Non-invasive versus invasive respiratory support in preterm infants.

Respiratory insufficiency is almost ubiquitous in infants born preterm, with its incidence increasing with lower gestational age. A wide range of respiratory support management strategies are available for these infants, separable into non-invasive and invasive forms of respiratory support. Here we review the history and evolution of respiratory care for the preterm infant and then examine evidence that has emerged to support a non-invasive approach to respiratory management where able. Continuous positive airway pressure (CPAP) is the non-invasive respiratory support mode currently with the most evidence for benefit. CPAP can be delivered safely and effectively and can commence in the delivery room. Particularly in early life, time spent on non-invasive respiratory support, avoiding intubation and mechanical ventilation, affords benefit for the preterm infant by virtue of a lessening of lung injury and hence a reduction in incidence of bronchopulmonary dysplasia. In recent years, enthusiasm for application of non-invasive support has been further bolstered by new techniques for administration of exogenous surfactant. Methods of less invasive surfactant delivery, in particular with a thin catheter, have allowed neonatologists to administer surfactant without resort to endotracheal intubation. The benefits of this approach appear to be sustained, even in those infants subsequently requiring mechanical ventilation. This cements the notion that any reduction in exposure to mechanical ventilation leads to alleviation of injury to the vulnerable preterm lung, with a long-lasting effect. Despite the clear advantages of non-invasive respiratory support, there will continue to be a role for intubation and mechanical ventilation in some preterm infants, particularly for those born <25 weeks' gestation. It is currently unclear what role early non-invasive support has in this special population, with more studies required.

Snoring Survivors: the impact of obstructive sleep apnoea and continuous positive airway pressure use on in-hospital mortality, length of stay and costs among patients hospitalised with acute cardiovascular disease - A retrospective analysis of 2016-2019 National Inpatient Sample Data.

BACKGROUND: The routine administration of supplemental oxygen to non-hypoxic patients with acute myocardial infarction (AMI) has been abandoned for lack of mortality benefit. However, the benefits of continuous positive airway pressure (CPAP) use in patients hospitalised with acute cardiovascular disease and concomitant obstructive sleep apnoea (OSA) remain to be elucidated. METHODS: In this retrospective case-control analysis, using 10th International Classification of Diseases, Clinical Modification (ICD-10) codes, we searched the 2016-2019 Nationwide Inpatient Sample for patients diagnosed with unstable angina (UA), AMI, acute decompensated heart failure (ADHF) and atrial fibrillation with rapid ventricular response (AFRVR), who also carried a diagnosis of OSA. We identified in-hospital CPAP use with ICD-10-Procedure Coding System codes. In-hospital death, length of stay (LOS) and hospital charges were compared between patients with and without OSA, and between OSA patients with and without CPAP use. RESULTS: Our sample included 2 959 991 patients, of which 1.5% were diagnosed with UA, 30.3% with AMI, 37.5% with ADHF and 45.8% with AFRVR. OSA was present in 12.3%. Patients with OSA were more likely to be younger, male, smokers, obese and have chronic obstructive pulmonary disease, renal failure and heart failure (p<0.001 for all). Patients with OSA had significantly lower in-hospital mortality (aOR 0.71, 95% CI (0.7 to 0.73)). Among patients with OSA, CPAP use significantly increased the odds of in-hospital death (aOR 1.51, 95% CI (1.44 to 1.60)), LOS (adjusted mean difference of 1.49 days, 95% CI (1.43 to 1.55)) and hospital charges (adjusted mean difference of US$1168, 95% CI (273 to 2062)). CONCLUSION: Our study showed that patients with recognised OSA hospitalised for AMI, ADHF and AFRVR had significantly lower mortality regardless of CPAP use, while CPAP treatment among these patients was associated with significantly higher in-hospital mortality and resource utilisation. The routine use of CPAP during acute cardiovascular encounters could neutralise the impact of chronic intermittent ischaemic preconditioning.

Boosting obstructive sleep apnea therapy by non-pharmacological approaches: A network meta-analysis.

