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.

Conservative management of COVID-19 associated hypoxaemia.

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

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.

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.

Evaluation and discussion of handmade face-masks and commercial diving-equipment as personal protection in pandemic scenarios.

OBJECTIVE: Pandemic scenarios like the current Corona outbreak show the vulnerability of both globalized markets and just-in-time production processes for urgent medical equipment. Even usually cheap personal protection equipment becomes excessively expensive or is not deliverable at all. To avoid dangerous situations especially to medical professionals, but also to affected patients, 3D-printer and maker-communities have teamed up to develop and print shields, masks and adapters to help the medical personnel. In this study, we investigate three home-made respiratory masks for filter and protection efficacy and discuss the results and legal aspects. MATERIALS AND METHODS: A home-printed respiratory mask with a commercial filter, a scuba-diving mask with a commercial filter and a mask sewn from a vacuum cleaner bag were investigated with 99mTc-labeled NaCl-aerosol, and the respective filter-efficacy was measured under a scintigraphic camera. RESULTS: The sewn mask from a vacuum cleaner bag had a filter efficacy of 69.76%, the 3D-printed mask of 39.27% and the scuba-diving mask of 85.07%. CONCLUSION: Home-printed personal protection equipment can be a-yet less efficient-alternative against aerosol in case professional masks are not available, but legal aspects of their use and distribution have to be kept in mind in order to avoid compensation claims.

[Early pulmonary rehabilitation after long term mechanical ventilation]. / Pneumologische Frührehabilitation nach Langzeitbeatmung.

BACKGROUND: The term early rehabilitation is defined as a rehabilitation that begins in the early phase after acute illness and is statutory positioned in §â€Š39SGB V. Aim of this investigation is to describe the quality of outcome of pulmonary early rehabilitation. METHOD: Prospective census of functional parameters, status of ventilation and discharge-disposition in a specialized unit for early pulmonary rehabilitation over a period of one year. RESULTS: Out of 190 patients 179 (94.2 %) were previously invasively ventilated. During the treatment period of 39 ±â€Š17 days, FAM-Index increased from 84.4 ±â€Š19.8 to 118.5 ±â€Š23.3 (Ci 30.9 - 37.3, Cohen'd 1.58; p < 0.001), Barthel-Index from 30.5 ±â€Š13.8 to 58.3 ±â€Š16.2 (Ci 25.4 - 33.8, Cohen's d 1.4; p < 0.001) six minute walking distance from 12.9 ±â€Š40.1 m to 131.4 ±â€Š85.2 m (Ci 105.6 - 131.4 m, Cohn's d 1.78; p < 0.001). Patients were less likely to be receive further post-discharge rehabilitation if they were ventilated. CONCLUSION: Patients admitted to the early pulmonary rehabilitation unit were severely compromised, however quality of outcome was favourable and independent of the breathing status (spontaneously breathing vs. non-invasive ventilation or invasive ventilation). Finding discharge dispositions appeared to be more difficult if patients were ventilated.

Spontaneous-timed versus controlled noninvasive ventilation in chronic hypercapnia - a crossover trial.

Background: There is an ongoing debate about optimal ventilator modes and settings during noninvasive ventilation (NIV). Objectives: To compare the effect of spontaneous-timed (ST) and controlled NIV on carbon dioxide reduction in patients suffering from chronic hypercapnia. Methods: Night and daytime blood gas analysis, lung function tests and 6 minute walking distance tests (6MWD) were done before and after every 6-week treatment. Results: This randomized prospective crossover trial included 42 patients. Pooled data analysis showed a decrease of nocturnal CO2 from 54.8±5.9 mmHg to 41.6±5.5 mmHg during ST ventilation (p<0.01) and from 56.2±7.5 mmHg to 42.7±5.4 mmHg during controlled NIV (p<0.01) with no difference between treatment forms (p=0.30). Daytime CO2 levels decreased from 49.3±5.5 mmHg to 45.6±4.5 mmHg when spontaneous timed ventilation was applied (p<0.01) and from 52.2±6.8 mmHg to 44.9±21114.4 mmHg in case of controlled ventilation (p<0.01) The amount of CO2 reduction was 3.8±5.6 mmHg after ST mode and 7.3±6.8 mmHg controlled ventilation (p<0.05). Nocturnal ventilator use was 5.7±2.1 and 6.7±2.3 hours for ST and controlled ventilation respectively (p=0.02). There was no effect on walking distance and lung function. Conclusion: Controlled NIV showed improved compliance compared to ST ventilation. We observed similar CO2 reductions during nocturnal ventilation, however controlled ventilation achieved a higher reduction of daytime CO2 levels.

