nataliezzz
Senior Member (Voting Rights)
This is a thread to discuss the evidence pertaining to obstructive sleep-disordered breathing - upper airway resistance syndrome/obstructive sleep apnea syndrome (UARS/OSAS) - and chronic insomnia. Many people with ME/CFS and related disorders like fibromyalgia experience chronic insomnia.
Sleep-disordered breathing (SDB) causing sleep maintenance insomnia due to awakenings may seem logical to most people; that it can also cause sleep-onset insomnia, less so (aren't SDB patients supposed to be sleepy?), which is why an alternative paradigm of SDB is needed to explain it: here is an updated version of the AI Summary of Dr. Gold's theory of UARS/OSAS (sensitization/physiological stress response to inspiratory flow limitation), which could explain how SDB can cause sleep-onset insomnia: the physiological stress response to inspiratory flow limitation may cause a state of physiological hyperarousal (often along with fatigue), leading to sleep-onset insomnia (and the "tired but wired" feeling many of us know so well). See also this relevant paper:
Somatic arousal and sleepiness/fatigue among patients with sleep-disordered breathing, 2016, Gold et al.
For context, the prevalence of obstructive sleep apnea (OSA) in the general population based on 11 epidemiological studies between 1993 and 2013 was 22% in men and 17% in women (some of these studies oversampled suspected OSA patients or habitual snorers):
Obstructive sleep apnea is a common disorder in the population—a review on the epidemiology of sleep apnea, 2015, Franklin et al.
The following 2 studies consist of samples of chronic insomnia patients after those with suspected sleep-disordered breathing were excluded, and yet close to 100% still met criteria for OSA/UARS.
Prospective Assessment of Nocturnal Awakenings in a Case Series of Treatment-Seeking Chronic Insomnia Patients: A Pilot Study..., 2012, Krakow et al.
Prospective study of 20 adult patients with chronic insomnia (17 reported both sleep-onset insomnia and sleep maintenance insomnia; 3 reported sleep maintenance insomnia only) who presented to a sleep clinic with a primary complaint of chronic insomnia, had never previously visited a sleep specialist, and reported no classic sleep-disordered breathing symptoms. 90% of their awakenings were preceded by a respiratory event: apnea, hypopnea, or respiratory effort-related arousal (RERA). 11 met criteria for OSA and 8 met criteria for UARS based on AHI <5 and RDI (AHI + RERA index) ≥ 15.
Prospective RCT on the Efficacy of CPAP and Adaptive Servo-Ventilation in the Treatment of Chronic Complex Insomnia, 2019, Krakow et al.
Participants were adult chronic insomnia disorder patients who believed their sleep problems were due to psychological, psychiatric, behavioral, or environmental factors; none believed sleep breathing symptoms or disorders caused or contributed to their insomnia. No recruitment advertising was conducted; primary care physicians were apprised of the research and instructed not to divulge the protocol to candidates, who were informed of a "chronic insomnia research study."
Patients with overt OSA signs, symptoms and risk factors (excessive daytime sleepiness, witnessed apneas, obesity, past evaluations at sleep centers) were excluded. After excluding 599 patients, the majority due to the aforementioned factors (but also some others including bipolar disorder, restless legs syndrome/periodic limb movement disorder), only 1/62 chronic insomnia patients who underwent polysomnography (PSG) did not meet criteria for OSA/UARS (UARS criteria was AHI <5, RDI ≥ 15). 21 out of the remaining 60 patients were excluded after randomization (to CPAP/ASV) for various reasons including treatment intolerance, work/school schedules, medical issues, etc. Of the 40 final patients, 90% met criteria for OSA and 10% UARS.
Average Insomnia Severity Index (ISI) was moderate-severe.
Clinically, ASV (adaptive servo-ventilation, a type of bilevel* positive airway pressure device that can alter pressure support - the difference between inspiratory and expiratory pressure - on a breath-to-breath basis) led to remission (ISI < 8) in 68% of cases compared to 24% on CPAP [Fisher's exact p = 0.010]. Measures of impairment, residual objective sleep breathing events, and normalized breathing periods consistently demonstrated larger beneficial effects for ASV over CPAP.
