Airway Pressure Research Articles

Atelectrauma can be avoided if expiration is sufficiently brief: evidence from inverse modeling and oscillometry during airway pressure release ventilation

BackgroundAirway pressure release ventilation (APRV) has been shown to be protective against atelectrauma if expirations are brief. We hypothesize that this is protective because epithelial surfaces are not given enough time to come together and adhere during expiration, thereby avoiding their highly damaging forced separation during inspiration.MethodsWe investigated this hypothesis in a porcine model of ARDS induced by Tween lavage. Animals were ventilated with APRV in 4 groups based on whether inspiratory pressure was 28 or 40 cmH2O, and whether expiration was terminated when end-expiratory flow reached either 75% (a shorter expiration) or 25% (a longer expiration) of its initial peak value. A mathematical model of respiratory system mechanics that included a volume-dependent elastance term characterized by the parameter E2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${E}_{2}$$\\end{document} was fit to airway pressure-flow data obtained each hour for 6 h post-Tween injury during both expiration and inspiration. We also measured respiratory system impedance between 5 and 19 Hz continuously through inspiration at the same time points from which we derived a time-course for respiratory system resistance (Rrs\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${R}_{rs}$$\\end{document}).ResultsE2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${E}_{2}$$\\end{document}during both expiration and inspiration was significantly different between the two longer expiration versus the two shorter expiration groups (ANOVA, p < 0.001). We found that E2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${E}_{2}$$\\end{document} was most depressed during inspiration in the higher-pressure group receiving the longer expiration, suggesting that E2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${E}_{2}$$\\end{document} reflects a balance between strain stiffening of the lung parenchyma and ongoing recruitment as lung volume increases. We also found in this group that Rrs\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${R}_{rs}$$\\end{document} increased progressively during the first 0.5 s of inspiration and then began to decrease again as inspiration continued, which we interpret as corresponding to the point when continuing derecruitment was reversed by progressive lung inflation.ConclusionsThese findings support the hypothesis that sufficiently short expiratory durations protect against atelectrauma because they do not give derecruitment enough time to manifest. This suggests a means for the personalized adjustment of mechanical ventilation.

Right subaxillary small incision on low-age and low-weight infants with congenital heart disease.

As a minimally invasive approach to treating congenital heart disease (CHD), the application of the right subaxillary small incision (RSSI) has been developing fast in its indication spectrum. However, RSSI's use is still quite challenging for the surgical treatment of the low-age and low-weight infant patient group. To investigate the safety and efficacy of performing RSSI surgery, treating CHD for infants with low-age and low-weight. Between March 2010 and April 2023, Low-age (≤6 months) and low-weight (≤5 kg) infants with ventricular or atrial septal defect (ASD) as the main diagnosis were retrospectively included in this study. The infants were divided into the RSSI group and the median sternotomy (MS) group. Preoperative conditions, general surgical conditions, perioperative and postoperative outcomes, and long-term follow-up results were compared between the 2 groups. The study included 783 cases. Of these, 434 were operated with MS, and 349 were operated with RSSI. A1:1 matched MS group (282 cases) and RSSI group (282 cases) were obtained after performing propensity score matching (PSM). Analysis of the 2 groups after PSM showed the differences in residual ASD/VSD, peak airway pressure, fraction of inspired oxygen/partial pressure of oxygen (PaO2/FiO2), and partial pressure of carbon dioxide (PaCO2) before return to the intensive care unit (ICU) and extubation were not statistically significant between groups, whereas mechanical ventilation time (P < 0.001), ICU stay (P < 0.001), and hospitalization time (P < 0.001) were lower in RSSI group; and the differences in perioperative complication outcomes were not statistically significant. Long-term outcomes revealed the rate of thoracic deformity was higher in the MS group. Based on the appropriate selection of patients, compared with MS, RSSI surgery for the treatment of low-age (≤6 months) and low-weight (≤5 kg) infants with CHD yields favorable therapeutic results without increasing surgical risks and causes less trauma, which deserves to be further promoted and applied.

Effect of Obstructive Sleep Disorder Treatment on Posttraumatic Stress Disorder Symptoms: A Literature Review.

To explore whether continuous positive airway pressure (CPAP) adherence among adult patients with obstructive sleep apnea (OSA) and posttraumatic stress disorder (PTSD) affects the PTSD Checklist (PCL), a validated tool that measures severity of PTSD symptoms. Studies focusing on PTSD and OSA were searched in PubMed and CINAHL databases. Inclusion and exclusion criteria were applied, decreasing the article yield to nine. All articles chosen focused on the adult population and were conducted in North America. The literature review yielded eight observational cohort studies and one descriptive study. Seven studies were conducted with Veterans and all studies used the PCL tool. Three themes were identified: (a) Trauma and OSA, (b) OSA and PTSD Symptoms, and (c) CPAP Therapy and PTSD Symptoms. An area of further study is assessing how CPAP adherence might affect improvement in PTSD symptoms and how adherence can be improved. OSA is correlated with more severe PTSD symptoms, but CPAP use is associated with improvement in PTSD symptoms. The literature reviewed found PCL scores improved up to 10 points within 3 months of CPAP use. These findings highlight the importance of collaboration between mental health and sleep medicine professionals and opportunity for further study in this area. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx-xx.].

