Multi-center safety and efficacy study of a negative-pressure intraoral device in obstructive sleep apnea.

BACKGROUND: Intraoral devices, with or without negative oral pressure, can stabilize the oropharynx and reduce obstructive sleep apneas. We tested the hypothesis that treatment with the iNAP® Sleep Therapy System, which applies negative oral pressure through an intra-oral appliance, would reduce the severity of obstructive sleep apnea in a multi-center, prospective, first-night-randomized-order cross-over study. METHODS/PATIENTS: 130 patients fulfilled the entry criteria (age <75, AHI 15-55, BMI <33), and 63 entered the primary endpoint cohort (Total Sleep Time ≥4 h/night on the baseline polysomnogram and an oral negative vacuum time maintained by iNAP® ≥ 4 h/night and total sleep time ≥4 h/night during the first treatment study). 54 patients completed a second treatment sleep study at least 28 days after the first sleep study. RESULTS: Among the primary endpoint cohort (n = 63, age = 53.2 ± 11.3, BMI = 27.1 ± 2.8), 33 patients (52 %; 95 % confidence interval = 40%-64 %, p < 0.001) responded to iNAP treatment according to the Sher criteria (>50 % reduction in AHI and an AHI ≤20 events/hr). The average oxy-hemoglobin saturation increased by 1-2%, and the average percent oxygen desaturation decreased (was less severe) by 1 % while using the iNAP device. The incidence of adverse events, all self-limited, was low. The reduction in the apnea-hypopnea index was durable over the 28-day study. Patients used iNAP on average 5.6 h per night during the study period. CONCLUSION: The iNAP® Sleep Therapy System achieved a durable benefit in more than half the patients with moderate to severe obstructive sleep apnea and may be considered in patients who object to or failed continuous positive airway pressure. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02698059.

[Task Force Dyspnoe unit (DU)]. / Task Force Dyspnoe Unit (DU).

Acute dyspnoea is one of the most common internal medicine symptoms in the emergency department. It arises from an acute illness or from the exacerbation of a chronic illness. Symptom-related emergency structures and corresponding structural guidelines already exist in the stroke and chest pain units for dealing with the leading symptoms of acute stroke and acute chest pain. These are lacking in Germany for the key symptom of dyspnoea, although the benefits of these structures have already been proven in other countries. The German Society for Pneumology and Respiratory Medicine (DGP) has now set up a task force together with the Association of Pneumology Clinics (VPK), in order to deal with the topic and develop appropriate structural guidelines for such "dyspnoea units" in Germany. At the end of the process, the certification of such units at German hospitals is optional.

[Technical aspects and innovations in non-invasive and invasive ventilation]. / Technische Aspekte und Neuerungen in der nicht-invasiven und invasiven Beatmung.

Non-invasive and invasive ventilation have become essential for therapy in acute and chronic respiratory failure. More than one-third of patients in intensive care units receive invasive ventilation, and the number of ventilated patients in out-of-hospital care is also steadily increasing. While normalization of blood gases was considered the most significant goal in past decades, and the idea that mechanical ventilation also poses dangers played little role, the dominant thought at present is the application of ventilation from the most protective point of view possible. Because fundamental change in equipment technology is likely to be difficult, improvement of protective ventilation and further development of understanding of pathophysiologic processes in acute and chronic respiratory failure will continue to be of great importance in the future. This article summarizes different aspects of the technical basis of noninvasive and invasive ventilation and their practical implementation.

[Non-invasive Mechanical Ventilation in Acute Respiratory Failure. Clinical Practice Guidelines - on behalf of the German Society of Pneumology and Ventilatory Medicine]. / S2k-Leitlinie Nichtinvasive Beatmung als Therapie der akuten respiratorischen Insuffizienz.

The guideline update outlines the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.Non-invasive ventilation (NIV) has a high value in therapy of hypercapnic acute respiratory failure, as it significantly reduces the length of ICU stay and hospitalization as well as mortality.Patients with cardiopulmonary edema and acute respiratory failure should be treated with continuous positive airway pressure (CPAP) and oxygen in addition to necessary cardiological interventions. This should be done already prehospital and in the emergency department.In case of other forms of acute hypoxaemic respiratory failure with only mild or moderately disturbed gas exchange (PaO2/FiO2 > 150 mmHg) there is no significant advantage or disadvantage compared to high flow nasal oxygen (HFNO). In severe forms of ARDS NIV is associated with high rates of treatment failure and mortality, especially in cases with NIV-failure and delayed intubation.NIV should be used for preoxygenation before intubation. In patients at risk, NIV is recommended to reduce extubation failure. In the weaning process from invasive ventilation NIV essentially reduces the risk of reintubation in hypercapnic patients. NIV is regarded useful within palliative care for reduction of dyspnea and improving quality of life, but here in concurrence to HFNO, which is regarded as more comfortable. Meanwhile NIV is also recommended in prehospital setting, especially in hypercapnic respiratory failure and pulmonary edema.With appropriate monitoring in an intensive care unit NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency.

