Continuous Positive Airway Pressure Withdrawal Research Articles

The association between irregularity in sleep-wake rhythm and CPAP adherence

This study aims to evaluate the association between sleep-wake rhythm regularity and continuous positive airway pressure (CPAP) adherence. We retrospectively analyzed sleep-wake rhythms with activity monitoring and CPAP adherence among obstructive sleep apnea (OSA) patients newly diagnosed and introduced to CPAP therapy at the Sapporo Hanazono Hospital from January 2018 to June 2022. Among a total of 45 patients, 10 withdrew from CPAP therapy within a year. Nineteen were classified into the good-adherence and 16 into the poor-adherence group. No significant differences were detected among the groups in apnea-hypopnea index (AHI), sleep efficiency, or subjective sleep quality, but a difference was observed in sleep latency, with the CPAP withdrawal group showing higher variability in sleep onset and lower regularity and/or amplitude in circadian behavior activity rhythm than the good-adherence group. Our results suggest that irregularities, particularly in sleep onset, and damped sleep-wake rhythm can be risk factors for CPAP withdrawal.

Prognostic Relevance of the Lung Ultrasound Score: A Multioutcome Study in Infants with Respiratory Distress Syndrome.

There is growing evidence for the usefulness of the lung ultrasound score (LUS) in neonatal intensive care. We evaluated whether the LUS is predictive of outcomes in infants with respiratory distress syndrome (RDS). Neonates less than 34 weeks of gestational age were eligible for this prospective, multicenter cohort study. The outcomes of interest were the need for mechanical ventilation (MV) at <72 hours of life, the need for surfactant (SF), successful weaning from continuous positive airway pressure (CPAP), extubation readiness, and bronchopulmonary dysplasia. Lung scans were taken at 0 to 6 hours of life (Day 1), on Days 2, 3, and 7, and before CPAP withdrawal or extubation. Sonograms were scored (range 0-16) by a blinded expert sonographer. The area under the receiver operating characteristic curve (AUC) was used to estimate the prediction accuracy of the LUS. A total of 647 scans were obtained from 155 newborns with a median gestational age of 32 weeks. On Day 1, a cutoff LUS of 6 had a sensitivity (Se) of 88% and a specificity (Sp) of 79% to predict the need for SF (AUC = 0.86), while a cutoff LUS of 7 predicted the need for MV at <72 hours of life (Se = 89%, Sp = 65%, AUC = 0.80). LUS acquired prior to weaning off CPAP was an excellent predictor of successful CPAP withdrawal, with a cutoff level of 1 (Se = 67%, Sp = 100%, AUC = 0.86). The LUS has significant predictive ability for important outcomes in neonatal RDS. · Lung ultrasound has significant prognostic abilities in neonatal RDS.. · Early sonograms (0-6 h of life) accurately predict the requirement for SF and ventilation.. · Weaning off CPAP is effective when the LUS (range 0-16) is less than or equal to 1..

OR14-4 Acute sleep disruption does not diminish pulsatile growth hormone secretion in pubertal children

