Use Of Non-invasive Respiratory Support Research Articles

Assitenza ventilatoria non invasiva: dalla teoria alla pratica

Noninvasive respiratory assistance strategies are becoming part of everyday life for paediatricians, both in hospitals and territorial settings. In the acute condition, a timely and correct use of noninvasive respiratory support can improve the outcome of acute respiratory failure, decreasing the need for invasive mechanical ventilation. An increasing number of chronic patients can benefit from appropriate treatment with home ventilators. Respiratory assistance may be performed using High Flow Nasal Cannula (HFNC), Continuous Positive Airway Pressure (CPAP) or NonInvasive Ventilation (NIV), depending on the primary cause of respiratory failure. Understanding the working mechanisms of the different techniques and the golden rules to use them is crucial for a satisfying outcome.

Focus on the Role of Non-Invasive Respiratory Support (NRS) during Palliative Care in Patients with Life-Limiting Respiratory Disease.

The management of patients with life-threatening respiratory disease in the ICU and at home has become increasingly of interest over the past decades. Growing knowledge supports the use of NRS, aimed at improving patient comfort and improving quality of life. However, its role during palliative care is not well defined, and evidence of support remains limited. The aim of this narrative review is to examine the recent evidence relating to the use of non-invasive respiratory support at the end of life, in order to clarify who benefits and when. The literature research was conducted on PubMed, using MeSH words. A review of the relevant literature showed that non-invasive respiratory support techniques for patients with life-limiting respiratory disease vary (from high-flow oxygen therapy to conventional oxygen therapy, from CPAP to NPPV) and each has precise indications. To date, from the hospital to the home setting, the monitoring and application of these respiratory support techniques have varied widely. In conclusion, the choice of respiratory support in this category of patients should be based on the technique that will optimize the comfort of the patient and improve the quality of their life. On the other hand, regarding monitoring, both telemedicine and ultrasound diagnostics help to satisfy the patient's wish to spend the last period of his life in the home environment, to avoid inappropriately aggressive diagnostic interventions, and to reduce the high costs of hospitalized procedures in this category of patients.

Surfactant treatment at birth in a contemporary cohort of preterm infants with bronchopulmonary dysplasia.

Initial surfactant studies demonstrated improvements in survival and need for respiratory support. However, as the use of non-invasive respiratory support has increased the use of surfactant has decreased. We examined in a contemporary cohort of BPD patients if surfactant use was associated with BPD severity. An observational study using data from the BPD Collaborative Registry. 971 infants with BPD met entry criteria, 864 (89%) had received surfactant in the first 72 h of life (SURF) and the remainder had not (no surfactant). There was an association between SURF and BPD grade, with a greater likelihood of grade 3 BPD in infants who received surfactant in the DR or who had 2 or more doses. We speculate that the use of surfactant in the DR and use of multiple doses reflect the impact of perinatal factors beyond immaturity alone that increase the risk for grade 3 BPD.

Advanced Respiratory Support Days as a Novel Marker of Mortality in COVID-19 Acute Respiratory Distress Syndrome Requiring Extracorporeal Membrane Oxygenation.

Emerging evidence suggests prolonged use of noninvasive respiratory support may increase mortality of patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome who require extracorporeal membrane oxygenation (ECMO). Using a database of adults receiving ECMO for COVID-19, we calculated survival curves and multivariable Cox regression to determine the risk of death associated with pre-ECMO use of high-flow nasal oxygen (HFNO), noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) days. We investigated the performance of a novel variable, advanced respiratory support days (composite of HFNO, NIV, and IMV days), on Respiratory ECMO Survival Prediction (RESP) score. Subjects (N = 146) with increasing advanced respiratory support days (<5, 5-9, and ≥10) had a stepwise increase in 90 day mortality (32.2%, 57.7%, and 75.4%, respectively; p = 0.002). Ninety-day mortality was significantly higher in subjects (N = 121) receiving NIV >4 days (81.8% vs. 52.4%, p < 0.001). Each additional pre-ECMO advanced respiratory support day increased the odds of right ventricular failure (odds ratio [OR]: 1.066, 95% confidence interval [CI]: 1.002-1.135) and in-hospital mortality (1.17, 95% CI: 1.08-1.27). Substituting advanced respiratory support days for IMV days improved RESP score mortality prediction (area under the curve (AUC) or: 0.64 vs. 0.71). Pre-ECMO advanced respiratory support days were associated with increased 90 day mortality compared with IMV days alone. Adjusting the RESP score for advanced respiratory support days improved mortality prediction.

