Pulmonary gas exchange and ventilatory efficiency during exercise in health and diseases.

INTRODUCTION: Cardiopulmonary exercise testing (CPET) is nowadays used to study the exercise response in healthy subjects and in disease. Ventilatory efficiency is one of the main determinants in exercise tolerance, and its main variables are a useful tool to guide pathophysiologists toward specific diagnostic pathways, providing prognostic information and improving disease management, treatment, and outcomes. AREAS COVERED: This review will be based on today's available scientific evidence, describing the main physiological determinants of ventilatory efficiency at rest and during exercise, and focusing also on how CPET variables are modified in specific diseases, leading to the possibility of early diagnosis and management. EXPERT OPINION: Growing knowledge on CPET interpretation and a wider use of this clinical tool is expected in order to offer more precise diagnostic and prognostic information to patients and clinicians, helping in the management of therapeutic decisions. Future research could be able to identify new and more simple markers of ventilatory efficiency, and to individuate new interventions for the improvement of symptoms, such as exertional dyspnea.

Influence of intercostal muscles contraction on sonographic evaluation of lung sliding: a physiological study on healthy subjects.

OBJECTIVES: To investigate the following: (a) effects of intercostal muscle contraction on sonographic assessment of lung sliding and (b) inter-rater and intra-observer agreement on sonographic detection of lung sliding and lung pulse. METHODS: We used Valsalva and Muller maneuvers as experimental models in which closed glottis and clipped nose prevent air from entering the lungs, despite sustained intercostal muscles contraction. Twenty-one healthy volunteers underwent bilateral lung ultrasound during tidal breathing, apnea, hyperventilation, and Muller and Valsalva maneuvers. The same expert recorded 420 B-mode clips and 420 M-mode images, independently evaluated for the presence or absence of lung sliding and lung pulse by three raters unaware of the respiratory activity corresponding to each imaging. RESULTS: During Muller and Valsalva maneuvers, lung sliding was certainly recognized in up to 73.0% and up to 68.7% of imaging, respectively, with a slight to fair inter-rater agreement for Muller maneuver and slight to moderate for Valsalva. Lung sliding was unrecognized in up to 42.0% of tidal breathing imaging, and up to 12.5% of hyperventilation imaging, with a slight to fair inter-rater agreement for both. During apnea, interpretation errors for sliding were irrelevant and inter-rater agreement moderate to perfect. Even if intra-observer agreement varied among raters and throughout respiratory patterns, we found it to be higher than inter-rater reliability. CONCLUSIONS: Intercostal muscles contraction produces sonographic artifacts that may simulate lung sliding. Clinical studies are needed to confirm this hypothesis. We found slight to moderate inter-rater agreement and globally moderate to almost perfect intra-observer agreement for lung sliding and lung pulse. TRIAL REGISTRATION: ClinicalTrials.gov registration number. NCT02386696.

Is prone positioning a valid intervention for ARDS in the deployed intensive care unit?

Prone positioning is an intervention used for patients with acute respiratory distress syndrome (ARDS) whose hypoxia is worsening despite conventional treatment. Previously used infrequently, it became an important treatment escalation strategy for hypoxia during the COVID-19 pandemic. Current evidence for prone positioning suggests increased survivability in intubated patients with moderate to severe ARDS who are prone for >12 hours a day. As a relatively low-cost, low-tech intervention with a growing evidence base, the viability of prone positioning in the deployed land environment is considered in this article. The practical technique of prone positioning is easy to teach to healthcare staff experienced in manual handling. However, it requires significant resources, in particular staff numbers, and time to execute and maintain, and necessitates a pressure-minimising mattress. Additionally, staff are placed at increased risk of musculoskeletal injuries and potential exposure to aerosolised microbes if there is a disconnection of the breathing system. We conclude that in the deployed 2/1/2/12 facility (or larger), with access to higher staff numbers and high-specification mattresses, prone positioning is a valid escalation technique for intubated hypoxic patients with ARDS. However, in smaller facilities where resources are constrained, its implementation is unlikely to be achievable.

Resolving the Complexity: A Comprehensive Review on Carbon Monoxide Diffusion Capacity in Chronic Obstructive Pulmonary Disease Patients.

