Assessment of Inspiratory Effort in Spontaneously Breathing COVID-19 ARDS Patients Undergoing Helmet CPAP: A Comparison between Esophageal, Transdiaphragmatic and Central Venous Pressure Swing.

INTRODUCTION: The clinical features of COVID-19 are highly variable. It has been speculated that the progression across COVID-19 may be triggered by excessive inspiratory drive activation. The aim of the present study was to assess whether the tidal swing in central venous pressure (ΔCVP) is a reliable estimate of inspiratory effort. METHODS: Thirty critically ill patients with COVID-19 ARDS underwent a PEEP trial (0-5-10 cmH2O) during helmet CPAP. Esophageal (ΔPes) and transdiaphragmatic (ΔPdi) pressure swings were measured as indices of inspiratory effort. ΔCVP was assessed via a standard venous catheter. A low and a high inspiratory effort were defined as ΔPes ≤ 10 and >15 cmH2O, respectively. RESULTS: During the PEEP trial, no significant changes in ΔPes (11 [6-16] vs. 11 [7-15] vs. 12 [8-16] cmH2O, p = 0.652) and in ΔCVP (12 [7-17] vs. 11.5 [7-16] vs. 11.5 [8-15] cmH2O, p = 0.918) were detected. ΔCVP was significantly associated with ΔPes (marginal R2 0.87, p < 0.001). ΔCVP recognized both low (AUC-ROC curve 0.89 [0.84-0.96]) and high inspiratory efforts (AUC-ROC curve 0.98 [0.96-1]). CONCLUSIONS: ΔCVP is an easily available a reliable surrogate of ΔPes and can detect a low or a high inspiratory effort. This study provides a useful bedside tool to monitor the inspiratory effort of spontaneously breathing COVID-19 patients.

Hospital Memories and Six-Month Psychological Outcome: A Prospective Study in Critical Ill Patients with COVID-19 Respiratory Failure.

ICU survivors suffer from various long-term physical and psychological impairments. Memories from the critical illness may influence long-term psychological outcome. In particular, the role of ICU memories in COVID-19 critically ill patients is unknown. In a prospective observational study, we aimed to investigate patients' memories from the experience of critical illness and their association with a six-month psychological outcome involving quality of life evaluation. Patients' memories were investigated with ICU Memory tool, while psychological outcome and quality of life were evaluated by means of a battery of validated questionnaires during an in-person interview at the follow-up clinic. 149 adult patients were enrolled. 60% retained memories from pre-ICU days spent on a general ward, while 70% reported memories from the in-ICU period. Delusional memories (i.e., memories of facts that never happened) were reported by 69% of patients. According to a multivariable analysis, the lack of pre-ICU memories was an independent predictor of worse psychological outcomes in terms of anxiety, depression and Post-traumatic Stress Disorder (PTDS). Factors associated with long-term outcome in ICU survivors are not still fully understood and patients' experience during the day spent before ICU admission may be associated with psychological sequelae.

Prognostic Performance of Bedside Lung Ultrasound Score (LUSS) and ROX Index in Hypoxemic Respiratory Failure Due to COVID-19.

Background: Noninvasive ventilation, mainly helmet CPAP, was widely used during the COVID-19 pandemic, even outside of intensive care units. Both the ROX index and the LUS score (LUSS) have been proposed as tools to predict negative outcomes in patients with hypoxemia treated with noninvasive ventilation (NIV) outside of ICUs. We aim to evaluate whether the combination of LUSS with the ROX index improves the predictive performance of these indices in patients with hypoxemia due to COVID-19 pneumonia, treated with NIV outside of ICUs. Methods: This is a monocentric prospective observational study conducted at the university teaching hospital Fondazione IRCCS San Gerardo dei Tintori (Monza, Italy) from February to April 2021. LUSS and ROX were collected at the same time in noninvasively ventilated patients outside of the ICU. An LUS exam was performed by 3 emergency medicine attending physicians with at least 5 years' experience in point-of-care ultrasonography using a 12-zone system. To evaluate the accuracy of the prognostic indices in predicting a composite outcome (endotracheal intubation and mortality), ROC curves were used. A logistic multivariable model was used to explore the predictors of the composite outcome of endotracheal intubation and in-hospital mortality. An unadjusted Kaplan-Meier analysis was used to explore the association with the composite outcome of survival without invasive mechanical ventilation at the 30-day follow-up by stratifying the 3 indices by their best cut-offs. Results: A total of 79 patients were included in the statistical analysis and stratified into 2 groups based on the presence of a negative outcome, which was reported in 24 patients out of 79 (30%). A great proportion of patients (66 patients-84%) were treated with helmet CPAP. All three indices (LUSS, ROX and LUSS/ROX) were independently associated with negative outcomes in the multivariable analyses. Although the comparison between the AUROC of LUSS or ROX versus LUSS/ROX did not reveal a statistically significant difference, we observed a trend toward a higher accuracy for predicting negative outcomes using the LUSS/ROX index as compared to using LUSS. With the Kaplan-Maier approach, all three indices stratified by the best cut-off reported a significant association with the outcome of 30-day survival without mechanical ventilation. Conclusions: A multimodal noninvasive approach that combines ultrasound (i.e., LUSS) and a bedside clinical evaluation (i.e., the ROX index) may help clinicians to predict outcomes and to identify patients who would benefit the most from invasive respiratory support.

