Background. The mechanisms underlying oxygenation improvement after prone positioning in COVID-19 ARDS have not been fully elucidated yet. We hypothesized that the oxygenation increase with prone positioning is secondary to the improvement of ventilation-perfusion matching. Methods. In a series of consecutive intubated COVID-19 ARDS patients receiving volume-controlled ventilation, we prospectively assessed the percent variation of ventilation-perfusion matching by electrical impedance tomography (EIT) before and 90 minutes after the first cycle of prone positioning (primary endpoint). We also assessed changes in the distribution and homogeneity of lung ventilation and perfusion, lung overdistention and collapse, respiratory system compliance, driving pressure, optimal positive end-expiratory pressure (PEEP), as assessed by EIT, and the ratio of partial pressure to fractional inspired oxygen (PaO2/FiO2) (secondary endpoints). Data are reported as medians [25th - 75th] or percentages. Results. We enrolled 30 consecutive patients, all analyzed without missing data. Compared to supine position, prone positioning overall improved ventilation-perfusion matching from 58 [43-69] % to 68 [56-75] % (p=0.042), with a median difference of 8.0% (95% Confidence Interval 0.1 to 16.0%) . Dorsal ventilation increased from 39 [31-43] % to 52 [44-62] % (p<0.001), while dorsal perfusion did not significantly vary. Prone positioning also reduced lung overdistension from 9 [4-11] % to 4 [2-6] % (p=0.025), while it did not significantly affect ventilation and perfusion homogeneity, lung collapse, static respiratory system compliance, driving pressure, and optimal PEEP. PaO2/FiO2 overall improved from 141 [104-182] mmHg to 235 [164-267] mmHg (p=0.019). However, 9 (30%) patients were non-responders, experiencing an increase in PaO2/FiO2 <20% with respect to baseline. Conclusions. In COVID-19 ARDS patients, prone positioning overall produced an early increase in ventilation-perfusion matching and dorsal ventilation. These effects were, however, heterogeneous among patients.

The efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the intensive care unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: (1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and (2) assessing whether the length of NIV application affects patient survival. This observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February–April 2020), who underwent endotracheal intubation after NIV failure. Among the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60–76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06–4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04–1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. In-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality.

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Right ventricular injury (RVI) in the context of acute respiratory distress syndrome (ARDS) is well recognized as an important determinant risk factor of mortality. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is part of the algorithm for the management of patients with severe ARDS and severely impaired gas exchange. Although VV-ECMO may theoretically protect the RV it is uncertain to what degree RVI persists despite VV-ECMO support, and whether it continues to influence mortality after ECMO initiation. The aim of this systematic review and meta-analysis was to investigate the impact of RVI on mortality in this context, testing the hypothesis that RVI worsens mortality in this cohort. We performed a systematic search that identified seven studies commenting on RVI and mortality in patients with ARDS receiving VV-ECMO. The presence of RVI was associated with greater mortality overall (odds ratios [OR]: 2.72; 95% confidence intervals [CI]: 1.52–4.85; p < 0.00) and across three subgroups (RV dilatational measures: OR: 3.51; 95% CI: 1.51–8.14; p < 0.01, RV functional measures: OR: 1.84; 95% CI: 0.99–3.42; p = 0.05, RV measurements post-ECMO initiation: OR: 1.94; 95% CI: 1.01–3.72; p < 0.05). Prospective studies are needed to investigate the causal relationship between RVI and mortality in this patient group and the best management strategies to reduce mortality.

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