This review comprehensively examines the intricate relationship between carbon monoxide (CO) diffusion capacity and chronic obstructive pulmonary disease (COPD). COPD, comprising chronic bronchitis and emphysema, presents a substantial global health burden, necessitating a nuanced understanding of pulmonary function parameters for effective diagnosis and management. The review delves into the physiological underpinnings, measurement techniques, and factors influencing CO diffusion capacity, emphasizing its pivotal role in assessing alveolar gas exchange efficiency. Key findings elucidate correlations between altered diffusion capacity and the severity of COPD, providing clinicians with valuable insights into disease progression. Considerations of age, gender, and ethnic disparities in normal CO diffusion capacity values highlight the importance of personalized interpretations. The clinical implications extend beyond diagnosis, influencing COPD management and prognostication, with potential applications in predicting treatment response. The review outlines avenues for future research, including advancements in measurement technologies and the exploration of novel imaging modalities and biomarkers. Ultimately, this review serves as a foundation for refining diagnostic approaches and treatment strategies and enhancing patient care in the dynamic landscape of COPD.

The Use of Bi-Nasal Prongs for Delivery of Non-Invasive Ventilation to Foals.

Non-invasive ventilation (NIV) is a method of providing respiratory support without the need for airway intubation. The current study was undertaken to assess tolerance to bi-nasal prongs and NIV in healthy, standing, lightly sedated foals. Bi-nasal prongs were well tolerated by foals, remaining in place for the allocated five minutes in four of six unsedated foals and, subsequently, in five of six lightly sedated foals. All foals tolerated NIV through bi-nasal prongs, although increasing airway pressures were associated with increases in inspiratory volume, duration of inspiration and air leakage in most foals. These changes preceded discontinuation/intolerance of NIV on the basis of behaviour changes consistent with discomfort. Increased circuit leakage was associated with reduced return of expired air to the ventilator and increasing disparity between inspiratory and expiratory times and tidal volumes. The study results suggest that bi-nasal prongs might be suitable for NIV but that design or fitting requires further optimization and that behaviour and ventilator variables should be monitored to assess patient tolerance of the procedure.

Disease burden of COPD attributable to PM2.5 in China, Japan and South Korea from 1990 to 2019: a comparative study based on Global Burden of Disease Study 2019.

OBJECTIVE: We hope to reveal the changing trends of chronic obstructive pulmonary disease (COPD) burden attributable to particulate matter pollution (PM2.5) and its age, period and cohort effects in China, Japan and Korea. DESIGN: We analysed the trend of COPD disease burden attributable to PM2.5 from 1990 to 2019 based on the latest Global Burden of Disease Database (GBD 2019) using JoinPoint model and analysed the effect of age, period and cohort on COPD burden attributable to PM2.5 in China, Japan and Korea from 1990 to 2019 using age-period-cohort model (model). SETTING: GBD data from 1990 to 2019. PARTICIPANTS: Data were publicly available and individuals were not involved. MAIN OUTCOMES: Outcomes included the age standardised mortality rate (ASMR), the age-standardised disability-adjusted life year (DALY), average annual per cent change (AAPC), net drift, local drift, longitudinal age curves, period (cohort) rate ratios, age (period, cohort) bias coefficient. RESULTS: From 1990 to 2019, the ASMR of COPD attributable to PM2.5 in China (AAPC=-5.862), Japan (AAPC=-1.715) and Korea (AAPC=-1.831) showed a downward trend. The age-standardised DALY of COPD attributable to PM2.5 in China (AAPC=-5.821), Japan (AAPC=-1.39) and Korea (AAPC=-1.239) showed a downward trend. Mortality of COPD attributable to PM2.5 increased slowly with age in Korea and Japan. Mortality of COPD attributable to PM2.5 in China decreased after rising (95% CI: 404.66 to 466.01). Mortality of COPD attributable to PM2.5 decreased over time in China and Korea, while it increased in Japan from 2015 to 2019. In China and Japan, mortality of COPD attributable to PM2.5 was approximately lower the later the birth, while in Korea it decreased after an increase (95% CI: 2.13 to 2.40) in the 1900-1910. CONCLUSIONS: Most COPD burden attributable to PM2.5 is on the decline; COPD mortality attributable to PM2.5 both increased with age and decreased with time and cohort. Countries with high burden should develop targeted measures to control PM2.5.