Impact of Respiratory Bacterial Codetection on Outcomes in Ventilated Infants With Bronchiolitis.

Viral bronchiolitis is a common cause of acute respiratory failure requiring intubation for infants. Bacterial respiratory tract infections can occur with bronchiolitis, although their prevalence and impact on outcomes are unclear, especially with increased use of noninvasive respiratory support. This was a single-center retrospective cohort study of children <2 years old requiring intubation in the emergency department for bronchiolitis from 2012 to 2017 who had viral testing plus a lower respiratory culture obtained. We evaluated the impact of bacterial codetection (positive respiratory culture plus moderate or many polymorphonuclear neutrophils on Gram stain) on mechanical ventilation (MV) duration and intensive care unit length of stay using multivariable gamma regression. Of 149 patients enrolled, 52% had bacterial codetection. In adjusted analysis, patients with codetection had shorter MV duration [adjusted relative risk (aRR) 0.819, 95% confidence interval (CI): 0.69-0.98; marginal mean duration of 5.31 days (4.71-5.99) compared to 6.48 days (5.72-7.35) without codetection]. Patients with codetection had a shorter intensive care unit stay [aRR 0.806 (0.69-0.94); marginal mean length of stay 6.9 days (6.21-7.68) vs. 8.57 days (7.68-9.56) without codetection]. The association between codetection and duration of ventilation appears confined to those receiving earlier antibiotics (less than the median time) rather than later antibiotics [aRR 0.738 (0.56-0.95) for earlier vs. aRR 0.92 (0.70-1.18) for later]. Respiratory bacterial codetection is common and associated with shorter MV duration in infants requiring early intubation for bronchiolitis. Early antibiotics may contribute to these outcomes, but further multicenter studies are needed to understand the role of codetection and antibiotics on bronchiolitis outcomes.

Nutrition practices in hospitalized adults receiving noninvasive forms of respiratory support: A scoping review.

The use of noninvasive respiratory support is increasing, with noninvasive ventilation (NIV) and high-flow nasal cannula providing unique barriers to nutrition support. Limited data related to nutrition management for these patients in the intensive care unit (ICU) exist; however, the literature in non-critically ill patients is not well described, and its improvement may help to inform practice within the ICU. Therefore, a scoping review was conducted of MEDLINE, EmCare, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases on August 18, 2022, to identify original publications that included adult patients receiving noninvasive respiratory support in a hospital setting with data related to nutrition management. Data were extracted on study design, population, details of respiratory support, and concepts relating to nutrition management (grouped into nutrition screening, assessment, delivery route, intake, and anthropometry). Eleven studies were included, most of which were small (<100 patients), single-center, observational trials in patients receiving NIV only. Five studies reported results related to route of nutrition and nutrition assessment, two on anthropometry, and one each on quantifying intake and nutrition screening; some studies reported multiple parameters. There was a lack of consensus regarding the ideal method for nutrition assessment and route of nutrition. Oral nutrition was the route most frequently reported, yet calorie and protein delivery via this route were inadequate, and barriers to intake included poor appetite, fatigue, and patient cognition. Future research should address barriers pertinent to this population and the impact of nutrition on outcomes.

Failure of Non-Invasive Respiratory Support in Patients with SARS-CoV-2.