8688 Pseudopheochromocytoma Due To Severe Obstructive Sleep Apnea

Abstract Disclosure: L.M. José: None. M. Ataide: None. F. Aratani: None. S. Beeby: None. G.F. Fagundes: None. F. Coelho: None. F. Ledesma: None. A. Latronico: None. B.B. Mendonca: None. M.C. Fragoso: None. M.Q. Almeida: None. Background: Obstructive sleep apnea (OSA) represents an independent risk factor for cardiovascular disease, and it is associated with a wide range of conditions, such as resistant hypertension and primary aldosteronism (PA). Patients with sleep apnea have a higher sympathetic activity during wakefulness due to chronic hypoxia. We present the case of pseudopheochromocytoma caused by severe OSA in an obese patient with RH and PA.Clinical Case: A 58-year-old female Brazilian patient was referred to an endocrinologist to investigate a 1.8 cm right adrenal nodule at computed tomography (CT) performed to investigate abdominal pain. Her medical history includes resistant hypertension diagnosed at 27 years of age, type 2 diabetes, dyslipidemia, Class II obesity, a previous acute myocardial infarction, and severe OSA (apnea-hypopnea index 61.6/hour). She has used irregularly the continuous positive airway pressure (CPAP) therapy at night. She is currently using carvedilol 50 mg bid, chlorthalidone 25 mg, olmesartan 40 mg, amlodipine 10 mg, spironolactone 50 mg, clonidine 0.2 mg tid, hydralazine 50 mg every 6 hours, acetylsalicylic acid 100 mg, atorvastatin 80 mg, and metformin XR 1000 mg. At physical examination, she had BMI 37 kg/m2, BP 150 x 90 mmHg, HR 64 bpm, and no signs of Cushing syndrome. Abdominal CT revealed a right adrenal nodule measuring 1.8 cm with 18 Hounsfield unit (HU) in the pre-contrast phase, reaching a density of 117 HU at the arterial phase and showing an absolute washout of 65% and a relative washout of 56%. A nodular thickening of 1.4 cm (-4 HU) at the left adrenal gland was also displayed at CT scan. Hormone evaluation showed basal cortisol 7 µg/dL, ACTH 15.7 pg/mL, DHEAS 1152 ng/mL (189-2050 ng/mL), 1 mg overnight dexamethasone suppression test 2.3 ug/dL, aldosterone 9.9 ng/dL, direct renin concentration 36.8 uIU/mL, plasma metanephrines 0.3 nmol/L (&amp;lt;0.5 nmol/L) and plasma normetanephrines 1.3 nmol/L (&amp;lt;0.9 nmol/L). It was not possible to change anti-hypertensive medications to investigate PA. A 0.3 mg clonidine suppression test did not suppress normetanephrine levels, confirming the biochemical diagnosis of pheochromocytoma. Then, alpha-blockade with doxazosin 4 mg was started and the patient underwent right adrenalectomy. Pathological examination revealed an adenoma with immunohistochemistry positive for CYP11B2. BP control was achieved with only two medications and aldosterone decreased to 3 ng/dL confirming PA. Plasma normetanephrine levels remained elevated post-surgery and only normalized after the CPAP regular use.Clinical lessons: Chronic activation of sympathetic autonomic drive in OSA can increase norepinephrine and normetanephrine levels. OSA is a very prevalent disease and it is frequently associated with RH. Therefore, OSA should be considered a possible cause of pseudopheochromocytoma in hypertensive patients. Presentation: 6/3/2024

