key: cord-0964251-jn07hn4l authors: Battaglini, Denise; Pelosi, Paolo; Rocco, Patricia R M title: Prone positioning in COVID-19 ARDS: more pros than cons date: 2022-04-30 journal: Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia DOI: 10.36416/1806-3756/e20220065 sha: bcbf6530abd458e682c2a154b5384ec7929a6dad doc_id: 964251 cord_uid: jn07hn4l nan Patients with severe COVID-19 may develop acute respiratory failure requiring mechanical ventilation. (1) Prone positioning is a rescue therapy for ARDS patients with hypoxemia refractory to protective mechanical ventilation with high Fio 2 . (2) In non-COVID-19 ARDS, prone positioning has been shown to improve oxygenation and is associated with improved outcomes. The improvement in oxygenation and the reduction in the risk of ventilation-induced lung injury have been explained by a more homogeneous distribution of transpulmonary pressures, which opens the dorsal atelectatic areas, thus reducing regional lung stress. (3) In COVID-19 ARDS, different phenotypes have been proposed. (1) In phenotype 1, lung weight and lung compliance may be relatively normal, alveolar recruitment is minimal, and hypoxemia is mainly due to increased lung regions with low ventilation/perfusion ratios. (4) On the other hand, in phenotype 2, lung weight is increased, lung compliance is markedly reduced, alveolar recruitment is variable, and hypoxemia is mainly due to increased true shunting. Both phenotypes are characterized by increased wasted ventilation (high dead space ventilation and lung regions with high ventilation/perfusion ratios). (5) Therefore, the effects of prone positioning in COVID-19 ARDS may differ from those seen in non-COVID-19 ARDS. To date, few randomized controlled trials have reported benefits of prone positioning in COVID-19 ARDS. In a study published in this issue of Jornal Brasileiro de Pneumologia, Cunha et al. (6) aimed to identify factors that lead to a positive oxygenation response and predictors of mortality after prone positioning in mechanically ventilated patients with COVID-19. A multicenter cohort study was performed across seven hospitals in Brazil, including patients with a suspected or confirmed diagnosis of COVID-19 who were on invasive mechanical ventilation, had a PaO 2 /Fio 2 < 150 mmHg, and were prone positioned. An improvement in the PaO 2 /Fio 2 ratio of at least 20 mmHg after the first prone positioning session was defined as a positive response. Of the 574 patients studied, 412 (72%) responded positively to the first prone positioning session. Multiple logistic regression showed that "responders" had lower Simplified Acute Physiology Score III and SOFA scores, lower D-dimer levels, and lower baseline PaO 2 /Fio 2 ratios. Age, time to the first prone positioning session, number of sessions, pulmonary impairment, and immunosuppression were associated with increased mortality. Overall, although prone positioning led to an improvement in oxygenation, this improvement was not associated with better survival. The definition of "responders" in COVID-19 patients is heterogeneous across studies, (7) (8) (9) including the use of different thresholds for response in oxygenation (e.g., a PaO 2 /Fio 2 increase ≥ 20 mmHg; a PaO 2 /Fio 2 increase ≥ the median percent change in PaO 2 /Fio 2 ; a PaO 2 /Fio 2 ≥ 150 mmHg after returning to the supine position) and the use of ventilatory ratio. The impact of improvement in oxygenation during prone positioning on ultimate outcomes is controversial. A beneficial effect of early prone positioning on survival has been reported in patients with a Pao 2 /Fio 2 ≤ 150 mmHg or a Pao 2 /Fio 2 ≤ 100 mmHg. (7) Other authors (8, 9) found higher mortality in nonresponders (Table 1 ). In the study by Cunha et al., (6) prone positioning increased oxygenation and respiratory rate, but it was not associated with improvement in respiratory system mechanics (compliance, driving pressure, or plateau pressure). In responders, prone positioning promotes alveolar recruitment with higher regional perfusion of dorsal areas. In nonresponders, prone positioning does not redistribute lung densities, and perfusion is mainly redistributed toward dependent lung regions. In COVID-19 phenotype 2, oxygenation may improve due to the redistribution of pulmonary blood flow from dorsal to ventral lung regions but not due to effective alveolar recruitment. (10) Data suggest that early use of prone positioning, as well as the number of prone positioning sessions, may be associated with better outcomes. (11, 12) In the study by Cunha et al., (6) the time to prone positioning was not fixed nor was it defined a priori, which may account for the nonresponders whose first prone positioning session occurred late in the course of COVID-19, even though the number of sessions did not differ between nonresponders and responders. This can be explained by the fact that clinicians play a crucial role in decision making, individualizing the timing and number of sessions. In most previous studies, the decision to prone patients was at the discretion of the attending physician rather than being standardized across centers (Table 1) . Data on timing of intubation have not been reported. Yet, optimal timing of intubation has become a cornerstone in COVID-19 management and is known to be associated with outcomes. Patients with COVID-19 phenotype 1 can initially benefit from noninvasive respiratory support, since they respond better to the higher oxygen fraction and moderate PEEP levels delivered by noninvasive CPAP. (13) On the other hand, worsening of oxygenation