Intermittent Hypoxemia Research Articles

Hypoxic burden and sleep hypoventilation in obese patients

IntroductionNovel biomarkers of hypoxic load have emerged, as sleep apnea-specific hypoxic burden which provides more precise assessment of intermittent hypoxemia severity. Our main objective was to assess the potential benefit of hypoxic burden to identify obesity-related sleep hypoventilation. We hypothesized that hypoxic burden may help diagnose obesity-related sleep hypoventilation better than usual sleep respiratory measures (i.e., apnea-hypopnea index (AHI), mean SpO2, time with SpO2 < 90 %). MethodsThis retrospective study was conducted from June 2022 to October 2023 at the University Hospital of Rouen, France. All consecutive obese patients (BMI ≥30 kg/m2), adults, with no other respiratory or neurological diseases who underwent a polysomnography or polygraphy with concomitant capnography were included. Sleep hypoventilation was defined according to American Academy of Sleep Medicine criteria based on transcutaneous CO2 monitoring (PtcCO2). Diagnostic performance of sleep-related respiratory measures i.e., sleep apnea-specific hypoxic burden, apnea-hypopnea index (AHI), mean SpO2, time with SpO2 < 90 % was evaluated using Receiver Operating Characteristic (ROC) curves. Correlations between sleep-related respiratory measures were assessed by a Spearman correlation matrix. ResultsAmong 107 obese patients with analyzed capnography, 37 (35 %) had sleep hypoventilation. Patients were 53 ± 14 years old, mean BMI = 38 ± 6 kg/m2, mean AHI = 26.5 ± 25/h, mean hypoxic burden = 67 ± 109 %min/h, mean SpO2 = 91.5 ± 3 %, mean time with SpO2<90 % = 19.4 ± 28 %, mean PtcCO2 = 6.2 ± 0.7 kPa. A low positive correlation was found between hypoxic burden and mean PtcCO2 (r = 0.4, p < 0.001). Multivariate logistic regression model explaining sleep hypoventilation was insufficient with area under ROC curve of hypoxic burden estimated at 0.74 (95 % CI 0.65 to 0.84). ConclusionHypoxic burden has low correlation with transcutaneous CO2 pressure and a low ability to diagnose obesity-related sleep hypoventilation.

Extended CPAP or low-flow nasal cannula for intermittent hypoxaemia in preterm infants: a 24-hour randomised clinical trial

ObjectiveOptimal timing of continuous positive airway pressure (CPAP) cessation in preterm infants remains undetermined. We hypothesised that CPAP extension compared with weaning to low-flow nasal cannula (NC) reduces intermittent hypoxaemia...

Control of breathing in preterm infants on incubator oxygen or nasal cannula oxygen.

Incubator oxygen may improve respiratory stability in preterm infants compared with nasal cannula oxygen. Single center randomized trial of infants <29 weeks' gestation on supplemental oxygen at ≥32 weeks' postmenstrual age. Infants were crossed-over every 24 hours for 96 hours between incubator oxygen and nasal cannula ≤1.0 L/kg/min. We measured episodes of intermittent hypoxemia (oxygen saturations (SpO2) < 85% ≥10 seconds), bradycardia, cerebral and abdominal hypoxemia, and end-tidal carbon dioxide. We enrolled 25 infants with a gestational age of 26 weeks 4 days±15 days (mean ± SD) and birth weight 805 ± 202 grams. There were no differences in episodes of intermittent hypoxemia, bradycardia, or cerebral hypoxemia between groups. There were fewer episodes of abdominal hypoxemia <40% ≥10 seconds with incubator oxygen compared with nasal cannula (132 ± 130 versus 158 ± 125; p < 0.01). Time with SpO2 < 85% and abdominal hypoxemia was lower among infants on incubator oxygen. Carbon dioxide values were higher while on incubator oxygen (41 ± 11 versus 36 ± 10 mmHg; p < 0.02). There was no difference in intermittent hypoxemia between incubator and nasal cannula oxygen among preterm infants on supplemental oxygen. Infants had higher levels of carbon dioxide while on incubator oxygen, which may have improved some measures of respiratory stability. CLINCALTRIALS. NCT03333174 and NCT03174301. In this randomized cross-over trial of preterm infants on supplemental oxygen, incubator oxygen did not decrease episodes of intermittent hypoxemia compared with nasal cannula oxygen. Incubator oxygen reduced time with oxygen saturations less than 85%, reduced abdominal hypoxemia, and increased carbon dioxide levels. Differences in measures of respiratory stability on incubator oxygen may be partly due to higher carbon dioxide levels compared with nasal cannula oxygen. The mode of supplemental oxygen administration may impact control of breathing in preterm infants through its effect on hypopharyngeal oxygen stability and carbon dioxide levels.

