Sedation, Analgesia, and Myorelaxants

Sedation in patients with coronavirus severe acute respiratory distress syndrome (SARS-CoV-2) is a challenge. Deep sedation favors adaptation to mechanical ventilation, promotes tolerance to hypercapnia and may reduce the risk of self-extubation, but it is not always necessary. It is essential to individualize sedation and analgesia, always prioritizing pain control. In situations of persistent ventilatory asynchrony, need for deep sedation, prone ventilation or persistently high plateau pressures, continuous infusion of a neuromuscular blocker is required, which should be used for up to 48 hours. The weaning process can be difficult, and the association of antipsychotics and alpha-2 agonists is indicated. Key words: SARS-CoV-2, sedation, analgesia, myorelaxants, weaning, mechanical ventilation, alpha-2 agonists, propofol. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Antibiotics, Antiretroviral, Corticosteroids, Other Therapies Against SARS-CoV-2

Pharmacological treatment for COVID-19 is still exclusively supportive [1]. Drugs have been tested based on the pathogenesis events, particularly considering the potential impact on? (1) the viral infection and replication cycle (early phase);and (2) the inflammatory response phase marked by a cytokine storm that leads to tissue damage [2, 3]. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Mortality rate, intensive care unit length of stay and time to orotracheal intubation of COVID-19 patients under different non-invasive ventilatory therapies: retrospective cohort study

Introduction: COVID-19 may lead to heterogeneous needs for ventilator therapy, whether oxygen therapy (OT), noninvasive ventilation (NIV), high-flow nasal catheter (HFNC) or their combination (NIV + HFNC). The purpose of the study was to describe, retrospectively, the mortality rate, intensive care unit length of stay (ICU-LOS) and time to orotracheal intubation of COVID-19 patients under OT, NIV, HFNC or combined (NIV + HFNC). A retrospective cohort study was done analyzing official medical data from March 2020 up to July 2021. (CAAE: 52534221.5.0000.5249). Method(s): The inclusion criteria were age > 18 years-old, and positive swab test for COVID-19 or computed tomography consistent of COVID-19. The exclusion criteria were hospital LOS less than 3 days, patients whose therapy (OT, NIV, HFNC or NIV + HFNC) lasted less than 48 h, and missing data about the outcome variables. The primary outcome was mortality rate, while secondary outcomes were ICU-LOS and time to orotracheal intubation. Chi-Square test was used to assess mortality rate. The Mann-Whitney U test was applied to assess differences in ICU-LOS and time to orotracheal intubation (p < 0.05). Result(s): Overall, 1371 patients were enrolled. 880, 120, 35, and 148 patients were submitted to OT, NIV, HFNC or NIV + HFNC, respectively. The mortality rates were 8.4%, 29.6%, 22.2%, and 33.2% for OT, NIV, HFNC or NIV + HFNC, respectively (p < 0.001). The ICU-LOS was higher in NIV + HFNC (median [IQR] 15 days [16]) than NIV (9 days [10]) and OT (4 days [5], p < 0.001). The time to orotracheal intubation was higher in NIV (6 days [6]), HFNC (6 days [4.5]), and NIV + HFNC (6 days [6]) than OT (2 days [4]), p < 0.001. Mortality rate and ICU-LOS were higher in those patients requiring the combination of NIV and HFNC. Conclusion(s): Although the type of ventilator therapy may be associated to increased mortality rate and ICU-LOS, we cannot assure causality due to exploratory nature of the retrospective study, but a marker of severity.

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.

Mesenchymal stem/stromal cell-based therapies for severe viral pneumonia: therapeutic potential and challenges.

Severe viral pneumonia is a significant cause of morbidity and mortality globally, whether due to outbreaks of endemic viruses, periodic viral epidemics, or the rarer but devastating global viral pandemics. While limited anti-viral therapies exist, there is a paucity of direct therapies to directly attenuate viral pneumonia-induced lung injury, and management therefore remains largely supportive. Mesenchymal stromal/stem cells (MSCs) are receiving considerable attention as a cytotherapeutic for viral pneumonia. Several properties of MSCs position them as a promising therapeutic strategy for viral pneumonia-induced lung injury as demonstrated in pre-clinical studies in relevant models. More recently, early phase clinical studies have demonstrated a reassuring safety profile of these cells. These investigations have taken on an added importance and urgency during the COVID-19 pandemic, with multiple trials in progress across the globe. In parallel with clinical translation, strategies are being investigated to enhance the therapeutic potential of these cells in vivo, with different MSC tissue sources, specific cellular products including cell-free options, and strategies to 'licence' or 'pre-activate' these cells, all being explored. This review will assess the therapeutic potential of MSC-based therapies for severe viral pneumonia. It will describe the aetiology and epidemiology of severe viral pneumonia, describe current therapeutic approaches, and examine the data suggesting therapeutic potential of MSCs for severe viral pneumonia in pre-clinical and clinical studies. The challenges and opportunities for MSC-based therapies will then be considered.

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.