Incidence, Risk Factors, and Consequences of Post-Traumatic Stress Disorder Symptoms in Survivors of COVID-19-Related ARDS.

Purpose: To assess the prevalence of symptoms of Post-Traumatic Stress Disorder (PTSD) in survivors of COVID-19 Acute Respiratory Distress Syndrome that needed ICU care; to investigate risk factors and their impact on the Health-Related Quality of life (HR-QoL). Materials and Methods: This multicenter, prospective, observational study included all patients who were discharged from the ICU. Patients were administered the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) questionnaire, the Short-Form Health Survey 36Version 2 (SF-36v2), a socioeconomic question set and the Impact of Event Scale-Revised (IES-R) to assess PTSD. Results: The multivariate logistic regression model found that an International Standard Classification of Education Score (ISCED) higher than 2 (OR 3.42 (95% CI 1.28-9.85)), monthly income less than EUR 1500 (OR 0.36 (95% CI 0.13-0.97)), and more than two comorbidities (OR 4.62 (95% CI 1.33-16.88)) are risk factors for developing PTSD symptoms. Patients with PTSD symptoms are more likely to present a worsening in their quality of life as assessed by EQ-5D-5L and SF-36 scales. Conclusion: The main factors associated with the development of PTSD-related symptoms were a higher education level, a lower monthly income, and more than two comorbidities. Patients who developed symptoms of PTSD reported a significantly lower Health-Related Quality of life as compared to patients without PTSD. Future research areas should be oriented toward recognizing potential psychosocial and psychopathological variables capable of influencing the quality of life of patients discharged from the intensive care unit to better recognize the prognosis and longtime effects of diseases.

Long-term physical impairments in survivors of COVID-19-associated ARDS compared with classic ARDS: A two-center study.

PURPOSE: This work aimed to compare physical impairment in survivors of classic ARDS compared with COVID-19-associated ARDS (CARDS) survivors. MATERIAL AND METHODS: This is a prospective observational cohort study on 248 patients with CARDS and compared them with a historical cohort of 48 patients with classic ARDS. Physical performance was evaluated at 6 and 12 months after ICU discharge, using the Medical Research Council Scale (MRCss), 6-min walk test (6MWT), handgrip dynamometry (HGD), and fatigue severity score (FSS). We also assessed activities of daily living (ADLs) using the Barthel index. RESULTS: At 6 months, patients with classic ARDS had lower HGD (estimated difference [ED]: 11.71 kg, p < 0.001; ED 31.9% of predicted value, p < 0.001), 6MWT distance (ED: 89.11 m, p < 0.001; ED 12.96% of predicted value, p = 0.032), and more frequent significant fatigue (OR 0.35, p = 0.046). At 12 months, patients with classic ARDS had lower HGD (ED: 9.08 kg, p = 0.0014; ED 25.9% of predicted value, p < 0.001) and no difference in terms of 6MWT and fatigue. At 12 months, patients with classic ARDS improved their MRCss (ED 2.50, p = 0.006) and HGD (ED: 4.13 kg, p = 0.002; ED 9.45% of predicted value, p = 0.005), while those with CARDS did not. Most patients in both groups regained independence in ADLs at 6 months. COVID-19 diagnosis was a significant independent predictor of better HGD (p < 0.0001) and 6MWT performance (p = 0.001), and lower prevalence of fatigue (p = 0.018). CONCLUSIONS: Both classic ARDS and CARDS survivors experienced long-term impairments in physical functioning, confirming that post-intensive care syndrome remains a major legacy of critical illness. Surprisingly, however, persisting disability was more common in survivors of classic ARDS than in CARDS survivors. In fact, muscle strength measured with HGD was reduced in survivors of classic ARDS compared to CARDS patients at both 6 and 12 months. The 6MWT was reduced and fatigue was more common in classic ARDS compared to CARDS at 6 months but differences were no longer significant at 12 months. Most patients in both groups regained independent function in ADLs at 6 months.