Changes in appetite during acute passive intermittent and continuous hypoxemia in postprandial and fasting states: A combined analysis of four laboratory-based randomized crossover trials

Hypoxemia occurs during exposure to high altitude (continuous hypoxemia) or in the context of breathing disorders such as obstructive sleep apnea (OSA; intermittent hypoxemia). Growing evidence demonstrates that hypoxemia induces an anorexigenic effect on appetite; however, few studies have assessed hypoxemia-related reductions in appetite during acute passive exposures and during intermittent hypoxemia. This study thus pooled together four same-single-site randomized crossover trials using simulated models of high altitude (fraction of inspired oxygen = 0.1200, ∼5000 m) and moderate OSA (∼15 hypoxemic cycles per hour, ∼85 oxyhemoglobin saturation). Changes in appetite were evaluated during 6 h of passive normoxia and intermittent or continuous hypoxemia in postprandial or fasting states among healthy young adults (n = 40) and middle-aged individuals living with OSA (n = 7). Our results demonstrate that (1) acute passive intermittent hypoxemia leads to statistically significant, but likely not clinically significant reductions in appetite in the postprandial state, (2) the anorexigenic effect of acute passive hypoxemia on appetite is not consistent across hypoxemic methods and nutritional states, and (3) variations in individual factors may influence appetite responses during normoxia and hypoxemia. These findings indicate that the effect of acute passive hypoxemia on appetite is heterogeneous, particularly across different hypoxemic methods and nutritional states.

Sleep-disordered breathing destabilizes ventricular repolarization: Cross-sectional, longitudinal, and experimental evidence

BackgroundSleep-disordered breathing (SDB) increases the risk of cardiac arrhythmias and sudden cardiac death. ObjectiveThis study sought to characterize the associations between SDB, intermittent hypoxemia, and the beat-to-beat QT variability index (QTVI), a measure of ventricular repolarization lability associated with cardiac arrhythmias and sudden cardiac death. MethodsThree distinct cohorts were used: a matched sample of 122 participants with and without severe SDB for cross-sectional analysis; a matched sample of 52 participants with and without incident SDB for longitudinal analysis; and a sample of 19 healthy adults exposed to acute intermittent hypoxia and ambient air on 2 separate days. The cross-sectional and longitudinal cohorts were the Sleep Heart Health Study participants with no known comorbidities who were not taking any drugs known to affect cardiac repolarization and satisfied the inclusion criteria. Electrocardiographic measures were calculated from 1-lead electrocardiograms. ResultsParticipants with severe SDB had greater QTVI than those without SDB (P = .027). Total sleep time with <90% oxygen saturation, but not the arousal frequency, was a predictor of QTVI. QTVI during sleep was predictive of all-cause mortality. With incident SDB, mean QTVI increased from −1.23 to −0.86 during 5 years (P = .017). Finally, experimental exposure of healthy adults to acute intermittent hypoxia for 4 hours progressively increased QTVI (P = .016). ConclusionThe results show that both prevalent SDB and incident SDB are associated with ventricular repolarization instability and suggest intermittent hypoxemia as the underlying mechanism that may contribute to increased mortality in SDB.