*Bilevel devices have adjustable pressure support (PS) - the difference between inspiratory pressure (IPAP) and expiratory pressure (EPAP) - whereas CPAP provides one fixed, continuous pressure on inhalation and exhalation (ResMed CPAP machines have expiratory pressure relief [EPR] and Philips CPAP machines have C-Flex/A-Flex, which lowers the pressure on exhalation, but EPR/Flex have different algorithms than PS and only go up to 3 cm H2O.
A discussion of bilevel devices by Dr. Krakow: https://apneaboard.com/wiki/index.php/Flow_Limitation/UARS_and_BiPAP
Studies referenced in the video that do not have S4ME threads:
Back to S4ME:
Chronic insomnia remitting after maxillomandibular advancement for mild obstructive sleep apnea: a case series, 2019, Proothi et al.
Three case reports of patients with mild OSA (one technically would have been classified as UARS [AHI 0.4, RDI 15.2] but UARS was classified as OSA here) and severe, chronic insomnia associated with "somatic arousal" and fatigue. One patient experienced a modest improvement in her somatic arousal, insomnia severity, and fatigue with auto-titrating nasal CPAP, but the other two did not tolerate nasal CPAP. All three patients underwent maxillomandibular advancement (double jaw surgery) to treat mild OSA and experienced prolonged, complete resolution of somatic arousal, chronic insomnia, and fatigue. The patient with bipolar disorder also experienced complete remission of his symptoms of depression during the 1 year he was followed postoperatively.
My thoughts on why positive airway pressure (CPAP/BiPAP/ASV) often only provides partial symptom relief in symptomatic sleep-disordered breathing patients while surgeries may be more curative for many (surgeries, however, do not always fully cure sleep-disordered breathing).
Feel free to add more studies.
Sleep-disordered breathing (SDB) causing sleep maintenance insomnia due to awakenings may seem logical to most people; that it can also cause sleep-onset insomnia, less so (aren't SDB patients supposed to be sleepy?), which is why an alternative paradigm of SDB is needed to explain it: here is an updated version of the AI Summary of Dr. Gold's theory of UARS/OSAS (sensitization/physiological stress response to inspiratory flow limitation), which could explain how SDB can cause sleep-onset insomnia: the physiological stress response to inspiratory flow limitation may cause a state of physiological hyperarousal (often along with fatigue), leading to sleep-onset insomnia (and the "tired but wired" feeling many of us know so well). See also this relevant paper:
Somatic arousal and sleepiness/fatigue among patients with sleep-disordered breathing, 2016, Gold et al.
For context, the prevalence of obstructive sleep apnea (OSA) in the general population based on 11 epidemiological studies between 1993 and 2013 was 22% in men and 17% in women (some of these studies oversampled suspected OSA patients or habitual snorers):
Obstructive sleep apnea is a common disorder in the population—a review on the epidemiology of sleep apnea, 2015, Franklin et al.
The following 2 studies consist of samples of chronic insomnia patients after those with suspected sleep-disordered breathing were excluded, and yet close to 100% still met criteria for OSA/UARS.
Prospective Assessment of Nocturnal Awakenings in a Case Series of Treatment-Seeking Chronic Insomnia Patients: A Pilot Study..., 2012, Krakow et al.
Prospective study of 20 adult patients with chronic insomnia (17 reported both sleep-onset insomnia and sleep maintenance insomnia; 3 reported sleep maintenance insomnia only) who presented to a sleep clinic with a primary complaint of chronic insomnia, had never previously visited a sleep specialist, and reported no classic sleep-disordered breathing symptoms. 90% of their awakenings were preceded by a respiratory event: apnea, hypopnea, or respiratory effort-related arousal (RERA). 11 met criteria for OSA and 8 met criteria for UARS based on AHI <5 and RDI (AHI + RERA index) ≥ 15.