Unsupervised segmentation and quantification of COVID-19 lesions on computed Tomography scans using CycleGAN.

BACKGROUND: Lesion segmentation is a critical step in medical image analysis, and methods to identify pathology without time-intensive manual labeling of data are of utmost importance during a pandemic and in resource-constrained healthcare settings. Here, we describe a method for fully automated segmentation and quantification of pathological COVID-19 lung tissue on chest Computed Tomography (CT) scans without the need for manually segmented training data. METHODS: We trained a cycle-consistent generative adversarial network (CycleGAN) to convert images of COVID-19 scans into their generated healthy equivalents. Subtraction of the generated healthy images from their corresponding original CT scans yielded maps of pathological tissue, without background lung parenchyma, fissures, airways, or vessels. We then used these maps to construct three-dimensional lesion segmentations. Using a validation dataset, Dice scores were computed for our lesion segmentations and other published segmentation networks using ground truth segmentations reviewed by radiologists. RESULTS: The COVID-to-Healthy generator eliminated high Hounsfield unit (HU) voxels within pulmonary lesions and replaced them with lower HU voxels. The generator did not distort normal anatomy such as vessels, airways, or fissures. The generated healthy images had higher gas content (2.45 ± 0.93 vs 3.01 ± 0.84 L, P < 0.001) and lower tissue density (1.27 ± 0.40 vs 0.73 ± 0.29 Kg, P < 0.001) than their corresponding original COVID-19 images, and they were not significantly different from those of the healthy images (P < 0.001). Using the validation dataset, lesion segmentations scored an average Dice score of 55.9, comparable to other weakly supervised networks that do require manual segmentations. CONCLUSION: Our CycleGAN model successfully segmented pulmonary lesions in mild and severe COVID-19 cases. Our model's performance was comparable to other published models; however, our model is unique in its ability to segment lesions without the need for manual segmentations.

The PROVENT-C19 registry: A study protocol for international multicenter SIAARTI registry on the use of prone positioning in mechanically ventilated patients with COVID-19 ARDS.

BACKGROUND: The worldwide use of prone position (PP) for invasively ventilated patients with COVID-19 is progressively increasing from the first pandemic wave in everyday clinical practice. Among the suggested treatments for the management of ARDS patients, PP was recommended in the Surviving Sepsis Campaign COVID-19 guidelines as an adjuvant therapy for improving ventilation. In patients with severe classical ARDS, some authors reported that early application of prolonged PP sessions significantly decreases 28-day and 90-day mortality. METHODS AND ANALYSIS: Since January 2021, the COVID19 Veneto ICU Network research group has developed and implemented nationally and internationally the "PROVENT-C19 Registry", endorsed by the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care…'(SIAARTI). The PROVENT-C19 Registry wishes to describe 1. The real clinical practice on the use of PP in COVID-19 patients during the pandemic at a National and International level; and 2. Potential baseline and clinical characteristics that identify subpopulations of invasively ventilated patients with COVID-19 that may improve daily from PP therapy. This web-based registry will provide relevant information on how the database research tools may improve our daily clinical practice. CONCLUSIONS: This multicenter, prospective registry is the first to identify and characterize the role of PP on clinical outcome in COVID-19 patients. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of a clinical intervention. Indeed observation-based registries could be effective tools aimed at identifying specific clusters of patients within a large study population with widely heterogeneous clinical characteristics. TRIAL REGISTRATION: The registry was registered (ClinicalTrial.Gov Trials Register NCT04905875) on May 28,2021.

Epidemiology and outcomes of early-onset AKI in COVID-19-related ARDS in comparison with non-COVID-19-related ARDS: insights from two prospective global cohort studies.

