Oxyhemoglobin Desaturation Research Articles

Unveiling the Impact of Respiratory Event-Related Hypoxia on Heart Sound Intensity During Sleep Using Novel Wearable Technology.

Cardiovascular disorders are the leading cause of mortality worldwide with obstructive sleep apnea (OSA) as the independent risk factor. Heart sounds are strong modalities to obtain clinically relevant information regarding the functioning of the heart valves and blood flow. The objective of this study was to use a small wearable device to record and investigate the changes in heart sounds during respiratory events (reduction and cessation of breathings) and their association with oxyhemoglobin desaturation (hypoxemia). Sleep assessment and tracheal respiratory and heart sounds were recorded simultaneously from 58 individuals who were suspected of having OSA. Sleep assessment was performed using in-laboratory polysomnography. Tracheal respiratory and heart sounds were recorded over the suprasternal notch using a small device with embedded microphone and accelerometer called the Patch. Heart sounds were extracted from bandpass filtered tracheal sounds using smoothed Hilbert envelope on decomposed signal. For each individual, data from 20 obstructive events during Non-Rapid Eye Movement stage-2 of sleep were randomly selected for analysis. A significant increase in heart sounds' intensities from before to after the termination of respiratory events was observed. Also, there was a significant positive correlation between the magnitude of hypoxemia and the increase in heart sounds' intensities (r>0.82, p<0.001). In addition, the changes in heart sounds were significantly correlated with heart rate and blood pressure. Our results indicate that heart sound analysis can be used as an alternative modality for assessing the cardiovascular burden of sleep apnea, which may indicate the risk of cardiovascular disorders.

Hypoxia-Induced Insulin Resistance Mediates the Elevated Cardiovascular Risk in Patients with Obstructive Sleep Apnea: A Comprehensive Review.

Patients with obstructive sleep apnea (OSA) experience insulin resistance and its clinical consequences, including hypertriglyceridemia, reduced high density lipoprotein-associated cholesterol (HDL-c), visceral adiposity, hepatic steatosis, increased epicardial fat thickness, essential hypertension, glucose intolerance, increased risk for type 2 diabetes, chronic kidney disease, subclinical vascular damage, and increased risk for cardiovascular events. Obesity is a major contributor to OSA. The prevalence of OSA is almost universal among patients with severe obesity undergoing bariatric surgery. However, insulin resistance and its clinical complications occur in OSA patients irrespective of general obesity (body mass index). In OSA patients, apnea episodes during sleep induce oxyhemoglobin desaturation and tissue hypoxia. Insulin resistance is an adaptive response to tissue hypoxia and develops in conditions with limited tissue oxygen supply, including healthy subjects exposed to hypobaric hypoxia (high altitude) and OSA patients. Indicators of oxyhemoglobin desaturation have been robustly and independently linked to insulin resistance and its clinical manifestations in patients with OSA. Insulin resistance mediates the elevated rate of type 2 diabetes, chronic kidney disease, and cardiovascular disease unexplained with traditional cardiovascular risk factors present in OSA patients. Pathophysiological processes underlying hypoxia-induced insulin resistance involve hypoxia inducible factor-1 upregulation and peroxisome proliferator-activated receptor-gamma (PPAR- ) downregulation. In human adipose tissue, PPAR- activity promotes glucose transport into adipocytes, lipid droplet biogenesis, and whole-body insulin sensitivity. Silencing of PPAR- in the adipose tissue reduces glucose uptake and fat accumulation into adipocytes and promotes insulin resistance. In conclusion, tissue hypoxia drives insulin resistance and its clinical consequences in patients with OSA, regardless of body mass index.

Older adults at greater risk for Alzheimer’s disease show stronger associations between sleep apnea severity in REM sleep and verbal memory

BackgroundObstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer’s disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk.MethodsEighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined.ResultsApnea–hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers.ConclusionGreater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.

Rapid cycle deliberate practice to improve airway skills and performance of trainees in a pediatric emergency department.