Pediatric Obstructive Sleep Apnea: An Updated Review

Abstract Pediatric obstructive sleep apnea (OSA) is a prevalent sleep disorder characterized by recurrent upper airway obstruction during sleep, leading to disrupted breathing patterns and intermittent hypoxemia. This review synthesizes current literature on pediatric OSA, covering epidemiology, etiology, clinical presentation, diagnosis, and management. OSA affects 1%–5% of children, with adenotonsillar hypertrophy as a primary cause. The interplay of anatomical and neuromuscular factors contributes to OSA pathophysiology. Clinical manifestations include snoring, witnessed apneas, and daytime sleepiness, although diagnosis can be challenging due to varied symptoms. Diagnostic methods encompass clinical assessment and polysomnography, while management strategies range from adenotonsillectomy to continuous positive airway pressure therapy. Early recognition and intervention are crucial to prevent complications and optimize outcomes in pediatric OSA. Further research is needed to refine diagnostic approaches and enhance treatment efficacy for this significant pediatric health concern.

Defining the role of exertional hypoxemia and pulmonary vasoconstriction on lung function decline, morbidity, and mortality in patients with chronic obstructive lung disease – the PROSA study: rationale and study design

BackgroundChronic obstructive lung disease (COPD) has diverse molecular pathomechanisms and clinical courses which, however, are not fully mirrored by current therapy. Intermittent hypoxemia is a driver of lung function decline and poor outcome, e.g., in patients with concomitant obstructive sleep apnea. Transient hypoxemia during physical exercise has been suggested to act in a similar manner. The PROSA study is designed to prospectively assess whether the clinical course of COPD patients with or without exertional desaturation differs, and to address potential pathophysiological mechanisms and biomarkers.Methods148 COPD patients (GOLD stage 2–3, groups B or C) will undergo exercise testing with continuous pulse oximetry. They will be followed for 36 months by spirometry, echocardiography, endothelial function testing, and biomarker analyses. Exercise testing will be performed by comparing the 6-min walk test (6MWT), bicycle ergometry, and a 15-sec breath-hold test. Exertional desaturation will be defined as SpO2 < 90% or delta-SpO2 ≥ 4% during the 6MWT. The primary endpoint will be the rate of decline of FEV1(LLN) between COPD patients with and without exertional desaturation.DiscussionThe PROSA Study is an investigator-initiated prospective study that was designed to prove or dismiss the hypothesis that COPD patients with exertional desaturation have a significantly more rapid rate of decline of lung function as compared to non-desaturators. A 20% difference in the primary endpoint was considered clinically significant; it can be detected with a power of 90%. If the primary endpoint will be met, exercise testing with continuous pulse oximetry can be used as a ubiquitously available, easy screening tool to prospectively assess the risk of rapid lung function decline in COPD patients at an early disease stage. This will allow to introduce personalized, risk-adapted therapy to improve COPD outcome in the long run. PROSA is exclusively funded by public funds provided by the European Research Council through an ERC Advanced Grant. Patient recruitment is ongoing; the PROSA results are expected to be available in 2028.Trial registrationThe PROSA Study has been prospectively registered at clinicaltrials.gov (register no. NCT06265623, dated 09.02.2024).

Pooled prevalences of obstructive sleep apnea and heart failure: a systematic review andmeta-analysis.