BACKGROUND: Acute kidney injury (AKI) is a frequent and severe complication of both COVID-19-related acute respiratory distress syndrome (ARDS) and non-COVID-19-related ARDS. The COVID-19 Critical Care Consortium (CCCC) has generated a global data set on the demographics, management and outcomes of critically ill COVID-19 patients. The LUNG-SAFE study was an international prospective cohort study of patients with severe respiratory failure, including ARDS, which pre-dated the pandemic. METHODS: The incidence, demographic profile, management and outcomes of early AKI in patients undergoing invasive mechanical ventilation for COVID-19-related ARDS were described and compared with AKI in a non-COVID-19-related ARDS cohort. RESULTS: Of 18,964 patients in the CCCC data set, 1699 patients with COVID-19-related ARDS required invasive ventilation and had relevant outcome data. Of these, 110 (6.5%) had stage 1, 94 (5.5%) had stage 2, 151 (8.9%) had stage 3 AKI, while 1214 (79.1%) had no AKI within 48 h of initiating invasive mechanical ventilation. Patients developing AKI were older and more likely to have hypertension or chronic cardiac disease. There were geo-economic differences in the incidence of AKI, with lower incidence of stage 3 AKI in European high-income countries and a higher incidence in patients from middle-income countries. Both 28-day and 90-day mortality risk was increased for patients with stage 2 (HR 2.00, p < 0.001) and stage 3 AKI (HR 1.95, p < 0.001). Compared to non-COVID-19 ARDS, the incidence of shock was reduced with lower cardiovascular SOFA score across all patient groups, while hospital mortality was worse in all groups [no AKI (30 vs 50%), Stage 1 (38 vs 58%), Stage 2 (56 vs 74%), and Stage 3 (52 vs 72%), p < 0.001]. The time profile of onset of AKI also differed, with 56% of all AKI occurring in the first 48 h in patients with COVID-19 ARDS compared to 89% in the non-COVID-19 ARDS population. CONCLUSION: AKI is a common and serious complication of COVID-19, with a high mortality rate, which differs by geo-economic location. Important differences exist in the profile of AKI in COVID-19 versus non-COVID-19 ARDS in terms of their haemodynamic profile, time of onset and clinical outcomes.

Association of COVID-19 Vaccinations With Intensive Care Unit Admissions and Outcome of Critically Ill Patients With COVID-19 Pneumonia in Lombardy, Italy.

Importance: Data 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. Objective: To 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 Participants: This 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. Exposures: COVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine). Main Outcomes and Measures: The 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. Results: Among 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 < .001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P < .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 < .001), primarily male individuals (110 patients [79.1%] vs 252 patients [60.9%]; P < .001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P < .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 Relevance: In 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.

Monitoring Lung Injury Severity and Ventilation Intensity during Mechanical Ventilation.

Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure burden by high hospital mortality. No specific pharmacologic treatment is currently available and its ventilatory management is a key strategy to allow reparative and regenerative lung tissue processes. Unfortunately, a poor management of mechanical ventilation can induce ventilation induced lung injury (VILI) caused by physical and biological forces which are at play. Different parameters have been described over the years to assess lung injury severity and facilitate optimization of mechanical ventilation. Indices of lung injury severity include variables related to gas exchange abnormalities, ventilatory setting and respiratory mechanics, ventilation intensity, and the presence of lung hyperinflation versus derecruitment. Recently, specific indexes have been proposed to quantify the stress and the strain released over time using more comprehensive algorithms of calculation such as the mechanical power, and the interaction between driving pressure (DP) and respiratory rate (RR) in the novel DP multiplied by four plus RR [(4 × DP) + RR] index. These new parameters introduce the concept of ventilation intensity as contributing factor of VILI. Ventilation intensity should be taken into account to optimize protective mechanical ventilation strategies, with the aim to reduce intensity to the lowest level required to maintain gas exchange to reduce the potential for VILI. This is further gaining relevance in the current era of phenotyping and enrichment strategies in ARDS.

Impact of dexamethasone on the incidence of ventilator-associated pneumonia in mechanically ventilated COVID-19 patients: a propensity-matched cohort study.

