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In ARDS patients, the change from supine to prone position generates a more even distribution of the gas–tissue ratios along the dependent–nondependent axis and a more homogeneous distribution of lung stress and strain. The change to prone position is generally accompanied by a marked improvement in arterial blood gases, which is mainly due to a better overall ventilation/perfusion matching. Improvement in oxygenation and reduction in mortality are the main reasons to implement prone position in patients with ARDS. The main reason explaining a decreased mortality is less overdistension in non-dependent lung regions and less cyclical opening and closing in dependent lung regions. The only absolute contraindication for implementing prone position is an unstable spinal fracture. The maneuver to change from supine to prone and vice versa requires a skilled team of 4–5 caregivers. The most frequent adverse events are pressure sores and facial edema. Recently, the use of prone position has been extended to non-intubated spontaneously breathing patients affected with COVID-19 ARDS. The effects of this intervention on outcomes are still uncertain.

To face these problems, we implemented a pronation protocol that allows to extend the time for the prone position beyond 16 h, aiming to reduce the number of pronation cycles per patient. [...]the aim of this report was to assess the feasibility and efficacy of prone position ventilation beyond the usual 16 h. We retrospectively collected data from 10 critically ill patients intubated and mechanically ventilated for SARS-CoV-2. [...]in the condition of work overload for healthcare assistants, this strategy might reduce the number of pronation cycles needed for a single patient. [...]we showed that prolonged prone position up to 36 h is feasible, safe, and may offer potential clinical and organizational advantages.

The baby lung was originally defined as the fraction of lung parenchyma that, in acute respiratory distress syndrome (ARDS), still maintains normal inflation. Its size obviously depends on ARDS severity and relates to the compliance of the respiratory system. CO 2 clearance and blood oxygenation primarily occur within the baby lung. While the specific compliance suggests the intrinsic mechanical characteristics to be nearly normal, evidence from positron emission tomography suggests that at least a part of the well-aerated baby lung is inflamed. The baby lung is more a functional concept than an anatomical one; in fact, in the prone position, the baby lung “shifts” from the ventral lung regions toward the dorsal lung regions while usually increasing its size. This change is associated with better gas exchange, more homogeneously distributed trans-pulmonary forces, and a survival advantage. Positive end expiratory pressure also increases the baby lung size, both allowing better inflation of already open units and adding new pulmonary units. Viewed as surrogates of stress and strain, tidal volume and plateau pressures are better tailored to baby lung size than to ideal body weight. Although less information is available for the baby lung during spontaneous breathing efforts, the general principles regulating the safety of ventilation are also applicable under these conditions.

Care for patients with acute respiratory distress syndrome (ARDS) has changed considerably over the 50 years since its original description. Indeed, standards of care continue to evolve as does how this clinical entity is defined and how patients are grouped and treated in clinical practice. In this narrative review we discuss current standards – treatments that have a solid evidence base and are well established as targets for usual care – and also evolving standards – treatments that have promise and may become widely adopted in the future. We focus on three broad domains of ventilatory management, ventilation adjuncts, and pharmacotherapy. Current standards for ventilatory management include limitation of tidal volume and airway pressure and standard approaches to setting PEEP, while evolving standards might focus on limitation of driving pressure or mechanical power, individual titration of PEEP, and monitoring efforts during spontaneous breathing. Current standards in ventilation adjuncts include prone positioning in moderate-severe ARDS and veno-venous extracorporeal life support after prone positioning in patients with severe hypoxemia or who are difficult to ventilate. Pharmacotherapy current standards include corticosteroids for patients with ARDS due to COVID-19 and employing a conservative fluid strategy for patients not in shock; evolving standards may include steroids for ARDS not related to COVID-19, or specific biological agents being tested in appropriate sub-phenotypes of ARDS. While much progress has been made, certainly significant work remains to be done and we look forward to these future developments.