The objective of this study is to assess the failure of therapies with HFNO (high-flow nasal oxygen), CPAP, Bilevel, or combined therapy in patients with hypoxemic acute respiratory failure due to SARS-CoV-2 during their hospitalization. This was a retrospective and observational study of SARS-CoV-2-positive patients who required non-invasive respiratory support (NIRS) at the Reina Sofía General University Hospital of Murcia between March 2020 and May 2021. Of 7355 patients, 197 (11.8%) were included; 95 of them failed this therapy (48.3%). We found that during hospitalization in the ward, the combined therapy of HFNO and CPAP had an overall lower failure rate and the highest treatment with Bilevel (p = 0.005). In the comparison of failure in therapy without two levels of airway pressure, HFNO, CPAP, and combined therapy of HFNO with CPAP, (35.6% of patients) presented with 24.2% failure, compared to those who had two levels of pressure with Bilevel and combined therapy of HFNO with Bilevel (64.4% of patients), with 75.8% associated failure (OR: 0, 374; CI 95%: 0.203-0.688. p = 0.001). The use of NIRS during conventional hospitalization is safe and effective in patients with respiratory failure secondary to SARS-CoV-2 infection. The therapeutic strategy of Bilevel increases the probability of failure, with the combined therapy strategy of CPAP and HFNO being the most promising option.

RISK FACTORS ASSOCIATED WITH PROLONGED MECHANICAL VENTILATION IN VERY LOW BIRTH WEIGHT INFANTS

Introduction. Mechanical ventilation (MV) remains a life-saving intervention for the sickest very low birth weight (VLBW) neonates. Despite the widespread use of non-invasive respiratory support, many VLBW neonates require some duration of MV during their initial hospitalization. As prolonged exposure to MV is associated with adverse outcomes in VLBW infants, it is important to identify the factors that influence the duration of this intervention.The study aimed to determine the factors affecting the duration of MV in VLBW infants.Material and methods. Data from a prospectively created computerized database were used in a retrospective cohort study. The database included information on 1086 VLBW infants &lt; 32 weeks' gestation who were ventilated at any time during their hospitalization at the tertiary care hospital between January 2010 and December 2020. Factors that potentially influenced the duration of MV were examined.The research was carried out in compliance with the requirements of bioethics as part of the planned scientific work of the department (state registration number 0117U001083).The data obtained were analyzed using descriptive and comparative statistics, as well as Spearman's rank correlation coefficient and one-way analysis of covariance (ANCOVA). Measurements with normal distribution are presented as mean (standard deviation). Non-parametric continuous data are presented as median (interquartile range). All values were considered significant when p &lt;0.05.The study was carried out as a part of the planned scientific work of the department "Clinical-laboratory and instrumental substantiation of differential approaches to diagnosis, treatment and prevention of childhood diseases" (state registration number 0122U000164) without external sources of funding.Results. According to univariant analysis, bronchopulmonary dysplasia (BPD) (rS=0.32, p&lt;0.05), severe BPD (rS=0.418, p&lt;0.05), pneumothorax (rS=0.06, p=0.05), severe intraventricular hemorrhages (IVH) (rS=0.255, p&lt;0.05), periventricular leukomalacia (PVL) (rS=0.15, p&lt;0.05), sepsis (rS=0.087, p&lt;0.05), necrotizing enterocolitis (rS=0.088, p&lt;0.05), longer duration of antibiotic therapy (rS=0.168, p&lt;0.05), and a lower gestational age (rS=-0.118, p&lt;0.05) were associated with longer duration of MV in VLBW infants. At the same time, BPD (F=18.544, p&lt;0.0001), severe BPD (F=109.810, p&lt;0.0001), severe IVH (F=23.859, p&lt;0.0001), PVL (F=15.031, p&lt;0.0001), and more days of antibiotic therapy (F=13.173, p&lt;0.0001) significantly and independently affected the duration of MV based on the results of one-way ANCOVA.Conclusion. Severe lung and brain injury and prolonged antibiotic exposure were the main risk factors that significantly and independently prolonged MV in VLBW infants.