Abstract Context: Growth hormone (GH) plays a critical role in glucose homeostasis and linear growth during childhood. GH secretion is controlled by multiple neurotransmitters and hormones. Sleep is also a powerful stimulus for GH secretion. In children, GH pulses occur after sleep onset in association with slow-wave sleep (SWS), but it is unclear if undisrupted sleep is required for normal GH secretion. Given the rising incidence of pediatric sleep disorders such as obstructive sleep apnea (OSA) that cause sleep fragmentation, it is critical to determine whether sleep fragmentation during childhood may dysregulate the somatotropic axis. Objective To quantify how undisrupted vs fragmented sleep affects GH secretion in children. Methods Pubertal subjects (10 M, 9 F; 9.1-14.4 yrs) were randomized to two overnight polysomnographic studies with frequent blood sampling (q10min) to measure GH: fourteen were healthy subjects studied with or without SWS disruption via auditory stimuli (3 sec, 1500 Hz tones, 40-100 dB followed by 18 sec of a 75 dB noise simulating a knock on the door) and five were subjects with OSA studied with or without prescribed continuous positive airway pressure (CPAP); the latter condition was expected to have sleep fragmentation due to untreated OSA. GH pulses were identified using sparse deconvolution. Studies without auditory stimuli or when using CPAP were combined and analyzed as 'undisrupted sleep'. The relationship between GH pulse rate per hour and sleep stage was evaluated using Poisson generalized estimating equations. Results In SWS disruption studies, an average of 77.51 ± 13.61 (range 23-190) auditory stimuli were delivered, causing a 40.02 ± 7.78% decrease in SWS in favor of lighter sleep stages. In subjects with OSA, CPAP withdrawal caused a slight increase in the apnea hypopnea index (1.08 ± 0.10 vs. 2.20 ± 1.70 events/hour of sleep, p=0.07) with no change in sleep stage durations. During undisrupted sleep, subjects had an average of 0.91 ± 0.067 GH pulses/hour with a mean pulse amplitude of 10.03 ± 1.00 ng/mL and mean basal secretion rate of 0.26 ± 0.10 ng/ml per min. GH pulses occurred more frequently during SWS (2.3 pulses/hour SWS, amplitude 9.92 ± 2.59 ng/mL) than during any other sleep stage (P &amp;lt; 0.001). Neither form of sleep disruption affected the distribution of GH pulses across sleep stages, GH pulse amplitude and frequency, nor basal GH secretion. Conclusion In children, nocturnal GH pulses are temporally associated with SWS. However, neither acute fragmentation of SWS nor nocturnal arousals from OSA altered basal or pulsatile GH secretion, indicating that somatotrophic axis activity is preserved in the face of acute sleep disruption in children. Presentation: Sunday, June 12, 2022 11:45 a.m. - 12:00 p.m.

The impact of thyroidectomy on obstructive sleep apnea: a systematic review and meta-analysis.

Various thyroid pathologies are speculated to contribute to obstructive sleep apnea (OSA). The underlying mechanisms of the intricate relationship between OSA and thyroid structure and function, and whether thyroidectomy can alleviate OSA symptoms remain unclear. An assessment of the impact of thyroidectomy on OSA is warranted. A systematic review of four electronic databases (PubMed (Medline), Embase, the Cochrane library, and ClinicalTrials.gov) was performed up to February 2022. The primary outcomes were preoperative and postoperative Apnea/Hypopnea Index (AHI), Epworth Sleepiness Scale (ESS), Berlin questionnaire scores, and continuous positive airway pressure (CPAP) use. A meta-analysis of continuous measures and odd ratios was conducted. Small-scale studies underwent a qualitative meta-analysis. Six cohort studies on 221 OSA patients who underwent thyroidectomies were included. The results showed that thyroidectomy was associated with significant reduction in postoperative AHI (Mean difference [MD], -6.39, 95% CI, -12.46 to -0.32), however, no significant association was found with CPAP withdrawal (Odd ratio [OR], 0.38, 95% CI, 0.12-1.18). Neither the Berlin questionnaire score (OR, 0.19, 95% CI, 0.03-1.17) nor the ESS improved postoperatively (MD, -1.04, 95% CI, -6.37 to 4.29). This meta-analysis provides a quantitative estimate for the effect of the thyroidectomy on OSA and suggests that thyroidectomy is associated with limited clinical improvement of polysomnographic measures. Future large-scale, well-designed prospective studies are necessary to validate these findings and to refine accordingly the preoperative assessment of both medical conditions individually and in combination.

The effects of long-term continuous positive airway pressure on apnea-hypopnea index change following short-term that withdrawal in patients with obstructive sleep apnea.