9398 Early Identification of Impending Thyroid Storm Leading to Improved Thyrotoxic Induce Cardiomyopathy

Abstract Disclosure: D.H. Sacoto: None. D. Patel: None. A. De Rosairo: None. K. Madani: None. B. Singh: None. A. Bonilla Campos: None. R. Belokovskaya: None. F. Alberto A.: None. Introduction: Heart failure can be the leading presentation in 6% of thyroid storm cases and is the leading cause of death, particularly in elderly patients. However, its importance lies in symptom control and heart function reversibility once the euthyroid state is achieved. We present a caseof thyroid storm-induced atrial fibrillation (Afib) leading to severe systolic dysfunction. Case: A 61-year-old female with a history of Graves’ disease (GD) presented to the ED with two months of palpitations and one week of shortness of breath. There were bibasilar lung crackles, irregular heart rhythm, pedal edema, and thyromegaly at the examination. EKG was consistent with Afib with rapid ventricular response (123-135 beats per minute); She was tachypneic (respiratory rate: 40 per minute) and hypoxemic (87% O2 saturation), which required bilevel positive airway pressure. Otherwise, hemodynamically stable (BP: 127/106 mmHg). Laboratories showed negative troponin T (&amp;lt;0.010 ng/mL, n &amp;lt;0.01 ng/mL). However, elevation of Pro-B-type natriuretic peptide (6000 pg/mL, n &amp;lt;125 pg/mL), an x-ray displaying bibasilar pleural effusions and an echocardiogram demonstrating a severely reduced ejection fraction (EF) (21%, n 50-70%), myocardial perfusion scan was normal. Thyroid evaluation showed a suppressed TSH (&amp;lt;0.01 uIU/mL, n 0.27-4.20 uIU/mL) with elevated free T4 (5.8 ng/dL, n 0.9-1.8 ng/dL), free T3 (202 ng/dL, n 2.0-4.4 ng/dL), and TSI (8.25 IU/L, n 0-0.55 IU/L). A thyroid ultrasound revealed increased vascular flow on the left thyroid lobe. A Burh-Schakowsky score of 45 points was consistent with impending thyroid storm. She was started on methimazole, cholestyramine, and propranolol. Three months follow-up, she was asymptomatic, TSH normalized (4.12 uIU/mL), and mild improvement of cardiac EF 25%. Discussion: A thyroid storm in the setting of GD often presents after precipitating factors such as surgery, infection, or, as in our case, anti-thyroid medication non-compliance. Increased thyroid hormone levels upregulate cardiac β receptors, enhancing sensitivity to sympathetic innervation. These can shorten the refractory period of cardiomyocytes, leading to tachyarrhythmias, with Afib occurring in 20% of patients. Chronic tachycardia finally impairs left ventricle function, with heart failure as an outcome. A high index of suspicion and the ability of early diagnosis of impending thyroid storm is critical since the first laboratory confirmation is often delayed, and second, either anti-thyroid medication, radioactive iodine ablation or thyroidectomy, in addition to non-selective beta-blockers, can reverse cardiac dysfunction and lead to clinical improvement as early as 12 -Twenty-four hours of medical treatment. In our case, the early diagnosis and treatment of thyroid storm, in addition to the rate control prevented a deadly outcome and contributed to the improvement of heart failure. Presentation: 6/1/2024

Phenotypes based on respiratory drive and effort to identify the risk factors when P0.1 fails to estimate ∆PES in ventilated children.

Monitoring respiratory effort and drive during mechanical ventilation is needed to deliver lung and diaphragm protection. Esophageal pressure (∆PES) is the gold standard measure of respiratory effort but is not routinely available. Airway occlusion pressure in the first 100ms of the breath (P0.1) is a readily available surrogate for both respiratory effort and drive but is only modestly correlated with ∆PES in children. We sought to identify risk factors for P0.1 over or underestimating ∆PES in ventilated children. Secondary analysis of physiological data from children and young adults enrolled in a randomized controlled trial testing lung and diaphragm protective ventilation in pediatric acute respiratory distress syndrome (PARDS) (NCT03266016). ∆PES (∆PES-REAL), P0.1 and predicted ∆PES (∆PES-PRED = 5.91*P0.1) were measured daily to identify phenotypes based upon the level of respiratory effort and drive: one passive (no spontaneous breathing), three where ∆PES-REAL and ∆PES-PRED were aligned (low, normal, and high effort and drive), two where ∆PES-REAL and ∆PES-PRED were mismatched (high underestimated effort, and overestimated effort). Logistic regression models were used to identify factors associated with each mismatch phenotype (High underestimated effort, or overestimated effort) as compared to all other spontaneous breathing phenotypes. We analyzed 953 patient days (222 patients). ∆PES-REAL and ∆PES-PRED were aligned in 536 (77%) of the active patient days. High underestimated effort (n = 119 (12%)) was associated with higher airway resistance (adjusted OR 5.62 (95%CI 2.58, 12.26) per log unit increase, p < 0.001), higher tidal volume (adjusted OR 1.53 (95%CI 1.04, 2.24) per cubic unit increase, p = 0.03), higher opioid use (adjusted OR 2.4 (95%CI 1.12, 5.13, p = 0.024), and lower set ventilator rate (adjusted OR 0.96 (95%CI 0.93, 0.99), p = 0.005). Overestimated effort was rare (n = 37 (4%)) and associated with higher alveolar dead space (adjusted OR 1.05 (95%CI 1.01, 1.09), p = 0.007) and lower respiratory resistance (adjusted OR 0.32 (95%CI 0.13, 0.81), p = 0.017). In patients with PARDS, P0.1 commonly underestimated high respiratory effort particularly with high airway resistance, high tidal volume, and high doses of opioids. Future studies are needed to investigate the impact of measures of respiratory effort, drive, and the presence of a mismatch phenotype on clinical outcome. NCT03266016; August 23, 2017.

Pilot Study: Behavioral and Medical Clinical Partnership for Optimization of Positive Airway Pressure Therapy in Pediatric Patients

BackgroundTo assess the effectiveness of a structured algorithm for pediatric positive airway pressure (PAP) initiation for the treatment of obstructive sleep apnea (OSA). MethodsAn algorithm was created to support pediatric PAP use and identify patients who could benefit from early behavioral consultation and education. Sleep providers implemented a unified introduction to PAP therapy with the PAP therapy toolkit. Through a collaborative approach with the medical equipment companies, pediatric patients were provided with PAP equipment before PAP titration studies and were allowed a gradual initiation of PAP therapy. PAP downloads were reviewed to determine improvements in compliance measured by percent of average days used and average minutes per night used. ResultsThirty-eight pediatric patients completed the PAP therapy algorithm. There was significant improvement in PAP compliance in percentage of days used (paired t test P value = 0.04), as well as an improvement (although not statistically significant) in average nightly use. Patients benefitted from close follow-up visits with the sleep advanced practice providers. Patients seen for the consultation with the pediatric behavioral psychologist showed statistically significant improvement in both percentage of days and average nightly use. ConclusionsOur pilot study shows that a behavioral and medical partnership using a structured algorithm was feasible and resulted in improved PAP compliance for our pediatric patients.