INTRODUCTION: Obstructive sleep apnea (OSA) is the most common breathing-related sleep disorder with a considerable economic burden, low diagnosis and treatment rates. Continuous positive airway pressure (CPAP/PAP) is the principal therapy for OSA treatment; nevertheless, effectiveness is often limited by suboptimal adherence. The present network meta-analysis aims to systematically summarize and quantify different interventions' effects on CPAP/PAP adherence (such as mean usage CPAP or PAP in hours per night) in OSA patients, comparing Behavioral, Educational, Supportive and Mixed interventions in Randomized Control Trials (RCT). METHODS: We conducted a computer-based search using the electronic databases of Pubmed, Psycinfo, Scopus, Embase, Chinal and Medline until August 2022, selecting 50 RCT. RESULTS: By means of a random effect model network meta-analysis, results suggested that the most effective treatment in improving CPAP/PAP adherence was the Supportive approach followed by Behavioral Therapy focused on OSA treatment adherence. CONCLUSION: This network meta-analysis might encourage the most experienced clinicians and researchers in the field to collaborate and implement treatments for improving CPAP/PAP treatment adherence. Moreover, these results support the importance of multidisciplinary approaches for OSA treatment, which should be framed within a biopsychological model.

Successful application of airway pressure release ventilation in a child with severe acute respiratory distress syndrome induced by trauma: a case report.

BACKGROUND: Trauma has been identified as one of the risk factors for acute respiratory distress syndrome. Respiratory support can be further complicated by comorbidities of trauma such as primary or secondary lung injury. Conventional ventilation strategies may not be suitable for all trauma-related acute respiratory distress syndrome. Airway pressure release ventilation has emerged as a potential rescue method for patients with acute respiratory distress syndrome and hypoxemia refractory to conventional mechanical ventilation. However, there is a lack of research on the use of airway pressure release ventilation in children with trauma-related acute respiratory distress syndrome. We report a case of airway pressure release ventilation applied to a child with falling injury, severe acute respiratory distress syndrome, hemorrhagic shock, and bilateral hemopneumothorax. We hope this case report presents a potential option for trauma-related acute respiratory distress syndrome and serves as a basis for future research. CASE PRESENTATION: A 15-year-old female with falling injury who developed severe acute respiratory distress syndrome, hemorrhagic shock, and bilateral hemopneumothorax was admitted to the surgical intensive care unit. She presented refractory hypoxemia despite the treatment of conventional ventilation with deep analgesia, sedation, and muscular relaxation. Lung recruitment was ineffective and prone positioning was contraindicated. Her oxygenation significantly improved after the use of airway pressure release ventilation. She was eventually extubated after 12 days of admission and discharged after 42 days of hospitalization. CONCLUSION: Airway pressure release ventilation may be considered early in the management of trauma patients with severe acute respiratory distress syndrome when prone position ventilation cannot be performed and refractory hypoxemia persists despite conventional ventilation and lung recruitment maneuvers.

Normal saline for children with bronchiolitis: study protocol for a randomised controlled non-inferiority trial.

INTRODUCTION: Bronchiolitis is one of the most common reasons for hospital admissions in early childhood. As supportive treatment, some treatment guidelines suggest using nasal irrigation with normal saline (NS) to facilitate clearance of mucus from the airways. In addition, most paediatric departments in Denmark use nebulised NS for the same purpose, which can mainly be administered as inpatient care. However, no studies have ever directly tested the effect of saline in children with bronchiolitis. METHODS AND ANALYSIS: The study is an investigator-initiated, multicentre, open-label, randomised, controlled non-inferiority trial and will be performed at six paediatric departments in eastern Denmark. We plan to include 300 children aged 0-12 months admitted to hospital with bronchiolitis. Participating children are randomised 1:1:1 to nebulised NS, nasal irrigation with NS or no saline therapy. All other treatment will be given according to standard guidelines.The primary outcome is duration of hospitalisation, analysed according to intention-to-treat analysis using linear regression and Cox regression analysis. By including at least 249 children, we can prove non-inferiority with a limit of 12 hours admission, alpha 2.5% and a power of 80%. Secondary outcomes are need for respiratory support with nasal continuous positive airway pressure or high-flow oxygen therapy and requirement of fluid supplements (either by nasogastric tube or intravenous). ETHICS AND DISSEMINATION: This study may inform current practice for supportive treatment of children with bronchiolitis. First, if NS is found to be helpful, it may be implemented into global guidelines. If no effect of NS is found, we can stop spending resources on an ineffective treatment. Second, if NS is effective, but nasal irrigation is non-inferior to nebulisation, it may reduce the workload of nurses, and possible duration of hospitalisation because the treatment can be delivered by the parents at home. TRIAL REGISTRATION NUMBER: NCT05902702.

Time-Controlled Adaptive Ventilation (TCAV): a personalized strategy for lung protection.