The study objective was to determine the effect of a rapid cycle deliberate practice (RCDP) program on simulated and actual airway skills by pediatric emergency medicine (PEM) fellows. We designed and implemented a 12-month RCDP airway skills curriculum for PEM fellows at an academic pediatric institution. The curriculum was designed using airway training literature, RCDP principals, and internal quality assurance airway video review program. Simulation training scenarios increased in complexity throughout the curriculum. PEM fellows participated in monthly sessions. Two PEM faculty facilitated the sessions, utilizing a step-by-step objective structured clinical evaluation (OSCE)-style tool for each scenario. Data were collected for all four levels of the Kirkpatrick Model of Training Evaluation-participant response (reaction, pre-post session survey), skills performance in the simulation setting (learning, pre-post OSCE), skills performance for actual patients (behavior, video review), and patient outcomes (results, video review). During the study period (August 2021 to June 2022), 13 PEM fellows participated in 112 sessions (mean nine sessions per fellow). PEM fellows reported improved comfort in all domains of airway management, including intubation performance. Participant OSCE scores improved posttraining (pretraining median score for trainees 57 [IQR 57-59], posttraining median 61 [IQR 61-62], p = 0.0005). Over the 12 months, PEM fellows performed 45 intubation attempts in the pediatric emergency department (median patient age 4 years [IQR 1-9 years]). Compared to a 5-year historical cohort, participants had higher first-pass success (87% vs. 71%, p = 0.028) and shorter attempt duration (22 s vs. 29 s, p = 0.018). There was no significant difference in the frequency of oxyhemoglobin desaturation in the training period versus the historical period (7% vs. 15%, p = 0.231). At multiple levels of educational outcomes, including participant behavior and patient outcomes, an RCDP program was associated with improved airway skills and performance of PEM fellows.

Appliances Therapy in Obstructive Sleep Apnoea: A Systematic Review and Meta-Analysis.

Obstructive sleep apnea (OSA) is a recurrent partial or complete obstruction of the upper airway during sleep caused by narrowing or collapse of the pharyngeal wall. It leads to microstimulation and oxyhemoglobin desaturation, resulting in sleepiness and loud snoring. OSA negatively affects the cardiovascular system and may contribute to neurocognitive impairment. The aim of this systematic review is to evaluate the effectiveness and efficacy of appliance therapy in obstructive sleep apnea. The effectiveness was assessed by using the Apnea Hypopnea Index (AHI). An electronic search of the Cochrane Library, PubMed, and Google Scholar was conducted between 1998 and 2021. Articles were independently assessed by three reviewers. The quality of a randomised control trial (RCT) is assessed using the Cochrane risk of bias method. The tool GRADE was used to achieve the desired level of confidence for each outcome reported.Several studies used continuous positive airway pressure (CPAP), mandibular advancement devices (MAD), and tongue retention devices (TRD). The meta-analysis included a total of six papers that met the inclusion criteria. Results showed that CPAP significantly improved AHI compared with an oral appliance (random effects: difference in means = 8.40, 95% CI = 7.21 to 9.60). It was also found that oral appliance (OA) therapy significantly improved AHI compared with baseline before appliance therapy (random effects: mean difference = 13.40, 95% CI = 10.87 to 15.93; p.00001). For mild to moderate OSA, CPAP is considered the gold standard. Our meta-analysis of six RCTs found favorable evidence for OSA patients receiving oral devices; however, they were less effective than CPAP. A subgroup analysis found that MAD may be a beneficial treatment for mild to moderate OSA patients who do not respond to CPAP. The findings suggest that oral appliances may be an effective treatment for OSA, especially in patients with mild to moderate OSA.

Study of Haematocrit Level in Obstructive Sleep Apnea Syndrome

Obstructive Sleep Apnea Syndrome can lead to oxyhaemoglobin desaturation and has the possibility of stimulating erythropoiesis, leading to an increased haematocrit. The aim of this study is to identify the level of haematocrit in obstructive sleep apnea syndrome (OSAS) patients and to determine the correlation between haematocrit levels and the severity of obstructive sleep apnea syndrome (OSAS). This is a descriptive cross-sectional study at Hospital Universiti Sains Malaysia. All consented patients were interviewed and underwent a polysomnography (PSG) study. The severity of OSAS was based on the apnea–hypopnea index (AHI) and average oxygen desaturation. The blood haematocrit level was also obtained. Thirty-six OSAS patients were in the study group, and 17 patients were in the control group. The mean haematocrit level in the control group was 41.6 (2.5 SD), whereas in the study group the mean haematocrit level was 44.0 (3.27 SD). Pearson correlation analysis showed there was no significant correlation between AHI and haematocrit level (p-value: 0.392), however, there is a significant correlation between haematocrit levels and average oxygen saturation level (P-value: 0.022). The independent t-test between mean haematocrit level between OSAS group and control group showed that there was a significant difference between the mean haematocrit level among the control and OSAS groups. The increased level of haematocrit is significantly correlated with average oxygen desaturation but not with AHI in OSAS patient. Average oxygen desaturation can be considered as a parameter to assess severity and hypoxic stress in OSA patients.

