Background Limited data are available on the use of prone position in intubated, invasively ventilated patients with Coronavirus disease-19 (COVID-19). Aim of this study is to investigate the use and effect of prone position in this population during the first 2020 pandemic wave. Methods Retrospective, multicentre, national cohort study conducted between February 24 and June 14, 2020, in 24 Italian Intensive Care Units (ICU) on adult patients needing invasive mechanical ventilation for respiratory failure caused by COVID-19. Clinical data were collected on the day of ICU admission. Information regarding the use of prone position was collected daily. Follow-up for patient outcomes was performed on July 15, 2020. The respiratory effects of the first prone position were studied in a subset of 78 patients. Patients were classified as Oxygen Responders if the PaO2/FiO2 ratio increased ≥ 20 mmHg during prone position and as Carbon Dioxide Responders if the ventilatory ratio was reduced during prone position. Results Of 1057 included patients, mild, moderate and severe ARDS was present in 15, 50 and 35% of patients, respectively, and had a resulting mortality of 25, 33 and 41%. Prone position was applied in 61% of the patients. Patients placed prone had a more severe disease and died significantly more (45% vs. 33%, p < 0.001). Overall, prone position induced a significant increase in PaO2/FiO2 ratio, while no change in respiratory system compliance or ventilatory ratio was observed. Seventy-eight % of the subset of 78 patients were Oxygen Responders. Non-Responders had a more severe respiratory failure and died more often in the ICU (65% vs. 38%, p = 0.047). Forty-seven % of patients were defined as Carbon Dioxide Responders. These patients were older and had more comorbidities; however, no difference in terms of ICU mortality was observed (51% vs. 37%, p = 0.189 for Carbon Dioxide Responders and Non-Responders, respectively). Conclusions During the COVID-19 pandemic, prone position has been widely adopted to treat mechanically ventilated patients with respiratory failure. The majority of patients improved their oxygenation during prone position, most likely due to a better ventilation perfusion matching. Trial registration: clinicaltrials.gov number: NCT04388670

Rationale: Prone positioning reduces mortality in severe ARDS patients. To date no evidence supports the use of prone positioning during venovenous extracorporeal oxygenation (ECMO).Objectives: Aim of the study was to assess feasibility, safety and effect on oxygenation and lung mechanics of prone positioning during ECMO. As a secondary exploratory aim, we assessed the association between PP and hospital mortality. Methods: We performed a multicenter retrospective cohort study in six italian ECMO centers, including patients managed with prone positioning (PP) during ECMO support (prone group, four centers) and patients managed in the supine position (control group, two centers). Physiological variables were analyzed at 4 time points (supine before PP, start of PP, end of PP, supine after PP). The association between prone positioning and hospital mortality was assessed by multivariate analysis and propensity score matching. Results: 240 patients were included, 107 in the prone group and 133 in the supine group.Median duration of the 326 pronation cycles was 15 [12][13][14][15][16][17][18] hours. Minor reversible complications were reported in 6% of prone positioning maneuvers. Prone positioning improved oxygenation and reduced intrapulmonary shunt. Unadjusted hospital mortality was lower in the prone group (34 vs 50%, p=0.017). After adjusting for covariates, prone positioning remained significantly associated with a reduction of hospital mortality (OR=0.50, 95%CI: 0.29-0.87). 66 propensity score-matched patients were identified in each group. In this matched sample, patients who underwent pronation had higher ECMO duration (16 vs10 days, p-value=0.0344) but lower hospital mortality (30% vs 53%, p=0.0241).

Optimal anticoagulation monitoring in patients with extracorporeal membrane oxygenation (ECMO) is fundamental to avoid hemorrhagic and thromboembolic complications. Besides conventional coagulation tests, there is growing interest in the use of viscoelastic hemostatic assays (VHA), in particular of tromboelastography (TEG). Evidence on the use of rotational thromboelastometry (ROTEM) is lacking in this setting. The aim of the study was to evaluate ROTEM as a tool for assessing hemostasis during ECMO, by comparing it to TEG and conventional coagulation assays. We conducted a prospective, observational, single-center study on adult patients on ECMO support anticoagulated with unfractioned heparin (UFH). Kaolin reaction time (R, min) for TEG and INTEM clotting time (CT, sec) for ROTEM were analyzed and compared with conventional coagulation tests. In the study period, we included 25 patients on ECMO support (14 V-A and 11 V-V); 84 data points were available for the analysis. Median UFH infusion rate was 15 [11–18] IU/min/kg. Median values for activated partial thromboplastin time (aPTT) ratio, Kaolin TEG R time, and INTEM CT were 1.44 [1.21–1.7], 22 [13–40] min, and 201 [183–225] sec, respectively. INTEM CT (ROTEM) showed a moderate correlation with standard coagulation tests (R 2 = 0.34 and 0.3 for aPTT and activated clotting time (ACT), respectively, p < 0.001). No significant correlation was found between INTEM CT and Kaolin R time (R 2 = 0.01). Further studies are needed to identify an appropriate anticoagulation target for ROTEM during ECMO.