The effect of long‐term continuous positive airway pressure (CPAP) treatment on apnea–hypopnea index (AHI) after CPAP withdrawal remains unclear, especially in obstructive sleep apnea (OSA) patients screened from the population. To examine that, 1241 civil servants who participated in the annual physical examination were screened for OSA between September and December 2017. Screened OSA firstly underwent 1‐week CPAP adherence assessment. Then, patients with good CPAP adherence would be freely provided CPAP to continued treatment. All OSA patients were followed for 2 years. At study end, all OSA patients underwent home sleep testing (HST) again within 1 week of CPAP withdrawal. The effect of 2‐year CPAP treatment on OSA severity was investigated by using linear regression and multinominal logistic regression. In total, 103 OSA patients were screened, including 41 cases (39.8%) in CPAP treatment group and 62 cases (60.2%) in non‐CPAP treatment group. At 2‐year follow‐up, compared with baseline, in CPAP treatment group, following CPAP withdrawal, a significant decrease in AHI was observed in patients with severe OSA (P = 0.014); in non‐CPAP treatment group, a significant increase in AHI was observed in patients with moderate OSA (P = 0.028). After adjustment for confounding factors, multivariate linear regression showed that △AHI was negatively associated with CPAP treatment (β = −4.930, 95% confidence interval [CI] [−9.361, −0.500], P = 0.030). Multinominal logistic regression showed that the AHI of patients not treated with CPAP tended to be unchanged or worsened with the AHI improvement group as a reference (OR [odds ration] [95% CI], 4.555 [1.307, 15.875], P = 0.017; 6.536 [1.171, 36.478], P = 0.032). In conclusion, active OSA screening and long‐term CPAP intervention may improve the severity of severe OSA patients following short‐term CPAP withdrawal in the general population.

Effect of obstructive sleep apnoea on retinal microvascular function: a randomised controlled trial

PurposeRetinal microvascular endothelial dysfunction is thought to be of importance in the development of ocular vascular diseases. Obstructive sleep apnoea (OSA) causes macrovascular endothelial dysfunction, but the effect of OSA on retinal microvascular endothelial function is not known. We aimed to determine the effect of OSA on retinal microvascular function.MethodsWe conducted a multi-centre, double-blind, randomised, parallel, controlled trial in patients with known moderate-to-severe OSA, established on continuous positive airway pressure (CPAP). Participants were randomised to 14 nights of either continued CPAP or sham CPAP to generate a return of OSA. Retinal vascular responses to flickering light were measured using dynamic vessel analysis both at baseline and after 14 nights of intervention. The primary outcome was the change from baseline to follow-up in the area under the curve of the arteriolar response to flickering light, sham CPAP versus continued CPAP.ResultsNineteen patients were randomised to sham CPAP, and 18 patients were randomised to continued CPAP. There was no significant effect of CPAP withdrawal and return of OSA on retinal responses, with a change in the area under the curve of the arteriole response to flickering light of + 3.8 arbitrary units (95% CI − 10.6 to + 18.2, p = 0.59), sham CPAP versus continued CPAP.ConclusionsCPAP withdrawal and a return of OSA had no significant effect on retinal microvascular responses. This contrasts with the effect of CPAP withdrawal on macrovascular endothelial function and suggests that OSA has different effects on macrovascular and microvascular endothelial function.ISRCTN 78082983, 23/10/2014, Prospectively registered.

Association Between Obstructive Sleep Apnea and Stroke and Contributory Risk Factors

Obstructive sleep apnea (OSA), a common comorbidity in patients with stroke, has shown increasing prevalence over the past few decades. OSA is an important risk factor for stroke in addition to other well-known contributors, including hypertension, hyperlipidemia, atrial fibrillation, and diabetes mellitus. Moreover, OSA is an independent predictor of neurological outcomes and mortality. The pathological mechanisms underlying the association between OSA and stroke include autonomic dysfunction, hypertension, cardiac arrhythmia, dyslipidemia, impaired glucose tolerance, hypoxia, and inflammation. Continuous positive airway pressure (CPAP) therapy has proven clinical utility in improvement of neurological symptoms in patients with stroke. Findings from a CPAP withdrawal model have shown increased sympathetic activity in OSA with a consequent significant elevation in blood pressure, relevant cerebral hypoxia, and disturbed cardiac repolarization. In this review, we present an overview of the literature that describes an association between OSA and stroke in addition to the vascular risk factors, including hypertension, hyperlipidemia, atrial fibrillation, and diabetes mellitus. This study highlights the importance of early and accurate diagnosis and management of OSA for stroke prevention and care and will benefit physicians in clinical practice.

