IMPORTANCE Many patients with coronavirus disease 2019 (COVID-19) are critically ill and require care in the intensive care unit (ICU). OBJECTIVE To evaluate the independent risk factors associated with mortality of patients with COVID-19 requiring treatment in ICUs in the Lombardy region of Italy. DESIGN, SETTING, AND PARTICIPANTS This retrospective, observational cohort study included 3988 consecutive critically ill patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinating center (Fondazione IRCCS [Istituto di Ricovero e Cura a Carattere Scientifico] Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network from February 20 to April 22, 2020. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by real-time reverse transcriptase-polymerase chain reaction assay of nasopharyngeal swabs. Follow-up was completed on May 30, 2020. EXPOSURES Baseline characteristics, comorbidities, long-term medications, and ventilatory support at ICU admission. MAIN OUTCOMES AND MEASURES Time to death in days from ICU admission to hospital discharge. The independent risk factors associated with mortality were evaluated with a multivariable Cox proportional hazards regression. RESULTS Of the 3988 patients included in this cohort study, the median age was 63 (interquartile range [IQR] 56-69) years; 3188 (79.9%; 95% CI, 78.7%-81.1%) were men, and 1998 of 3300 (60.5%; 95% CI, 58.9%-62.2%) had at least 1 comorbidity. At ICU admission, 2929 patients (87.3%; 95% CI, 86.1%-88.4%) required invasive mechanical ventilation (IMV). The median follow-up was 44 (95% CI, 40-47; IQR, 11-69; range, 0-100) days; median time from symptoms onset to ICU admission was 10 (95% CI, 9-10; IQR, 6-14) days; median length of ICU stay was 12 (95% CI, 12-13; IQR, 6-21) days; and median length of IMV was 10 (95% CI, 10-11; IQR, 6-17) days. Cumulative observation time was 164 305 patient-days. Hospital and ICU mortality rates were 12 (95% CI, 11-12) and 27 (95% CI, 26-29) per 1000 patients-days, respectively. In the subgroup of the first 1715 patients, as of May 30, 2020, 865 (50.4%) had been discharged from the ICU, 836 (48.7%) had died in the ICU, and 14 (0.8%) were still in the ICU; overall, 915 patients (53.4%) died in the hospital. Independent risk factors associated with mortality included older age (hazard ratio [HR], 1.75; 95% CI, 1.60-1.92), male sex (HR, 1.57; 95% CI, 1.31-1.88), high fraction of inspired oxygen (FiO 2) (HR, 1.14; 95% CI, 1.10-1.19), high positive end-expiratory pressure (HR, 1.04; 95% CI, 1.01-1.06) or low PaO 2 :FiO 2 ratio (HR, 0.80; 95% CI, 0.74-0.87) on ICU admission, and history of chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.28-2.19), hypercholesterolemia (HR, 1.25; 95% CI, 1.02-1.52), and type 2 diabetes (HR, 1.18; 95% CI, 1.01-1.39). No medication was independently associated with mortality (angiotensin-converting enzyme inhibitors HR, 1.17; 95% CI, 0.97-1.42; angiotensin receptor blockers HR, 1.05; 95% CI, 0.85-1.29). CONCLUS...

We studied 16 patients with acute lung injury receiving volume-controlled ventilation to assess the relationships between gas exchange and respiratory mechanics before, during, and after 2 h in the prone position. We measured the end-expiratory lung volume (EELV, helium dilution), the total respiratory system (Cst,rs), the lung (Cst,L) and the thoracoabdominal cage (Cst,w) compliances (end-inspiratory occlusion technique and esophageal balloon), the hemodynamics, and gas exchange. In the prone position, PaO2 increased from 103.2 +/- 23.8 to 129.3 +/- 32.9 mm Hg (p < 0.05) without significant changes of Cst,rs and EELV. However, Cst,w decreased from 204.8 +/- 97.4 to 135.9 +/- 52.5 ml/cm H2O (p < 0.01) and the decrease was correlated with the oxygenation increase (r = 0.62, p < 0.05). Furthermore, the greater the baseline supine Cst,w, the greater its decrease in the prone position (r = 0.82, p< 0.01). Consequently, the oxygenation changes in the prone position were predictable from baseline supine Cst,w (r = 0.80, p < 0.01). Returning to the supine position, Cst,rs increased compared with baseline (42.3 +/- 14.4 versus 38.4 +/- 13.7 ml/cm H2O; p < 0.01), mainly because of the lung component (57.5 +/- 25.1 versus 52.4 +/- 23.3 ml/cm H2O; p < 0.01). Thus, (1) baseline Cst,w and its changes may play a role in determining the oxygenation response in the prone position; (2) the prone position improves Cst,rs and Cst,L when the supine position is resumed.