OBJECTIVE: To assess the impact of treatment with steroids on the incidence and outcome of ventilator-associated pneumonia (VAP) in mechanically ventilated COVID-19 patients. DESIGN: Propensity-matched retrospective cohort study from February 24 to December 31, 2020, in 4 dedicated COVID-19 Intensive Care Units (ICU) in Lombardy (Italy). PATIENTS: Adult consecutive mechanically ventilated COVID-19 patients were subdivided into two groups: (1) treated with low-dose corticosteroids (dexamethasone 6 mg/day intravenous for 10 days) (DEXA+); (2) not treated with corticosteroids (DEXA-). A propensity score matching procedure (1:1 ratio) identified patients' cohorts based on: age, weight, PEEP Level, PaO2/FiO2 ratio, non-respiratory Sequential Organ Failure Assessment (SOFA) score, Charlson Comorbidity Index (CCI), C reactive protein plasma concentration at admission, sex and admission hospital (exact matching). INTERVENTION: Dexamethasone 6 mg/day intravenous for 10 days from hospital admission. MEASUREMENTS AND MAIN RESULTS: Seven hundred and thirty-nine patients were included, and the propensity-score matching identified two groups of 158 subjects each. Eighty-nine (56%) DEXA+ versus 55 (34%) DEXA- patients developed a VAP (RR 1.61 (1.26-2.098), p = 0.0001), after similar time from hospitalization, ICU admission and intubation. DEXA+ patients had higher crude VAP incidence rate (49.58 (49.26-49.91) vs. 31.65 (31.38-31.91)VAP*1000/pd), (IRR 1.57 (1.55-1.58), p < 0.0001) and risk for VAP (HR 1.81 (1.31-2.50), p = 0.0003), with longer ICU LOS and invasive mechanical ventilation but similar mortality (RR 1.17 (0.85-1.63), p = 0.3332). VAPs were similarly due to G+ bacteria (mostly Staphylococcus aureus) and G- bacteria (mostly Enterobacterales). Forty-one (28%) VAPs were due to multi-drug resistant bacteria. VAP was associated with almost doubled ICU and hospital LOS and invasive mechanical ventilation, and increased mortality (RR 1.64 [1.02-2.65], p = 0.040) with no differences among patients' groups. CONCLUSIONS: Critically ill COVID-19 patients are at high risk for VAP, frequently caused by multidrug-resistant bacteria, and the risk is increased by corticosteroid treatment. TRIAL REGISTRATION: NCT04388670, retrospectively registered May 14, 2020.

Inhaled nitric oxide: role in the pathophysiology of cardio-cerebrovascular and respiratory diseases.

Nitric oxide (NO) is a key molecule in the biology of human life. NO is involved in the physiology of organ viability and in the pathophysiology of organ dysfunction, respectively. In this narrative review, we aimed at elucidating the mechanisms behind the role of NO in the respiratory and cardio-cerebrovascular systems, in the presence of a healthy or dysfunctional endothelium. NO is a key player in maintaining multiorgan viability with adequate organ blood perfusion. We report on its physiological endogenous production and effects in the circulation and within the lungs, as well as the pathophysiological implication of its disturbances related to NO depletion and excess. The review covers from preclinical information about endogenous NO produced by nitric oxide synthase (NOS) to the potential therapeutic role of exogenous NO (inhaled nitric oxide, iNO). Moreover, the importance of NO in several clinical conditions in critically ill patients such as hypoxemia, pulmonary hypertension, hemolysis, cerebrovascular events and ischemia-reperfusion syndrome is evaluated in preclinical and clinical settings. Accordingly, the mechanism behind the beneficial iNO treatment in hypoxemia and pulmonary hypertension is investigated. Furthermore, investigating the pathophysiology of brain injury, cardiopulmonary bypass, and red blood cell and artificial hemoglobin transfusion provides a focus on the potential role of NO as a protective molecule in multiorgan dysfunction. Finally, the preclinical toxicology of iNO and the antimicrobial role of NO-including its recent investigation on its role against the Sars-CoV2 infection during the COVID-19 pandemic-are described.

Noninvasive respiratory support outside the intensive care unit for acute respiratory failure related to coronavirus-19 disease: a systematic review and meta-analysis.