Variation of respiratory and pulse events in multiple system atrophy

IntroductionA study is eagerly awaited that will reveal the unknown mechanisms of multiple system atrophy (MSA), in which the risk of sudden death is the greatest during sleep. The blunted pulse response to nocturnal respiratory events suggests an abnormal cardiac response to a sleep-related breathing disorder. Patients with MSA have a lower pulse event index (PEI), despite a greater hypoxic burden and a similar frequency of respiratory events. However, the evidence is speculative and not directly proven, and many limitations require further study. MethodsWe conducted a retrospective analysis of 26 patients with MSA who had undergone overnight oximetry between April 2016 and December 2022. ResultsThe median 4% oxyhemoglobin desaturation index (ODI) was 11.6/h, the 6-bpm PEI was 8.9/h, and the PEI/ODI ratio was as low as 0.91. There were three patients with suspected sudden death; all had low PEI/ODI ratios. The PEI/ODI ratio was followed over time in seven patients, all of whom had a decrease in the ratio. However, the PEI was higher than the ODI in 12/26 (46%) of the patients. ConclusionA low PEI/ODI ratio, reflecting a blunted pulse response to nocturnal respiratory events in patients with MSA, may indicate a worse prognosis. This finding and the significance of the longitudinal decrease in the PEI/ODI ratio will require a prospective study.

Resting pulmonary function and artery pressure and cardiopulmonary exercise testing in chronic heart failure patients in Taiwan − a prospective observational cross-sectional study comparing healthy subjects and interstitial lung disease patients

Background Restrictive ventilatory defects and elevated pulmonary artery pressure (PAP) are common in patients with chronic heart failure (CHF) and those with interstitial lung disease (ILD). However, as oxyhemoglobin desaturation seldom occurs in stable CHF patients at peak exercise, we hypothesized that the pathophysiology may be different between them. This study aimed to investigate: (1) PAP and lung function at rest, (2) pulmonary gas exchange (PGX) and breathing patterns at peak exercise, (3) mechanisms of dyspnea at peak exercise in patients with CHF compared to healthy subjects and ILD patients. Methods We consecutively enrolled 83 participants (27 with CHF, 23 with ILD, and 33 healthy controls). The CHF and ILD groups had similar functional status. Lung function and cardiopulmonary exercise tests with Borg Dyspnea Score were performed. PAP was estimated using echocardiography. Resting lung function, PAP and peak exercise data in the CHF group were compared to the healthy and ILD groups. Correlation analysis was performed to elucidate the mechanisms of dyspnea in the CHF and ILD groups. Results Compared to the healthy group, the CHF group had normal lung function, PAP at rest, and normal dyspnea score and PGX at peak exercise, whereas the ILD group had abnormal values compared to the CHF group. Dyspnea score was positively correlated with pressure gradient, lung expansion capabilities, and expiratory tidal flow in the CHF group (all p < 0.05), but inversely correlated with inspiratory time-related variables in the ILD group (all p < 0.05). Conclusion Normal lung function and PAP at rest, and dyspnea scores and PGX at peak exercise indicated that pulmonary hypertension and fibrosis were insignificant in the patients with CHF. The factors affecting dyspnea at peak exercise were different between the CHF and ILD groups. As the sample size in this study was small, large-scale studies are warranted to confirm our findings.

Effect of Ambulatory Oxygen on the Respiratory Pattern during the 6 Min Walking Test in Patients with Interstitial Lung Diseases.

