Essential Multiorgan Pathophysiology of COVID-19

Typical manifestations of coronavirus disease-2019 (COVID-19) include mild-to-moderate "flu-like” symptoms, although more severe manifestations have been reported. The pathophysiology of COVID-19 is complex, and its clinical spectrum might not be limited to local pneumonia, but rather may represent a multisystem illness with potential for severe acute respiratory distress syndrome (ARDS) and multiorgan impairment. In this context, the aim of the present handbook is to provide an overview of possible multisystemic manifestations and therapeutic strategies, in order to guide the clinician to deal with COVID-19 critical illness and to prevent potential systemic consequences. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

COVID-19 Critical and Intensive Care Medicine Essentials

This book provides healthcare professionals in Critical Care setting an easy consultation guide to fight against COVID-19. The book is divided into sections: Fundamentals of COVID-19, Pneumological critical care, Neurological manifestations, Cardiovascular manifestations, Renal manifestations, Haemostasis and coagulation, Other multi-organs involvement, Principles of therapy. Each section includes: · brief pathophysiology of COVID-19 (ventilation, neurological, cardiovascular, etc.);· principles of management (enriched with flowcharts and figures);· principles of therapy;· tips and key messages. Readers can find the most updated advices on how to face the ongoing pandemic: from principles of conventional oxygen therapy, assisted and invasive mechanical ventilation in critically ill COVID-19 patients to the complications sometimes underestimated. Tables and flowcharts provided are based on current knowledge in COVID-19 to help the clinician managing COVID-19 patients by a multiple-organs prospective. Written by international key opinion leaders of each field, the book represents a point of reference for all professionals involved in the management of COVID-19 pandemic. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

[Pre-clinical validation of a turbine-based ventilator for invasive ventilation-The ACUTE-19 ventilator]. / Validación preclínica de un respirador de turbina para la ventilación invasiva: el respirador ACUTE-19.

Background: The severe acute respiratory syndrome-coronavirus 2 pandemic pressure on healthcare systems can exhaust ventilator resources, especially where resources are restricted. Our objective was a rapid preclinical evaluation of a newly developed turbine-based ventilator, named the ACUTE-19, for invasive ventilation. Methods: Validation consisted of (a) testing tidal volume delivery in 11 simulated models, with various resistances and compliances; (b) comparison with a commercial ventilator (VIVO-50) adapting the United Kingdom Medicines and Healthcare products Regulatory Agency-recommendations for rapidly manufactured ventilators; and (c) in vivo testing in a sheep before and after inducing acute respiratory distress syndrome by saline lavage. Results: Differences in tidal volume in the simulated models were marginally different (largest difference 33 ml [95% CI 31 to 36]; P < .001). Plateau pressure was not different (-0.3 cmH2O [95% CI -0.9 to 0.3]; P = .409), and positive end-expiratory pressure was marginally different (0.3 cmH2O [95% CI 0.2 to 0.3]; P < .001) between the ACUTE-19 and the commercial ventilator. Bland-Altman analyses showed good agreement (mean bias -0.29 [limits of agreement 0.82 to -1.42], and mean bias 0.56 [limits of agreement 1.94 to -0.81], at a plateau pressure of 15 and 30 cmH2O, respectively). The ACUTE-19 achieved optimal oxygenation and ventilation before and after acute respiratory distress syndrome induction. Conclusions: The ACUTE-19 performed accurately in simulated and animal models yielding a comparable performance with a VIVO-50 commercial device. The ACUTE-19 can provide the basis for the development of a future affordable commercial ventilator.

Validación preclínica de un respirador de turbina para la ventilación invasiva: el respirador ACUTE-19 Pre-clinical validation of a turbine-based ventilator for invasive ventilation–The ACUTE-19 ventilator