The COVID-19 Driving Force: How It Shaped the Evidence of Non-Invasive Respiratory Support.

During the COVID-19 pandemic, the use of non-invasive respiratory support (NIRS) became crucial in treating patients with acute hypoxemic respiratory failure. Despite the fear of viral aerosolization, non-invasive respiratory support has gained attention as a way to alleviate ICU overcrowding and reduce the risks associated with intubation. The COVID-19 pandemic has led to an unprecedented increased demand for research, resulting in numerous publications on observational studies, clinical trials, reviews, and meta-analyses in the past three years. This comprehensive narrative overview describes the physiological rationale, pre-COVID-19 evidence, and results of observational studies and randomized control trials regarding the use of high-flow nasal oxygen, non-invasive mechanical ventilation, and continuous positive airway pressure in adult patients with COVID-19 and associated acute hypoxemic respiratory failure. The review also highlights the significance of guidelines and recommendations provided by international societies and the need for further well-designed research to determine the optimal use of NIRS in treating this population.

Timing of intubation and ICU mortality in COVID-19 patients: a retrospective analysis of 4198 critically ill patients during the first and second waves

BackgroundThe optimal time to intubate patients with SARS-CoV-2 pneumonia has not been adequately determined. While the use of non-invasive respiratory support before invasive mechanical ventilation might cause patient-self-induced lung injury and worsen the prognosis, non-invasive ventilation (NIV) is frequently used to avoid intubation of patients with acute respiratory failure (ARF). We hypothesized that delayed intubation is associated with a high risk of mortality in COVID-19 patients.MethodsThis is a secondary analysis of prospectively collected data from adult patients with ARF due to COVID-19 admitted to 73 intensive care units (ICUs) between February 2020 and March 2021.Intubation was classified according to the timing of intubation. To assess the relationship between early versus late intubation and mortality, we excluded patients with ICU length of stay (LOS) < 7 days to avoid the immortal time bias and we did a propensity score and a cox regression analysis.ResultsWe included 4,198 patients [median age, 63 (54‒71) years; 71% male; median SOFA (Sequential Organ Failure Assessment) score, 4 (3‒7); median APACHE (Acute Physiology and Chronic Health Evaluation) score, 13 (10‒18)], and median PaO2/FiO2 (arterial oxygen pressure/ inspired oxygen fraction), 131 (100‒190)]; intubation was considered very early in 2024 (48%) patients, early in 928 (22%), and late in 441 (10%). ICU mortality was 30% and median ICU stay was 14 (7‒28) days. Mortality was higher in the “late group” than in the “early group” (37 vs. 32%, p < 0.05). The implementation of an early intubation approach was found to be an independent protective risk factor for mortality (HR 0.6; 95%CI 0.5‒0.7).ConclusionsEarly intubation within the first 24 h of ICU admission in patients with COVID-19 pneumonia was found to be an independent protective risk factor of mortality.Trial registrationThe study was registered at Clinical-Trials.gov (NCT04948242) (01/07/2021).

REVIEW OF SURFACTANT DELIVERY STRATEGIES IN NEONATOLOGICAL PRACTICE

Administration of surfactant by minimally invasive techniques that promote spontaneous breathing may be safer and more effective than administration with endotracheal intubation and mechanical ventilation. At present, the use of INSURE and LISA/MIST methods is well researched and widely used, their effectiveness has been largely proven and beyond doubt. However, current trends towards greater use of non-invasive respiratory support in surfactant-deficient preterm infants have created a demand for similar non-invasive methods of administering exogenous surfactant, one of which is the potentially promising method of inhaled delivery of a substance to the lungs using a nebulizer.

Non-invasive respiratory support in the management of COVID-19: a synthesis of systematic reviews.