Cone beam computed tomography changes upon oral appliance therapy for adult patients with obstructive sleep apnea: A non-randomized clinical trial.

Obstructive sleep apnea (OSA) is caused by narrowing or obstruction of the airway lumen at single or multiple levels of the airway, starting from the nasal cavity up to the larynx. Oral appliance therapy for the management of OSA is prescribed as an alternative treatment option for patients with mild to moderate OSA who fail to adhere to Continuous Positive Airway Pressure (CPAP) therapy. Treatment with oral appliances addresses the craniofacial deficiencies that cause OSA by providing means to mandibular advancement and palatal expansion, thus opening the airways and potentially preventing airway collapse during sleep. Imaging the upper airway is employed to investigate the narrowing or the obstruction in the airway. Three-dimensional imaging modalities such as cone beam computed tomography (CBCT) allow for detecting obstructions before commencing treatment and for evaluating changes in the upper airway dimensions after treatment. To evaluate the effect of the biomimetic oral appliance therapy (BOAT) device on the airway measurements taken from a CBCT before and after treatment in correlation with the changes in the AHI. A non-randomized clinical trial. About 17 patients with mild-moderate OSA (9 males, 8 females; age, mean [SD]: 45.76 [10.31]) underwent BOAT therapy. Subjects had 2 months of follow-up visits, including examinations for progress and adjustment of the appliances. The mean apnea-hypopnea index (AHI) with no appliance in the mouth before BOAT and after treatment was recorded. The midpalate screw mechanism of the appliance was advanced once per week. The subjects were asked to wear the appliance for 10 to 12 h/d and night. Pre and Post CBCT were taken. Paired T-test was used to analyze the results. The treatment duration was 15.4 ± 6.3 months. Before treatment, at the diagnosis stage, the mean AHI of the sample (n = 17) was 24.0. After treatment, the mean AHI fell by 5% to 22.8% (P = .019), indicating enhanced upper airway functions. Airway measurements from the CBCT were not statistically significant despite improvement in the polysomnographic parameters. CBCT is a valuable tool for airway assessment and the determination of upper airway anatomic risk factors for OSA.

Clinical characteristics of obstructive sleep apnea patients with residual sleepiness

ObjectiveThis meta-analysis examines the clinical characteristics of CPAP-treated obstructive sleep apnea (OSA) patients with residual excessive sleepiness (RES).MethodWe conducted a search for articles published from inception to March 16, 2024, in PubMed, Embase, Cochrane Library, and Web of Science. Seven studies were included in this meta-analysis.ResultsThe meta-analysis revealed that continuous positive airway pressure (CPAP)-treated OSA patients with RES were characterized by higher Epworth Sleepiness Scale and Depression Scale scores, lower body mass index (BMI) and apnea-hypopnea index (AHI) before CPAP treatment. RES patients also exhibit poorer CPAP adherence. Being female was also associated with RES.ConclusionBeing female, having lower BMI and AHI, and more severe daytime sleepiness and depressive symptoms before CPAP treatment, and lower CPAP adherence were characteristics of OSA patients with RES. These factors may prove helpful in identifying CPAP-treated OSA patients who may need additional treatment to minimize RES.

Impact of early continuous positive airway pressure in the delivery room (DR-CPAP) on neonates < 1500 g in a low-resource setting: a protocol for a pilot feasibility and acceptability randomized controlled trial

BackgroundPreterm birth is the leading cause of childhood mortality, and respiratory distress syndrome is the predominant cause of these deaths. Early continuous positive airway pressure is effective in high-resource settings, reducing the rate of continuous positive airway pressure failure, and the need for mechanical ventilation and surfactant. However, most deaths in preterm infants occur in low-resource settings without access to mechanical ventilation or surfactant. We hypothesize that in such settings, early continuous positive airway pressure will reduce the rate of failure and therefore preterm mortality.MethodsThis is a mixed methods feasibility and acceptability, single-center pilot randomized control trial of early continuous positive airway pressure among infants with birthweight 800–1500 g. There are two parallel arms: (i) application of continuous positive airway pressure; with optional oxygen when indicated; applied in the delivery room within 15 min of birth; transitioning to bubble continuous positive airway pressure after admission to the neonatal unit if Downes Score ≥ 4 (intervention), (ii) supplementary oxygen at delivery when indicated; transitioning to bubble continuous positive airways pressure after admission to the neonatal unit if Downes Score ≥ 4 (control). A two-stage consent process (verbal consent during labor, followed by full written consent within 24 h of birth) and a low-cost third-party allocation process for randomization will be piloted.We will use focus group discussions and key informant interviews to explore the acceptability of the intervention, two-stage consent process, and trial design. We will interview healthcare workers, mothers, and caregivers of preterm infants. Feasibility will be assessed by the proportion of infants randomized within 15 min of delivery; the proportion of infants in the intervention arm receiving CPAP within 15 min of delivery; and the proportion of infants with primary and secondary outcomes measured successfully.DiscussionThis pilot trial will enhance our understanding of methods and techniques that can enable emergency neonatal research to be carried out effectively, affordably, and acceptably in low-resource settings. This mixed-methods approach will allow a comprehensive exploration of parental and healthcare worker perceptions, experiences, and acceptance of the intervention and trial design.Trial registrationThe study is registered on the Pan African Clinical Trials Registry (PACTR) PACTR202208462613789. Registered 08 August 2022. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=23888.