Patients with pulmonary fibrosis experience early oxyhemoglobin desaturation under effort, which limits their ability to exercise and their quality of life. Recent studies have shown that in resting normoxaemic patients who become hypoxemic under exertion, administration of outpatient oxygen significantly improves stress dyspnoea and quality of life. It is unclear how this happens, since oxygen administration does not act directly on dyspnoea, and does not appear to have much effect on the heart rate and pulmonary artery pressure. We tested the hypothesis that correcting the hypoxaemia could reduce the increase in respiratory effort during the 6 min walking test, recording the breathing pattern during administration of oxygen or placebo. We evaluated 20 patients with fibrotic interstitial lung diseases (17 males and 3 females; mean age 72 ± 2 years; M ± SE) with a resting SpO2 ≥92 that fell to ≤88% during the 6 min walk test (6MWT). After first establishing the oxygen flow necessary to prevent desaturation, the patients underwent two further 6MWT, 15-20 min apart, one with administration of medical air and one with oxygen at the same flow, in randomized double-blind order. During the test, SpO2, heart rate, respiratory rate, tidal volume and minute ventilation (VE) were recorded, using a Spiropalm spirometer (Cosmed, Rome, Italy). Oxygen saturation during the 6MWT decreased to a minimum value of 82.3% (95% CI 80.1-84.5%) during placebo and to 92% (90.3-93.7%) during oxygen with an average difference of 9.7% (7.8-11.6%, p < 0.0001). On the contrary, heart rate showed an increasing trend with walking time reaching a significantly higher maximum rate during placebo, with a difference of 5.4 bpm (2.9-8.7, p < 0.005) compared to oxygen. The distance walked was slightly but significantly greater after oxygen by 28 m (2-53, p < 0.05) and end of test dyspnoea after placebo by 0.6 points (0.1-1.1, p < 0.05). Respiratory rate increased over time, without differences between oxygen and placebo in the first minute of walking, then increasing significantly more during placebo (p < 0.0005). With placebo, tidal volume increased rapidly reaching a plateau at about 48% of FVC after 3 min, while with oxygen, the increase was slower, reaching a maximum of about 45% of FVC at the end of the test. Nevertheless, the difference was highly significant (p < 0.0005) at all the time points. Minute ventilation also increased significantly with walking time but remained at a highly significant lower level during oxygen than placebo at all the time points. Mean reduction in VE during the test with oxygen compared to placebo was 4.4 L/min (3.9-4.9, p < 0.0005). In our ILD patients, administration of outpatient oxygen during walking was related to a reduced increase in heart rate, respiratory rate, tidal volume and minute ventilation necessary to meet increased oxygen requirements, resulting in a lower workload on the cardiovascular system and on respiratory muscles and a consequent reduction in dyspnoea.

Epinephrine-induced Effects on Cerebral Microcirculation and Oxygenation Dynamics Using Multimodal Monitoring and Functional Photoacoustic Microscopy.

The administration of epinephrine after severe refractory hypotension, shock, or cardiac arrest restores systemic blood flow and major vessel perfusion but may worsen cerebral microvascular perfusion and oxygen delivery through vasoconstriction. The authors hypothesized that epinephrine induces significant microvascular constriction in the brain, with increased severity after repetitive dosing and in the aged brain, eventually leading to tissue hypoxia. The authors investigated the effects of intravenous epinephrine administration in healthy young and aged C57Bl/6 mice on cerebral microvascular blood flow and oxygen delivery using multimodal in vivo imaging, including functional photoacoustic microscopy, brain tissue oxygen sensing, and follow-up histologic assessment. The authors report three main findings. First, after epinephrine administration, microvessels exhibited severe immediate vasoconstriction (57 ± 6% of baseline at 6 min, P < 0.0001, n = 6) that outlasted the concurrent increase in arterial blood pressure, while larger vessels demonstrated an initial increase in flow (108 ± 6% of baseline at 6 min, P = 0.02, n = 6). Second, oxyhemoglobin decreased significantly within cerebral vessels with a more pronounced effect in smaller vessels (microvessels to 69 ± 8% of baseline at 6 min, P < 0.0001, n = 6). Third, oxyhemoglobin desaturation did not indicate brain hypoxia; on the contrary, brain tissue oxygen increased after epinephrine application (from 31 ± 11 mmHg at baseline to 56 ± 12 mmHg, 80% increase, P = 0.01, n = 12). In the aged brains, microvascular constriction was less prominent yet slower to recover compared to young brains, but tissue oxygenation was increased, confirming relative hyperoxia. Intravenous application of epinephrine induced marked cerebral microvascular constriction, intravascular hemoglobin desaturation, and paradoxically, an increase in brain tissue oxygen levels, likely due to reduced transit time heterogeneity.

Prognostic Significance of Obstructive Sleep Apnea in a Population of Subjects with Interstitial Lung Diseases.