Hospitalised patients with COVID-19 often require oxygen because of the increased risk of hypoxia, and one of the main treatment goals is to avoid mechanical ventilation where possible. Non-invasive respiratory support such as high-flow nasal oxygen, bi-level positive airway pressure and continuous positive airway pressure appear to be clinical alternatives. However, further research is needed to assess the effectiveness of non-invasive respiratory support and its varying modes as a treatment for COVID-19 within a diverse population. This commentary aims to critically appraise three reviews concerning the use of non-invasive respiratory support in patients with COVID-19 and expand upon the findings with regards to clinical practice.

Noninvasive Respiratory Support following Extubation in Preterm Infants.

The use of noninvasive respiratory support is widespread in newborn infants with respiratory distress. As the use of noninvasive respiratory support has increased, so too have the number of modes available. Among these modes, low-flow nasal cannula and nasal continuous positive airway pressure (NCPAP) have been used for a long time and have known efficacy and safety in newborn infants needing respiratory support. High-flow nasal cannula (HFNC) has been newly introduced, and its efficacy and safety are currently being investigated. Bilevel nasal continuous positive airway pressure and nasal intermittent positive-pressure ventilation are often used when NCPAP or HFNC therapy fails. More recently, noninvasive neurally adjusted ventilatory assist and noninvasive high-frequency oscillatory ventilation have been introduced, and their efficacy and safety are currently under evaluation. Comparison of the efficacy and safety among various modes of noninvasive respiratory support after extubation in preterm infants is helping to clarify the position of each mode. The clarification of the strength and characteristics of each device within the same mode will become important as a future direction of noninvasive respiratory support after extubation in such subjects. However, no research has yet reported on long-term outcomes in preterm infants receiving noninvasive respiratory support after extubation. Therefore, further research is needed to evaluate the long-term outcomes.

Impact of Changes in Early Respiratory Support Management on Respiratory Outcomes of Preterm Infants.

In the period immediately after birth, preterm infants are highly susceptible to lung injury. Ventilator-induced lung injury has been recognized as a major contributing factor for bronchopulmonary dysplasia (BPD) in preterm infants. Noninvasive respiratory support (NIRS) could decrease lung injury, and early respiratory support management might affect pulmonary outcomes. We conducted a study to evaluate the changes in early respiratory support management and their impact on respiratory outcome and complications of preterm infants in 3 different time periods over the last 13 years. This study was a retrospective, single-center cohort study. We retrospectively reviewed the medical records of preterm infants < 32 weeks of gestational age born in our hospital from 2007-2020. The study period was divided into three 3-y discrete periods: 2007-2009 (period A), 2013-2015 (period B), and 2018-2020 (period C). Changes in early respiratory support management were assessed in the 3 periods. The outcomes measured included mortality, BPD, other major neonatal complications, initial respiratory support, and duration of mechanical ventilation. In all, 1,880 clinical records were assessed in our study, with 358 in period A, 825 in period B, and 697 in period C. The use of antenatal corticosteroids increased over time (56.1% in period A, 56.7% in period B, and 74.0% in period C (P < .001). The need for surfactant decreased from 65.6% in period A to 40.7% in period B and 45.9% in period C. Increased utilization of NIRS was associated with decreased invasive mechanical ventilation within 24 h after birth. NIRS only during the hospital stay increased from 22.9% in period A to 36.8% and 45.1% in the latter 2 periods (P < .001). Oxygen therapy duration decreased from 24.3 d in period A to 14.4 d in period B and 17.2 d in period C (P < .001). The overall incidence of BPD was 32.4% in the first period, 23.9% in the second period, and 25.4% in the third period (P < .001). The moderate-to-severe forms of BPD decreased from 12.8% in period A to 7.9% in period B and 7.6% in period C (P = .009). Other neonatal complications, such as pneumothorax, pulmonary hemorrhage, persistent pulmonary hypertension of the newborn, surgical necrotizing enterocolitis, intraventricular hemorrhage grade III/IV, and periventricular leukomalacia, were unchanged among the 3 periods. From 2007-2020, respiratory management was characterized by a marked reduction in invasive mechanical ventilation and an increase in the use of NIRS. Changes in early respiratory support management resulted in improved respiratory outcomes with a decrease in the overall incidence of BPD. It is likely that our aim to reduce lung injury by improving our respiratory management has contributed to a favorable outcome.