Large animal ventilator-integrated volumetric capnography generates clinically acceptable values of physiologic dead space in anesthetized healthy adult horses.

OBJECTIVE: To evaluate the agreement between the Tafonius large animal ventilator-integrated volumetric capnography (vCap) software and the Respironics NICO noninvasive cardiac output monitor reference system. ANIMALS: Data were collected from 56 healthy adult horses undergoing general anesthesia. METHODS: Animals were placed under general anesthesia and connected to the Tafonius large animal ventilator circle system. A flow partitioning device with CO2 and flow sensors was utilized to couple the endotracheal tube to the NICO monitor. Tafonius CO2 and flow sensors are incorporated into the Y-piece of the breathing circuit. Arterial blood samples were collected to determine the partial pressure of arterial carbon dioxide (PaCO2) immediately before data collection. The PaCO2 was input into the Tafonius and NICO monitor, and dead space ventilation (%Vd), end-tidal CO2 partial pressure (ETco2), mixed-expired CO2 partial pressure (Peco2), and expired tidal volume (Vt) were calculated over a single breath. Multiple measurements were completed for each patient, with a total of 200 paired data points collected for analysis. Data were assessed for normality, and Bland-Altman analysis was performed. Bias and 95% limits of agreement were calculated. RESULTS: The limits of agreement for %Vd of the ventilator-derived measurements fell within ± 10% of the NICO monitor reference method. CLINICAL RELEVANCE: Our results indicate that, when compared to the NICO monitor method, the Tafonius-integrated vCap software provides clinically acceptable values of Peco2, Vt, and %Vd in healthy adult horses.

State of the art: Monitoring of the respiratory system during veno-venous extracorporeal membrane oxygenation.

Monitoring the patient receiving veno-venous extracorporeal membrane oxygenation (VV ECMO) is challenging due to the complex physiological interplay between native and membrane lung. Understanding these interactions is essential to understand the utility and limitations of different approaches to respiratory monitoring during ECMO. We present a summary of the underlying physiology of native and membrane lung gas exchange and describe different tools for titrating and monitoring gas exchange during ECMO. However, the most important role of VV ECMO in severe respiratory failure is as a means of avoiding further ergotrauma. Although optimal respiratory management during ECMO has not been defined, over the last decade there have been advances in multimodal respiratory assessment which have the potential to guide care. We describe a combination of imaging, ventilator-derived or invasive lung mechanic assessments as a means to individualise management during ECMO.

Pre-oxygenation using high-flow nasal oxygen versus tight facemask in trauma patients undergoing emergency anaesthesia.

BACKGROUND: Patients suffering from major traumatic injuries frequently require emergency anaesthesia. Due to often compromised physiology and the time-sensitive management, trauma patients may be more prone to desaturate during induction of anaesthesia. We hypothesised that pre-oxygenation using high-flow nasal oxygen would decrease the risk of desaturation during induction of anaesthesia in trauma patients and the study therefore aimed to compare the frequency of desaturation when pre-oxygenation was performed with high-flow nasal oxygen or a traditional facemask. METHODS: This exploratory, prospective, before-and-after study was conducted at the Karolinska University Hospital, Sweden. Adult (≥18 years of age) patients suffering major traumatic injuries needing emergency anaesthesia were included around the clock. Patients were pre-oxygenated using a tight-fitting facemask during the first nine months of enrollment. High-flow nasal oxygen was then introduced as a method for pre-oxygenation of trauma patients. The primary outcome was the proportion of patients desaturating <93% during induction of anaesthesia, assessed from the start of pre-oxygenation until one minute after intubation. Secondary outcomes included perceived difficulty of pre-oxygenation among anaesthetists (assessed on a scale between 1 and 10) and safety outcomes, such as incidence of regurgitations and intracranial gas (assessed radiologically). RESULTS: Data from 96 patients were analysed. Facemask pre-oxygenation was performed in 66 patients, while 30 patients were pre-oxygenated with high-flow nasal oxygen. The most frequent trauma mechanisms were stabbing injuries (n = 34 (35%)) and fall injuries (n = 21 (22%)). There were no differences in patient characteristics between the groups. Eight (12%) versus three (10%) patients desaturated <93% in the facemask and high-flow nasal oxygen group respectively, OR 0.81 (95% CI 0.20-3.28), p = .76. Anaesthetists assessed pre-oxygenation using high-flow nasal oxygen as easier compared to facemask pre-oxygenation. No patient in any group showed signs of regurgitation. Among patients with facial or skull fractures requiring anaesthesia before radiology was performed, intracranial gas was seen in four (40%) patients pre-oxygenated with a facemask and in no patient pre-oxygenated with HFNO (p = .23). CONCLUSION: In this prospective study investigating trauma patients undergoing emergency anaesthesia, we could not see any difference in the number of patients desaturating when pre-oxygenation was performed with high-flow nasal oxygen compared to a tight-fitting facemask. Pre-oxygenation using high-flow nasal oxygen was assessed as easier compared to facemask pre-oxygenation.