Induction of subject-ventilator asynchrony by variation of respiratory parameters in a lung injury model in pigs

BackgroundSubject-ventilator asynchrony (SVA) was shown to be associated with negative clinical outcomes. To elucidate pathophysiology pathways and effects of SVA on lung tissue histology a reproducible animal model of artificially induced asynchrony was developed and evaluated.MethodsAlterations in ventilator parameters were used to induce the three main types of asynchrony: ineffective efforts (IE), auto-triggering (AT), and double-triggering (DT). Airway flow and pressure, as well as oesophageal pressure waveforms, were recorded, asynchrony cycles were manually classified and the asynchrony index (AIX) was calculated. Bench tests were conducted on an active lung simulator with ventilator settings altered cycle by cycle. The developed algorithm was evaluated in three pilot experiments and a study in pigs ventilated for twelve hours with AIX = 25%.ResultsIE and AT were induced reliably and fail-safe by end-expiratory hold and adjustment of respiratory rate, respectively. DT was provoked using airway pressure ramp prolongation, however not controlled specifically in the pilots. In the subsequent study, an AIX = 28.8% [24.0%-34.4%] was induced and maintained over twelve hours.ConclusionsThe method allows to reproducibly induce and maintain three clinically relevant types of SVA observed in ventilated patients and may thus serve as a useful tool for future investigations on cellular and inflammatory effects of asynchrony.

Noninvasive Respiratory Support for Pediatric Critical Asthma.

Pediatric asthma is a significant cause of emergency department visits and hospital admissions. While most patients respond well to standard pharmacologic treatments, those with more severe disease frequently require noninvasive respiratory support (NRS) and adjunct therapies, or admission to an intensive care unit-a condition termed critical asthma. NRS modalities include high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and noninvasive ventilation (NIV) to deliver standard air-oxygen mixtures or helium-oxygen (heliox). Each NRS modality offers distinct physiological benefits, primarily aimed at reducing work of breathing, enhancing gas exchange, and optimizing aerosol delivery. Despite the growing use of NRS, robust evidence supporting its efficacy in pediatric critical asthma is limited, with few published clinical trials and a heavy reliance on observational studies to inform clinical practice. This narrative review explores the current evidence, physiological rationale, practical considerations, and future research directions for the use of NRS in pediatric critical asthma. The goal is to provide clinicians with a comprehensive overview of the benefits and limitations of NRS modalities to better inform therapeutic decisions and improve patient outcomes.

Signal detection of drugs associated with obstructive and central sleep apnoea

We aim to discover new safety signals of drug-induced sleep apnoea (SA), a global health problem affecting approximately 1 billion people worldwide.We first conducted a series of sequence symmetry analyses (SSA) in a cohort composed from all patients who received a first SA diagnosis or treatment between 2006 and 2018 in the Echantillon Généraliste des Bénéficaires (EGB), a random sample of the French healthcare database. We used two primary outcomes to estimate the sequence ratio (SR) for all drug classes available in France: a sensitive one (diagnosis or treatment of SA) and a specific one (Positive Airway Pressure (PAP) therapy). We then performed disproportionality analyses using the “Bayesian neural network method” on all cases of sleep apnoea (MedDRA high level term) reported up to November 2023 in the World Health Organisation (WHO) pharmacovigilance database.Among the 728,167 individuals, 46,193 had an incident diagnosis or treatment for SA and 17,080 had started an incident treatment by PAP therapy. Fifty-eight drug classes had a significant SR, with 7 considered highly plausible: opium alkaloids and derivatives, benzodiazepine derivatives, other centrally acting agents, other anxiolytics, carbamic acid esters, quinine and derivatives and antivertigo preparations; with consistent signals found for the first 3 drug classes in the disproportionality analysis.In this signal detection study, we found that opioids, benzodiazepines (but not Z-drugs) and myorelaxing agents are associated with the onset or aggravation of SA. Moreover, a new safety signal for antivertigo preparations such as betahistine emerged and needs to be further explored.

Non-invasive positive pressure ventilation for acute asthma in children.