Selective Continuous Positive Airway Pressure Withdrawal With Supplemental Oxygen During Slow-Wave Sleep as a Method of Dissociating Sleep Fragmentation and Intermittent Hypoxemia-Related Sleep Disruption in Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is considered to impair memory processing and increase the expression of amyloid-β (Aβ) and risk for Alzheimer’s disease (AD). Given the evidence that slow-wave sleep (SWS) is important in both memory and Aβ metabolism, a better understanding of the mechanisms by which OSA impacts memory and risk for AD can stem from evaluating the role of disruption of SWS specifically and, when such disruption occurs through OSA, from evaluating the individual contributions of sleep fragmentation (SF) and intermittent hypoxemia (IH). In this study, we used continuous positive airway pressure (CPAP) withdrawal to recapitulate SWS-specific OSA during polysomnography (PSG), creating conditions of both SF and IH in SWS only. During separate PSGs, we created the conditions of SWS fragmentation but used oxygen to attenuate IH. We studied 24 patients (average age of 55 years, 29% female) with moderate-to-severe OSA [Apnea-Hypopnea Index (AHI); AHI4% > 20/h], who were treated and adherent to CPAP. Participants spent three separate nights in the laboratory under three conditions as follows: (1) consolidated sleep with CPAP held at therapeutic pressure (CPAP); (2) CPAP withdrawn exclusively in SWS (OSASWS) breathing room air; and (3) CPAP withdrawn exclusively in SWS with the addition of oxygen during pressure withdrawal (OSASWS + O2). Multiple measures of SF (e.g., arousal index) and IH (e.g., hypoxic burden), during SWS, were compared according to condition. Arousal index in SWS during CPAP withdrawal was significantly greater compared to CPAP but not significantly different with and without oxygen (CPAP = 1.1/h, OSASWS + O2 = 10.7/h, OSASWS = 10.6/h). However, hypoxic burden during SWS was significantly reduced with oxygen compared to without oxygen [OSASWS + O2 = 23 (%min)/h, OSASWS = 37 (%min)/h]. No significant OSA was observed in non-rapid eye movement (REM) stage 1 (NREM 1), non-REM stage 2 (NREM 2), or REM sleep (e.g., non-SWS) in any condition. The SWS-specific CPAP withdrawal induces OSA with SF and IH. The addition of oxygen during CPAP withdrawal results in SF with significantly less severe hypoxemia during the induced respiratory events in SWS. This model of SWS-specific CPAP withdrawal disrupts SWS with a physiologically relevant stimulus and facilitates the differentiation of SF and IH in OSA.

Period-to-Period Variability of Moderate/Severe Obstructive Sleep Apnoea.

IntroductionThe severity of obstructive sleep apnoea (OSA) is highly variable on a night-to-night basis. Patients are commonly categorised based on the severity of their OSA, and this is then used to influence management and reimbursement, including continuous positive airway pressure (CPAP). We aimed to establish to what extent the OSA severity category changes during two periods of OSA, based on mean and maximum oxygen desaturation index (ODI).MethodsPatients with a diagnosis of moderate to severe OSA who had been on CPAP for greater than 1 year were included in this study. Subjects underwent two periods of CPAP withdrawal for four nights each.ResultsTwenty-five patients completed the study. Based on the mean ODI of the four nights, 14 (56%) patients changed OSA severity categorisation, with three (12%) changing category to mild. Based on the maximum ODI of the four nights, nine (36%) patients changed OSA severity categorisation, with one (4%) changing category to mild. One third to a half of patients’ OSA severity category changed between the two periods of four night’s CPAP withdrawal.ConclusionsOSA is highly variable on a period-to-period basis as well as on a night-to-night basis. We believe the concept of patients having a definable and ‘real’ level of OSA severity is therefore flawed. OSA severity should be based mainly on symptoms, as these are the dominant reasons for treatment, and the sleep study should be used qualitatively to ascertain whether respiratory events are the likely cause of the symptoms.Trial RegistrationISRCTN17987510.

Implementing a novel protocol for withdrawal of CPAP support in COVID-19 patients: a case series

No published protocol to guide the withdrawal of continuous positive airway pressure (CPAP) for patients with COVID-19 exists. Description of the introduction of a novel protocol, developed by consensus to guide the withdrawal of CPAP for patients diagnosed as dying with COVID-19 in an acute hospital. 19 patients died on the high-dependency respiratory unit following treatment with CPAP. 89% died with CPAP withdrawn. The dying trajectory was difficult to predict. Symptoms were managed promptly and effectively with a combination of opioids, benzodiazepines and close medical supervision. No concerns were raised by families regarding the decision making or withdrawal process. The use of the protocol ensures a comfortable and dignified death and supports the delivery of individualised care at the end of life. Future research on this topic should focus on qualitative outcomes and consider the applicability of this protocol in other patient groups.

