Amedeo Guzzardella

Bio: Amedeo Guzzardella is an academic researcher from University of Milan. The author has contributed to research in topics: Medicine & Mechanical ventilation. The author has an hindex of 6, co-authored 9 publications receiving 333 citations. Previous affiliations of Amedeo Guzzardella include Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico.

Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients.

Abstract: 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 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 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 < 0001) 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 = 0047) 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 = 0189 for Carbon Dioxide Responders and Non-Responders, respectively) 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: clinicaltrialsgov number: NCT04388670

Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave: the global UNITE-COVID study

Abstract: To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%–50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality.

Exhaled air dispersion during high-flow nasal cannula therapy versus CPAP via different masks.

Abstract: Background High-flow nasal cannula (HFNC) is an emerging therapy for respiratory failure but the extent of exhaled air dispersion during treatment is unknown. We examined exhaled air dispersion during HFNC therapy versus continuous positive airway pressure (CPAP) on a human patient simulator (HPS) in an isolation room with 16 air changes·h−1. Methods The HPS was programmed to represent different severity of lung injury. CPAP was delivered at 5–20 cmH2O via nasal pillows (Respironics Nuance Pro Gel or ResMed Swift FX) or an oronasal mask (ResMed Quattro Air). HFNC, humidified to 37°C, was delivered at 10–60 L·min−1 to the HPS. Exhaled airflow was marked with intrapulmonary smoke for visualisation and revealed by laser light-sheet. Normalised exhaled air concentration was estimated from the light scattered by the smoke particles. Significant exposure was defined when there was ≥20% normalised smoke concentration. Results In the normal lung condition, mean±sd exhaled air dispersion, along the sagittal plane, increased from 186±34 to 264±27 mm and from 207±11 to 332±34 mm when CPAP was increased from 5 to 20 cmH2O via Respironics and ResMed nasal pillows, respectively. Leakage from the oronasal mask was negligible. Mean±sd exhaled air distances increased from 65±15 to 172±33 mm when HFNC was increased from 10 to 60 L·min−1. Air leakage to 620 mm occurred laterally when HFNC and the interface tube became loose. Conclusion Exhaled air dispersion during HFNC and CPAP via different interfaces is limited provided there is good mask interface fitting.

SARS-CoV-2 pathogenesis

Abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating pandemic. Although most people infected with SARS-CoV-2 develop a mild to moderate disease with virus replication restricted mainly to the upper airways, some progress to having a life-threatening pneumonia. In this Review, we explore recent clinical and experimental advances regarding SARS-CoV-2 pathophysiology and discuss potential mechanisms behind SARS-CoV-2-associated acute respiratory distress syndrome (ARDS), specifically focusing on new insights obtained using novel technologies such as single-cell omics, organoid infection models and CRISPR screens. We describe how SARS-CoV-2 may infect the lower respiratory tract and cause alveolar damage as a result of dysfunctional immune responses. We discuss how this may lead to the induction of a 'leaky state' of both the epithelium and the endothelium, promoting inflammation and coagulation, while an influx of immune cells leads to overexuberant inflammatory responses and immunopathology. Finally, we highlight how these findings may aid the development of new therapeutic interventions against COVID-19.