Acute respiratory distress syndrome (ARDS) alters the dynamics of lung inflation during mechanical ventilation. Repetitive alveolar collapse and expansion (RACE) predisposes the lung to ventilator-induced lung injury (VILI). Two broad approaches are currently used to minimize VILI: (1) low tidal volume (LVT) with low-moderate positive end-expiratory pressure (PEEP); and (2) open lung approach (OLA). The LVT approach attempts to protect already open lung tissue from overdistension, while simultaneously resting collapsed tissue by excluding it from the cycle of mechanical ventilation. By contrast, the OLA attempts to reinflate potentially recruitable lung, usually over a period of seconds to minutes using higher PEEP used to prevent progressive loss of end-expiratory lung volume (EELV) and RACE. However, even with these protective strategies, clinical studies have shown that ARDS-related mortality remains unacceptably high with a scarcity of effective interventions over the last two decades. One of the main limitations these varied interventions demonstrate to benefit is the observed clinical and pathologic heterogeneity in ARDS. We have developed an alternative ventilation strategy known as the Time Controlled Adaptive Ventilation (TCAV) method of applying the Airway Pressure Release Ventilation (APRV) mode, which takes advantage of the heterogeneous time- and pressure-dependent collapse and reopening of lung units. The TCAV method is a closed-loop system where the expiratory duration personalizes VT and EELV. Personalization of TCAV is informed and tuned with changes in respiratory system compliance (CRS) measured by the slope of the expiratory flow curve during passive exhalation. Two potentially beneficial features of TCAV are: (i) the expiratory duration is personalized to a given patient's lung physiology, which promotes alveolar stabilization by halting the progressive collapse of alveoli, thereby minimizing the time for the reopened lung to collapse again in the next expiration, and (ii) an extended inspiratory phase at a fixed inflation pressure after alveolar stabilization gradually reopens a small amount of tissue with each breath. Subsequently, densely collapsed regions are slowly ratcheted open over a period of hours, or even days. Thus, TCAV has the potential to minimize VILI, reducing ARDS-related morbidity and mortality.

Cost-Utility Analysis of Continuous Positive Airway Pressure Therapy Compared With Usual Care for Obstructive Sleep Apnea in the Public Health System in Brazil.

OBJECTIVES: This study aimed to conduct a cost-utility analysis of continuous positive airway pressure (CPAP) therapy compared with usual care as treatment of moderate to severe cases of obstructive sleep apnea (OSA) in Brazil, where decentralized policies of CPAP provision are in place. METHODS: Markov cohort model comparing CPAP therapy with usual care, that is, no specific treatment for OSA, for moderate to severe cases was used. The payer perspective from the Unified Health System, Brazil, was adopted. Effectiveness parameters and costs related to health states were informed by literature review. Resource use related to CPAP therapy was defined by specialists and costs informed by recent purchase and leasing contracts. Incremental cost-effectiveness ratios were generated for purchase and leasing contracts to reflect current practices. A conservative willingness-to-pay threshold was set at 1 gross domestic product per capita per quality-adjusted life-year (QALY) (Brazilian reais [BRL] 40 712/QALY). Uncertainties were explored in deterministic and probabilistic sensitivity analyses. RESULTS: Incremental cost-effectiveness ratio for the purchase modality was 8303 BRL/QALY and for leasing 45 192 BRL/QALY. Considering the adopted willingness-to-pay threshold, provision of CPAP by the purchase modality was considered cost-effective but not the leasing modality. The parameter related to the greatest uncertainty was the reduction in the risk of having a stroke attributable to CPAP. Probabilistic analysis confirmed the robustness of results. CONCLUSIONS: CPAP therapy is a cost-effective alternative compared with usual care for moderate to severe OSA for the purchase modality. These results should help underpinning the decision making related to a uniform policy of CPAP provision across the country.

High-flow nasal cannula use in pediatric patients for other indications than acute bronchiolitis-a scoping review of randomized controlled trials.