Graphical Antecedentes La pandemia producida por el síndrome respiratorio agudo severo por coronavirus 2 puede agotar los recursos sanitarios, especialmente de respiradores, en situaciones de escasez de recursos sanitarios. Nuestro objetivo fue realizar una evaluación preclínica rápida de un prototipo de respirador de turbina para la ventilación invasiva denominado ACUTE-19. Métodos La validación consistió en: a) evaluación de la administración de un volumen corriente en 11 modelos pulmonares simulados, con diversas resistencias y compliancias;b) comparación con un ventilador comercial (VIVO-50) adaptando las recomendaciones de la Agencia Reguladora de Medicamentos y Productos Sanitarios del Reino Unido para ventiladores de fabricación rápida, y c) realización de pruebas in vivo en una oveja antes y después de inducir el síndrome de distrés respiratorio agudo mediante lavado salino. Resultados Las diferencias de volumen corriente en los modelos simulados fueron mínimamente diferentes (la mayor diferencia fue de 33 ml [IC 95%: 31 a 36];p < 0,001). La presión de meseta no fue diferente (−0,3 cmH2O [IC 95%: −0,9 a 0,3];p = 0,409), y la presión positiva al final de la espiración fue levemente diferente (0,3 cmH2O [IC 95%: 0,2 a 0,3];p < 0,001) comparando el ACUTE-19 y el ventilador comercial. El análisis de Bland-Altman mostró una buena concordancia (sesgo medio −0,29 [límites de concordancia 0,82 a −1,42], y sesgo medio 0,56 [límites de concordancia 1,94 a −0,81], a una presión de meseta de 15 y 30 cmH2O, respectivamente). El ACUTE-19 consiguió una oxigenación y ventilación óptimas antes y después de la inducción del síndrome de distrés respiratorio agudo en el modelo animal. Conclusiones El ACUTE-19 se comportó con precisión en los modelos simulados y animales, con un rendimiento comparable al del dispositivo comercial VIVO-50. El ACUTE-19 puede servir de base para el desarrollo de un futuro ventilador comercial asequible.

Pre-clinical validation of a turbine-based ventilator for invasive ventilation-The ACUTE-19 ventilator.

BACKGROUND: The Severe Acute Respiratory Syndrome (SARS)-Coronavirus 2 (CoV-2) pandemic pressure on healthcare systems can exhaust ventilator resources, especially where resources are restricted. Our objective was a rapid preclinical evaluation of a newly developed turbine-based ventilator, named the ACUTE-19, for invasive ventilation. METHODS: Validation consisted of (a) testing tidal volume (V_T) delivery in 11 simulated models, with various resistances and compliances; (b) comparison with a commercial ventilator (VIVO-50) adapting the United Kingdom Medicines and Healthcare products Regulatory Agency-recommendations for rapidly manufactured ventilators; and (c) in vivo testing in a sheep before and after inducing acute respiratory distress syndrome (ARDS) by saline lavage. RESULTS: Differences in V_T in the simulated models were marginally different (largest difference 33ml [95%-confidence interval (CI) 31-36]; P<.001ml). Plateau pressure (P_plat) was not different (-0.3cmH₂O [95%-CI -0.9 to 0.3]; P=.409), and positive end-expiratory pressure (PEEP) was marginally different (0.3 cmH₂O [95%-CI 0.2 to 0.3]; P<.001) between the ACUTE-19 and the commercial ventilator. Bland-Altman analyses showed good agreement (mean bias, -0.29, [limits of agreement, 0.82 to -1.42], and mean bias 0.56 [limits of agreement, 1.94 to -0.81], at a P_plat of 15 and 30cmH₂O, respectively). The ACUTE-19 achieved optimal oxygenation and ventilation before and after ARDS induction. CONCLUSIONS: The ACUTE-19 performed accurately in simulated and animal models yielding a comparable performance with a VIVO-50 commercial device. The acute 19 can provide the basis for the development of a future affordable commercial ventilator.

New insights in mechanical ventilation and adjunctive therapies in ARDS

Patients with acute respiratory distress syndrome (ARDS) often require mechanical ventilation (MV) and may experience high morbidity and mortality. The ventilatory management of ARDS patients has changed over the years to mitigate the risk of ventilator-induced lung injury (VILI) and improve outcomes. Current recommended MV strategies include the use of low tidal volume (VT) at 4–6 mL/kg of predicted body weight (PBW) and plateau pressure (PP LAT) below 27 cmH2O. Some patients achieve better outcomes with low VT than others, and several strategies have been proposed to individualize VT, including standardization for end-expiratory lung volume or inspiratory capacity. To date, no strategy for individualizing positive-end expiratory pressure (PEEP) based on oxygenation, recruitment, respiratory mechanics, or hemodynamics has proven superior for improving survival. Driving pressure, transpulmonary pressure, and mechanical power have been proposed as markers to quantify risk of VILI and optimize ventilator settings. Several rescue therapies, including neuromuscular blockade, prone positioning, recruitment maneuvers (RMs), vasodilators, and extracorporeal membrane oxygenation (ECMO), may be considered in severe ARDS. New ventilator strategies such as airway pressure release ventilation (APRV) and time-controlled adaptive ventilation (TCAV) have demonstrated potential benefits to reduce VILI, but further studies are required to evaluate their clinical relevance. This review aims to discuss the cornerstones of MV and new insights in ARDS ventilatory management, as well as their rationales, to guide the physician in an individually tailored rather than a fixed, sub-physiological approach. We recommend that MV be individualized based on physiological targets to achieve optimal ventilatory settings for each patient. © 2022 The Author(s). Published by MRE Press.