Cost-effectiveness of the COPD Patient Management European Trial home-based disease management program.

Purpose: Efficient management of COPD represents an international challenge. Effective management strategies within the means of limited health care budgets are urgently required. This analysis aimed to evaluate the cost-effectiveness of a home-based disease management (DM) intervention vs usual management (UM) in patients from the COPD Patient Management European Trial (COMET). Methods: Cost-effectiveness was evaluated in 319 intention-to-treat patients over 12 months in COMET. The analysis captured unplanned all-cause hospitalization days, mortality, and quality-adjusted life expectancy. Costs were evaluated from a National Health Service perspective for France, Germany, and Spain, and in a pooled analysis, and were expressed in 2015 Euros (EUR). Quality of life was assessed using the 15D health-related quality-of-life instrument and mapped to utility scores. Results: Home-based DM was associated with improved mortality and quality-adjusted life expectancy. DM and UM were associated with equivalent direct costs (DM reduced costs by EUR -37 per patient per year) in the pooled analysis. DM was associated with lower costs in France (EUR -806 per patient per year) and Spain (EUR -51 per patient per year), but higher costs in Germany (EUR 391 per patient per year). Evaluation of cost per death avoided and cost per quality-adjusted life year (QALY) gained showed that DM was dominant (more QALYs and cost saving) in France and Spain, and cost-effective in Germany vs UM. Nonparametric bootstrapping analysis, assuming a willingness-to-pay threshold of EUR 20,000 per QALY gained, indicated that the probability of home-based DM being cost-effective vs UM was 87.7% in France, 81.5% in Spain, and 75.9% in Germany. Conclusion: Home-based DM improved clinical outcomes at equivalent cost vs UM in France and Spain, and in the pooled analysis. DM was cost-effective in Germany with an incremental cost-effectiveness ratio of EUR 2,541 per QALY gained. The COMET home-based DM intervention could represent an attractive alternative to UM for European health care payers.

[Tremendous Increase of Home Care in Ventilated and Tracheostomized Patients - Reasons, Consequences, Solutions]. / Explosive Zunahme der häuslichen Krankenpflege bei Beatmeten und Tracheotomierten.

Since 2005, invasive long-term ventilation in Germany has increased significantly from around 1000 to 20 000 patients in Germany. Due to complex home care, the health care system incurs additional costs of around 4 billion euros per year. In addition, in the last 2 - 3 years more tracheostomized patients have been discharged home without ventilation (usually after stroke), and they receive the same complex home care. These patients have almost never been given the chance of a professional weaning trial by a weaning center. They are discharged from hospitals directly into the care. As a result, the quality of care is significantly worse than traditional care with structured discharge management via a weaning center. The solutions are difficult to find due to the interface problems between inpatient and outpatient care and the different organizational structures with different delivery systems. Possible solutions are shown, but most of them require a change in the law.

[Witch hunt and hypotheses loss]. / Von Hexenverfolgung und Hypothesenverlust.

At this time randomized controlled studies (RCT) in clinical trials usually have high quality. But this quality is only true for the included patients (intrinsic validity). It is common to generalize the results to more or less similar patients. This inductive method is prohibited in epistemology what is known for 250 years (D Hume, K R Popper). Therefore the external validity for the data of RCT is low. To solve this problem additional clinical and pathophysiological based data are necessary to generalize the results. Unfortunately RCT show less quality in their premises. This is partly due to the influence of the pharmaceutical industry. A loss of universality of the hypothesis for RCT decreases basically the extrinsic validity. The articles describe this problem with examples.

[Do we use the wrong target value for the supportive therapy of sepsis?]. / Supportive Sepsistherapie: Benutzen wir die falsche Zielgröße?

