Respiratory Insufficiency

Non-invasive respiratory support including high flow nasal therapy (HFNT), continuous positive airway pressure (CPAP) and Bilevel positive airway pressure (BiPAP), exerts distinct physiological effects and requires specific settings and technicalities. HFNT, delivered through dedicated nasal cannulas, provides low levels of positive airway pressure, anatomical dead space washout, allows good patient tolerance and can be used during CPAP or BiPAP breaks. CPAP and BiPAP, administered through various interfaces (e.g., facemasks, oro-nasal masks, or helmets), can deliver higher positive pressure, thereby increasing end-expiratory lung volume, reducing intrapulmonary shunt and oxygenation, with potential benefits on respiratory mechanics as well. BiPAP also delivers pressure support, aiding CO₂ clearance and respiratory muscle unloading, which is especially useful in hypercapnic respiratory failure. Increased intrathoracic pressure also reduces right ventricle preload and left ventricle afterload, which is beneficial in patients with impaired left ventricular function. Non-invasive respiratory support indications depend on the cause of acute respiratory failure. In hypercapnic respiratory failure with respiratory acidosis, BiPAP via facemask is strongly recommended to prevent intubation and reduce mortality. In cardiogenic pulmonary edema, either CPAP or BiPAP is recommended, while HFNT can be useful for patients requiring prolonged support or when CPAP/BiPAP is not tolerated even after ventilator and interface settings optimization. In de-novo acute hypoxemic respiratory failure, HFNT should be considered as the first-line treatment, regardless of the aetiology: however, in COVID-19-related AHRF CPAP can be considered to avoid intubation. The choice of non-invasive respiratory support interface in both cardiogenic and non-cardiogenic AHRF should aim at minimizing leaks, optimizing CO2 clearance, and maximizing patient tolerance. Monitoring is essential during non-invasive respiratory support to assess patient's response to treatment and to avoid delaying invasive respiratory support when needed, particularly in hypoxemic patients to avoid intubation delays and prevent patient-self-inflicted lung injury: physiological parameters, clinical scores, and lung ultrasound may help assess the risk of NIV failure. Monitoring tidal volume is valuable but challenging because of leaks. Though not widely used, esophageal pressure monitoring can assess patient effort and transpulmonary pressure. Additionally, electrical impedance tomography is an emerging tool for detecting asynchronous breathing and pendelluft phenomena.

ImportanceAwake prone positioning (APP) has shown inconstant associations with improved clinical outcomes in nonintubated patients with COVID-19 developing severe pneumonia.ObjectiveTo evaluate the effects of APP on the need for intubation or incidence of death among patients with COVID-19-related hypoxemic respiratory failure.Design, setting, and participantsThis randomized clinical trial was conducted at 20 hospitals in France and 1 hospital in Mexico between July 2020 and August 2021. The study included patients from wards and intensive care units. Adult patients (18 years or older) who were not intubated and required at least 3 L/min of oxygen flow due to COVID-19 infection were included and randomly assigned in a 1:1 ratio to either APP or standard care. Intention-to-treat statistical analysis was performed from September to December 2024.InterventionPatients randomly assigned to the APP group were offered the intervention lasting at least 6 hours a day. Patients randomly assigned to standard care had no positioning constraint, including no contraindication to spontaneous APP.Main outcomes and measuresThe primary outcome was a composite criterion of intubation and/or death in the first 28 days of randomization. Prespecified secondary outcomes at 28 days of enrollment were days alive outside the intensive care unit (ICU), days alive outside the hospital, proportion of patients admitted to ICU (for patients not in ICU at baseline), and days alive and free from mechanical ventilation. A bayesian approach was used to provide insights into the complete distribution of the effect estimates.ResultsA total of 445 patients were included in the final analysis (mean [SD] age, 60 [11] years; 329 males [74%]; median [IQR] SpO2 to FIO2 [peripheral oxygen saturation to fraction of inspired oxygen] ratio, 150 [114-194] and 155 [109-221] in the standard care and APP groups, respectively). With a noninformative prior distribution, the posterior probability that APP decreased intubation and/or death compared with standard care was 93.8% (mean odds ratio [OR], 0.74; 95% credible interval [CrI], 0.48-1.09). For secondary outcomes, between the APP and standard care groups, the mean difference in the number of days alive and free from mechanical ventilation was 0.33 (95% CrI, -1.37 to 2.03) days; in the number of days alive outside the ICU was 1.28 (95% CrI, -0.78 to 3.34) days; and in the number of days alive outside the hospital was 1.55 (95% CrI, -0.22 to 3.32) days.Conclusions and relevanceIn this randomized clinical trial of nonintubated patients with COVID-19 and hypoxemic respiratory failure, daily APP of 6 hours showed a high probability of reduced endotracheal intubation and/or death over a wide range of prior distributions. These results support APP's use in patients with hypoxemic pneumonia due to COVID-19 infection.Trial registrationClinicalTrials.gov Identifier: NCT04366856.

Purpose of reviewMechanical ventilation is essential in acute hypoxemic respiratory failure (AHRF), yet excessive respiratory drive and inspiratory effort may aggravate injury, a phenomenon termed patient self-inflicted lung injury (P-SILI). This review summarizes mechanistic insights, preclinical and clinical evidence, and current strategies to prevent P-SILI while preserving diaphragmatic function.Recent findingsPreclinical experimental studies show that vigorous inspiratory efforts amplify pleural pressure swings, regional overdistension, pendelluft, and inflammation, with damage involving both lung and diaphragm. positive end-expiratory pressure (PEEP) and continuous positive airway pressure (CPAP) can homogenize ventilation, reduce strain-rate, and protect diaphragmatic mechanics, whereas uncontrolled effort worsens outcomes. Clinical investigations confirm that high drive and effort increase total lung stress despite protective tidal volumes and are linked to mortality, ventilator dependence, and complications such as pneumomediastinum. Emerging approaches include titrated pressure support and sedation and ventilatory assistance, neuromuscular blockade, phrenic nerve block, pharmacological drive modulation, prone positioning, and extracorporeal CO 2 removal. Strategies aimed at preserving diaphragm activity, such as electrical phrenic stimulation or inspiratory muscle training, further broaden protective options.SummaryP-SILI arises when excessive inspiratory effort translates into injurious lung and diaphragm stress. Preventive strategies should not abolish but shape effort, integrating ventilatory settings, sedation, and drive-modulating interventions across the continuum from the acute phase to weaning and rehabilitation.