Background Benefit of early awake prone positioning for COVID-19 patients hospitalised in medical wards and who need oxygen therapy remains to be demonstrated. The question was considered at the time of COVID-19 pandemic to avoid overloading the intensive care units. We aimed to determine whether prone position plus usual care could reduce the rate of non-invasive ventilation (NIV) or intubation or death as compared to usual care alone. Methods In this multicentre randomised clinical trial, 268 patients were randomly assigned to awake prone position plus usual care ( N  = 135) or usual care alone ( N  = 132). The primary outcome was the proportion of patients who underwent NIV or intubation or died within 28 days. Main secondary outcomes included the rates of NIV, of intubation or death, within 28 days. Results Median time spent each day in the prone position within 72 h of randomisation was 90 min (IQR 30–133). The proportion of NIV or intubation or death within 28 days was 14.1% (19/135) in the prone position group and 12.9% (17/132) in the usual care group [odds ratio adjusted for stratification (aOR) 0.43; 95% confidence interval (CI) 0.14–1.35]. The probability of intubation, or intubation or death (secondary outcomes) was lower in the prone position group than in the usual care group (aOR 0.11; 95% CI 0.01–0.89 and aOR 0.09; 95% CI 0.01–0.76, respectively) in the whole study population and in the prespecified subgroup of patients with SpO 2  ≥ 95% on inclusion (aOR 0.11; 95% CI 0.01–0.90, and aOR 0.09; 95% CI 0.03–0.27, respectively). Conclusions Awake prone position plus usual care in COVID-19 patients in medical wards did not decrease the composite outcome of need for NIV or intubation or death. Trial registration ClinicalTrials.gov Identifier: NCT04363463 . Registered 27 April 2020.

Background Acute respiratory distress syndrome (ARDS) is a heterogeneous condition with varying response to prone positioning. We aimed to identify subphenotypes of ARDS patients undergoing prone positioning using machine learning and assess their association with mortality and response to prone positioning. Methods In this retrospective observational study, we enrolled 353 mechanically ventilated ARDS patients who underwent at least one prone positioning cycle. Unsupervised machine learning was used to identify subphenotypes based on respiratory mechanics, oxygenation parameters, and demographic variables collected in supine position. The primary outcome was 28-day mortality. Secondary outcomes included response to prone positioning in terms of respiratory system compliance, driving pressure, PaO 2 /FiO 2 ratio, ventilatory ratio, and mechanical power. Results Three distinct subphenotypes were identified. Cluster 1 (22.9% of whole cohort) had a higher PaO 2 /FiO 2 ratio and lower Positive End-Expiratory Pressure (PEEP). Cluster 2 (51.3%) had a higher proportion of COVID-19 patients, lower driving pressure, higher PEEP, and higher respiratory system compliance. Cluster 3 (25.8%) had a lower pH, higher PaCO 2 , and higher ventilatory ratio. Mortality differed significantly across clusters (p = 0.03), with Cluster 3 having the highest mortality (56%). There were no significant differences in the proportions of responders to prone positioning for any of the studied parameters. Transpulmonary pressure measurements in a subcohort did not improve subphenotype characterization. Conclusions Distinct ARDS subphenotypes with varying mortality were identified in patients undergoing prone positioning; however, predicting which patients benefited from this intervention based on available data was not possible. These findings underscore the need for continued efforts in phenotyping ARDS through multimodal data to better understand the heterogeneity of this population.