Hypoxic, anemic and cardiac hypoxemia: When does tissue hypoxia begin? / Hypoxische, anämische und kardial bedingte Hypoxämie: Wann beginnt die Hypoxie im Gewebe?

In case of hypoxemia, the oxygen content is often still in the lower normal range, so that there is no hypoxia in the tissue. If the hypoxia-threshold is reached in the tissue in hypoxic, anemic and also cardiac-related hypoxemia, identical counterregulations occur in the cell metabolism, regardless of the cause of hypoxemia. In clinical practice, this pathophysiologic fact is sometimes ignored, although depending on the cause of hypoxemia, assessment and therapy vary widely. While restrictive and generally accepted rules are specified in the transfusion guidelines for anemic hypoxemia, in the case of hypoxic hypoxia, the indication for invasive ventilation is made very early. The clinical assessment and indication are limited to the parameters oxygen saturation, oxygen partial pressure and oxygenation index. During the corona pandemic, misinterpretations of pathophysiology have become evident and may have led to unnecessary intubations. However, there is no evidence for the treatment of hypoxic hypoxia with ventilation. This review addresses the pathophysiology of the different types of hypoxia focusing on the problems associated with intubation and ventilation in the intensive care unit.

[Interdisciplinary Perspectives on the Role of Aerosol Transmission in SARS-CoV-2 Infections]. / Interdisziplinäre Perspektiven zur Bedeutung der Aerosolübertragung für das Infektionsgeschehen von SARS-CoV-2.

The relevance of aerosols for the transmission of the Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is still debated. However, over time, in addition to distancing and hygiene rules, aerosol physics-based measures such as wearing face masks and ventilating indoor spaces were found to be efficient in reducing infections. In an interdisciplinary workshop "Aerosol & SARS-CoV-2" of the Association for Aerosol Research (GAeF) in cooperation with the German Society for Pneumology and Respiratory Medicine (DGP), the Professional Association of General Air Technology of the VDMA, the German Society for Virology (GfV), the Health Technology Society (GG) and the International Society for Aerosols in Medicine (ISAM) under the auspices of the Robert Koch Institute (RKI) in March 2021, the need for research and coordination on this topic was addressed. Fundamental findings from the various disciplines as well as interdisciplinary perspectives on aerosol transmission of SARS-CoV-2 and infection mitigation measures are summarized here. Finally, open research questions and needs are presented.

Hemoglobin Rothschild - Unimpaired physical performance and oxygen uptake - A case report with literature review.

Asymptomatic patients with hemoglobin (Hb) variants can be detected by low oxygen levels in pulse oximetry (SpO2). Depending on the type of Hb variant, low SpO2 values are either falsely low, with corresponding normal arterial oxygen saturation (SaO2), or truly low, with low SaO2 values, as observed in Hb variants with low oxygen binding affinity. In this context, attention must be paid to the method of determining SaO2. Low oxygen affinity Hb variants such as Hb Rothschild (HbR) might compensate for low oxygen loading in the lung through unloading more oxygen in peripheral tissues. This is the first case report to illustrate that maximal oxygen uptake and the workload are unimpaired in HbR variant patients.

Influence of wearing masks on exhaled air aerodynamics.

Since aerosol inhalation is the most common mechanism for COVID-19 infection, the respiratory protective devices (RPDs) have the highest importance in personal protection. The aim of this study was to assess the efficiency of 10 different RPDs in shortening the travelling distance of exhaled air by range measurement using the schlieren imaging technique. When a RPD is worn by a person resting in a seated position, the expired air does not exceed the human convective boundary layer (CBL). Instead, the CBL lifts the expired aerosols vertically up. Thus, they have a prolonged travelling time in the surrounding air and become less harmful by several mechanisms of virus content decay. Coughing as well as expiration valves can cause far reaching expiration air clouds that cross horizontally the human CBL by opening leakage airway corridors into different directions. Measured by the range of expired air an FFP2 mask provided high security under all conditions tested. A non-vented full-face mask with two viral filters performed even better because of its airtight fit and the excellent filtering capacity of the viral filters during inspiration and expiration, even during cough manoeuvres.

Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients.

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged ⩾18 years on invasive mechanical ventilation for ⩾4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) (n = 57) or standard of care (control) (n = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [-10 to 25]), P = 0.59. Mechanical ventilation duration (mean ± SD) was 12.7 ± 9.9 days and 14.1 ± 10.8 days, respectively, P = 0.50; maximal inspiratory pressure increased by 16.6 cm H2O and 4.8 cm H2O, respectively (difference [95% CI], 11.8 [5 to 19]), P = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and -14%, respectively, P = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).

Conservative management of COVID-19 associated hypoxaemia.

Treat hypoxia, not hypoxaemia https://bit.ly/3hwPLCL.

Exhalation Spreading During Nasal High-Flow Therapy at Different Flow Rates.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 is transmitted through aerosols and droplets. Nasal high-flow therapy could possibly increase the spreading of exhalates from patients. The aim of this study is to investigate whether nasal high-flow therapy affects the range of the expiratory plume compared with spontaneous breathing. DESIGN: Interventional experiment on single breaths of a healthy volunteer. SETTING: Research laboratory at the Bauhaus-University Weimar. SUBJECTS: A male subject. INTERVENTIONS: Videos and images from a schlieren optical system were analyzed during spontaneous breathing and different nasal high-flow rates. MEASUREMENTS AND MAIN RESULTS: The maximal exhalation spread was 0.99, 2.18, 2.92, and 4.1 m during spontaneous breathing, nasal high-flow of 20 L/min, nasal high-flow of 40 L/min, and nasal high-flow of 60 L/min, respectively. Spreading of the expiratory plume in the sagittal plane can completely be blocked with a surgical mask. CONCLUSIONS: Nasal high-flow therapy increases the range of the expiratory air up to more than 4 meters. The risk to pick up infectious particles could be increased within this range. Attachment of a surgical mask over the nasal high-flow cannula blocks the expiratory airstream.

Conservative management of COVID-19 associated hypoxaemia.

This correspondence argues that happy hypoxaemic patients should not be intubated as long as they remain happy https://bit.ly/3csrpWO.

Conservative management of COVID-19 associated hypoxaemia.

BACKGROUND: Invasive mechanical ventilation of hypoxaemic coronavirus disease 2019 (COVID-19) patients is associated with mortality rates of >50%. We evaluated clinical outcome data of two hospitals that agreed on a predefined protocol for restrictive use of invasive ventilation where the decision to intubate was based on the clinical presentation and oxygen content rather than on the degree of hypoxaemia. METHOD: Data analysis was carried out of patients with positive PCR-testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), typical history, and symptoms and pulmonary infiltrates who exhibited oxygen saturation values of <93%. RESULTS: We identified 78 patients who met the inclusion criteria. The oxygen saturation nadir was 84.4±6.5% for the whole group. 53 patients (68%) received nasal oxygen (group 1), 17 patients (22%) were treated with nasal high-flow continuous positive airway pressure (CPAP), noninvasive ventilation or a combination thereof (group 2), and eight patients (10%) were intubated (group 3). The Horovitz index was 216±8 for group 1, 157±13 for group 2 and 106±15 for group 3. Oxygen content was 14.5±2.5, 13.4±1.9 and 11.6±2.6 mL O2·dL-1 for the three respective groups. Overall mortality was 7.7%; the mortality of intubated patients was 50%. Overall, 93% of patients could be discharged on room air. CONCLUSION: Permissive hypoxaemia where decisions for the level of respiratory therapy were based on the clinical presentation and oxygen content resulted in low intubation rates, low overall mortality and a low number of patients who require oxygen after discharge.

The Feasibility of High-Intensity Interval Training in Patients with Intensive Care Unit-Acquired Weakness Syndrome Following Long-Term Invasive Ventilation.