Risk Stratification in Noninvasive Respiratory Support Failure: A Narrative Review

The use of noninvasive respiratory support, including noninvasive ventilation and high-flow nasal cannula therapy, has increased over the years. Failure of noninvasive respiratory support, defined as the need for invasive mechanical ventilation, increases the mortality rate. To familiarize critical care nurses with available risk stratification assessments and identify common concepts and limitations. Few risk stratification assessments are available to identify patients at risk of failure of noninvasive respiratory support. Although many studies have analyzed risk, substantial variation in study design, definitions, terminology, and outcomes have led to a wide range of findings, making clinical application difficult. Further study is needed to broaden known assessments to general patient populations, determine diagnostic accuracy during critical periods, and analyze noninvasive ventilation and high-flow nasal cannula therapy. Risk stratification could allow for better implementation of preventive strategies and patient education. Future research opportunities include improving study design for risk stratification and implementing preventive strategies for patients requiring noninvasive respiratory support. Clinically, risk stratification can provide an opportunity to share knowledge and facilitate conversations with patients and families.

Trends in the use of non-invasive respiratory support for term infants in tertiary neonatal units in Australia and New Zealand

ObjectiveTo determine whether the use of non-invasive respiratory support, such as continuous positive airway pressure and nasal high flow, to treat term infants in Australian and New Zealand tertiary neonatal...

Noninvasive respiratory support and invasive ventilation in COVID‑19 : Where do we stand today?

Die Kontroverse um das Thema Beatmung bei vorliegender „coronavirus disease 2019“ (COVID-19) hält an. Zu Beginn der Pandemie wurde postuliert, dass die hohe Letalität auf den Intensivstationen möglicherweise auf eine zu frühe Intubation zurückzuführen sei. Im Verlauf der Pandemie änderten sich die Empfehlungen der Fachgesellschaften, und die Häufigkeit der Anwendung von nichtinvasiver respiratorischer Unterstützung (NIRS) nahm zu. Weiterhin fehlen große Studien zur optimalen Beatmung von COVID-19-Patienten. Der vorliegende Übersichtsbeitrag fasst die pathophysiologischen Grundlagen, den aktuellen Stand der Wissenschaft und die Auswirkungen der unterschiedlichen Behandlungsmodalitäten auf das Outcome zusammen.

Different Methods to Improve the Monitoring of Noninvasive Respiratory Support of Patients with Severe Pneumonia/ARDS Due to COVID-19: An Update.

The latest guidelines for the hospital care of patients affected by coronavirus disease 2019 (COVID-19)-related acute respiratory failure have moved towards the widely accepted use of noninvasive respiratory support (NIRS) as opposed to early intubation at the pandemic onset. The establishment of severe COVID-19 pneumonia goes through different pathophysiological phases that partially resemble typical acute respiratory distress syndrome (ARDS) and have been categorized into different clinical–radiological phenotypes. These can variably benefit on the application of external positive end-expiratory pressure (PEEP) during noninvasive mechanical ventilation, mainly due to variable levels of lung recruitment ability and lung compliance during different phases of the disease. A growing body of evidence suggests that intense respiratory effort producing excessive negative pleural pressure swings (Ppl) plays a critical role in the onset and progression of lung and diaphragm damage in patients treated with noninvasive respiratory support. Routine respiratory monitoring is mandatory to avoid the nasty continuation of NIRS in patients who are at higher risk for respiratory deterioration and could benefit from early initiation of invasive mechanical ventilation instead. Here we propose different monitoring methods both in the clinical and experimental settings adapted for this purpose, although further research is required to allow their extensive application in clinical practice. We reviewed the needs and available tools for clinical–physiological monitoring that aims at optimizing the ventilatory management of patients affected by acute respiratory distress syndrome due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.