during noninvasive respiratory support or the presence of COVID-19 phenotype 2 requires prompt and early intubation and invasive mechanical ventilation. Cunha et al. (6) listed some limitations of their study, including its retrospective design (not all data could be found in the electronic medical records, and they were unable to control for the prescription and timing of prone positioning), the absence of an a priori power analysis or preplanned protocol, the small sample size, the lack of control groups, and the lack of description of other rescue therapies (e.g., inhaled nitric oxide, recruitment maneuvers, and extracorporeal membrane oxygenation), which may affect patient outcomes. Overall mortality in the study by Cunha et al. (6) was 69.3%, which suggests that those patients with severe COVID-19 are at high risk of death. This mortality rate is high compared with those reported in other studies involving COVID-19 patients who underwent prone positioning (Table 1) . Prone positioning is just one part of a therapeutic concept including a sophisticated ventilation strategy, strict fluid balance control, and dedicated hemodynamic management, all of which may affect outcomes. (3) In conclusion, the study by Cunha et al. (6) improves our knowledge about the use of prone positioning in COVID-19 patients with severe hypoxemic respiratory failure, suggesting that this maneuver should be used early regardless of oxygenation response. However, their findings cannot be generalized without confirmation in larger randomized controlled trials. DB: review and approval of the final manuscript. PP and PRMR: senior authorship and approval of the final manuscript. Distinct phenotypes require distinct respiratory management strategies in severe COVID-19 Prone Position and COVID-19: Mechanisms and Effects COVID-19 and VILI: developing a mobile app for measurement of mechanical power at a glance Effects of higher PEEP and recruitment manoeuvres on mortality in patients with ARDS: a systematic review, meta-analysis, metaregression and trial sequential analysis of randomized controlled trials Computed tomography assessment of PEEP-induced alveolar recruitment in patients with severe COVID-19 pneumonia Impact of prone positioning on patients with COVID-19 and ARDS on invasive mechanical ventilation: a multicenter cohort study Prone Positioning and Survival in Mechanically Ventilated Patients With Coronavirus Disease 2019-Related Respiratory Failure Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients Sustained oxygenation improvement after first prone positioning is associated with liberation from mechanical ventilation and mortality in critically ill COVID-19 patients: a cohort study Mechanisms of oxygenation responses to proning and recruitment in COVID-19 pneumonia The efficacy and safety of prone positioning in adults patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials Prone Position for Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial Hemodynamic response to positive end-expiratory pressure and prone position in COVID-19 ARDS Short and long-term complications due to standard and extended prone position cycles in CoViD-19 patients Muscle strength and functional outcome after prone positioning in COVID-19 ICU survivors. Intensive Crit Care Nurs Incidence and Practice of Early Prone Positioning in Invasively Ventilated COVID-19 Patients-Insights from the PRoVENT-COVID Observational Study Prone position during ECMO in patients with COVID-19 in Morocco: Case series Respiratory Mechanics in a Cohort of Critically Ill Subjects With COVID-19 Infection Effect of prone positioning on Prone positioning in COVID-19 ARDS: more pros than cons oxygenation and static respiratory system compliance in COVID-19 ARDS vs. non-COVID ARDS Difference between prolonged versus standard duration of prone position in COVID-19 patients: a retrospective study Differential effects of prone position in COVID-19-related ARDS in low and high recruiters Early prone positioning therapy for patients with mild COVID-19 disease Prone Position in Mechanically Ventilated COVID-19 Patients: A Multicenter Study Lung Recruitment, Individualized PEEP, and Prone Position Ventilation for COVID-19-Associated Severe ARDS: A Single Center Observational Study Prone positioning improves oxygenation and lung recruitment in patients with SARS-CoV-2 acute respiratory distress syndrome; a single centre cohort study of 20 consecutive patients Safety and Outcomes of Prolonged Usual Care Prone Position Mechanical Ventilation to Treat Acute Coronavirus Disease Hypoxemic Respiratory Failure Prone Positioning in Moderate to Severe Acute Respiratory Distress Syndrome Due to COVID-19: A Cohort Study and Analysis of Physiology Prone positioning in mechanically ventilated patients with severe acute respiratory distress syndrome and coronavirus disease 2019 Prone positioning for patients intubated for severe acute respiratory distress syndrome (ARDS) secondary to COVID-19: a retrospective observational cohort study Hypoxemia and prone position in mechanically ventilated COVID-19 patients: a prospective cohort study Evaluation of Oxygenation in 129 Proning Sessions in 34 Mechanically Ventilated COVID-19 Patients COVID-19 Early Prone Position Study Group. Efficacy of early prone position for COVID-19 patients with severe hypoxia: a single-center prospective cohort study Prone positioning under VV-ECMO in SARS-CoV-2-induced acute respiratory distress syndrome Prolonged prone position ventilation for SARS-CoV-2 patients is feasible and effective None declared.