Asthma is one of the most common reasons for hospital admission among children, with significant economic burden and impact on quality of life. Non-invasive positive pressure ventilation (NPPV) is increasingly used in the care of children with acute asthma, although the evidence supporting it is weak, and clinical guidelines do not offer any recommendations on its routine use. However, NPPV might be an effective way to improve outcomes for some children with asthma. A previous review did not demonstrate a clear benefit, but was limited by few studies with small sample sizes. This is an update of the previous review. To assess the benefits and harms of NPPV as an add-on therapy to usual care (e.g. bronchodilators and corticosteroids) in children (< 18 years) with acute asthma. We searched the Cochrane Airways Group Specialised Register, CENTRAL, MEDLINE, and Embase. We also conducted a search of ClinicalTrials.gov and the WHO ICTRP. We searched all databases from their inception to March 2023, with no restrictions on language of publication. We included randomised clinical trials (RCTs) assessing NPPV as add-on therapy to usual care versus usual care for children hospitalised for acute asthma exacerbations. We used standard Cochrane methods. We included three RCTs randomising 60 children with acute asthma to NPPV and 60 children to control. All included trials assessed the effects of bilevel positive airway pressure (BiPAP) for acute asthma in a paediatric intensive care unit (PICU) setting. None of the trials used continuous positive airway pressure (CPAP). The controls received standard care. The median age of children ranged from three to six years, and asthma severity ranged from moderate to severe. Our primary outcome measures were all-cause mortality, serious adverse events, and asthma symptom score. Secondary outcomes were non-serious adverse events, health-related quality of life, arterial blood gases and pH, pneumonia, cost, and PICU length of stay. None of the trials reported any deaths or serious adverse events (except one trial that reported intubation rate). Two trials reported asthma symptom score, each demonstrating reductions in asthma symptoms in the BiPAP group. In one trial, the asthma symptom score was (mean difference (MD) -2.50, 95% confidence interval (CI) -4.70 to -0.30, P = 0.03; 19 children) lower in the BiPAP group. In the other trial, a cross-over trial, BiPAP was associated with a lower mean asthma symptom score (MD -3.7; 16 children; very low certainty evidence) before cross-over, but investigators did not report a standard deviation, and it could not be estimated from the first phase of the trial before cross-over. The reduction in both trials was above our predefined minimal important difference. Overall, NPPV with standard care may reduce asthma symptom score compared to standard care alone, but the evidence is very uncertain. The only reported serious adverse event was intubation rate in one trial. The trial had an intubation rate of 40% and showed that BiPAP may result in a large reduction in intubation rate (risk ratio 0.47, 95% CI 0.23 to 0.95; 78 children), but the evidence is very uncertain. Post hoc analysis showed that BiPAP may result in a slight decrease in length of PICU stay (MD -0.87 day, 95% CI -1.52 to -0.22; 100 children), but the evidence is very uncertain. Meta-analysis or Trial Sequential Analysis was not possible because of insufficient reporting and different scoring systems. All three trials had high risk of bias with serious imprecision of results, leading to very low certainty of evidence. The currently available evidence for NNPV is uncertain. NPPV may lead to an improvement in asthma symptom score, decreased intubation rate, and slightly shorter PICU stay; however, the evidence is of very low certainty. Larger RCTs with low risk of bias are warranted.

Timing of induction of labor in suspected macrosomia: retrospective cohort study, systematic review and meta-analysis.

Large-for-gestational age (LGA) is associated with several adverse maternal and neonatal outcomes. Although many studies have found that early induction of labor (IOL) in case of a LGA fetus reduces the incidence of shoulder dystocia, no current guidelines recommend this particular clinical strategy, owing to concerns about increased rates of Cesarean delivery (CD) and neonatal complications. The purpose of this study was to assess whether the timing of IOL in LGA fetuses affected maternal and neonatal outcomes in a single center, and to combine these results with evidence reported in the literature. This study comprised two parts. The first part was a retrospective cohort study that included consecutive patients with a singleton pregnancy and an estimated fetal weight ≥ 90th percentile on ultrasound between 35 + 0 and 39 + 0 weeks' gestation, who were eligible for normal vaginal delivery. The second part of the study was a systematic review of the literature and meta-analysis, including the results of our cohort study as well as those of previous studies that compared IOL with expectant management in patients with a LGA fetus. The perinatal outcomes of the study were CD, operative vaginal delivery, shoulder dystocia, brachial plexus palsy, anal sphincter injury, postpartum hemorrhage, Apgar score, umbilical artery pH, admission to the neonatal intensive care unit, use of continuous positive airway pressure, intracranial hemorrhage, need for phototherapy and bone fracture. Of the 547 patients included in this retrospective cohort study, 329 (60.1%) underwent IOL and 218 (39.9%) experienced spontaneous labor. Following covariate balancing, the odds of CD were significantly higher in the IOL group compared with the spontaneous-labor group. This difference only became apparent beyond 40 weeks' gestation (hazard ratio, 1.90; P = 0.030). The difference between the IOL and spontaneous-labor groups for the rate of shoulder dystocia was not statistically significant (hazard ratio, 1.57; P = 0.200). Seventeen studies, in addition to our own results, were included in the systematic review and meta-analysis, giving a total population of 111 300 participants. Although there was no significant difference in the rate of CD between IOL and expectant management after pooling the results of included studies, the risk for shoulder dystocia was significantly lower in the IOL group (odds ratio (OR), 0.64 (95% CI, 0.42-0.98); I2 = 19% from 12 studies) when considering only IOL performed before 40 + 0 weeks. When the studies in which IOL was carried out exclusively before 40 + 0 weeks were removed from the analysis, the risk for CD in the remaining studies was significantly higher in the IOL group (OR, 1.46 (95% CI, 1.02-2.09); I2 = 56%). There were no statistically significant differences between the IOL and expectant-management groups for the remaining perinatal outcomes. Nulliparity, history of CD and low Bishop score, but not method of induction, were independent risk factors for intrapartum CD in patients that underwent IOL for LGA. The timing of IOL in patients with suspected macrosomia significantly impacts on perinatal adverse outcomes. IOL has no impact on rates of shoulder dystocia but increases the odds of CD when considered irrespective of gestational age; in contrast, IOL may decrease the risk of shoulder dystocia without increasing the risk of other adverse maternal outcomes, in particular CD, when performed before 40 + 0 weeks (GRADE: low/very low). © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Activation of Automatic Tube Compensation Mode Attenuates Auto-PEEP in Chronic Obstructive Pulmonary Disease Patients.