Objectives: Severe cases of coronavirus disease 2019 develop the acute respiratory distress syndrome, requiring admission to the ICU. This study aimed to describe specific pathophysiological characteristics of acute respiratory distress syndrome from coronavirus disease 2019. Design: Prospective crossover physiologic study. Setting: ICU of a university-affiliated hospital from northern Italy dedicated to care of patients with confirmed diagnosis of coronavirus disease 2019. Patients: Ten intubated patients with acute respiratory distress syndrome and confirmed diagnosis of coronavirus disease 2019. Interventions: We performed a two-step positive end-expiratory pressure trial with change of 10 cm H 2 O in random order. Measurements and Main Results: At each positive end-expiratory pressure level, we assessed arterial blood gases, respiratory mechanics, ventilation inhomogeneity, and potential for lung recruitment by electrical impedance tomography. Potential for lung recruitment was assessed by the recently described recruitment to inflation ratio. In a subgroup of seven paralyzed patients, we also measured ventilation-perfusion mismatch at lower positive end-expiratory pressure by electrical impedance tomography. At higher positive end-expiratory pressure, respiratory mechanics did not change significantly: compliance remained relatively high with low driving pressure. Oxygenation and ventilation inhomogeneity improved but arterial co 2 increased despite unchanged respiratory rate and tidal volume. The recruitment to inflation ratio presented median value higher than previously reported in acute respiratory distress syndrome patients but with large variability (median, 0.79 [0.53-1.08]; range, 0.16-1.40). The Fio 2 needed to obtain viable oxygenation at lower positive endexpiratory pressure was significantly correlated with the recruitment to inflation ratio (r = 0.603; p = 0.05). The ventilation-perfusion mismatch was elevated (median, 34% [32-45%] of lung units) and, in six out of seven patients, ventilated nonperfused units represented a much larger proportion than perfused nonventilated ones. Conclusions: In patients with acute respiratory distress syndrome from coronavirus disease 2019, potential for lung recruitment presents large variability, while elevated dead space fraction may be a specific pathophysiological trait. These findings may guide selection of personalized mechanical ventilation settings. (Crit

Background We evaluate the clinical feasibility of spontaneous breathing on extracorporeal membrane oxygenation and the interactions between artificial and native lungs in patients bridged to lung transplant or with acute exacerbation of chronic obstructive pulmonary disease (COPD) or acute respiratory distress syndrome. Methods The clinical course of a total of 48 patients was analyzed. Twenty-three of 48 patients were enrolled in the prospective study (nine bridged to lung transplant, six COPD, and eight acute respiratory distress syndrome). The response to the carbon dioxide removal was evaluated in terms of respiratory rate and esophageal pressure swings by increasing (“relief” threshold) and decreasing (“distress” threshold) the extracorporeal membrane oxygenation gas flow, starting from baseline condition. Results Considering all 48 patients, spontaneous breathing extracorporeal membrane oxygenation was performed in 100% bridge to lung transplant (9 of 9 extubated), 86% COPD (5 of 6 extubated), but 27% acute respiratory distress syndrome patients (6 of 8 extubated; P &lt; 0.001) and was maintained for 92, 69, and 38% of the extracorporeal membrane oxygenation days (P = 0.021), respectively. In all the 23 patients enrolled in the study, gas flow increase (from 2.3 ± 2.2 to 9.2 ± 3.2 l/min) determined a decrease of both respiratory rate (from 29 ± 6 to 8 ± 9 breaths/min) and esophageal pressure swings (from 20 ± 9 to 4 ± 4 cm H2O; P &lt; 0.001 for all). All COPD and bridge to lung transplant patients were responders (reached the relief threshold), while 50% of acute respiratory distress syndrome patients were nonresponders. Conclusions Carbon dioxide removal through extracorporeal membrane oxygenation relieves work of breathing and permits extubation in many patients, mainly bridge to lung transplant and COPD. Only few patients with acute respiratory distress syndrome were able to perform the spontaneous breathing trial, and in about 50% of these, removal of large amount of patient’s carbon dioxide production was not sufficient to prevent potentially harmful spontaneous respiratory effort.