Sepsis is a generalized, usually infectious disease with a complex dsyregulated immune response and capillary leak. The leakage leads to a severe drop of blood pressure with hypoperfusion and sympathetic counterregulation. The lung is frequently involved either as a source of the inflammation or by emergence of an ARDS, both resulting into severe hypoxemia. The supportive therapy is used to stabilize the hemodynamics and to keep the target value partial pressure of arterial oxygen (PaO2) in the lower limit of normal. Pathophysiologically it is not plausible to define hypoxemia on the basis of PaO2 or SaO2, because the supply of the cells is determined by the amount of oxygen molecules. This is mirrored by the oxygen content (CaO2) and the hemodynamic transport, the cardiac output. As far as data about the hypoxic tolerance of organs are available, the critical value respective the threshold for anaerobic metabolism is 5-10 folds lower than values achieved by application of current guidelines. If CaO2 would be used as the target value, a lot of measures aiming for normoxia, which potentially harm patients, could be avoided. Among these measures are high, often toxic inspiratory concentrations of oxygen, high ventilation pressure, dangerous body position changes and excessive volume administration. It is not surprising, that there are no plausible data in the literature which have shown a positive effect for the target value PaO2 or SaO2. Studies are urgent needed to compare CaO2 as a target value to the standards in the current guidelines. Additional animal experiments should be done to get information on the critical range of CaO2, in order to translate these results into treatment strategies for intensive care unit patients with severe hypoxemia.

Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial.

BACKGROUND: Evidence is weak for the ability of long-term non-invasive positive pressure ventilation (NPPV) to improve survival in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD). Previous prospective studies did not target a reduction in hypercapnia when adjusting ventilator settings. This study investigated the effect of long-term NPPV, targeted to markedly reduce hypercapnia, on survival in patients with advanced, stable hypercapnic COPD. METHODS: This investigator-initiated, prospective, multicentre, randomised, controlled clinical trial enrolled patients with stable GOLD stage IV COPD and a partial carbon dioxide pressure (PaCO2) of 7 kPa (51.9 mm Hg) or higher and pH higher than 7.35. NPPV was targeted to reduce baseline PaCO2 by at least 20% or to achieve PaCO2 values lower than 6.5 kPa (48.1 mm Hg). Patients were randomly assigned (in a 1:1 ratio) via a computer-generated randomisation sequence with a block size of four, to continue optimised standard treatment (control group) or to receive additional NPPV for at least 12 months (intervention group). The primary outcome was 1-year all-cause mortality. Analysis was by intention to treat. The intervention was unblinded, but outcome assessment was blinded to treatment assignment. This study is registered with ClinicalTrials.gov, number NCT00710541. FINDINGS: Patients were recruited from 36 respiratory units in Germany and Austria, starting on Oct 29, 2004, and terminated with a record of the vital status on July 31, 2011. 195 patients were randomly assigned to the NPPV group (n=102) or to the control group (n=93). All patients from the control group and the NPPV group were included in the primary analysis. 1-year mortality was 12% (12 of 102 patients) in the intervention group and 33% (31 of 93 patients) in the control group; hazard ratio 0.24 (95% CI 0.11-0.49; p=0.0004). 14 (14%) patients reported facial skin rash, which could be managed by changing the type of the mask. No other intervention-related adverse events were reported. INTERPRETATION: The addition of long-term NPPV to standard treatment improves survival of patients with hypercapnic, stable COPD when NPPV is targeted to greatly reduce hypercapnia. FUNDING: German Lung Foundation; ResMed, Germany; Tyco Healthcare, Germany; and Weinmann, Germany.

In vitro validation of a Respimat® adapter for delivery of inhaled bronchodilators during mechanical ventilation.

BACKGROUND: Inhaled bronchodilators are frequently used in patients with chronic obstructive pulmonary disease (COPD). However, there has been no efficient way to administer the long-acting anticholinergic tiotropium to mechanically ventilated patients. The aim of this in vitro study was to compare the fine particle dose (FPD) output of a specifically designed adapter with other accessory devices for the delivery of bronchodilators using the Respimat® (RMT) inhaler by simulating the specific inhalation flow profiles of patients with COPD. METHODS: Using characteristic flow profiles from COPD patients being weaned off mechanical ventilation, an in vitro study was performed analyzing the FPD achieved with different accessory devices (connectors, spacers, AeroTrachPlus valved holding chamber), which can be used to deliver drugs from pressurized metered dose inhalers (pMDI) and RMT inhalers to artificial airways. Fenoterol pMDI, tiotropium RMT, and a fixed-dose combination of salbutamol and ipratropium delivered by pMDI or RMT, were used as bronchodilators. Aerosols were collected by a next-generation impactor. RESULTS: The RMT inhaler, combined with a new in-line adapter, was superior to other inhaler device connector or spacer combinations in FPD delivery during simulated mechanical ventilation (p<0.01). The outcome with the RMT inhaler/RMT adapter combination during simulation of mechanical ventilation was comparable to the measurements with the RMT/AeroTrachPlus valved holding chamber during simulation of spontaneous breathing. The delivery rates of the RMT adapter were not significantly affected by the administered bronchodilators or by the type of artificial airway (endotracheal or tracheostomy tube) employed. CONCLUSIONS: The RMT inhaler combined with the prototype in-line adapter was better than the other accessory device combinations in fine particle deposition of inhaled bronchodilators during mechanical ventilation. Further research is required to determine the clinical relevance of these in vitro findings.