Regional associations between inspiratory tongue dilatory movement and genioglossus activity during wakefulness in people with obstructive sleep apnoea.

Inspiratory tongue dilatory movement is believed to be mediated via changes in neural drive to genioglossus. However, this has not been studied during quiet breathing in humans. Therefore, this study investigated this relationship and its potential role in obstructive sleep apnoea (OSA). During awake supine quiet nasal breathing, inspiratory tongue dilatory movement, quantified with tagged magnetic resonance imaging, and inspiratory phasic genioglossus EMG normalised to maximum EMG were measured in nine controls [apnoea-hypopnea index (AHI) ≤5 events/h] and 37 people with untreated OSA (AHI >5 events/h). Measurements were obtained for 156 neuromuscular compartments (85%). Analysis was adjusted for nadir epiglottic pressure during inspiration. Only for 106 compartments (68%) was a larger anterior (dilatory) movement associated with a higher phasic EMG [mixed linear regression, beta = 0.089, 95% CI [0.000, 0.178], t(99) = 1.995, P = 0.049, hereafter EMG↗/mvt↗]. For the remaining 50 (32%) compartments, a larger dilatory movement was associated with a lower phasic EMG [mixed linear regression, beta = -0.123, 95% CI [-0.224, -0.022], t(43) = -2.458, P = 0.018, hereafter EMG↘/mvt↗]. OSA participants had a higher odds of having at least one decoupled EMG↘/mvt↗ compartment (binary logistic regression, odds ratio [95% CI]: 7.53 [1.19, 47.47] (P = 0.032). Dilatory tongue movement was minimal (>1 mm) in nearly all participants with only EMG↗/mvt↗ compartments (86%, 18/21). These results demonstrate that upper airway dilatory mechanics cannot be predicted from genioglossus EMG, particularly in people with OSA. Tongue movement associated with minimal genioglossus activity suggests co-activation of other airway dilator muscles. KEY POINTS: Inspiratory tongue movement is thought to be mediated through changes in genioglossus activity. However, it is unknown if this relationship is altered by obstructive sleep apnoea (OSA). During awake supine quiet nasal breathing, inspiratory tongue movement, quantified with tagged magnetic resonance imaging (MRI), and inspiratory phasic genioglossus EMG normalised to maximum EMG were measured in four tongue compartments of people with and without OSA. Larger tongue anterior (dilatory) movement was associated with higher phasic genioglossus EMG for 68% of compartments. OSA participants had an ∼7-times higher odds of having at least one compartment for which a larger anterior tongue movement was not associated with a higher phasic EMG than controls. Therefore, higher genioglossus phasic EMG does not consistently translate into tongue dilatory movement, particularly in people with OSA. Large dilatory tongue movements can occur despite minimal genioglossus inspiratory activity, suggesting co-activation of other pharyngeal muscles.

Changes in respiratory mechanics in response to crystalloid infusions in extremely premature infants.