The objective of the study is to summarize current literature on high-flow nasal cannula (HFNC) use for different indications in pediatric patient excluding acute bronchiolitis and neonatal care. The study design is a systematic scoping review. Pubmed, Scopus, and Web of Science databases were searched in February, 2023. All abstracts and full texts were screened by two independent reviewers. Randomized controlled trials focusing on HFNC use in pediatric patients (age < 18 years) were included. Studies focusing on acute bronchiolitis and neonatal respiratory conditions were excluded. Study quality was assessed by Cochrane risk of bias 2.0 tool. The main outcomes are patient groups and indications, key outcomes, and risk of bias. After screening 1276 abstracts, we included 22 full reports. Risk of bias was low in 11 and high in 5 studies. We identified three patient groups where HFNC has been studied: first, children requiring primary respiratory support for acute respiratory failure; second, perioperative use for either intraprocedural oxygenation or postoperative respiratory support; and third, post-extubation care in pediatric intensive care for other than postoperative patients. Clinical and laboratory parameters were assessed as key outcomes. None of the studies analyzed cost-effectiveness.Conclusion: This systematic scoping review provides an overview of current evidence for HFNC use in pediatric patients. Future studies should aim for better quality and include economic evaluation with cost-effectiveness analysis.Protocol registration: Protocol has been published https://osf.io/a3y46/ .

Obstructive sleep apnea for the rhinologist.

PURPOSE: Obstructive sleep apnea (OSA) is a ubiquitous disease defined by repetitive partial or complete cessation of airflow during sleep caused by upper airway collapse. Otolaryngologists play a crucial role in the management of OSA, which is rapidly evolving with the advent of new surgical techniques and medical devices. Here we review the medical and surgical treatment options for OSA with a focus on unique considerations for patients with OSA who undergo nasal, sinus, and skull base surgery. RECENT FINDINGS: Treatment of OSA includes both nonsurgical and surgical options. Positive airway pressure (PAP) therapy remains the first-line medical treatment for OSA, but alternatives such as oral appliance and positional therapy are viable alternatives. Surgical treatments include pharyngeal and tongue base surgery, hypoglossal nerve stimulation therapy, and skeletal surgery. Nasal surgery has been shown to improve sleep quality and continuous positive airway pressure (CPAP) tolerance and usage. Sinus and skull base patients with comorbid OSA have special perioperative considerations for the rhinologist to consider such as the need for overnight observation and timing of CPAP therapy resumption. SUMMARY: OSA patients present with special considerations for the rhinologist. Patients with moderate to severe OSA may benefit from overnight observation after ambulatory surgery, especially those with an elevated BMI, cardiopulmonary comorbidities, and those who are not using CPAP regularly at home. Though CPAP may be safely resumed in the perioperative setting of nasal, sinus, and skull base surgery, the exact timing depends on patient, surgeon, and systemic factors such as severity of OSA, CPAP pressures required, extent of surgery, and the postoperative monitoring setting. Lastly, nasal and sinus surgery can improve sleep quality and CPAP tolerance and compliance in patients with OSA.

Opioid sensitivity in treated and untreated obstructive sleep apnoea: a prospective cohort study.

BACKGROUND: Opioid administration to patients with obstructive sleep apnoea (OSA) is controversial because they are believed to be more sensitive to opioids. However, objective data on opioid effects in OSA are lacking. We tested the hypothesis that subjects with untreated OSA have increased sensitivity to opioids compared with subjects without OSA, or with OSA treated with continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BIPAP). METHODS: This was a single-centre, prospective cohort study in subjects without OSA (n=20), with untreated OSA (n=33), or with treated OSA (n=21). OSA diagnosis was verified using type III (in-home) polysomnography. Subjects received a stepped-dose remifentanil infusion (target effect-site concentrations of 0.5, 1, 2, 3, 4 ng ml-1). Primary outcome was miosis (pupil area fractional change), the most sensitive opioid effect. Secondary outcomes were ventilatory rate, end-expired CO2, sedation, and thermal analgesia. RESULTS: There were no differences in miosis between untreated OSA subjects (mean=0.51, 95% confidence interval [CI] 0.41-0.61) and subjects without OSA (mean=0.49, 95% CI 0.36-0.62) (mean difference=0.02, 95% CI -0.18 to 0.22); between treated OSA subjects (mean=0.56, 95% CI 0.43-0.68) and subjects without OSA (difference=0.07, 95% CI -0.16 to 0.29); or between untreated OSA and treated OSA (difference=-0.05, 95% CI -0.25 to 0.16). There were no significant differences between subjects without OSA, untreated OSA, and treated OSA in ventilatory rate, end-expired CO2, sedation, or thermal analgesia responses to remifentanil. There was no relationship between OSA severity and magnitude of opioid effects. CONCLUSIONS: Neither obstructive sleep apnoea nor obstructive sleep apnoea treatment affected sensitivity to the miotic, sedative, analgesic, or respiratory depressant effects of the opioid remifentanil in awake adults. These results challenge conventional notions of opioid effects in obstructive sleep apnoea. CLINICAL TRIAL REGISTRATION: NCT02898792 (clinicaltrials.gov).