What can we Learn from Patients who Died from Covid-19 Following Escalation to a Respiratory High Dependency Unit for Trial of Non-Invasive Respiratory Support?

Background: Covid-19 infection is associated with significant risk of death, particularly in older, comorbid patients. Emerging evidence supports use of non-invasive respiratory support (CPAP and high-flow nasal oxygen [HFNO]) in this context, but little is known about its use in patients receiving end-of-life care. Methods: This was a retrospective study of 33 patients who died of Covid-19 on the Respiratory High Dependency Unit at the John Radcliffe Hospital, Oxford between 28/03/20 and 20/05/20. Data was sourced via retrospective review of electronic patient records and drug charts. Results: Patients dying from Covid-19 on the Respiratory HDU were comorbid with median Charlson Comorbidity Index 5 (IQR 4-6); median age 78 (IQR 72-85). Respiratory support was trialled in all but one case with CPAP being the most common form of first line respiratory support (84.8%) however, was only tolerated in 44.8% of patients. Median time to death was 10.7 days from symptom onset (IQR 7.5-14.6) and 4.9 days from hospital admission (IQR 3.1-8.3). 48.5% of patients remained on respiratory support at the time of death. Conclusions: End-of-life care for patients with Covid-19 remains a challenge. Patients tend to be frail and comorbid with a rapid disease trajectory. Non-Invasive Respiratory Support may play a key role in symptom management in select patients, however, further work is needed in order to identify patients who will most benefit from Respiratory Support and those for whom withdrawal may prevent unnecessary distress at the end of life or potential prolongation of suffering.

Awake prone positioning in nonintubated spontaneous breathing ICU patients with acute hypoxemic respiratory failure (PRONELIFE)\u2014protocol for a randomized clinical trial

BackgroundIt is uncertain whether awake prone positioning can prevent intubation for invasive ventilation in spontaneous breathing critically ill patients with acute hypoxemic respiratory failure. Awake prone positioning could benefit these patients for various reasons, including a reduction in direct harm to lung tissue, and prevention of tracheal intubation-related complications.Design and methodsThe PRONELIFE study is an investigator-initiated, international, multicenter, randomized clinical trial in patients who may need invasive ventilation because of acute hypoxemic respiratory failure. Consecutive patients admitted to participating ICUs are randomly assigned to standard care with awake prone positioning, versus standard care without awake prone positioning. The primary endpoint is a composite of tracheal intubation and all-cause mortality in the first 14 days after enrolment. Secondary endpoints include time to tracheal intubation and effects of awake prone positioning on oxygenation parameters, dyspnea sensation, and complications. Other endpoints are the number of days free from ventilation and alive at 28 days, total duration of use of noninvasive respiratory support, total duration of invasive ventilation, length of stay in ICU and hospital, and mortality in ICU and hospital, and at 28, 60, and 90 days. We will also collect data regarding the tolerance of prone positioning.DiscussionThe PRONELIFE study is among the first randomized clinical trials investigating the effect of awake prone positioning on intubation rate in ICU patients with acute hypoxemic failure from any cause. The PRONELIFE study is sufficiently sized to determine the effect of awake prone positioning on intubation for invasive ventilation—patients are eligible in case of acute hypoxemic respiratory failure without restrictions regarding etiology. The PRONELIFE study is a pragmatic trial in which blinding is impossible—however, as around 35 ICUs worldwide will participate in this study, its findings will be highly generalizable. The findings of the PRONELIFE study have the potential to change clinical management of patients who may need invasive ventilation because of acute hypoxemic respiratory failure.Trial registrationISRCTN ISRCTN11536318. Registered on 17 September 2021. The PRONELIFE study is registered at clinicaltrials.gov with reference number NCT04142736 (October, 2019).