Obstructive sleep apnea (OSA) is a disease with intermittent hypoxemia during sleep. It has been shown that OSA is related to several cardiovascular diseases including heart failure. Both OSA and heart failure have a close association bidirectionally. This study aimed to estimatethe pooled prevalence of OSA in patients with heart failure as well as pooled prevalence of heart failure in patients with OSA. This was a systematic review with a meta-analysis. The inclusion criteria were observational or epidemiological studies conducted in adult patients with heart failure to evaluate the prevalence of OSA and patients with OSA to evaluate the prevalence of heart failure. The outcomes of this study were prevalence of OSA in patients with heart failure and prevalence of heart failure in patients with OSA. Four databases were used for systematic searching including PubMed, Science Direct, Scopus, and CINAHL Plus. Manual searches for related studies were also conducted. Proportion meta-analyses using a random-effects model were conducted to identify pooled proportion (prevalence) of heart failure in patients with OSA and vice versa. Among 3,941 articles from the four databases met the study criteria. Thirty-three studies showed the prevalence of OSA in patients with heart failure, while thirteen studies presented the prevalence of heart failure in patients with OSA. The prevalence of OSA in patients with heart failure was 38.4% (95% CI 31.9 to 45.2; I2 of 96.1%). Using a diagnostic criterion of OSA of more than 10 events/hr had the highest prevalence of OSA in patients with heart failure at 53.4% (95% CI 42.0 to 64.5). The highest prevalence of OSA in patients with heart failure was 60.1% (95% CI 51.4 to 68.3) in a report from India. The pooled prevalence of heart failure in patients with OSA was 12.8% (95% CI 8.1 to 19.5; I2 of 94.6%). The prevalence in Romania was highest at 22.6% (95% CI 20.4 to 24.9). The pooled prevalence of OSA in patients with heart failure was higher than the pooled prevalence of heart failure in patients with OSA. The pooled prevalence rates of these associations varied among the diagnostic criteria of OSA and countries.

Highly comparative time series analysis of oxygen saturation and heart rate to predict respiratory outcomes in extremely preterm infants

Objective. Highly comparative time series analysis (HCTSA) is a novel approach involving massive feature extraction using publicly available code from many disciplines. The Prematurity-Related Ventilatory Control (Pre-Vent) observational multicenter prospective study collected bedside monitor data from >700 extremely preterm infants to identify physiologic features that predict respiratory outcomes. Approach. We calculated a subset of 33 HCTSA features on >7 M 10 min windows of oxygen saturation (SPO2) and heart rate (HR) from the Pre-Vent cohort to quantify predictive performance. This subset included representatives previously identified using unsupervised clustering on >3500 HCTSA algorithms. We hypothesized that the best HCTSA algorithms would compare favorably to optimal PreVent physiologic predictor IH90_DPE (duration per event of intermittent hypoxemia events below 90%). Main Results. The top HCTSA features were from a cluster of algorithms associated with the autocorrelation of SPO2 time series and identified low frequency patterns of desaturation as high risk. These features had comparable performance to and were highly correlated with IH90_DPE but perhaps measure the physiologic status of an infant in a more robust way that warrants further investigation. The top HR HCTSA features were symbolic transformation measures that had previously been identified as strong predictors of neonatal mortality. HR metrics were only important predictors at early days of life which was likely due to the larger proportion of infants whose outcome was death by any cause. A simple HCTSA model using 3 top features outperformed IH90_DPE at day of life 7 (.778 versus .729) but was essentially equivalent at day of life 28 (.849 versus .850). Significance. These results validated the utility of a representative HCTSA approach but also provides additional evidence supporting IH90_DPE as an optimal predictor of respiratory outcomes.

Ethanol pre-exposure attenuates the hypoxic ventilatory response and may attenuate expression of long term facilitation following intermittent hypoxia treatment in adult rats