BACKGROUND: Intensive care unit-acquired weakness syndrome (ICUAWS) can be a consequence of long-term mechanical ventilation. Despite recommendations of early patient mobilisation, little is known about the feasibility, safety and benefit of interval training in early rehabilitation facilities (ERF) after long-term invasive ventilation. METHODS AND RESULTS: We retrospectively analysed two established training protocols of bicycle ergometry in ERF patients after long-term (> 7 days) invasive ventilation (n = 46). Patients conducted moderate continuous (MCT, n = 24, mean age 70.3 ± 10.1 years) or high-intensity interval training (HIIT, n = 22, mean age 63.6 ± 12.6 years). The intensity of training was monitored with the BORG CR10 scale (intense phases ≥ 7/10 and moderate phases ≤ 4/10 points). The primary outcome was improvement (∆-values) of six-minute-walk-test (6 MWT), while the secondary outcomes were improvement of vital capacity (VCmax), forced expiratory volume in 1 s (FEV1), maximal inspiratory pressure (PImax) and functional capabilities (functional independence assessment measure, FIM/FAM and Barthel scores) after 3 weeks of training. No adverse events were observed. There was a trend towards a greater improvement of 6 MWT in HIIT than MCT (159.5 ± 64.9 m vs. 120.4 ± 60.4 m; p = .057), despite more days of invasive ventilation (39.6 ± 16.8 days vs. 26.8 ± 16.2 days; p = .009). VCmax (∆0.5l ± 0.6 vs. ∆0.5l ± 0.3; p = .462), FEV1 (∆0.2l ± 0.3 vs. ∆0.3l ± 0.2; p = .218) PImax (∆0.8 ± 1.1 kPa vs. ∆0.7 ± 1.3pts; p = .918) and functional status (FIM/FAM: ∆29.0 ± 14.8pts vs. ∆30.9 ± 16.0pts; p = .707; Barthel: ∆28.9 ± 16.0 pts vs. ∆25.0 ± 10.5pts; p = .341) improved in HIIT and MCT. CONCLUSIONS: We demonstrate the feasibility and safety of HIIT in the early rehabilitation of ICUAWS patients. Larger trials are necessary to find adequate dosage of HIIT in ICUAWS patients.

Bench testing of noninvasive ventilation masks with viral filters for the protection from inhalation of infectious respirable particles.

During the beginning of the SARS-CoV-2 pandemic, there was a shortage of masks and respirators for the protection of health care professionals. Masks for noninvasive ventilation (NIV) in combination with viral-proof filters, worn by healthcare workers, could serve as an alternative protection measure. We determined the simulated protection factor (SPF) of such devices in comparison to conventional surgical masks, N95, and FFP3 respirators. Masks and respirators were mounted on a ventilated mannequin head in a test-chamber. Isotonic saline containing 150 MBq 99mTC-DTPA (99mTc-diethylenetriamine pentaacetate (DTPA) was nebulized inside the box. The aerosol had a mass median aerodynamic diameter of 0.6 ± 0.4 µm. SPFs were measured using radioactive DTPA particles in the mannequin test system by calculating the ratio of unfiltered particles (Pu) and filtered particles (Pf) for each tested device (SPF = Pu/Pf). Simulated protection factors were 15.6 ± 3.6 for a ResMed AcuCare mask plus filter, 3.5 ± 0.2 for a ResMed Mirage Quattro FX mask plus filter, 9.5 ± 0.8 for a Loewenstein JOYCEclinc FF mask plus filter, 1.9 ± 0.2 for a surgical mask with a rubber band, 2.7 ± 0.7 for a surgical mask with ribbons, 2.3 ± 0.3 for an FFP3 respirator, and 3.6 ± 1.3 for an N95 respirator. The ResMed AcuCare and the Loewenstein JOYCEclinic FF mask were more effective than any other of the tested devices (p < 0.001). In conclusion, masks normally used for NIV with viral-proof filters can effectively filter respirable particles.

Community Masks During the SARS-CoV-2 Pandemic: Filtration Efficacy and Air Resistance.

Background: Many countries have introduced a compulsory use of community masks for certain public areas during the SARS-CoV-2 pandemic. Different manufacturers offer reusable community masks in large quantities. The efficacy of these masks, however, is unknown. Method: We tested available community masks of major manufactures and determined the filtration efficacy using radioactive aerosol particles as well as air resistance with a vacuum measurement. Results: Filtration efficacy of the tested reusable community masks ranged from 34.9% ± 1.25% to 88.7% ± 1.18%. Air resistance ranged from 4.3 ± 0.06 to 122.4 ± 0.12 Pa/cm2. There was a good correlation between filtration efficacy and air resistance (Pearson correlation 0.938, p < 0.0001). Conclusions: Filtration efficacy and air resistance differ significantly between the different community masks, but the two measurements correlate well with each other within the entire test series. For optimal protection, one should select a rather airtight mask. When selecting a mask, the highest level of tolerable air resistance can be used as a selection criterion.

Normal and obstructive breathing physiology during sleep.