The role of trunk inclination on respiratory function has been explored in patients with "typical" Acute Respiratory Distress Syndrome (ARDS) (1-3). Data regarding patients with COVID-19-associated ARDS (C-ARDS) are currently lacking.Aim of our study was to assess the effects of changes in trunk inclination on lung mechanics and gas exchange in mechanically ventilated patients with C-ARDS. MethodsThis single-center physiological cross-over study (ethical committee approval #70-11022021) was conducted on adult patients admitted to our COVID-ICU between March 3 and May 4, 2021. Diagnosis of C-ARDS, deep sedation, paralysis, and volume-controlled mechanical ventilation, were the inclusion criteria. Contraindications to mobilization (e.g., intracranial hypertension, spinal cord injury, tracheal lesions) and pregnancy constituted exclusion criteria. Patients were enrolled according to study personnel availability. A 5-Fr esophageal balloon (CooperSurgical, Trumbull, Connecticut) was inserted. The balloon was inflated with 1 ml of air and the correct position/function was verified before each measurement (4).Mechanical ventilation parameters, kept constant throughout the study, were set by the attending physician. Usually, PEEP is set according to the best respiratory system compliance (C RS ) assessed with a recruitment maneuver followed by a decremental PEEP trial. Of note, trunk inclination during PEEP selection is not standardized.Patients underwent three 15-minute steps in which trunk inclination was changed from 40° (semi-recumbent, baseline) to 0° (supine-flat), and back to 40° during the last step.At the end of each step, partitioned respiratory mechanics, arterial/central venous blood gas analysis and basic hemodynamics were recorded. Ventilatory ratio was calculated.

Background External chest-wall compression (ECC) is sometimes used in ARDS patients despite lack of evidence. It is currently unknown whether this practice has any clinical benefit in patients with COVID-19 ARDS (C-ARDS) characterized by a respiratory system compliance (Crs) < 35 mL/cmH2O. Objectives To test if an ECC with a 5 L-bag in low-compliance C-ARDS can lead to a reduction in driving pressure (DP) and improve gas exchange, and to understand the underlying mechanisms. Methods Eleven patients with low-compliance C-ARDS were enrolled and underwent 4 steps: baseline, ECC for 60 min, ECC discontinuation and PEEP reduction. Respiratory mechanics, gas exchange, hemodynamics and electrical impedance tomography were recorded. Four pigs with acute ARDS were studied with ECC to understand the effect of ECC on pleural pressure gradient using pleural pressure transducers in both non-dependent and dependent lung regions. Results Five minutes of ECC reduced DP from baseline 14.2 ± 1.3 to 12.3 ± 1.3 cmH2O (P < 0.001), explained by an improved lung compliance. Changes in DP by ECC were strongly correlated with changes in DP obtained with PEEP reduction (R2 = 0.82, P < 0.001). The initial benefit of ECC decreased over time (DP = 13.3 ± 1.5 cmH2O at 60 min, P = 0.03 vs. baseline). Gas exchange and hemodynamics were unaffected by ECC. In four pigs with lung injury, ECC led to a decrease in the pleural pressure gradient at end-inspiration [2.2 (1.1–3) vs. 3.0 (2.2–4.1) cmH2O, P = 0.035]. Conclusions In C-ARDS patients with Crs < 35 mL/cmH2O, ECC acutely reduces DP. ECC does not improve oxygenation but it can be used as a simple tool to detect hyperinflation as it improves Crs and reduces Ppl gradient. ECC benefits seem to partially fade over time. ECC produces similar changes compared to PEEP reduction.