Obstructive sleep apnea (OSA) is a highly prevalent breathing disorder in which airway collapse or obstruction during sleep leads to periodic bouts of inadequate (hypopneic) or absent (apneic) ventilation despite neurorespiratory effort. Repetitive apneic and hypopneic exposures during sleep can induce intermittent hypoxemia, sympathetic activation, and sleep fragmentation which can lead to a host of maladaptive behavioral and physiological outcomes. Intermittent hypoxia, which consists of alternating exposure to hypoxia and normal oxygen levels (normoxia), can induce a long-lasting increase in breathing motor output called long term facilitation (LTF) and is currently being investigated as a therapeutic treatment. Interestingly, experts in the field of LTF have noted how IH models some key aspects of OSA. It has been well established through clinical studies that ethanol consumption prior to sleep exacerbates existing OSA, increasing the apnea/hypopnea index and worsening arterial blood oxygen desaturations during the night. However, it is unknown whether ethanol affects expression of LTF following IH treatment. If LTF might serve as a means of increasing ventilatory output to compensate for periods of apnea and hypopnea during OSA, ethanol might not only worsen the severity of OSA, but impede individuals’ compensatory response. Thus, for this study we hypothesized that ethanol treatment would attenuate LTF expression and the magnitude of the hypoxic ventilatory response during IH treatment. Using adult female Sprague-Dawley rats, we administered either low-dose (0.8 g/kg) or high-dose (3 g/kg) ethanol through intraperitoneal injection to model a 2-drink nightcap or binge drinking-type ethanol exposure, respectively. Immediately afterwards, we measured subjects’ ventilatory output during baseline, then during a 5 by 3-minute moderate IH protocol, and for one hour following the end of IH using whole-body plethysmography. Finally, we took venous blood samples to assay serum ethanol concentration at the end of the approximately 2.5 hour plethysmography measurement. Results from the high-dose ethanol group indicate that ethanol pre-exposure might attenuate respiratory rate and minute volume LTF in comparison to saline-treated control. Furthermore, high-dose ethanol attenuated the hypoxic ventilatory response with respect to respiratory rate and minute volume. Low dosage of ethanol attenuated subjects’ HVR of respiratory rate and minute volume, but conflictingly trends towards increasing LTF of tidal volume while diminishing LTF of respiratory rate when compared to saline control. Overall, our findings indicate that high levels of ethanol exposure dramatically diminish the acute ventilatory response to hypoxic exposure and may impede long-term increases in ventilatory output following IH treatment. On the other hand, lower doses of ethanol have a subtler effect on the ventilatory response to hypoxia. Future directions will include analysis of additional parameters of ventilatory function to gain a more detailed understanding of how ethanol effects respiratory plasticity in the context of intermittent hypoxic exposure. NIH 5T32 AA027488 to ALSUniversity of Kentucky Endowment to WJA. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sleep-disordered breathing destabilizes ventricular repolarization: Role of intermittent hypoxemia

Sleep-disordered breathing destabilizes ventricular repolarization: Role of intermittent hypoxemia

The Effect of Continuous Positive Airway Pressure (CPAP) Therapy on Serum Caspase-3 Level in Patients with Obstructive Sleep Apnea (OSA).

Intermittent hypoxemia has an important role in the physiopathogenesis of obstructive sleep apnea (OSA) complications. Increased apoptosis due to intermittent hypoxemia may be an important clinical entity in OSA. In this study, we aimed to evaluate caspase-3 enzyme level, which is an indirect marker of increased apoptosis in patients with OSA and to evaluate the effect of OSA treatment with continuous positive airway pressure on caspase-3 enzyme level. This study included 141 consecutive patients admitted to the sleep-disordered breathing laboratory within 6 months. Caspase-3 was measured in routine blood samples obtained on the morning of polysomnography (PSG) performed at night. The compliance of the patients to CPAP treatment was evaluated and caspase-3 levels were checked again after treatment. A total of 141 patients, 39 females (27,7%) and 102 males (72,3%) were included in the study. The mean age of the patients was 49 ± 12 years (min-17, max-77). According to PSG results, OSA was detected in 95.7% (135/141) of the cases. Mild OSA was 35 (24.8%), moderate OSA 39 (27.7%) and severe OSA 61 (43.3%) cases. Median caspase-3 enzyme levels were similar in men and women in the study group. There was no statistically significant difference in hemogram parameters and caspase-3 enzyme levels between the groups divided according to the presence and severity of OSA. It was determined that caspase-3 enzyme level did not change significantly after 3 months of CPAP treatment in OSA compared to pretreatment. Caspase-3 was found to have a negative correlation with both the percentage of daily use of CPAP therapy and the percentage of CPAP device use for more than 1 h per night. It was found that the control caspase-3 level decreased statistically significantly as the percentage of daily use of CPAP therapy increased (r = -0.397, p = 0.030). It was found that the control caspase-3 level decreased statistically significantly as the percentage of CPAP therapy use for more than 1 h per night increased (r = -0.411, p = 0.024). The results of this study did not reveal a relationship between the severity of OSA and caspase-3 levels. However, blood caspase-3 levels decreased as treatment compliance increased, suggesting that CPAP treatment may correct increased apoptosis in OSA. There is a need for more comprehensive studies on this issue.