Obstructive sleep apnea (OSA) is often observed in subjects with interstitial lung disease (ILD). It may have a negative impact on the course of ILD, but its prognostic significance in relation to other known indicators of poor outcome is unclear. After a detailed work-up, including overnight unattended type III polygraphy, all subjects newly diagnosed with ILDs referred to our clinics were followed-up for at least 1.5years or until death or progression of disease [> 10% decline in forced vital capacity (FVC) below baseline]. We analyzed relationships between some prespecified variables of interest, including sleeping results, to establish parameters predictive of progressive course. Our population consisted of 46 subjects (mean age 59.6years; males 61%); 23.9% and 41% had idiopathic pulmonary fibrosis and ILD associated with systemic diseases, respectively. Mean baseline forced vital capacity and diffusion capacity of carbon monoxide were 83% and 57% of predicted, respectively. Mean (± SE) Apnea-Hypopnea Index (AHI) was 17 (± 3) events/h. AHI in the ranges 5-14.9, 15-29.9, and ≥ 30 was recorded in 14 (31%), 6 (13%), and 9 (20%) subjects, respectively. Mean distance covered in the 6-MWG walk test (6MWT) was 302 (± 19) m and 26 subjects (57%) showed exertional oxyhemoglobin desaturation. The median follow-up was about 18months. Multivariate logistic regression analysis showed that exertional desaturation (HR 8.2; 1.8-36.5 95% CI; p = 0.006) and AHI ≥ 30, namely the threshold of severe OSA (HR 7.5; 1.8-30.6; p = 0.005), were the only independent variables related to progressive disease course. We conclude that exertional desaturation and elevated AHI had independent negative prognostic significance in our ILD population.

Nocturnal Pulse Event Frequency Is Reduced in Multiple System Atrophy.

Risk of sudden death in multiple system atrophy (MSA) is greatest during sleep with unknown mechanisms. We compared nocturnal pulse event frequency in 46 MSA patients and age-/sex-matched controls undergoing overnight pulse oximetry. Nocturnal oxyhemoglobin desaturation indices and pulse event indices (PEIs) were recorded, and relationships between pulse oximetry variables and survival were analyzed. MSA patients had lower PEI (3.1± 5.3 vs. 12.8± 10.8, p< 0.001) despite greater hypoxic burden and similar frequency of respiratory events. Nocturnal pulse events were not associated with severity of daytime autonomic failure. Two MSA patients had suspected sudden death, both with severely reduced PEI. MSA patients have fewer nocturnal pulse events compared with controls, despite similar respiratory event frequency, suggesting abnormal cardiac responses to sleep-disordered breathing. Whether this contributes to sudden death in MSA requires further study. ANN NEUROL 2023;93:205-212.

Obstructive sleep apnea and headache: an integrative review of the last 18 years

Introduction Obstructive sleep apnea (OSA) is a prevalent and underdiagnosed clinical condition, characterized by the presence of repetitive airway collapse during sleep, resulting in oxyhemoglobin desaturation and sleep fragmentation. Among the most frequent reports of patients with OSA, is morning headache or chronic daily headache, which in 2004 received its own classification in the International Classification of Headache Disorders (ICHD-2) as sleep apnea headache. Objective The present review aims to evaluate the available scientific literature on the association between OSA and headache after classification, totaling a period of 18 years. Results In 8 included studies, 1,637 patients were analyzed, observing a bilateral and frequent association between the two pathologies. Conclusion However, there is still no consensus on the mechanism behind this relationship, and the results of studies are divergent.