To investigate the effects of prone positioning during extracorporeal membrane oxygenation (ECMO) and its effects on short-term and long-term survival. A computerized search was performed for all studies in PubMed, Web of Science, Embase, and the Cochrane Library up to December 31, 2023, including prospective and retrospective clinical studies of ECMO-treated patients with or without prone positioning. Titles, abstracts, and full-text articles were screened in duplicate by two investigators. The primary outcome was short-term survival (survival at discharge or 1-month survival). The secondary outcomes included long-term survival (60-day survival, 90-day survival), ECMO duration, length of intensive care unit (ICU) stay and ECMO weaning. Fifteen studies with 2608 patients were included, most of which were retrospective. The effect of prone versus non-prone positioning in ECMO patients was OR =  1.32; 95% CI, 0.88-1.97; P =  0.18 for short-term survival from the original data. The effects of prone positioning during ECMO were a significant increase in 28-day survival (OR = 2.54; 95% CI 1.71-3.76; P < 0.00001) and survival at discharge (OR = 1.49; 95% CI 1.11-2.00; P = 0.009), which appeared in the non-COVID-19 patient group. Furthermore, the short-term effects of prone ventilation in ECMO patients were also improved in the matching analysis (OR = 1.66; 95% CI, 1.23-2.23; P = 0.0008), but did not in the long-term survival rate (OR = 1.57; 95% CI, 0.90-2.76; P = 0.11). The durations of ECMO (OR = 1.99; 95% CI, 1.99-2.70; P < 0.00001) and ICU stay (OR = 1.17; 95% CI, 0.58-1.75; P < 0.0001) were significantly different between the prone group and the non-prone group. Prone position ventilation during ECMO confers no significant advantage in improving long-term survival and only slightly benefits short-term survival. Therefore, the prone position during ECMO should be carefully considered because further randomized clinical trials on this subject are needed.

PurposeSevere acute respiratory distress syndrome (ARDS) with PaO2/FiO2 < 80 mmHg is a life-threatening condition. The optimal management strategy is unclear. The aim of this meta-analysis was to compare the effects of low tidal volumes (Vt), moderate Vt, prone ventilation, and venovenous extracorporeal membrane oxygenation (VV-ECMO) on mortality in severe ARDS.MethodsWe performed a frequentist network meta-analysis of randomised controlled trials (RCTs) with participants who had severe ARDS and met eligibility criteria for VV-ECMO or had PaO2/FiO2 < 80 mmHg. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to discern the relative effect of interventions on mortality and the certainty of the evidence.ResultsTen RCTs including 812 participants with severe ARDS were eligible. VV-ECMO reduces mortality compared to low Vt (risk ratio [RR] 0.77, 95% confidence interval [CI] 0.59–0.99, moderate certainty) and compared to moderate Vt (RR 0.75, 95% CI 0.57–0.98, low certainty). Prone ventilation reduces mortality compared to moderate Vt (RR 0.78, 95% CI 0.66–0.93, high certainty) and compared to low Vt (RR 0.81, 95% CI 0.63–1.02, moderate certainty). We found no difference in the network comparison of VV-ECMO compared to prone ventilation (RR 0.95, 95% CI 0.72–1.26), but inferences were based solely on indirect comparisons with very low certainty due to very wide confidence intervals.ConclusionsIn adults with ARDS and severe hypoxia, both VV-ECMO (low to moderate certainty evidence) and prone ventilation (moderate to high certainty evidence) improve mortality relative to low and moderate Vt strategies. The impact of VV-ECMO versus prone ventilation remains uncertain.

To investigate short and long-term complications due to standard (≤24 hours) and extended (>24 hours) prone position in COVID-19 patients. Retrospective cohort study conducted in an Italian general intensive care unit. We enrolled patients on invasive mechanical ventilation and treated with prone positioning. We recorded short term complications from the data chart and long-term complications from the scheduled follow-up visit, three months after intensive care discharge. A total of 96 patients were included in the study. Median time for each prone positioning cycle (302 cycles) was equal to 18 (16–32) hours. In 37 (38%) patients at least one cycle of extended pronation was implemented. Patients with at least one pressure sore due to prone position were 38 (40%). Patients with pressure sores showed a statistically significative difference in intensive care length of stay, mechanical ventilation days, numbers of prone position cycles, total time spent in prone position and the use of extended prone position, compared to patients without pressure sores. All lesions were low grade. Cheekbones (18%) and chin (10%) were the most affected sites. Follow-up visit, scheduled three months after intensive care discharge, was possible in 58 patients. All patients were able to have all 12 muscle groups examined using theMedical Research Council scale examination. No patient reported sensory loss or presence of neuropathic pain for upper limbs. Extended prone position is feasible and might reduce the workload on healthcare workers without significant increase of major prone position related complications.