0856 Association of Naturally Occurring Mild Intermittent Hypoxemia and Health Outcomes in Sleep Apnea

0856 Association of Naturally Occurring Mild Intermittent Hypoxemia and Health Outcomes in Sleep Apnea

Burden of obstructive sleep apnea in patients with lung cancer and its effect on performance status.

The association between lung cancer and obstructive sleep apnea has remained a matter of debate for years. Obstructive sleep apnea is thought to increase the incidence of lung cancer due to intermittent hypoxaemia and sleep fragmentation. The aim of this study is to assess the prevalence of obstructive sleep apnea in patients with lung cancer and its effect on those patients' performance status. This is a prevalence study that was conducted at Chest Diseases Department, Alexandria Main University Hospitals. We enrolled 153 patients with lung cancer. All patients underwent cardiorespiratory monitoring using a home sleep-testing device. Performance status was assessed using Karnofsky performance status scale. The study included 120 (78.4%) males and 33 (21.6%) females newly diagnosed with lung cancer. The mean age was 59.98 ± 11.11 years. Obstructive sleep apnea (apnea-hypopnea index ≥ 5) was present in 134 (87.6%) patients. Eighty-five (63.4%) patients had mild obstructive sleep apnea, 39 (29.1%) patients had moderate obstructive sleep apnea, and 10 (7.46%) patients had severe obstructive sleep apnea. Prolonged nocturnal oxygen desaturation as demonstrated by time of oxygen saturation spent below 90% (T90%) during total sleep time > 30% was present in 25 (16.3%) patients. There was a significant difference in the median value of Karnofsky performance status scale between patients with lung cancer and associated obstructive sleep apnea and those without obstructive sleep apnea. In conclusion, obstructive sleep apnea is highly prevalent among patients with lung cancer. Performance status is worse among patients with lung cancer in the presence of obstructive sleep apnea. Screening patients with lung cancer for obstructive sleep apnea is important regardless of the presence of classical symptoms of obstructive sleep apnea.

The impact of intermittent hypoxemia on type 1 retinopathy of prematurity in preterm infants.

Intermittent hypoxemia (IH) may influence retinopathy of prematurity (ROP) development in preterm infants, however, previous studies had mixed results. This study tests the hypothesis that increased IH is associated with Type 1 ROP; a stage beyond which treatment is indicated. IH was quantified by continuously monitoring oxygen saturation (SpO2) using high-resolution pulse oximeters during the first 10 weeks of life. Statistical analyses assessed the relationship and predictive ability of weekly and cumulative IH for Type 1 ROP development. Most analyses showed no association between IH and Type 1 ROP adjusting for gestational age (GA) and birth weight (BW). However, cumulative IH of longer duration during weeks 5-10, 6-10, and 7-10 were significantly associated with Type 1 ROP adjusting for GA and BW, e.g., the adjusted odds ratio of Type 1 ROP was 2.01 (p = 0.03) for every 3.8 seconds increase in IH duration from week 6-10. IH did not provide statistically significant added predictive ability above GA and BW. For most analyses there was no significant association between IH and Type 1 ROP adjusting for GA and BW. However, infants with longer IH duration during the second month of life had higher risk for Type 1 ROP. The relationship and predictive ability of intermittent hypoxemia (IH) on retinopathy of prematurity (ROP) is controversial. This study shows no significant association between IH events and Type 1 ROP after adjusting for gestational age (GA) and birth weight (BW), except for cumulative IH of longer duration in the second month of life. In this cohort, IH does not provide a statistically significant improvement in ROP prediction over GA and BW. This study is the first to assess the cumulative impact of IH measures on Type 1 ROP. Interventions for reducing IH duration during critical postnatal periods may improve ROP outcomes.