BACKGROUND: Noninvasive respiratory support (NIRS) has been diffusely employed outside the intensive care unit (ICU) to face the high request of ventilatory support due to the massive influx of patients with acute respiratory failure (ARF) caused by coronavirus-19 disease (COVID-19). We sought to summarize the evidence on clinically relevant outcomes in COVID-19 patients supported by NIV outside the ICU. METHODS: We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register, along with medRxiv and bioRxiv repositories for pre-prints, for observational studies and randomized controlled trials, from inception to the end of February 2021. Two authors independently selected the investigations according to the following criteria: (1) observational study or randomized clinical trials enrolling ≥ 50 hospitalized patients undergoing NIRS outside the ICU, (2) laboratory-confirmed COVID-19, and (3) at least the intra-hospital mortality reported. Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed. Data extraction was independently performed by two authors to assess: investigation features, demographics and clinical characteristics, treatments employed, NIRS regulations, and clinical outcomes. Methodological index for nonrandomized studies tool was applied to determine the quality of the enrolled studies. The primary outcome was to assess the overall intra-hospital mortality of patients under NIRS outside the ICU. The secondary outcomes included the proportions intra-hospital mortalities of patients who underwent invasive mechanical ventilation following NIRS failure and of those with 'do-not-intubate' (DNI) orders. RESULTS: Seventeen investigations (14 peer-reviewed and 3 pre-prints) were included with a low risk of bias and a high heterogeneity, for a total of 3377 patients. The overall intra-hospital mortality of patients receiving NIRS outside the ICU was 36% [30-41%]. 26% [21-30%] of the patients failed NIRS and required intubation, with an intra-hospital mortality rising to 45% [36-54%]. 23% [15-32%] of the patients received DNI orders with an intra-hospital mortality of 72% [65-78%]. Oxygenation on admission was the main source of between-study heterogeneity. CONCLUSIONS: During COVID-19 outbreak, delivering NIRS outside the ICU revealed as a feasible strategy to cope with the massive demand of ventilatory assistance. REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/prospero/ , CRD42020224788, December 11, 2020.

Tracheal intubation in the critically ill patient.

Tracheal intubation is among the most commonly performed and high-risk procedures in critical care. Indeed, 45% of patients undergoing intubation experience at least one major peri-intubation adverse event, with cardiovascular instability being the most common event reported in 43%, followed by severe hypoxemia in 9% and cardiac arrest in 3% of cases. These peri-intubation adverse events may expose patients to a higher risk of 28-day mortality, and they are more frequently observed with an increasing number of attempts to secure the airway. The higher risk of peri-intubation complications in critically ill patients, compared with the anaesthesia setting, is the consequence of their deranged physiology (e.g. underlying respiratory failure, shock and/or acidosis) and, in this regard, airway management in critical care has been defined as "physiologically difficult". In recent years, several randomised studies have investigated the most effective preoxy-genation strategies, and evidence for the use of positive pressure ventilation in moderate-to-severe hypoxemic patients is established. On the other hand, evidence on interventions to mitigate haemodynamic collapse after intubation has been elusive. Airway management in COVID-19 patients is even more challenging because of the additional risk of infection for healthcare workers, which has influenced clinical choices in this patient group. The aim of this review is to provide an update of the evidence for intubation in critically ill patients with a focus on understanding peri-intubation risks and evaluating interventions to prevent or mitigate adverse events.

External chest-wall compression in prolonged COVID-19 ARDS with low-compliance: a physiological study.

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.

One-year pulmonary impairment after severe COVID-19: a prospective, multicenter follow-up study.

BACKGROUND: Long-term pulmonary sequelae following hospitalization for SARS-CoV-2 pneumonia is largely unclear. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 12-month from discharge. METHODS: In this multicentre, prospective, observational study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support ("oxygen only", "continuous positive airway pressure (CPAP)" and "invasive mechanical ventilation (IMV)") and followed up at 12 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 min walking test, high resolution CT (HRCT) scan, and modified Medical Research Council (mMRC) dyspnea scale were collected. RESULTS: Out of 287 patients hospitalized with SARS-CoV-2 pneumonia and followed up at 1 year, DLCO impairment, mainly of mild entity and improved with respect to the 6-month follow-up, was observed more frequently in the "oxygen only" and "IMV" group (53% and 49% of patients, respectively), compared to 29% in the "CPAP" group. Abnormalities at chest HRCT were found in 46%, 65% and 80% of cases in the "oxygen only", "CPAP" and "IMV" group, respectively. Non-fibrotic interstitial lung abnormalities, in particular reticulations and ground-glass attenuation, were the main finding, while honeycombing was found only in 1% of cases. Older patients and those requiring IMV were at higher risk of developing radiological pulmonary sequelae. Dyspnea evaluated through mMRC scale was reported by 35% of patients with no differences between groups, compared to 29% at 6-month follow-up. CONCLUSION: DLCO alteration and non-fibrotic interstitial lung abnormalities are common after 1 year from hospitalization due to SARS-CoV-2 pneumonia, particularly in older patients requiring higher ventilatory support. Studies with longer follow-ups are needed.