PURPOSE: To estimate the severity of flow limitation in patients with OSA, the number of breaths with flattened inspiratory flow curves should be identified. Attempts to do a quantitative analysis of the flattening degree for all breaths in a nighttime recording have failed up to now. METHODS: SOMNOmedics (Randersacker, Germany) developed an automated flattening analysis parameter called the obstructive coefficient (OC). Polysomnographic measurement including esophageal manometry was done in 25 subjects (10 healthy, 9 patients with mild OSA, and 6 with severe OSA). For each breath, the data couple of OC and esophageal pressure (EP) was used for analysis. RESULTS: Data couples of OC and EP were recorded for 104,608 breaths. Airway patency histogram profiles for each study group showed no remarkable differences between each other. Increase in EP with increasing RDI was identified as the only marker of OSA severity. A strong shift was observed in N3 breaths from maximum OC/lowest EP values in healthy subjects to low OC values in association with maximum EP values in OSA. CONCLUSION: The OC enables quantification of all breaths of a nighttime recording according to their degree of flattening. The relation of strong limited to less strong limited breaths is the same across the three study groups. The analysis of the corresponding EP to a given OC value for each study group identified the EP that is necessary to cause a given flow as the only parameter that discriminates degrees of severity of OSA. The trial registration number is DRKS00018095 from 2019 to 10-09.

Prolonged Weaning: S2k Guideline Published by the German Respiratory Society.

Mechanical ventilation (MV) is an essential part of modern intensive care medicine. MV is performed in patients with severe respiratory failure caused by respiratory muscle insufficiency and/or lung parenchymal disease; that is, when other treatments such as medication, oxygen administration, secretion management, continuous positive airway pressure (CPAP), or nasal high-flow therapy have failed. MV is required for maintaining gas exchange and allows more time to curatively treat the underlying cause of respiratory failure. In the majority of ventilated patients, liberation or "weaning" from MV is routine, without the occurrence of any major problems. However, approximately 20% of patients require ongoing MV, despite amelioration of the conditions that precipitated the need for it in the first place. Approximately 40-50% of the time spent on MV is required to liberate the patient from the ventilator, a process called "weaning". In addition to acute respiratory failure, numerous factors can influence the duration and success rate of the weaning process; these include age, comorbidities, and conditions and complications acquired during the ICU stay. According to international consensus, "prolonged weaning" is defined as the weaning process in patients who have failed at least 3 weaning attempts, or require more than 7 days of weaning after the first spontaneous breathing trial (SBT). Given that prolonged weaning is a complex process, an interdisciplinary approach is essential for it to be successful. In specialised weaning centres, approximately 50% of patients with initial weaning failure can be liberated from MV after prolonged weaning. However, the heterogeneity of patients undergoing prolonged weaning precludes the direct comparison of individual centres. Patients with persistent weaning failure either die during the weaning process, or are discharged back to their home or to a long-term care facility with ongoing MV. Urged by the growing importance of prolonged weaning, this Sk2 Guideline was first published in 2014 as an initiative of the German Respiratory Society (DGP), in conjunction with other scientific societies involved in prolonged weaning. The emergence of new research, clinical study findings and registry data, as well as the accumulation of experience in daily practice, have made the revision of this guideline necessary. The following topics are dealt with in the present guideline: Definitions, epidemiology, weaning categories, underlying pathophysiology, prevention of prolonged weaning, treatment strategies in prolonged weaning, the weaning unit, discharge from hospital on MV, and recommendations for end-of-life decisions. Special emphasis was placed on the following themes: (1) A new classification of patient sub-groups in prolonged weaning. (2) Important aspects of pulmonary rehabilitation and neurorehabilitation in prolonged weaning. (3) Infrastructure and process organisation in the care of patients in prolonged weaning based on a continuous treatment concept. (4) Changes in therapeutic goals and communication with relatives. Aspects of paediatric weaning are addressed separately within individual chapters. The main aim of the revised guideline was to summarize both current evidence and expert-based knowledge on the topic of "prolonged weaning", and to use this information as a foundation for formulating recommendations related to "prolonged weaning", not only in acute medicine but also in the field of chronic intensive care medicine. The following professionals served as important addressees for this guideline: intensivists, pulmonary medicine specialists, anaesthesiologists, internists, cardiologists, surgeons, neurologists, paediatricians, geriatricians, palliative care clinicians, rehabilitation physicians, intensive/chronic care nurses, physiotherapists, respiratory therapists, speech therapists, medical service of health insurance, and associated ventilator manufacturers.