Apnea, Intermittent Hypoxemia, and Bradycardia Events Predict Late-Onset Sepsis in Infants Born Extremely Preterm

ObjectiveTo examine the association of cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, with late-onset sepsis for extremely preterm infants (<29 weeks’ gestational age [GA]) on versus off invasive mechanical ventilation. Study designThis is a retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in five level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean GA 26.4 weeks, SD 1.71). Monitoring data were available and analyzed for 719 infants (47,512 patient-days), of whom 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72 hours after birth and ≥5d antibiotics). ResultsFor infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer events with oxygen saturation <80% (IH80) and more bradycardia events before sepsis. IH events were associated with higher sepsis risk, but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model including post menstrual age, cardiorespiratory variables (apnea, periodic breathing, IH80, and bradycardia), and ventilator status predicted sepsis with an AUC of 0.783. ConclusionWe identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.

Predicting Extubation Readiness in Preterm Infants Utilizing Machine Learning: A Diagnostic Utility Study

ObjectiveTo predict extubation readiness in preterm infants using machine learning analysis of bedside pulse oximeter and ventilator data. Study designThis is an observational study with prospective recordings of oxygen saturation (SpO2) and ventilator data from infants < 30 weeks’ gestation age (GA). Research pulse oximeters collected SpO2 (1 Hz sampling rate) to quantify intermittent hypoxemia (IH). Continuous ventilator metrics were collected (4-5 min sampling) from bedside ventilators. Data modeling was completed using unbiased machine learning algorithms. Three model sets were created using the following data source combinations: [1] IH and ventilator (IH + SIMV), [2] IH, and [3] ventilator (SIMV). Infants were also analyzed separated by postnatal age (infants < 2 or ≥ 2 weeks of age). Models were compared by area under the ROC curve (AUC). ResultsA total of 110 extubation events from 110 preterm infants were analyzed. Infants had a median GA and birth weight of 26 weeks and 825 grams, respectively. Of the three models presented, the IH + SIMV model achieved the highest AUC of 0.77 for all infants. Separating infants by postnatal age increased accuracy further achieving AUC of 0.94 for < 2 weeks of age group and AUC of 0.83 for ≥ 2 weeks group. ConclusionsMachine learning analysis has the potential to enhance prediction accuracy of extubation readiness in preterm infants while utilizing readily available data streams from bedside pulse oximeters and ventilators.

Prolonged lung-to-finger circulation time indicates an increased risk of intermittent hypoxaemia in sleep apnoea patients.

Intermittent hypoxaemia is closely associated with cardiovascular dysfunction and may be a more accurate indicator of obstructive sleep apnoea (OSA) severity than conventional metrics. Another key factor is the lung-to-finger circulation time (LFCt), defined as the duration from the cessation of a respiratory event to the lowest point of oxygen desaturation. LFCt serves as a surrogate marker for circulatory delay and is linked with cardiovascular function. Yet, the specific associations between respiratory and hypoxaemia characteristics and LFCt in patients with OSA remain unclear. This study aims to investigate these associations, ultimately contributing to a more nuanced understanding of OSA severity. The study comprised 878 in-lab polysomnographies of patients with suspected OSA. The conventional OSA metrics were computed along with nine hypoxaemia metrics and then divided into quartiles (Q1-Q4) based on respiratory event duration. In addition, these were further divided into subquartiles based on LFCt. The empirical cumulative distribution functions (CDFs) and linear regression models were used to investigate the association between desaturation metrics and LFCt. The results showed that prolonged LFCt was associated with increased hypoxic severity. Based on CDFs, the hypoxic severity significantly increased with longer LFCt despite the duration of respiratory events. Furthermore, fall duration was elevated in patients with longer LFCt (Q1- desaturation fall duration (FallDur): 14.6 s; Q4-FallDur: 29.8 s; p<0.0001). The regression models also showed significant association between hypoxic severity and LFCt (Q1-desaturation fall slope (FallSlope): β=-3.224; Q4-FallSlope: β=-6.178; p<0.0001). Considering LFCt along with desaturation metrics might be useful in estimating the association between the severity of OSA, physiological consequences of respiratory events and cardiac health.