Prospective RCT on the Efficacy of CPAP and Adaptive Servo-Ventilation in the Treatment of Chronic Complex Insomnia, 2019, Krakow et al.
Participants were adult chronic insomnia disorder patients who believed their sleep problems were due to psychological, psychiatric, behavioral, or environmental factors; none believed sleep breathing symptoms or disorders caused or contributed to their insomnia. No recruitment advertising was conducted; primary care physicians were apprised of the research and instructed not to divulge the protocol to candidates, who were informed of a "chronic insomnia research study."
Patients with overt OSA signs, symptoms and risk factors (excessive daytime sleepiness, witnessed apneas, obesity, past evaluations at sleep centers) were excluded. After excluding 599 patients, the majority due to the aforementioned factors (but also some others including bipolar disorder, restless legs syndrome/periodic limb movement disorder), only 1/62 chronic insomnia patients who underwent polysomnography (PSG) did not meet criteria for OSA/UARS (UARS criteria was AHI <5, RDI ≥ 15). 21 out of the remaining 60 patients were excluded after randomization (to CPAP/ASV) for various reasons including treatment intolerance, work/school schedules, medical issues, etc. Of the 40 final patients, 90% met criteria for OSA and 10% UARS.
Average Insomnia Severity Index (ISI) was moderate-severe.
Clinically, ASV (adaptive servo-ventilation, a type of bilevel* positive airway pressure device that can alter pressure support - the difference between inspiratory and expiratory pressure - on a breath-to-breath basis) led to remission (ISI < 8) in 68% of cases compared to 24% on CPAP [Fisher's exact p = 0.010]. Measures of impairment, residual objective sleep breathing events, and normalized breathing periods consistently demonstrated larger beneficial effects for ASV over CPAP.
*Bilevel devices have adjustable pressure support (PS) - the difference between inspiratory pressure (IPAP) and expiratory pressure (EPAP) - whereas CPAP provides one fixed, continuous pressure on inhalation and exhalation (ResMed CPAP machines have expiratory pressure relief [EPR] and Philips CPAP machines have C-Flex/A-Flex, which lowers the pressure on exhalation, but EPR/Flex have different algorithms than PS and only go up to 3 cm H2O.
A discussion of bilevel devices by Dr. Krakow: https://apneaboard.com/wiki/index.php/Flow_Limitation/UARS_and_BiPAP
A discussion of why many patients tolerate and benefit from bilevel devices (BiPAP/ASV) over CPAP by Dr. Krakow:
Studies referenced in the video that do not have S4ME threads:
- Complex insomnia: insomnia and sleep-disordered breathing in a consecutive series of crime victims with nightmares and PTSD
- Retrospective, nonrandomized controlled study on autoadjusting, dual-pressure positive airway pressure therapy for a consecutive series of complex insomnia disorder patients
Back to S4ME:
Chronic insomnia remitting after maxillomandibular advancement for mild obstructive sleep apnea: a case series, 2019, Proothi et al.
Three case reports of patients with mild OSA (one technically would have been classified as UARS [AHI 0.4, RDI 15.2] but UARS was classified as OSA here) and severe, chronic insomnia associated with "somatic arousal" and fatigue. One patient experienced a modest improvement in her somatic arousal, insomnia severity, and fatigue with auto-titrating nasal CPAP, but the other two did not tolerate nasal CPAP. All three patients underwent maxillomandibular advancement (double jaw surgery) to treat mild OSA and experienced prolonged, complete resolution of somatic arousal, chronic insomnia, and fatigue. The patient with bipolar disorder also experienced complete remission of his symptoms of depression during the 1 year he was followed postoperatively.
My thoughts on why positive airway pressure (CPAP/BiPAP/ASV) often only provides partial symptom relief in symptomatic sleep-disordered breathing patients while surgeries may be more curative for many (surgeries, however, do not always fully cure sleep-disordered breathing).
Feel free to add more studies.
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