A Covid-19 outbreak developed in Lombardy, Veneto and Emilia-Romagna (Italy) at the end of February 2020. Fear of an imminent saturation of available ICU beds generated the notion that rationing of intensive care resources could have been necessary. In order to evaluate the impact of Covid-19 on the ICU capacity to manage critically ill patients, we performed a retrospective analysis of the first 2 weeks of the outbreak (February 24–March 8). Data were collected from regional registries and from a case report form sent to participating sites. ICU beds increased from 1545 to 1989 (28.7%), and patients receiving respiratory support outside the ICU increased from 4 (0.6%) to 260 (37.0%). Patients receiving respiratory support outside the ICU were significantly older [65 vs. 77 years], had more cerebrovascular (5.8 vs. 13.1%) and renal (5.3 vs. 10.0%) comorbidities and less obesity (31.4 vs. 15.5%) than patients admitted to the ICU. PaO2/FiO2 ratio, respiratory rate and arterial pH were higher [165 vs. 244; 20 vs. 24 breath/min; 7.40 vs. 7.46] and PaCO2 and base excess were lower [34 vs. 42 mmHg; 0.60 vs. 1.30] in patients receiving respiratory support outside the ICU than in patients admitted to the ICU, respectively. Increase in ICU beds and use of out-of-ICU respiratory support allowed effective management of the first 14 days of the Covid-19 outbreak, avoiding resource rationing.

Objectives: To determine the impact of positive end-expiratory pressure during mechanical ventilation with and without spontaneous breathing activity on regional lung inflammation in experimental nonsevere acute respiratory distress syndrome. Design: Laboratory investigation. Setting: University hospital research facility. Subjects: Twenty-four pigs (28.1–58.2 kg). Interventions: In anesthetized animals, intrapleural pressure sensors were placed thoracoscopically in ventral, dorsal, and caudal regions of the left hemithorax. Lung injury was induced with saline lung lavage followed by injurious ventilation in supine position. During airway pressure release ventilation with low tidal volumes, positive end-expiratory pressure was set 4 cm H₂O above the level to reach a positive transpulmonary pressure in caudal regions at end-expiration (best-positive end-expiratory pressure). Animals were randomly assigned to one of four groups (n = 6/group; 12 hr): 1) no spontaneous breathing activity and positive end-expiratory pressure = best-positive end-expiratory pressure – 4 cm H₂O, 2) no spontaneous breathing activity and positive end-expiratory pressure = best-positive end-expiratory pressure + 4 cm H₂O, 3) spontaneous breathing activity and positive end-expiratory pressure = best-positive end-expiratory pressure + 4 cm H₂O, 4) spontaneous breathing activity and positive end-expiratory pressure = best-positive end-expiratory pressure – 4 cm H₂O. Measurements and Main Results: Global lung inflammation assessed by specific [¹⁸F]fluorodeoxyglucose uptake rate (median [25–75% percentiles], min^–1) was decreased with higher compared with lower positive end-expiratory pressure both without spontaneous breathing activity (0.029 [0.027–0.030] vs 0.044 [0.041–0.065]; p = 0.004) and with spontaneous breathing activity (0.032 [0.028–0.043] vs 0.057 [0.042–0.075]; p = 0.016). Spontaneous breathing activity did not increase global lung inflammation. Lung inflammation in dorsal regions correlated with transpulmonary driving pressure from spontaneous breathing at lower (r = 0.850; p = 0.032) but not higher positive end-expiratory pressure (r = 0.018; p = 0.972). Higher positive end-expiratory pressure resulted in a more homogeneous distribution of aeration and regional transpulmonary pressures at end-expiration along the ventral-dorsal gradient, as well as a shift of the perfusion center toward dependent zones in the presence of spontaneous breathing activity. Conclusions: In experimental mild-to-moderate acute respiratory distress syndrome, positive end-expiratory pressure levels that stabilize dependent lung regions reduce global lung inflammation during mechanical ventilation, independent from spontaneous breathing activity.

Ex-situ machine perfusion (MP) has been increasingly used to enhance liver quality in different settings. Small animal models can help to implement this procedure. As most normothermic MP (NMP) models employ sub-physiological levels of oxygen delivery (DO₂), the aim of this study was to investigate the effectiveness and safety of different DO₂, using human red blood cells (RBCs) as oxygen carriers on metabolic recovery in a rat model of NMP. Four experimental groups (n = 5 each) consisted of (1) native (untreated/control), (2) liver static cold storage (SCS) 30 min without NMP, (3) SCS followed by 120 min of NMP with Dulbecco-Modified-Eagle-Medium as perfusate (DMEM), and (4) similar to group 3, but perfusion fluid was added with human RBCs (hematocrit 15%) (BLOOD). Compared to DMEM, the BLOOD group showed increased liver DO₂ (p = 0.008) and oxygen consumption ( $\dot{VO}$ ₂) (p < 0.001); lactate clearance (p < 0.001), potassium (p < 0.001), and glucose (p = 0.029) uptake were enhanced. ATP levels were likewise higher in BLOOD relative to DMEM (p = 0.031). $\dot{VO}$ ₂ and DO₂ were highly correlated (p < 0.001). Consistently, the main metabolic parameters were directly correlated with DO₂ and $\dot{VO}$ ₂. No human RBC related damage was detected. In conclusion, an optimized DO₂ significantly reduces hypoxic damage-related effects occurring during NMP. Human RBCs can be safely used as oxygen carriers.

Background: The role of intravenous immunoglobulins (IVIG) during sepsis is controversial, as different trials on IVIG have observed inconsistent survival benefits. We aimed to elucidate the possible association and clinical significance between circulating levels of immunoglobulins. Methods: In a subset of 956 patients with severe sepsis and septic shock of the multicentre, open-label RCT ALBIOS, venous blood samples were serially collected 1, 2, and 7 days after enrolment (or at ICU discharge, whichever came first). IgA, IgG and IgM concentrations were assayed in all patients on day 1 and in a subgroup of 150 patients on days 2 and 7. Ig concentrations were measured employing a turbidimetric assay, OSR61171 system. Results: IgA on day 1 had a significant predictive value for both 28-day and 90-day mortality (28-day mortality, HR: 1.50 (95% CI 1.18–1.92); 90-day mortality, HR: 1.54 (95% CI 1.25–1.91)). IgG, but not IgM, on day 1 showed similar results for 28-day (HR 1.83 (95% CI 1.33–2.51) and 90-day mortality HR: 1.66 (95% CI 1.23–2.25)). In addition, lower levels of IgG but not of IgA and IgM, at day 1 were associated with significantly higher risk of secondary infections (533 [406–772] vs 600 [452–842] mg/dL, median [Q1–Q3], p = 0.007). Conclusions: In the largest cohort study of patients with severe sepsis or septic shock, we found that high levels of IgA and IgG on the first day of diagnosis were associated with a decreased 90-day survival. No association was found between IgM levels and survival. As such, the assessment of endogenous immunoglobulins could be a useful tool to identify septic patients at high risk of mortality. Trial registration #NCT00707122, Clinicaltrial.gov, registered 30 June 2008