Obstructive sleep apnea and pulmonary hypertension: a bidirectional relationship.

Citation:Mesarwi O, Malhotra A. Obstructive sleep apnea and pulmonary hypertension: a bidirectional relationship. J Clin Sleep Med. 2020;16(8):1223–1224.

Predictors of changes in subjective daytime sleepiness in response to CPAP therapy withdrawal in OSA: A post-hoc analysis.

Subjective sleepiness is the hallmark symptom of untreated obstructive sleep apnea (OSA) and leads to an increased risk of motor vehicle accidents and impaired quality of life. Continuous positive airway pressure (CPAP) is the standard therapy for OSA and improves sleepiness. The aim was to identify factors that might predict recurrence of sleepiness in times off CPAP and to define OSA patient types with a likely effect of CPAP on sleepiness. A post-hoc analysis of six clinical trials, including 132 patients with OSA effectively treated with CPAP prior to study inclusion, who were allocated to 2weeks of CPAP withdrawal, was conducted to assess predictors of a change in subjective sleepiness. A multivariate regression model was used to assess predictors of a change in the Epworth Sleepiness Scale (ESS) score. In response to CPAP withdrawal, the median apnea-hypopnea index (AHI) and the ESS score significantly increased compared to baseline on CPAP by 32.6/hr (95% CI, 28.8, 36.4)/hr and 2.5 (95% CI, 1.8,3.2), respectively (p<.001), in the included 132 patients. There was an independent positive association of AHI (Coef. [95% CI] 0.04 [0.01, 0.08]) with an increase in ESS score upon CPAP withdrawal, and an independent negative association of age (coef. [95% CI], -0.10 [-0.18, -0.2]), ESS on CPAP (coef. [95% CI], -0.21 [-0.40, -0.015]) and active smoking status (coef. [95% CI], -1.22 [-2.26, -0.17]). These findings suggest that younger patients with a low residual sleepiness on CPAP and a recurrence of more severe OSA during CPAP withdrawal are at highest risk of suffering from a clinically relevant return of daytime sleepiness in times off CPAP.

Comorbidities and medical course in a young patient diagnosed with severe obstructive sleep apnea

Abstract We present the 6-year evolution of a young patient (32 years at diagnosis), smoker (10 pack years), diagnosed in September 2011 by cardiorespiratory polygraphy with severe obstructive sleep apnea syndrome (OSA)-apnea–hypopnea index (AHI) 82/h, mean SaO2 76%, which associate class II obesity (body mass index [BMI] 37.5 kg/m2), dyslipidemia, hypertension, mixed ventilatory dysfunction with hypoxemia and hypercapnia, pulmonary hypertension, and right bundle branch block. It was administered drug treatment, oxygen therapy, and continuous positive airway pressure (CPAP) with favorable evolution. One year later, we notice a significant improvement in the severity of OSA (AHI 13/h) and significant weight loss (about 24 kg). He was diagnosed with thyroid papillary carcinoma and left laterocervical node metastasis. Total thyroidectomy, treatment with radioactive iodine, and Euthirox replacement were done. In 2013, the patient presents moderate OSA (AHI 25/h) and class I obesity (BMI 31.8 kg/m2). Withdrawal of CPAP on its own initiative and weight gain (BMI 43 kg/m2) causes clinical deterioration in 2014, with diurnal drowsiness, dyspnea at rest, peripheral edema, hypoxemia, and hypercapnia, requiring admission. The cardiorespiratory polygraphic evaluation highlights severe OSA with AHI 84/h. Evolution was favorable with medication, oxygen therapy, and CPAP. Over the next 3 years, the patient continues CPAP treatment at home, but variations in body weight help improve or worsen OSA severity.

Effects of short-term continuous positive airway pressure withdrawal on cerebral vascular reactivity measured by blood oxygen level-dependent magnetic resonance imaging in obstructive sleep apnoea: a randomised controlled trial.