Dynamic hyperinflation in chronic obstructive pulmonary disease (COPD) results in intrinsic positive end-expiratory pressure (auto-PEEP). Automatic tube compensation (ATC) is used to increase airway pressure in COPD and overcome endotracheal tube (ETT)-imposed respiratory workload. We aim to investigate effects of ATC activation on auto-PEEP decrease in COPD. ATC was activated three times a day (1 min duration) in the morning, evening, and night shift. Auto-PEEP was measured for the 1 min period (every 6 s) following ATC activation. Linear mixed model (LMM) was used to measure changes in auto-PEEP and compare with baseline value. Age, gender, and COPD types were inserted in model as covariates and analyzed using SPSS. A total of 60 patients including COPD (n = 40) and COPD with exacerbation (n = 20) were included. Compared with exacerbated COPD, baseline auto-PEEP in COPD was significantly lower in morning (p = 0.011), evening (p = 0.043), and night shift (p = 0.007). After ATC activation, auto-PEEP decreased significantly in COPD in morning, evening, and night (p = 0.001), but magnitude of this decrease was notably larger in COPD than in exacerbated COPD (p = 0.001). Moreover, there was a significant relationship between COPD exacerbation and changes in auto-PEEP in morning (β = -0.27, p = 0.001), evening (β = -0.16, p = 0.001), and night (β = -0.26, p = 0.001). The activation of ATC mode in COPD patients under mechanical ventilation could decrease the value of auto-PEEP. Nevertheless, COPD patients with an exacerbation appear to benefit less from ATC activation.

The combination of postmortem sevoflurane ventilation and in situ topical cooling provides improved 6 hours lung preservation in an uncontrolled DCD porcine model

BackgroundRecent clinical series on donation after uncontrolled cardiovascular death (uDCD) reported successful transplantation of lungs preserved by pulmonary inflation up to 3h post-mortem. This study aims to investigate the additive effects of in situ lowering of intrathoracic temperature and sevoflurane preconditioning on lung grafts in a porcine uDCD model. MethodsAfter uDCD induction, donor pigs were allocated to one of the following groups: Control – static lung inflation only (SLI); TC – SLI + continuous intrapleural topical cooling (TC); or TC+Sevo – SLI + TC + sevoflurane. Lungs were retrieved 6h post-asystole and evaluated via ex vivo lung perfusion (EVLP) for 6h. A left single lung transplant was performed using lungs from the best performing group, followed by 4h of graft evaluation. ResultsAnimals that received topical cooling achieved intrathoracic temperature < 15°C within 1 hour after chest filling of coolant. Only lungs from donors that received TC and TC+Sevo completed the planned post-preservation 6h EVLP assessment. Despite similar early performance of the two groups on EVLP, the TC+Sevo group was superior - associated with overall lower airway pressures, higher pulmonary compliances, less edema development, and less release of inflammatory cytokines. Transplantation was performed using lungs from the TC+Sevo group, and excellent graft function was observed post-reperfusion. ConclusionPreservation of uDCD lungs with a combination of static lung inflation, topical cooling and sevoflurane treatment maintains good pulmonary function up to 6h post-mortem with excellent early post-lung transplant function. These interventions may significantly expand the clinical utilization of uDCD donor lungs.