P-022: THERAPEUTIC EFFECTS OF GBT1118 ON SKELETAL MUSCLE ENERGETICS AND FUNCTION IN SICKLE CELL MICE

Purpose: Sickle cell disease (SCD) is an hemoglobinopathy ultimately resulting red blood cells sickling. SCD patients suffer from anemia, arterial oxyhemoglobin desaturation, hematologic and hemodynamic abnormalities, all of which disrupt oxygen supply and can reduce exercise capacity and quality of life. Strenuous exercise in SCD patients may induce hemolysis, an early lactate accumulation, an intracellular acidosis, all of which are potential triggering factors for sickling and vaso-occlusive crises. GBT1118 is a HbS polymerization inhibitor which can increase hemoglobin affinity for oxygen and the corresponding supply to tissues. On that basis, we hypothesized that GBT1118 could dampen skeletal muscle energetics and function. Materials and methods: Skeletal muscle energetics and function of sixteen Townes mice (2 ± 0.5 month-old) were assessed in response to a standardized Rest-Stimulation(1Hz)-Recovery protocol before and after an 8-week period (8WP). Investigations were conducted using a setup designed to be operational inside a 7T horizontal MRI scanner (PharmaScan-Bruker). The setup allows (i) magnetic resonance imaging, (ii) muscle force measurements and (iii) 31P-magnetic resonance spectroscopy. Assessments conducted before and after the 8WP were identified with number 1 (SCDGBT1) and two (SCDGBT2). Ten mice received a chronic supplementation of GBT1118 (4g/kg in chow) during the 8WP (SCDGBT), whereas six mice had access to not supplemented chow (SCDCON). Results: The specific peak force (sPf) measured at the beginning of stimulation significantly increased over the 8WP (SCDCON2 +68%, p < 0.05). This increased initial sPf was also present in SCDGBT2 as compared to SCDGBT1 (+ 30%, p < 0.05). Over the entire stimulation session, the overall specific [TM1] force production (sTFP) significantly increased over the 8WP (SCDCON2 +32%, p < 0.05, Figure 1). The increased sTFP was also present in SCDGBT2 as compared to SCDGBT1 (+ 25 %, p < 0.05). However, the sTFP-normalized pHi reduction and sTFP-normalized phosphocreatine (PCr) breakdown significantly decreased in SCDGBT2 as compared to SCDGBT1 (p < 0.05, Table 1). Conclusion: In the control condition, the 8-week period was accompanied by a significant increase in specific total force production. Such an increase has been previously reported from 3 to 10 weeks of age (+ 33%). Overall, the increased specific total force production we reported was related to time and cannot be accounted for by GBT supplementation. In SCDGBT, the expected increased force production related to time was associated to a reduced acidosis and PCr breakdown which were not found in the control condition. For a given amount of force, SCDGBT mice muscle would experience a lower net proton accumulation and a reduced net PCr consumption. This reduction of both acidosis and PCr consumption could illustrate a diminished cost of contraction in response to GBT1118 supplementation which could be related to an improved contractile efficiency as previously described in humans. SCD mice treated with GBT1118 exhibit a reduced acidosis for a given force. Given that acidosis is a potential triggering factor of sickling, GBT would protect SCD muscle against the consequences of sickling. One could speculate that SCD patients receiving GBT1118 might be able to perform exercise with a reduced exposure to sickling.Specific total force production in SCDCON and SCDGBT before and after the 8-week period. Each point represents a single measurement and lines are linking consecutive points. p-values are mentioned on the top of the figure.Metabolic indices in SCDCON and SCDGBT before and after the 8-week period. The authors do not declare any conflict of interest

Frequent hypoxemia found in infants with bronchopulmonary dysplasia after weaning home oxygen.

Parental reports and brief clinical examinations are the primary information used to assist clinicians in weaning home supplemental oxygen in infants with bronchopulmonary dysplasia (BPD). Recorded nocturnal oximetry provides an objective assessment of hypoxemia; however, it is unknown if it identifies clinically undetected hypoxemia in the home setting. Our objective was to determine if nocturnal oximetry can identify unreported hypoxemia in infants with BPD who appear ready to wean from supplemental oxygen. We conducted a retrospective chart review of infants born <32 weeks gestation with BPD who were discharged to home receiving supplemental oxygen and completed recorded nocturnal oximetry in room air during an 18-month period. Abnormal oximetry was defined as >5 min with SpO2 < 90% and/or an oxyhemoglobin desaturation index (ODI4) >5. Comparative analysis of patients with normal and abnormal overnight oximetry was performed using Fisher Exact and Wilcoxon signed-rank test. Thirty-five former premature infants completed nocturnal oximetry at 5.8 (3.4-8.3) months corrected age. Nocturnal oximetry was abnormal as defined in 67% of the cohort (n = 21). Five percent of patients were hypoxemic, 52% had frequent desaturation events, and 43% had both. No significant differences existed in neonatal characteristics between patients with normal and abnormal studies. Nocturnal oximetry was abnormal in the majority of infants with BPD who were otherwise clinically ready to wean from oxygen support, suggesting that recorded home oximetry could be a feasible and useful tool to evaluate for otherwise clinically unapparent nocturnal hypoxemia in patients with BPD.

Isovolemic hemodilution in chronic mountain sickness acutely worsens nocturnal oxygenation and sleep apnea severity.