Comparative Effectiveness of Supine Avoidance versus Continuous Positive Airway Pressure for Treating Supine-isolated Sleep Apnea: A Clinical Trial.

Rationale: About 20-35% of patients with obstructive sleep apnea (OSA) have supine-isolated OSA, for which supine sleep avoidance could be an effective therapy. However, traditional supine discomfort-based methods show poor tolerance and compliance to treatment and so cannot be recommended. Supine alarm devices show promise, but evidence to support favorable adherence to treatment and effectiveness at reducing excessive daytime sleepiness compared with continuous positive airway pressure (CPAP) remains limited. Objectives: To establish if alarm-based supine-avoidance treatment in patients with supine-isolated OSA is noninferior to CPAP in reducing daytime sleepiness. Methods: After baseline questionnaire administration and in-home supine-time and polysomnography assessments, patients with supine-isolated OSA and Epworth Sleepiness Scale scores ⩾8 were randomized to ⩾6 weeks of supine-avoidance or CPAP treatment, followed by crossover to the remaining treatment with repeat assessments. Noninferiority was assessed from change in Epworth Sleepiness Scale with supine avoidance compared with CPAP using a prespecified noninferiority margin of 1.5. Average nightly treatment use over all nights and treatment efficacy and effectiveness at reducing respiratory disturbances were also compared between treatments. Results: The reduction in sleepiness score with supine avoidance (mean [95% confidence interval], -1.9 [-2.8 to -1.0]) was noninferior to that with CPAP (-2.4 [-3.3 to -1.4]) (supine avoidance-CPAP difference, -0.4 [-1.3 to 0.6]), and the lower confidence limit did not cross the noninferiority margin of 1.5 (P = 0.021). Average treatment use was higher with supine avoidance compared with CPAP (mean ± standard deviation, 5.7 ± 2.4 vs. 3.9 ± 2.7 h/night; P < 0.001). Conclusions: In patients with supine-isolated OSA, vibrotactile supine alarm device therapy is noninferior to CPAP for reducing sleepiness and shows superior treatment adherence. Clinical trial registered with www.anzctr.org.au (ACTRN 12613001242718).

Less Invasive Surfactant Administration: A Viewpoint.

The standard of care in treating respiratory distress syndrome in preterm infants is respiratory support with nasal continuous positive airway pressure or a combination of continuous positive airway pressure and exogenous surfactant replacement. Endotracheal intubation, the conventional method for surfactant administration, is an invasive procedure associated with procedural and mechanical ventilation complications. The INSURE (intubation, surfactant administration, and extubation soon after) technique is an accepted method aimed at reducing the short-term complications and long-term morbidities related to mechanical ventilation but does not eliminate risks associated with endotracheal intubation and mechanical ventilation. Alternative methods of surfactant delivery that can overcome the problems associated with the INSURE technique are surfactant through a laryngeal mask, surfactant through a thin intratracheal catheter, and aerosolized surfactant delivered using nebulizers. The three alternative methods of surfactant delivery studied in the last two decades have advantages and limitations. More than a dozen randomized controlled trials have aimed to study the benefits of the three alternative techniques of surfactant delivery compared with INSURE as the control arm, with promising results in terms of reduction in mortality, need for mechanical ventilation, and bronchopulmonary dysplasia. The need to find a less invasive surfactant administration technique is a clinically relevant problem. Before broader adoption in routine clinical practice, the most beneficial technique among the three alternative strategies should be identified. This review aims to summarize the current evidence for using the three alternative techniques of surfactant administration in neonates, compare the three techniques, highlight the knowledge gaps, and suggest future directions. KEY POINTS: · The need to find a less invasive alternative method of surfactant delivery is a clinically relevant problem.. · Clinical trials that have studied alternative surfactant delivery methods have shown promising results but are inconclusive for broader adoption into clinical practice.. · Future studies should explore novel clinical trial methodologies and select clinically significant long term outcomes for comparison..

Bright light therapy for CPAP-resistant OSA symptoms.