Impaired cerebral vascular reactivity (CVR) increases long-term stroke risk. Obstructive sleep apnoea (OSA) is associated with peripheral vascular dysfunction and vascular events. The aim of this trial was to evaluate the effect of continuous positive airway pressure (CPAP) withdrawal on CVR.41 OSA patients (88% male, mean age 57±10 years) were randomised to either subtherapeutic or continuation of therapeutic CPAP. At baseline and after 2 weeks, patients underwent a sleep study and magnetic resonance imaging (MRI). CVR was estimated by quantifying the blood oxygen level-dependent (BOLD) MRI response to breathing stimuli.OSA did recur in the subtherapeutic CPAP group (mean treatment effect apnoea-hypopnoea index +38.0 events·h-1, 95% CI 24.2-52.0; p<0.001) but remained controlled in the therapeutic group. Although there was a significant increase in blood pressure upon CPAP withdrawal (mean treatment effect +9.37 mmHg, 95% CI 1.36-17.39; p=0.023), there was no significant effect of CPAP withdrawal on CVR assessed via BOLD MRI under either hyperoxic or hypercapnic conditions.Short-term CPAP withdrawal did not result in statistically significant changes in CVR as assessed by functional MRI, despite the recurrence of OSA. We thus conclude that, unlike peripheral endothelial function, CVR is not affected by short-term CPAP withdrawal.

Effect of Supplemental Oxygen on Blood Pressure in Obstructive Sleep Apnea (SOX). A Randomized Continuous Positive Airway Pressure Withdrawal Trial.

Obstructive sleep apnea (OSA) is associated with systemic hypertension. Either overnight intermittent hypoxia, or the recurrent arousals that occur in OSA, could cause the daytime increases in blood pressure (BP). To establish the role of intermittent hypoxia in the increased morning BP in patients with OSA. Randomized, double-blinded, crossover trial assessing the effects of overnight supplemental oxygen versus air (sham) on morning BP, after continuous positive airway pressure (CPAP) withdrawal in patients with moderate to severe OSA. The primary outcome was the change in home morning BP after CPAP withdrawal for 14 nights, oxygen versus air. Secondary outcomes included oxygen desaturation index (ODI), apnea-hypopnea index (AHI), subjective sleepiness (Epworth Sleepiness Scale score), and objective sleepiness (Oxford Sleep Resistance Test). Supplemental oxygen virtually abolished the BP rise after CPAP withdrawal and, compared with air, significantly reduced the rise in mean systolic BP (-6.6 mm Hg; 95% confidence interval [CI], -11.3 to -1.9; P = 0.008), mean diastolic BP (-4.6 mm Hg; 95% CI, -7.8 to -1.5; P = 0.006), and median ODI (-23.8/h; interquartile range, -31.0 to -16.3; P < 0.001) after CPAP withdrawal. There was no significant difference, oxygen versus air, in AHI, subjective sleepiness, or objective sleepiness. Supplemental oxygen virtually abolished the rise in morning BP during CPAP withdrawal. Supplemental oxygen substantially reduced intermittent hypoxia, but had a minimal effect on markers of arousal (including AHI), subjective sleepiness, or objective sleepiness. Therefore intermittent hypoxia, and not recurrent arousals, appears to be the dominant cause of daytime increases in BP in OSA.

Understanding effects of obstructive sleep apnoea and its treatment on the brain and autonomic regulation needs further research

We thank Dr. Jaster for reading our articles with interest and sharing his thoughts on the potential impacts of untreated obstructive sleep apnoea (OSA) and continuous positive airway pressure (CPAP) effects on medullary brain nuclei. There are three topics we would like to address: (I) the hypothesis of an association between OSA and ischemic pathology of medullary brain nuclei and a potential exacerbation by CPAP, (II) the different roles of pCO2 in OSA and central sleep apnoea (CSA), and (III) the effects of a short-term CPAP withdrawal on the brain and the heart.

Nocturnal cerebral hypoxia in obstructive sleep apnoea: a randomised controlled trial.