Extremely premature infants are at a higher risk of developing respiratory distress syndrome and circulatory impairments in the first few weeks of life. Administration of normal saline boluses to manage hypotension is a common practice in preterm infants. As a crystalloid, a substantial proportion might leak into the interstitium; most consequently the lungs in the preterm cohorts, putatively affecting ventilation. We downloaded and analyzed ventilator mechanics data in infants managed by conventional mechanical ventilation and administered normal saline bolus for clinical reasons. Data were downloaded for 30 min prebolus, 60 min during the bolus followed by 30 min postbolus. Sixteen infants (mean gestational age 25.2 ± 1 wk and birth weight 620 ± 60 g) were administered 10 mL/kg normal saline over 60 min. The most common clinical indication for saline was hypotension. No significant increase was noted in mean blood pressure after the saline bolus. A significant reduction in pulmonary compliance (mL/cmH2O/kg) was noted (0.43 ± 0.07 vs. 0.38 ± 0.07 vs. 0.33 ± 0.07, P = 0.003, ANOVA). This was accompanied by an elevation in the required peak inspiratory pressure to deliver set volume-guarantee (19 ± 2 vs. 22 ± 2 vs. 22 ± 3 mmHg, P < 0.0001, ANOVA), resulting in a higher respiratory severity score. Normal saline infusion therapy was associated with adverse pulmonary mechanics. Relevant pathophysiologic mechanisms might include translocation of fluid across pulmonary capillaries affected by low vascular tone and heightened permeability in extremes of prematurity, back-pressure effects from raised left atrial volume due to immature left-ventricular myocardium; complemented by the effect of cytokine release from positive pressure ventilation.NEW & NOTEWORTHY Administration of saline boluses is common in premature infants although hypovolemia is an uncommon underlying cause of hypotension. This crystalloid can redistribute into pulmonary interstitial space. In the presence of an immature myocardium and diastolic dysfunction, excess fluid can also be "edemagenic." This study on extremely premature infants (25 wk gestation) noted adverse influence on respiratory physiology after saline infusion. Clinicians need to choose judiciously and reconsider routine use of saline boluses in premature infants.

Exercise testing to guide safe discharge from hospital in COVID-19: a scoping review to identify candidate tests.

OBJECTIVES: We aimed to identify exercise tests that have been validated to support a safe discharge to home in patients with or without COVID-19. STUDY DESIGN: Scoping review, using PRISMA-ScR reporting standards. Medline, PubMed, AMED, Embase, CINAHL and LitCovid databases were searched between 16 and 22 February 2021, with studies included from any publication date up to and including the search date. INTERVENTION: Short exercise tests. PRIMARY OUTCOME MEASURES: Safe discharge from hospital, readmission rate, length of hospital stay, mortality. Secondary outcomes measures: safety, feasibility and reliability. RESULTS: Of 1612 original records screened, 19 studies were included in the analysis. These used a variety of exercise tests in patients with chronic obstructive pulmonary disease, suspected pulmonary embolism and pneumocystis carinii pneumonia, heart failure or critical illness. Only six studies had examined patients with COVID-19, of these two were still recruiting to evaluate the 1 min sit-to-stand test and the 40-steps test. There was heterogeneity in patient populations, tests used and outcome measures. Few exercise tests have been validated to support discharge decisions. There is currently no support for short exercise tests for triage of care in patients with COVID-19. CONCLUSIONS: Further research is needed to aid clinical decision-making at discharge from hospital.

Maxillary ostium preservation in ethmoidectomy.

The paranasal sinuses play a role in producing and storing nitric oxide (NO). NO is a powerful antiviral and antibacterial gas which may be involved in the non-specific immune defenses of the respiratory tract. Conducted by the inspiratory current at the alveolar-capillary membrane, it increases pulmonary venous blood oxygenation. NO is actively released in the form of independent boluses in the respiratory tract, thanks to a sphincter function that can be identified during ethmoidectomy under general anesthesia. Safeguarding paranasal sinus physiology necessarily involves conserving this ostial sphincter function, which is essential to the respiratory role of the paranasal sinuses. Although it has not yet been demonstrated that the destruction of this ostial function has measurable consequences for respiratory function, it makes sense to avoid systematic antrostomy and to preserve this ostial function whenever possible, depending on the clinical conditions. This technical note describes step-by-step how to conserve the maxillary ostium, in the example of radical ethmoidectomy with mucosal ablation for nasal polyposis (nasalization). It is illustrated by two videos. The discussion focuses on the respective indications for ostial preservation and middle meatotomy (antrostomy).