ImportanceData on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2–related pneumonia are scarce.ObjectiveTo evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU.Design, Setting, and ParticipantsThis retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021.ExposuresCOVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine).Main Outcomes and MeasuresThe incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders.ResultsAmong the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] age was 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dose was 0.03 (95% CI, 0.03-0.04; P &amp;lt; .001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P &amp;lt; .001). There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period: 139 patients (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Compared with unvaccinated patients, vaccinated patients were older (median [IQR]: 72 [66-76] vs 60 [51-69] years; P &amp;lt; .001), primarily male individuals (110 patients [79.1%] vs 252 patients [60.9%]; P &amp;lt; .001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P &amp;lt; .001) and had higher ratio of arterial partial pressure of oxygen (Pao2) and fraction of inspiratory oxygen (FiO2) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P = .007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower Pao2/FiO2 at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients.Conclusions and RelevanceIn this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status. These findings suggest a substantial reduction of the risk of developing COVID-19–related severe acute respiratory failure requiring ICU admission among vaccinated people.

Background: Limited data are available on the use of prone position in intubated, invasively ventilated patients with Coronavirus disease-19 (COVID-19). Aim of this study is to investigate the use and effect of prone position in this population during the first 2020 pandemic wave.Methods: Retrospective, multicentre, national cohort study conducted between February 24 and June 14, 2020 in 24 Italian Intensive Care Units (ICU) on adult patients needing invasive mechanical ventilation for respiratory failure caused by COVID-19.Clinical data were collected on the day of ICU admission. Information regarding the use of prone position were collected daily. Follow-up for patient outcomes was performed on July 15, 2020. The respiratory effects of the first prone position were studied in a subset of 78 patients. Patients were classified as Responders if the PaO2/FiO2 ratio increased ≥ 20 mmHg during prone position. Results: Of 1057 included patients, mild, moderate and severe ARDS was present in 15, 50 and 35% of patients, respectively and had a resulting mortality of 25, 33 and 41%. Prone position was applied in 61% of the patients. Patients placed prone had a more severe disease and died significantly more (45% vs 33%, p<0.001). Overall, prone position induced a significant increase in PaO2/FiO2 ratio, while no change in respiratory system compliance was observed. Seventy-eight % of patients were Responders to prone position. Non-Responders had a more severe respiratory failure and died more often in the ICU (65% vs. 38%, p=0.047).Conclusions: During the COVID-19 pandemic, prone position has been widely adopted to treat mechanically ventilated patients with respiratory failure. The majority of patients improved their oxygenation during prone position, most likely due to a better ventilation perfusion matching.Trial registration: clinicaltrials.gov number: NCT04388670

Background During the first coronavirus disease 2019 (COVID-19) pandemic wave, an unprecedented number of patients with respiratory failure due to a new, highly contagious virus needed hospitalization and intensive care unit (ICU) admission. The aim of the present study was to describe the communication and visiting policies of Italian intensive care units (ICUs) during the first COVID-19 pandemic wave and national lockdown and compare these data with prepandemic conditions. Methods A national web-based survey was conducted among 290 Italian hospitals. Each ICU (active between February 24 and May 31, 2020) was encouraged to complete an individual questionnaire inquiring the hospital/ICU structure/organization, communication/visiting habits and the role of clinical psychology prior to, and during the first COVID-19 pandemic wave. Results Two hundred and nine ICUs from 154 hospitals (53% of the contacted hospitals) completed the survey (202 adult and 7 pediatric ICUs). Among adult ICUs, 60% were dedicated to COVID-19 patients, 21% were dedicated to patients without COVID-19 and 19% were dedicated to both categories (Mixed). A total of 11,102 adult patients were admitted to the participating ICUs during the study period and only approximately 6% of patients received at least one visit. Communication with family members was guaranteed daily through an increased use of electronic devices and was preferentially addressed to the same family member. Compared to the prepandemic period, clinical psychologists supported physicians more often regarding communication with family members. Fewer patients received at least one visit from family members in COVID and mixed-ICUs than in non-COVID ICUs, l (0 [0–6]%, 0 [0–4]% and 11 [2–25]%, respectively, p < 0.001). Habits of pediatric ICUs were less affected by the pandemic. Conclusions Visiting policies of Italian ICUs dedicated to adult patients were markedly altered during the first COVID-19 wave. Remote communication was widely adopted as a surrogate for family meetings. New strategies to favor a family-centered approach during the current and future pandemics are warranted.