STUDY OBJECTIVES: Sleep fragmentation and daytime sleepiness often persist in patients with sleep apnea despite correctly administered continuous positive airway pressure (CPAP). Our proof-of-concept study tested the acceptability and efficacy of morning bright light therapy (BLT) to improve sleep, circadian rhythms, and CPAP-resistant daytime symptoms in patients with sleep apnea. METHODS: In this within-subject crossover study, 14 individuals completed 4 weeks of BLT and sham BLT in randomized order. Outcomes included actigraphy-based objective sleep measures, sleepiness, depressive symptoms, and sleep-related functional impairment, analyzed with multilevel models. RESULTS: Patients experienced greater reductions in wake after sleep onset and increased amplitude of rest-activity rhythms in a shorter photoperiod with BLT compared with sham. Patients also reported reductions in self-reported sleepiness and depressive symptoms with BLT compared with sham only during the early stages of treatment and shorter photoperiod. CONCLUSIONS: These results suggest the potential for novel applications for existing chronotherapeutic interventions for improving symptoms and quality of life for those patients who experience residual symptoms with current available treatments. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Bright Light Therapy for Residual Daytime Symptoms Associated With Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT04299009; Identifier: NCT04299009. CITATION: Soreca I, Arnold N, Dombrovski AY. Bright light therapy for CPAP-resistant OSA symptoms. J Clin Sleep Med. 2024;20(2):211-219.

Continuous Positive Airway Pressure Effect on Progression of Retinal Disease in Patients with Sleep Apnea and Nonproliferative Diabetic Retinopathy: A Randomized Clinical Trial.

Rationale: Obstructive sleep apnea (OSA) is associated with impaired glycemic control and a higher risk of vascular complications, such as diabetic retinopathy. However, the effect of apnea-hypopnea suppression on retinal disease progression is unclear. Objectives: To evaluate the efficacy and safety of continuous positive airway pressure (CPAP) for the reduction of retinal lesions in patients with non-proliferative diabetic retinopathy (NPDR) and OSA. Methods: This open-label, parallel-group, randomized controlled trial was conducted between October 2016 and February 2020 at a university hospital in Spain. The date of final follow-up was March 2, 2021. Eighty-three patients with OSA and mild to moderate NPDR receiving stable treatment were randomized to receive CPAP and usual care (43 patients with 79 available eyes) or usual care alone (40 patients with 67 available eyes) for 52 weeks. The primary outcomes were the change in the percentage of eyes with retinal exudates and the number of retinal microhemorrhages from baseline to week 52. We also assessed the effects of both interventions on retinal thickness by means of optical coherence tomography, serum concentrations of glycated hemoglobin, blood pressure, lipid concentrations, sleepiness, and quality of life. Results: Fifty-two weeks of CPAP treatment was associated with reductions from baseline in the percentage of eyes with hard exudates (overall difference, -21.7%; P = 0.035) and in optical coherence tomography indices of retinal edema, including central subfield thickness and cube volume. However, in patients who met prespecified criteria for CPAP adherence, treatment was also associated with a higher number of retinal microhemorrhages at 52 weeks (intergroup adjusted difference, 6.0 [95% confidence interval, 0.6-11.5]; P = 0.029), which was directly related to prescribed pressure levels. CPAP treatment also improved glycemic control, sleepiness, and general health-related quality of life. Conclusions: In patients with OSA and NPDR, long-term CPAP treatment in addition to usual care may result in slower progression of retinal disease, although it could also induce an increase in retinal microhemorrhages. Clinical trial registered with www.clinicaltrials.gov (NCT02874313).

Continuous Positive Airway Pressure but Not GLP1-mediated Weight Loss Improves Early Cardiovascular Disease in Obstructive Sleep Apnea: A Randomized Proof-of-Concept Study.

