling of treatment because you are too focused on daily stats that aren't telling you anything. The OSCAR data doesn't show any issues, there is no obvious worsening or improvement when changing settings other than the decline when using high PS. You are putting every single night, apnea, breath under a microscope, changing settings every day/few days, self medicating randomly and it is clear you have health anxiety on the subject. Set the machine, stop looking at the data, use it for a few weeks and if you don't think it is helping then stop using it. That is when you will notice if it is helping or not. If you notice you are more tired etc after discontinuing use then start using the machine again knowing it is helping and change focus to other health issues.

I almost guarantee that if you have IBS, LPR and nasal congestion you have gut issues that need to be addressed. I almost guarantee these are affecting your sleep, anxiety and health as a whole like they were mine. The first step is getting anxiety and digestive symptoms under control, if you do that I believe you will see a noticeable improvement and then you may be able to start noticing any underlying remaining symptoms and start treating them. For the gut stuff again I recommend reading Healthy Gut, Healthy You as the author does a good job explaining a lot of this stuff, how it ties together and a method to determine and improve your specific gut issue. If you want some data to support if gut issues might be part of your problem then find a doctor (probably naturopath) that will do a SIBO breath test.

I went through something similar to yourself. What helped me determine issues and fix them was when I finally gave up thinking that obstructive apnea was causing my health issues. I was so wrapped up in thinking my apnea was the problem that it was the only thing I focused on (much like you do now). I was at the point where my only options were to buy a bilevel machine out of pocket to try higher PS or to get a PSG to collect more data. Doctor ordered a PSG but then covid happened and I wasn't able to get it until this winter. It was the best thing that could have happened to me because giving up on chasing apnea led me to the diet changes and antimicrobial treatments that significantly improved my health, far more than PAP treatment ever did. My physical health improved, my sleep data in OSCAR improved, my sleep quality/video data improved. All this stuff is tied together and you need to find out what is actually causing your health issues and fix it. I am now fairly sure that I don't have sleep apnea (at least not in any typical sense). I am still waiting on my recent PSG results but the technician said there were no indications of it and she wouldn't let me proceed with titration/CPAP use because of it (even though I argued I would sleep better because I am used to it...). I believe my home study test that diagnosed me with apnea was positive because of nasal congestion issues I was having (which greatly improved with diet and antimicrobial treatments). Even though I don't have apnea I still find I sleep better with CPAP though. I think the extra humidity and increased airflow helps keep my nasal passage clear. If I don't sleep with CPAP I get a dry crusty nose and often wake up a bit more plugged up and if I go without using CPAP for a few days I start feeling more tired. Imo that is all you need to try and figure out right now (do you sleep better with ASV or without it), if you can get some good PSG/titration data it might help confirm or deny if breathing is an issue. If you keep running around chasing your tail and unicorn settings I don't think you will get anywhere.