Wearable fiber-free optical sensor for continuous monitoring of neonatal cerebral blood flow and oxygenation.

Unstable cerebral hemodynamics places preterm infants at high risk of brain injury. We adapted an innovative, fiber-free, wearable diffuse speckle contrast flow-oximetry (DSCFO) device for continuous monitoring of both cerebral blood flow (CBF) and oxygenation in neonatal piglets and preterm infants. DSCFO uses two small laser diodes as focused-point and a tiny CMOS camera as a high-density two-dimensional detector to detect spontaneous spatial fluctuation of diffuse laser speckles for CBF measurement, and light intensity attenuations for cerebral oxygenation measurement. The DSCFO was first validated against the established diffuse correlation spectroscopy (DCS) in neonatal piglets and then utilized for continuous CBF and oxygenation monitoring in preterm infants during intermittent hypoxemia (IH) events. Significant correlations between the DSCFO and DCS measurements of CBF variations in neonatal piglets were observed. IH events induced fluctuations in CBF, cerebral oxygenation, and peripheral cardiorespiratory vitals in preterm infants. However, no consistent correlation patterns were observed among peripheral and cerebral monitoring parameters. This pilot study demonstrated the feasibility of DSCFO technology to serve as a low-cost wearable sensor for continuous monitoring of multiple cerebral hemodynamic parameters. The results suggested the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations. The innovative DSCFO technology may serve as a low-cost wearable sensor for continuous bedside monitoring of multiple cerebral hemodynamic parameters in neonatal intensive care units. Concurrent DSCFO and DCS measurements of CBF variations in neonatal piglet models generated consistent results. No consistent correlation patterns were observed among peripheral and cerebral monitoring parameters in preterm neonates, suggesting the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations during IH events. Integrating and correlating multiple cerebral functional parameters with clinical outcomes may identify biomarkers for prediction and management of IH associated brain injury.

Association between Intermittent Hypoxemia and NICU Length of Stay in Preterm Infants

Introduction: Length of hospitalization varies widely in preterm infants and can be affected by multiple maternal and neonatal factors including respiratory instability. Therefore, we aimed to determine the association between postnatal intermittent hypoxemia (IH) and prolonged hospitalization. Methods: This prospective single-center cohort study followed infants born at <31 weeks of gestational age through 2 years corrected age with detailed oxygen saturation data captured from days 7 to 30 of age. Results: 51/164 (31%) of infants were discharged after 400/7 weeks of corrected gestational age (CGA). A greater average daily number of IH events (OR per 10 events/day 1.33 [95% CI 1.03–1.72]), duration of events (OR per minute 1.14 [1.07–1.21]), and percent time with oxygen saturation <80% (OR per percent 1.88 [1.25–2.85]) on days 7–30 of age were all significantly associated with prolonged hospitalization past 400/7 weeks CGA. In survival analyses, infants with a greater average daily number of IH events (HR per 10 events/day 0.89 [0.81–0.98]), percent time with oxygen saturation <80% (HR per percent 0.79 [0.67–0.94]), and duration of events (HR per minute 0.93 [0.91–0.95]) on days 7–30 of age all had significantly lower probability of earlier discharge. In addition, there was a significant interaction with gestational age; the association between IH and prolonged hospitalization was stronger in more mature infants (p = 0.024). Conclusions: Physiological instability on days 7–30 of age, as manifested by IH, is significantly associated with prolonged hospitalization. IH likely represents both a marker of initial severity of illness and the beginning of biological cascades, leading to prematurity-associated morbidities.