Nasal Pressure Swings as the Measure of Inspiratory Effort in Spontaneously Breathing Patients with De Novo Acute Respiratory Failure

Background. Excessive inspiratory effort could translate into self-inflicted lung injury, thus worsening clinical outcomes of spontaneously breathing patients with acute respiratory failure (ARF). Although esophageal manometry is a reliable method to estimate the magnitude of inspiratory effort, procedural issues significantly limit its use in daily clinical practice. The aim of this study is to describe the correlation between esophageal pressure swings (ΔPes) and nasal (ΔPnos) as a potential measure of inspiratory effort in spontaneously breathing patients with de novo ARF. Methods. From January 1st, 2021 to September 1st, 2021, 61 consecutive patients with ARF (83.6% related to COVID-19) admitted to the Respiratory Intensive Care Unit (RICU) of the University Hospital of Modena (Italy) and candidate to escalation of non-invasive respiratory support (NRS) were enrolled. Clinical features and tidal changes in esophageal and nasal pressure were recorded on admission and 24 hours after starting NRS. Correlation between ΔPes and ΔPnos served as primary outcome. The effect of ΔPnos measurements on respiratory rate and ΔPes was also assessed. Results. ΔPes and ΔPnos were strongly correlated at admission (R2=0.88, p<0.001) and 24 hours apart (R2=0.94, p<0.001). The nasal plug insertion and the mouth closure required for ΔPnos measurement did not result in significant change of respiratory rate and ΔPes. The correlation between measures at 24 hours remained significant even after splitting the study population according to the type of NRS (high-flow nasal cannulas [R2=0.79, p<0.001] or noninvasive ventilation [R2=0.95, p<0.001]). Conclusions. In a cohort of patients with ARF, nasal pressure swings did not alter respiratory mechanics in the short term and were highly correlated with esophageal pressure swings during spontaneous tidal breathing. ΔPnos might warrant further investigation as a measure of inspiratory effort in patients with ARF.

Time course of chest computed tomography findings and biomarkers in COVID-19 pneumonia patients

RATIONALE: Chest computed tomography (CT) has a potential role in the diagnosis, detection of complications, and prognosis of coronavirus disease 2019 (COVID-19). The value of chest CT can be further amplified when associated to physiological variables. Some studies have done efforts to correlate chest CT findings with overall oxygenation and respiratory mechanics, which although they are easily obtained may not be specifically related to COVID-19. Very few studies have tried to correlate chest CT findings with specific biomarkers related to COVID-19. For this purpose, temporal changes of chest CT were evaluated and then correlated with laboratory data in multicenter randomized clinical trial. METHODS: Adult patients who presented chest CT scan features compatible with viral pneumonia were admitted in the hospital and followed during 7 days (NCT: 04561219). CT scans and laboratory data [D-dimer, ferritin, and lactate dehydrogenase (LDH)] in blood were obtained at the moment of admission (Baseline) and on day 7 (Final). Qualitative and quantitative chest CT scan parameters were evaluated in ventral, middle and dorsal regions of interest (ROI) and classified as: hyper-, normal-, poor-, and non-aerated. RESULTS: In this study involving 45 COVID-19 patients no statistically significant differences in the overall Hounsfield Units (HU) ranges and percent of whole lung mass were found overtime. Normally aerated lung tissue reduced from Baseline to Final (p=0.004), mainly associated with a decrease in ventral (p=0.001) and middle (p=0.026) ROIs. At dorsal ROI, a reduction in CT lung mass in poorly aerated areas was observed from Baseline to Final. Poorly aerated and non-aerated lung areas were well correlated only with D-dimer blood levels (r=0.55, p<0.001;and r=0.52, p=0.001, respectively). CONCLUSION: In patients with COVID-19 pneumonia, changes in poor-and non-aerated were associated to changes in D-dimer blood levels, which may be a specific biomarker to be follow in facilities without CT as a way to infer radiologic changes.