Chronic mountain sickness (CMS) is commonly observed among Andean and other highland populations. Sleep-disordered breathing (SDB) is highly prevalent at high altitude, and SDB and nocturnal hypoxemia have been observed in CMS. Phlebotomy is commonly performed to treat CMS, but it is unknown whether reducing hematocrit improves SDB. We hypothesized that isovolemic hemodilution (IVHD) in CMS would reduce SBD severity and improve sleep efficiency. Six participants with CMS and 8 without CMS, all residents of Cerro de Pasco, Peru (altitude 4340 m), completed baseline nocturnal sleep studies. CMS participants then underwent IVHD, and nocturnal sleep studies were repeated 24-48 hours after IVHD. We analyzed sleep apnea severity, nocturnal oxygenation, and sleep quality in those with CMS relative to those without CMS, and the effects of IVHD in CMS participants. Participants with CMS did not have altered sleep architecture, sleep apnea severity, or nocturnal oxygenation relative to non-CMS participants. However, IVHD in CMS increased apnea-hypopnea index (40.9 ± 6.9 events/h to 61.5 ± 7.7 events/h, P = .009). IVHD increased oxyhemoglobin desaturation index (P = .008) and the percentage of sleep time spent with oxyhemoglobin saturation at or below 80% (P = .012). There was no effect of IVHD on sleep efficiency, arousal index, or sleep staging. In this cohort, CMS was not associated with worsened SDB or changes in sleep architecture. IVHD, a putative therapeutic option for participants with CMS, appears to worsen nocturnal oxygenation and SDB within 48 hours post-IVHD. Sanchez-Azofra A, Villafuerte FC, DeYoung PN, etal. Isovolemic hemodilution in chronic mountain sickness acutely worsens nocturnal oxygenation and sleep apnea severity. J Clin Sleep Med. 2022;18(10):2423-2432.

The Efficacy of Twin-Block Appliances for the Treatment of Obstructive Sleep Apnea in Children: A Systematic Review and Meta-Analysis.

Objective To evaluate the efficacy of twin-block appliance in the treatment of children with obstructive sleep apnea (OSA). Methods Two independent reviewers conducted a systematic review of seven databases from database establishment until October 16, 2021. There were no language restrictions. The outcomes were changes in apnea-hypopnea index (AHI), oxyhemoglobin desaturation index (ODI), and lowest arterial oxygen saturation (lowest SaO2). National Institute for Health and Clinical Excellence (NICE) tool was used to assess the quality of the studies included. Results A total of 207 articles were screened for relevance, and 6 of them met the inclusion criteria for our meta-analysis. Four of the studies were case series, 1 was nonrandomized control trial, and 1 was a randomized crossover clinical trial. After twin-block therapy, there was a significant decrease in AHI (4.35 events/hour, 95% CI: 4.04, 4.66, p ≤ 0.001). The lowest SaO2 significantly increased by 9.17% (95% CI: 12.05, 6.28, p ≤ 0.001). Sensitivity analysis by excluding studies one by one showed stable and favorable results in lowest SaO2 and AHI. Conclusions Results from the meta-analysis showed that the use of twin-block appliance significantly decreased AHI and significantly increased lowest SaO2. Hence, twin-block appliance therapy may be an effective method for the treatment of pediatric OSA. Further large sample size randomized controlled trials are needed to assess this treatment efficacy in children with obstructive sleep apnea.

Fraction of Expired Oxygen as a Measure of Preoxygenation Prior to Rapid Sequence Intubation in the Pediatric Emergency Department

BackgroundPulse oximetry (SpO2) is a flawed measure of adequacy of preoxygenation prior to intubation. The fraction of expired oxygen (FeO2) is a promising but understudied alternative. ObjectiveTo investigate FeO2 as a measure of preoxygenation prior to intubation in a pediatric emergency department. MethodsWe conducted a prospective, observational study of patients 18 and younger. We collected data using video review, and FeO2 was measured via inline sampling. The main outcomes were FeO2 and SpO2 at the start of preoxygenation, end of preoxygenation/start of intubation attempt, and the end of intubation attempt. We compared FeO2 and SpO2 at the end of preoxygenation for patients with and without oxyhemoglobin desaturation. ResultsWe enrolled 85 of 88 eligible patients during the 14-month study period. FeO2 data were available at the start of preoxygenation for 53 of 85 patients (62%), and for the end of preoxygenation for 59 of 85 patients (69%). Median FeO2 at the start and end of preoxygenation was 90% (interquartile range [IQR] 88, 92) and 90% (IQR 88, 92). Median SpO2 at the start and end of preoxygenation was 100% (IQR 100, 100). There were 11 episodes of desaturation, with median FeO2 at the start of intubation attempt of 89.5 (IQR 54.5, 91.5) and median SpO2 of 100 (IQR 99, 100). Patients who did not have a desaturation event had a median FeO2 of 90.0 (IQR 88.0, 92.0). ConclusionsMeasuring FeO2 during rapid sequence intubation is challenging with feasibility limitations, but may be a more discriminatory metric of adequate preoxygenation.