Rationale: Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular (CV) morbidity and mortality, but the benefit of continuous positive airway pressure (CPAP) is uncertain. However, most randomized controlled trials have focused on the role of CPAP in secondary prevention, although there is growing evidence of a potential benefit on early CV disease. Weight loss in combination with CPAP may be superior but is difficult to achieve and maintain with conventional measures alone. Objectives: The aim of this study was to gain insights into the effect of CPAP on early atherosclerotic processes and to compare it with a glucagon-like peptide (GLP)-1-mediated weight loss regimen in patients with OSA. Methods: We performed a randomized proof-of-concept study comparing CPAP, a GLP1-mediated weight-loss regimen (liraglutide [Lir]), and both in combination for 24 weeks in 30 consecutive patients with OSA (apnea-hypopnea index >15 events/h; body mass index 30-40 kg/m2; and no history of diabetes, heart failure, or unstable CV disease). In addition to extensive evaluation for CV risk factors and endothelial function at baseline and end of study, subjects underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (18F-FDG PET-CT) for the measurement of aortic wall inflammation (target-to-background ratio) and coronary computed tomography angiography for semiautomated coronary plaque analysis. Results: Baseline characteristics were similar between groups. CPAP alone and in combination resulted in greater reduction in apnea-hypopnea index than Lir alone (mean difference, -45 and -43 events/h, respectively, vs. -12 events/h; P < 0.05). Both Lir and combination treatment led to significant weight loss, but only CPAP alone resulted in significant decrease in vascular inflammation (aortic wall target-to-background ratio from 2.03 ± 0.34 to 1.84 ± 0.43; P = 0.010), associated with an improvement in endothelial function and a decrease in C-reactive protein. Low-attenuation coronary artery plaque volume as a marker of unstable plaque also decreased with CPAP (from 571 ± 490 to 334 ± 185 mm3) and with combination therapy (from 401 ± 145 to 278 ± 126 mm3) but not with Lir. Conclusions: These data suggest that CPAP therapy, but not GLP1-mediated weight loss, improves vascular inflammation and reduces unstable plaque volume in patients with OSA. Further large randomized controlled studies are warranted to assess the benefit of CPAP therapy in modifying early CV disease. Clinical trial registered with www.clinicaltrials.gov (NCT04186494).

Airway pressure release ventilation for lung protection in acute respiratory distress syndrome: an alternative way to recruit the lungs.

PURPOSE OF REVIEW: Airway pressure release ventilation (APRV) is a modality of ventilation in which high inspiratory continuous positive airway pressure (CPAP) alternates with brief releases. In this review, we will discuss the rationale for APRV as a lung protective strategy and then provide a practical introduction to initiating APRV using the time-controlled adaptive ventilation (TCAV) method. RECENT FINDINGS: APRV using the TCAV method uses an extended inspiratory time and brief expiratory release to first stabilize and then gradually recruit collapsed lung (over hours/days), by progressively 'ratcheting' open a small volume of collapsed tissue with each breath. The brief expiratory release acts as a 'brake' preventing newly recruited units from re-collapsing, reversing the main drivers of ventilator-induced lung injury (VILI). The precise timing of each release is based on analysis of expiratory flow and is set to achieve termination of expiratory flow at 75% of the peak expiratory flow. Optimization of the release time reflects the changes in elastance and, therefore, is personalized (i.e. conforms to individual patient pathophysiology), and adaptive (i.e. responds to changes in elastance over time). SUMMARY: APRV using the TCAV method is a paradigm shift in protective lung ventilation, which primarily aims to stabilize the lung and gradually reopen collapsed tissue to achieve lung homogeneity eliminating the main mechanistic drivers of VILI.

Pediatric long-term noninvasive respiratory support in children with central nervous system disorders.

RATIONALE: The use of long-term noninvasive respiratory support is increasing in children along with an extension of indications, in particular in children with central nervous system (CNS) disorders. OBJECTIVE: The aim of this study was to describe the characteristics of children with CNS disorders treated with long-term noninvasive respiratory support in France. METHODS: Data were collected from 27 French pediatric university centers through an anonymous questionnaire filled for every child treated with noninvasive ventilatory support ≥3 months on 1st June 2019. MAIN RESULTS: The data of 182 patients (55% boys, median age: 10.2 [5.4;14.8] years old [range: 0.3-25]) were collected: 35 (19%) patients had nontumoral spinal cord injury, 22 (12%) CNS tumors, 63 (35%) multiple disabilities, 26 (14%) central alveolar hypoventilation and 36 (20%) other CNS disorders. Seventy five percent of the patients were treated with noninvasive ventilation (NIV) and 25% with continuous positive airway pressure (CPAP). The main investigations performed before CPAP/NIV initiation were nocturnal gas exchange recordings, alone or coupled with poly(somno)graphy (in 29% and 34% of the patients, respectively). CPAP/NIV was started in an acute setting in 10% of the patients. Median adherence was 8 [6;10] hours/night, with 12% of patients using treatment <4 h/day. Nasal mask was the most common interface (70%). Airway clearance techniques were used by 31% of patients. CONCLUSION: CPAP/NIV may be a therapeutic option in children with CNS disorders. Future studies should assess treatment efficacy and patient reported outcome measures.

Prophylactic Oropharyngeal Surfactant for Preterm Newborns at Birth: A Randomized Clinical Trial.