Transforming growth factor-ß and matrix metalloproteinases as potential biomarkers of fibrotic lesions induced by tuberculosis: a systematic review and meta-analysis.

OBJECTIVES: Very few studies and limited information are available regarding the mechanism of fibrosis in tuberculosis (TB). This study aimed to identify, describe and synthesise potential biomarkers of the development of tissue fibrosis induced by TB through a systematic method and meta-analysis. METHODS: A literature search was performed using keywords according to the topic from electronic databases (ScienceDirect and PubMed) and other methods (websites, organisations and citations). Studies that matched predetermined eligibility criteria were included. The quality assessment tool used was the Quality Assessment of Diagnostic Accuracy Score 2, and the data obtained were processed using Review Manager V.5.3. RESULTS: Of the 305 studies, 7 met the eligibility criteria with a total sample of 365. The results of the meta-analysis showed that the post-TB group of patients with pulmonary parenchymal fibrosis had a higher transforming growth factor (TGF)-ß level (6.09) than the control group (1.82), with a 4.27 (95% CI: 0.92 to 7.61) mean difference. Moreover, patients with residual pleural thickening post-TB had a higher mean of TGF-ß (0.61) than the control group (0.56), with a 0.05 (95% CI: 0.04 to 0.06) mean difference. Besides TGF-ß, our qualitative synthesis also found that matrix metalloproteinase-1 might have a role in forming and developing pulmonary tissue fibrosis, thus, could be used as a predictor marker in the formation of fibrotic lesions in patients with TB. In addition, several other biomarkers were assessed in the included studies, such as tumour necrosis factor-α, interleukin (IL)-4, IL-8, IL-10, plasminogen activator inhibitor-1 and platelet-derived growth factor. However, this study is not intended to examine these biomarkers. CONCLUSIONS: There were differences in the results of TGF-ß levels in patients with fibrotic lesions compared with controls. TGF-ß might be a biomarker of fibrotic tissue formation or increased pulmonary tissue fibrosis in post-TB patients. However, further studies are needed on a larger scale.

Outcomes of right heart dysfunction in the acutely and severely unwell: protocol for a prospective, longitudinal observational study using multimodal assessment.

INTRODUCTION: The relationship of acute right heart dysfunction (RHD) with long-term cardiopulmonary dysfunction and its' associated morbidity has not been clearly elucidated. We propose a prospective, observational study to assess the natural history of acute RHD using a combination of imaging, functional and qualitative assessment methods, including the recently described combination of simultaneous maximal effort cardiopulmonary exercise testing and stress echocardiography. METHODS AND ANALYSIS: We propose a single-centre study of patients ≥18 years admitted to either the intensive care or respiratory close observation units with RHD on transthoracic echocardiography (TTE). Participants will undergo a repeat TTE ~72 hours after the initial study, with a final TTE performed prior to discharge in patients who have a prolonged (>1 week) stay. Inpatient clinical, biochemical and therapeutic indices will be collected contemporaneously. At ~6 months postdischarge, participants will undergo evaluation with validated symptom assessment tools (Dyspnoea-12 and PAH-SYMPACT Questionnaires) and a combined maximal effort cardiopulmonary exercise test and stress echocardiogram. This study is an observational, hypothesis-generating study with a recruitment target of 100 patients established based on typical admission rates of the relevant hospital departments. Measures of central tendency and dispersion will be used to describe the cohort. Inferential statistics will be used to compare the two a priori defined groups of those whose RHD had resolved prior to hospital discharge and those whose dysfunction persisted at time of discharge. ETHICS AND DISSEMINATION: This study has received ethics approval from the local ethics committee (Nepean and Blue Mountains Local Health District approval, project 2021/ETH12111). Written informed consent will be sought from all patients prior to recruitment. The results will be submitted for publication in a relevant peer-reviewed journal and presented at an appropriate national/international conference. STUDY REGISTRATION: Australian New Zealand Clinical Trials Registry, ANZCTR12623000309684.