Cerebral hypoxia may promote cerebral damage in patients with obstructive sleep apnoea (OSA). We investigated whether OSA patients experience nocturnal cerebral hypoxia that is prevented by continuous positive airway pressure (CPAP).OSA patients using CPAP underwent sleep studies including pulse oximetry (arterial oxygen saturation (SpO2 )) and near-infrared spectroscopy to monitor cerebral tissue oxygenation (CTO) at baseline and after 2 weeks on either subtherapeutic or therapeutic CPAP according to randomised allocation. Changes in oxygenation at end of the 2-week intervention were compared between groups.Among 21 patients (mean apnoea/hypopnoea index 50.3 events·h-1), OSA recurred in all nine patients using subtherapeutic CPAP and in none of the patients using therapeutic CPAP: mean (95% CI) between-group differences in changes of oxygen desaturation index from baseline to 2 weeks +40.7 (31.1-50.4) events·h-1 for SpO2 and +37.0 (25.3-48.7) events·h-1 for CTO (both p<0.001). Mean nocturnal SpO2 and CTO decreased more in patients using subtherapeutic versus therapeutic CPAP: -2.4 (-3.4--1.1)% and -3.8 (-7.4--0.1)%, respectively; both p<0.03. Severe CTO drops ≥13% associated with cerebral dysfunction inprevious studies occurred in four out of nine patients using subtherapeutic CPAP, but in none out of 12 patients using therapeutic CPAP (p=0.01).In patients with OSA, CPAP withdrawal resulted in nocturnal cerebral deoxygenation, suggesting a role of cerebral hypoxia in predisposing untreated OSA patients to cerebral damage.

Physiological consequences of CPAP therapy withdrawal in patients with obstructive sleep apnoea-an opportunity for an efficient experimental model.

Randomised controlled trials (RCTs) of continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA) are time consuming, and their findings often inconclusive or limited due to suboptimal CPAP adherence in CPAP-naïve patients with OSA. Short-term CPAP withdrawal in patients with prior optimal CPAP adherence results in recurrence of OSA and its consequences. Thus, this experimental model serves as an efficient tool to investigate both the consequences of untreated OSA, and potential treatment alternatives to CPAP. The CPAP withdrawal protocol has been thoroughly validated, and applied in several RCTs focusing on cardiovascular and metabolic consequences of untreated OSA, as well as the assessment of treatment alternatives to CPAP.

Night-to-night variability of obstructive sleep apnea.

www.controlled-trials.com (ISRCTN 93153804, ISRCTN 73047833) and www.clinicaltrials.gov (NCT01332175 & NCT02050425).

Blood Pressure Variability in Obstructive Sleep Apnoea: Data from 4 Randomised Controlled CPAP Withdrawal Trials

Background: Increased daytime blood pressure variability (BPV) is associated with cardiovascular risk. Preliminary data suggest that obstructive sleep apnoea (OSA) might contribute to increased daytime BPV. Objective: The aim of this study was to evaluate the effect of continuous positive airway pressure (CPAP) therapy withdrawal on daytime BPV. Methods: A total of 183 patients previously diagnosed with OSA and treated with CPAP were randomised to either continue or withdraw from CPAP within 4 trials. Office morning BP was measured in triplicate at baseline and at follow-up (day 14). In addition, the participants performed BP measurements at home on a daily basis (days 1-13). The main outcome of interest was the treatment effect on within-visit BPV expressed as the standard deviation (SD) of the triplicate measurements. Additional outcomes included morning home BPV and day-to-day home BPV. Results: Within-visit variability in systolic BP significantly increased in response to recurrence of OSA in the CPAP withdrawal group (difference between groups in SD of systolic BPV, +1.14 mm Hg, 95% CI +0.20/+2.09, p = 0.02). There was no statistically significant effect on within-visit variability in diastolic BP (p = 0.38) or heart rate (p = 0.07). Neither morning home BP variability (systolic BPV, p = 0.81; diastolic BPV, p = 0.46) nor day-to-day variability in home BP measurements (systolic BPV, p = 0.61; diastolic BPV, p = 0.58) differed significantly between the groups. Conclusion: CPAP withdrawal results in a minor increase in within-visit variability in office systolic BP, but it has no effect on home BPV or day-to-day BPV. Although the treatment effect may be blunted by antihypertensives, it is unlikely that OSA contributes to cardiovascular risk via elevated daytime BPV.