Determinants of skin contact pressure formation during non-invasive ventilation.

There is no published data about mask features that impact skin contact pressure during mask ventilation. To investigate the physical factors of skin contact pressure formation. We measured masks with original and reduced air cushion size and recorded contact pressure. We determined cushion contact and mask areas by planimetric measurements. Contact pressures necessary to prevent air leakage during inspiration exceed inspiratory pressure by 1.01+/-0.41 hPa independent of cushion size. Contact area, ventilator pressure and mask area during inspiration and expiration impact contact pressure. Mask contact pressures are higher during expiration. The contact pressure increases with increase in inspiratory pressures independent of the ventilator cycle. During expiration, the contact pressure will increase in proportion to the expiratory pressure reduction of the ventilator. The mask with reduced air cushion size developed higher contact pressures. Contact pressure can be reduced by selecting masks with a small mask area in combination with a large mask cushion.

[TISS-28 in difficult to wean patients after long-term mechanical ventilation]. / Stellenwert des TISS-28-Scores in der schwierigen Entwöhnung vom Respirator.

PURPOSE: To compare the Therapeutic Intervention Scoring System (TISS) 28 in difficult to wean patients before and after transfer to a weaning center. PATIENTS AND METHODS: Using TISS-28, the authors investigated the difference between regular intensive care units (ICUs) and the respiratory ICU (RICU) of their hospital in difficult to wean patients after long-term mechanical ventilation (MV). Special emphasis was placed on the appropriateness of TISS-28 to cover the specific weaning activities. 63 tracheotomized patients ventilated for more than 14 days were included. RESULTS: In total, 15.9% of patients were not weaned, 20.6% of population was successfully weaned with noninvasive ventilation (NIV), and 63.5% of patients was successfully weaned without NIV. The transfer of patients from other ICUs to a weaning facility resulted in a significant reduction of total TISS-28 from 29.5 to 23.8 points (p<0.001) on average. CONCLUSION: The high weaning success rate in a specialized facility is associated with a significant reduction of TISS-28 scores. The use of TISS-28 in a weaning center for patients with prolonged MV to measure workload does not adequately mirror the efforts by physicians, nurses, physiotherapists, and other health-care personnel.

Impact of breathing pattern on work of breathing in healthy subjects and patients with COPD.

The impact of the respiratory pattern on respiratory muscle workload represents an unresolved controversy and is important for the treatment of patients with respiratory disorders and respiratory muscle failure. We designed this study to investigate the relationship of respiratory pattern and inspiratory workload. We measured esophageal pressure and inspiratory flow and calculated work of breathing, tidal volume and respiratory rate. Ten healthy subjects and 10 COPD patients participated and performed five different breathing patterns starting from respiratory rate 12 and tidal volume 1l or quiet breathing, respectively. They were instructed to increase respiratory rate by 50 and 100% as well as tidal volume by 50 and 100% while maintaining constant minute-ventilation. In healthy subjects Delta VT was the single best parameter to predict Delta WOB (R=0.958, R(2)=0.918, p<0.0001). The relationships of changes in tidal volume, respiratory rate and rapid shallow breathing index to changes in WOB were linear. In the COPD Delta VT was also the single best parameter to predict changes in work of breathing (R=0.777, R(2)=0.604, p<0.0001), however the relation of respiratory rate and rapid shallow breathing index to work of breathing was exponential (e-function) with lower indices generating higher workload. We conclude that rapid shallow breathing might be a strategy to compensate for burdensome respiratory mechanics. In COPD patients however we observed a critical threshold where any further increases in rapid shallow breathing index will be of no further benefit.