Effects of the antipsychotic quetiapine on sleep and breathing: a review of clinical findings and potential mechanisms.

Quetiapine is an antipsychotic medication indicated for schizophrenia and bipolar disorder. However, quetiapine also has hypnotic properties and as such is increasingly being prescribed at low doses 'off-label' in people with insomnia symptoms. Pharmacologically, in addition to its dopaminergic properties, quetiapine also modulates multiple other transmitter systems involved in sleep/wake modulation and potentially breathing. However, very little is known about the impact of quetiapine on obstructive sleep apnoea (OSA), OSA endotypes including chemosensitivity, and control of breathing. Given that many people with insomnia also have undiagnosed OSA, it is important to understand the effects of quetiapine on OSA and its mechanisms. Accordingly, this concise review covers the existing knowledge on the effects of quetiapine on sleep and breathing. Further, we highlight the pharmacodynamics of quetiapine and its potential to alter key OSA endotypes to provide potential mechanistic insight. Finally, an agenda for future research priorities is proposed to fill the current key knowledge gaps.

Examining the haemodynamic repercussions of ventilator hyperinflation in elderly patients: An explanatory study.

This study assessed the cardiovascular repercussions of two VHI (ventilation hyperinflation) protocols using the volume-controlled mode, one with an inspiratory pause (VHI-P) and the other without an inspiratory pause (VHI-NP), in mechanically ventilated elderly patients. The patients underwent both VHI protocols in a randomized order, and impedance cardiography was used to record cardiovascular variables. During VHI-P, the diastolic blood pressure was lower than during VHI-NP (Δ = 10%; p = 0.009). VHI-NP and VHI-P demonstrated a decrease in cardiac output (CO) during the first and third sets compared to baseline (p < 0.05; ES=0.23 and 0.29, respectively). Arterial oxygen delivery decreased simultaneously with CO compared to baseline values (p < 0.05; ES=0.22 and 0.23, respectively). Five minutes after the intervention, the systolic time ratio values were lower for VHI-P than VHI-NP (Δ = 10%; p = 0.01). Left ventricular ejection time values were consistently lower in VHI-NP compared to VHI-P (Δ = 2%; p = 0.02). In conclusion, our study shows that VHI in volume-controlled mode induces hemodynamic changes in mechanically ventilated elderly patients, albeit with a small effect size and within the normal range.

Observational cohort study to validate SEARCH, a novel hierarchical algorithm to define long-term outcomes after pulmonary embolism.

BACKGROUND: Chronic dyspnoea and exercise impairment are common after acute pulmonary embolism (PE) but are not defined and quantified sufficiently to serve as outcomes in clinical trials. The planned project will clinically validate a novel method to determine discrete, clinically meaningful diagnoses after acute PE. The method uses an algorithm entitled SEARCH, for symptom screen, exercise testing, arterial perfusion, resting echocardiography, confirmatory imaging and haemodynamic measurements. SEARCH is a stepwise algorithm that sorts patients by a hierarchical series of dichotomous tests into discreet categories of long-term outcomes after PE: asymptomatic, post-PE deconditioning, symptoms from other causes, chronic thromboembolism with ventilatory inefficiency, chronic thromboembolism with small stroke volume augmentation, chronic thromboembolic disease and chronic thromboembolic pulmonary hypertension. METHODS: The project will test the inter-rater reliability of the SEARCH algorithm by determining whether it will yield concordant post-PE diagnoses when six independent reviewers review the same diagnostic data on 150 patients evaluated at two time points after PE. The project will also determine whether the post-PE diagnoses are stable, according to the SEARCH algorithm, between the first evaluation and the subsequent one 6 months later. IMPLICATIONS: Validation of the SEARCH algorithm would offer clinicians a straightforward method to diagnose post-PE conditions that are rarely distinguished clinically. Their categorisation and definition will allow post-PE conditions to be used as endpoints in clinical trials of acute PE treatment. TRIAL REGISTRATION NUMBER: NCT05568927.