The Effect of Lactic Acidosis on Neonatal Outcomes in Premature Infants

The aim of the study was to evaluate neonatal outcomes in preterm infants.Materials and methods. The study included 58 premature neonates divided into 2 groups: «A» (N=34) with an adverse neonatal period ending in death and «B» (N=24) who survived. Clinical assessment of the infant, measurement of blood gases, acid-base balance (ABB) and lactate, recording of lung ventilation parameters, calculation of mean airway pressure, oxygenation index (OI) and ventilation efficiency index (VEI), neurosonography and, in case of death, pathological and histological examination of the brain were performed.Results. Elevated lactate was found in 24 patients (70.5%) in group A and in 12 patients (50%) in group B. The mean lactate levels in groups A and B were 8.1±3.3 and 6.3±2.8 mmol/L, respectively. In group A, 19 (55.9%) infants had severe acidosis, corresponding to a pH of 7.19 to 6.80. In group B, only 8 (33.3%) infants had a pH between 7.0 and 7.19. At birth, neonates in both groups were found to have a base deficit (BD), which was significantly lower in group A than in group B (P=0.004). There were no trends toward reduction of acidosis or normalization of ABB in infants in group A. Plasma BE levels in group B had returned to normal by 96 hours postpartum. The frequency of grade II, III peri/intraventricular hemorrhage (PIVH) and hemorrhage of other localization in group A were 8 (23.5%), 9 (26.5%), and 3 (8.8%), respectively. In group B, grade I PIVH and hemorrhage of other localization occurred in 5 (20.8%) and 1 (4.2%) cases, respectively. In neonates with grade II PIVH, severe lactic acidosis was diagnosed at birth: venous blood pH was 6.97 [6.8; 7.22], BE was (–21.6) [–30; –7.2] mmol/L, lactate level was 8.5 [6.3; 12.9] mmol/L, and pO₂ was 50.5 [20.5; 64] mm Hg. In infants with grade III PIVH, pH was –7.26 [7.12; 7.28], BE was (–8.1) [–8.9; –7] mmol/L, lactate was 7.6 [4.8; 8.9] mmol/L, and pO₂ was 33 [30; 50] mm Hg. Cell damage of varying severity affected all brain structures, as evidenced by absence or deformation of nuclei and nucleoli, and peripheral chromatin condensation. Morphological immaturity of brain structures was another negative factor.Conclusion. Lactic acidosis diagnosed at birth in premature infants is one of the indicators of perinatal hypoxia severity. Critical pH, BE, and lactate levels, as well as lack of response to treatment, contribute to structural brain damage and worsen prognosis. Severe changes in oxygen and lactate levels that persist for two days after birth lead to severe PIVH and irreversible brain changes.

Effect of telemonitoring and as-needed patient support on positive airway pressure therapy adherence.

Obstructive sleep apnea (OSA) affects patient health and public welfare. Positive airway pressure (PAP) therapy is the preferred treatment of OSA, but therapy adherence rates remain suboptimal. Current literature demonstrates telemonitoring interventions to support improved PAP therapy adherence. To evaluate the effect of interval telemonitoring of PAP therapy data at 2 and 4 weeks after treatment initiation in patients with moderate-to-severe obstructive sleep apnea with as-needed patient support and troubleshooting by telephone consultation. Ninety-nine participants were enrolled in this study, 50 in the control group and 49 in the intervention group. Data were analyzed using descriptive and inferential statistics using SPSS 28.0 software. The primary outcome of interest was 90-day PAP adherence. Mean PAP adherence scores diverged at 90 days after PAP initiation, with the intervention group having a significantly higher mean score (M = 49.24, SD = 38.18) relative to the control group (M = 36.38, SD = 37.69). Likewise, continued PAP usage at 90 days after therapy initiation diverged between participant groups, with the intervention group having a significantly higher mean score (M = 89.80, SD = 30.58) relative to the control group (M = 72.00, SD = 45.36). The intervention resulted in significantly higher mean PAP adherence and a greater percentage of participants demonstrating continued PAP usage at 90 days after therapy initiation but did not result in a statistically significant increase in what is considered and defined as "good PAP adherence" (adherence of ≥70%). Data-triggered telemonitoring protocols offer supplementary support to patients in need and improve PAP adherence.

Cardiac remodelling in patients with atrial fibrillation and obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) can cause left atrial (LA) and left ventricular (LV) remodelling, which is linked to atrial fibrillation (AF). Whether continuous positive airway pressure (CPAP) can reverse LA and LV remodelling in patients with OSA and paroxysmal AF (PAF) has yet to be studied. We assessed the impact of CPAP treatment on LA and LV size and function in patients with OSA and PAF before and after catheter ablation. In a randomised controlled trial, we screened patients with PAF for OSA. We enrolled patients with an Apnoea-Hypopnoea Index ≥15/hour. The burden of AF was monitored by an implantable loop recorder in all patients. Patients were then randomised to CPAP treatment or standard care. Transthoracic echocardiography was performed at baseline and after 6 and 12 months to assess LV and LA function and remodelling with advanced echocardiographic imaging techniques. We enrolled 109 patients (63±7 years, body mass index 29.6±4.3, 76% men). 83 patients were scheduled for pulmonary vein isolation (PVI) and 26 for clinical follow-up only. 55 patients were randomised to CPAP and 54 to standard care. The burden of AF decreased significantly in patients who underwent PVI irrespective of treatment with CPAP (p for difference ≤0.001). Patients in the study group had LV ejection fraction (LVEF) and LV global longitudinal strain (GLS) within the normal range, increased LA Volume Index (LAVI), LA volume (by speckle tracking) and decreased LA reservoir strain at baseline. We did not observe any improvement in LVEF, GLS, LAVI, LA volume or LA reservoir strain in either group during the 12 months of follow-up. In patients with PAF and OSA, treatment with CPAP was not associated with reverse LA remodelling within 12 months of follow-up.