Body composition and obstructive sleep apnoea assessment in adult patients with Prader–Willi syndrome: a case control study

IntroductionIn Prader–Willi syndrome (PWS) adult patients, sleep-breathing disorders, especially obstructive sleep apnoea syndrome (OSAS), are very common, whose missed or delayed diagnosis can contribute to further increase cardiovascular morbidity and mortality.PurposeThe aim of this cross-sectional study was to evaluate differences in sleep-breathing parameters obtained by overnight cardiorespiratory polygraphy in 13 adult PWS patients and 13 individuals with non-syndromic obesity as controls matched by age, sex, and BMI.MethodsIn all subjects’ anthropometric parameters, body composition using bioimpedance analysis and overnight cardiorespiratory monitoring parameters were obtained.ResultsTen (76.9%) PWS patients were diagnosed with OSAS, most notably nine (69.2%) and one PWS (7.7%) with mild and severe OSAS, respectively. Compared with the control group, PWS patients had evidence of higher apnoea–hypopnea index (AHI) (p = 0.04) and oxyhaemoglobin desaturation index (ODI) (p = 0.009). However, no differences were found between the two groups regarding OSAS categories or diagnosis of nocturnal respiratory failure. In the PWS group, there were no significant correlations among AHI, ODI and hypoxemia index (T90) and anthropometric measurements, fat mass (FM), and FM percentage (%). Conversely, in the control group, the sleep-related respiratory indices evaluated correlated positively with BMI, waist circumference, FM and FM%.ConclusionsThis study confirmed that AHI and ODI indices were worse in PWS than in age, sex and BMI-matched controls. The lack of their significant association with the anthropometric parameters and FM supported the existence of PWS-related mechanisms in OSAS pathophysiology that are independent of visceral obesity and FM.

0626 Nocturnal Pulse Event Frequency in Multiple System Atrophy: An Exploratory Pilot Study

Abstract Introduction Risk of sudden death in multiple system atrophy (SuD-MSA) is greatest during sleep. Mechanisms underlying SuD-MSA may involve impaired brainstem arousal and cardiovascular responses to hypercapnia in MSA patients. We hypothesized that nocturnal arousal-related tachycardia events are reduced in MSA patients. We analyzed whether nocturnal pulse event frequency was altered in patients with MSA compared to patients with sleep disordered breathing without MSA utilizing portable overnight oximetry. Methods We retrospectively analyzed 46 probable MSA and 46 age-sex matched patients with sleep disordered breathing (SDB) without MSA, excluding patients receiving cardioactive medications. Nocturnal oxyhemoglobin desaturation indices (ODI) and pulse event indices (PEI) were automatically recorded for all patients using portable overnight oximetry. We calculated a PEI/ODI ratio to determine the relationship between probable breathing-related arousals and pulse rate change. Cardiovagal function was assessed by heart rate to deep breathing and Valsalva ratio in patients with MSA and Composite Autonomic Severity Score was assigned. Group comparisons were made with non-parametric tests. Multivariable regression explored relationships between oximetry variables and clinical characteristics. Results Average age at overnight oximetry was 62.9 ± 7.7 years. Total respiratory events between MSA patients compared with OSA controls were similar (95.0 ± 118.6 vs 73.5± 54.2, p=0.61). Total pulse events were lower in MSA than OSA controls without MSA (25.5±44.2 vs 111.6±120.2, p&amp;lt;0.001), as were pulse events per hour (3.1 ± 5.3 vs. 12.8 ± 10.8, p &amp;lt;0.001). The ratio of PEI/ODI was lower in MSA than OSA patients without MSA (p&amp;lt;0.001). Twelve (26%) MSA patients had zero pulse rate events, while all OSA patients without MSA had at least 1 pulse rate event (p&amp;lt;0.001). The number of pulse events was not associated with severity of cardiovagal dysfunction on daytime autonomic function testing. Conclusion Patients with MSA have fewer pulse rate events when compared with SDB patients without MSA, despite similar overall respiratory event frequency. The number of pulse events was not explained by severity of daytime autonomic dysfunction in those with MSA. Whether nocturnal pulse event response to sleep disordered breathing is a marker of disease severity or plays a role in SuD-MSA deserves further study. Support (If Any)