Importance: Preterm newborns at risk of respiratory distress syndrome are supported with continuous positive airway pressure (CPAP). Many newborns worsen despite CPAP and are intubated for surfactant administration, an effective therapy for treatment of respiratory distress syndrome. Endotracheal intubation is associated with adverse effects. Pharyngeal administration of surfactant to preterm animals and humans has been reported as an alternative. Objective: To assess whether giving prophylactic oropharyngeal surfactant to preterm newborns at birth would reduce the rate of intubation for respiratory failure. Design, Setting, and Participants: This unblinded, parallel-group randomized clinical trial (Prophylactic Oropharyngeal Surfactant for Preterm Infants [POPART]) was conducted from December 17, 2017, to September 11, 2020, at 9 tertiary neonatal intensive care units in 6 European countries. Newborns born before 29 weeks of gestation without severe congenital anomalies, for whom intensive care was planned, were eligible for inclusion. The data were analyzed from July 27, 2022, to June 20, 2023. Intervention: Newborns were randomly assigned to receive oropharyngeal surfactant at birth in addition to CPAP or CPAP alone. Randomization was stratified by center and gestational age (GA). Main Outcomes and Measures: The primary outcome was intubation in the delivery room for bradycardia and/or apnea or in the neonatal intensive care unit for prespecified respiratory failure criteria within 120 hours of birth. Caregivers were not masked to group assignment. Results: Among 251 participants (mean [SD] GA, 26 [1.5] weeks) who were well matched at study entry, 126 (69 [54.8%] male) with a mean (SD) birth weight of 858 (261) grams were assigned to the oropharyngeal surfactant group, and 125 (63 [50.4%] male) with a mean (SD) birth weight of 829 (253) grams were assigned to the control group. The proportion of newborns intubated within 120 hours was not different between the groups (80 [63.5%) in the oropharyngeal surfactant group and 81 [64.8%] in the control group; relative risk, 0.98 [95% CI, 0.81-1.18]). More newborns assigned to the oropharyngeal surfactant group were diagnosed with and treated for pneumothorax (21 [16.6%] vs 8 [6.4%]; P = .04). Conclusions and Relevance: This randomized clinical trial found that administration of prophylactic oropharyngeal surfactant to newborns born before 29 weeks' GA did not reduce the rate of intubation in the first 120 hours of life. These findings suggest that administration of surfactant into the oropharynx immediately after birth in addition to CPAP should not be routinely used. Trial Registration: EudraCT: 2016-004198-41.

Successful Virtual CPAP Set up in Obstructive Sleep Apnoea: A positive innovation during the pandemic.

BACKGROUND: Traditionally continuous positive airways pressure (CPAP) trials for obstructive sleep apnoea (OSA) are through face to face (F2F) set up. During Covid-19 pandemic CPAP was classed as aerosol-generating hence Leeds sleep service moved to a virtual service. Patients received equipment by post followed by virtual reviews (VR). We evaluated the adherence and symptomatic benefit of postal compared to F2F method. METHODS: Observational data were collected from databases monitoring CPAP loans. F2F patients met a sleep technician for hands on setup in 2019, and in 2020 postal patients received equipment, written guides, and links to custom made YouTube videos. All (F2F and postal) patients had a telephone and VR appointment to discuss symptoms, and CPAP machine (AirSense 10, ResMed Inc., San Diego, USA) data including data on usage and treatment apnoea-hypopnoea index (AHI). Data was analysed using unpaired T-tests, Mann-Whitney U tests, and chi-square tests to examine differences in means, medians, and proportions, respectively of the F2F and postal groups. RESULTS: Both groups (n = 1,221, 656 F2F, 53.7%) were similar in all categories except length of CPAP trial (postal 33 vs F2F 84 days,p < 0.0001), change in AHI (postal 22.4/Hr vs F2F 25.1/Hr,p = 0.04), and trial average use (postal 4.9 vs F2F 5.2 h,p = 0.04). There was no significant difference in the proportion of patients continuing with CPAP (postal 64%, F2F 66%, p = 0.71), the improvement in Epworth Sleepiness Score (ESS) (postal 6.9/24, F2F 7.1/24, p = 0.31) or the patient's subjective rating on whether they felt much better, better, the same or worse on CPAP (p = 0.27). Logistic regression showed factors which affected odds ratios of continuing CPAP were diagnostic AHI, treatment AHI, treatment ESS and how they felt on CPAP. Trial type did not affect the odds ratios of continuing CPAP. CONCLUSIONS: Postal CPAP trial patients had similar odds of continuing CPAP therapy compared to patients with F2F trials and achieved similar levels of ESS improvement and reporting feeling better on CPAP. This provides support for postal trials as a viable option post-pandemic.