Multidrug-Resistant Bacterial Colonization and Infections in Large Retrospective Cohort of Mechanically Ventilated COVID-19 Patients1.

Few data are available on incidence of multidrug-resistant organism (MDRO) colonization and infections in mechanically ventilated patients, particularly during the COVID-19 pandemic. We retrospectively evaluated all patients admitted to the COVID-19 intensive care unit (ICU) of Hub Hospital in Milan, Italy, during October 2020‒May 2021. Microbiologic surveillance was standardized with active screening at admission and weekly during ICU stay. Of 435 patients, 88 (20.2%) had MDROs isolated ≤48 h after admission. Of the remaining patients, MDRO colonization was diagnosed in 173 (51.2%), MDRO infections in 95 (28.1%), and non-MDRO infections in 212 (62.7%). Non-MDRO infections occurred earlier than MDRO infections (6 days vs. 10 days; p<0.001). Previous exposure to antimicrobial drugs within the ICU was higher in MDRO patients than in non-MDRO patients (116/197 [58.9%] vs. 18/140 [12.9%]; p<0.001). Our findings might serve as warnings for future respiratory viral pandemics and call for increased measures of antimicrobial stewardship and infection control.

Genomic Characterization of Carbapenem-Resistant Acinetobacter baumannii (CRAB) in Mechanically Ventilated COVID-19 Patients and Impact of Infection Control Measures on Reducing CRAB Circulation during the Second Wave of the SARS-CoV-2 Pandemic in Milan, Italy.

COVID-19 has significantly affected hospital infection prevention and control (IPC) practices, especially in intensive care units (ICUs). This frequently caused dissemination of multidrug-resistant organisms (MDROs), including carbapenem-resistant Acinetobacter baumannii (CRAB). Here, we report the management of a CRAB outbreak in a large ICU COVID-19 hub Hospital in Italy, together with retrospective genotypic analysis by whole-genome sequencing (WGS). Bacterial strains obtained from severe COVID-19 mechanically ventilated patients diagnosed with CRAB infection or colonization between October 2020 and May 2021 were analyzed by WGS to assess antimicrobial resistance and virulence genes, along with mobile genetic elements. Phylogenetic analysis in combination with epidemiological data was used to identify putative transmission chains. CRAB infections and colonization were diagnosed in 14/40 (35%) and 26/40 (65%) cases, respectively, with isolation within 48 h from admission in 7 cases (17.5%). All CRAB strains belonged to Pasteur sequence type 2 (ST2) and 5 different Oxford STs and presented blaOXA-23 gene-carrying Tn2006 transposons. Phylogenetic analysis revealed the existence of four transmission chains inside and among ICUs, circulating mainly between November and January 2021. A tailored IPC strategy was composed of a 5-point bundle, including ICU modules' temporary conversion to CRAB-ICUs and dynamic reopening, with limited impact on ICU admission rate. After its implementation, no CRAB transmission chains were detected. Our study underlies the potentiality of integrating classical epidemiological studies with genomic investigation to identify transmission routes during outbreaks, which could represent a valuable tool to ensure IPC strategies and prevent the spread of MDROs. IMPORTANCE Infection prevention and control (IPC) practices are of paramount importance for preventing the spread of multidrug-resistant organisms (MDROs) in hospitals, especially in the intensive care unit (ICU). Whole-genome sequencing (WGS) is seen as a promising tool for IPC, but its employment is currently still limited. COVID-19 pandemics have posed dramatic challenges in IPC practices, causing worldwide several outbreaks of MDROs, including carbapenem-resistant Acinetobacter baumannii (CRAB). We present the management of a CRAB outbreak in a large ICU COVID-19 hub hospital in Italy using a tailored IPC strategy that allowed us to contain CRAB transmission while preventing ICU closure during a critical pandemic period. The analysis of clinical and epidemiological data coupled with retrospective genotypic analysis by WGS identified different putative transmission chains and confirmed the effectiveness of the IPC strategy implemented. This could be a promising approach for future IPC strategies.

Psychotherapeutic and Psychiatric Intervention in Patients With COVID-19 and Their Relatives: Protocol for the DigiCOVID Trial.

BACKGROUND: The COVID-19 pandemic is negatively impacting the mental health of both patients with COVID-19 and the general population. As current guidelines are limiting in-person contacts to reduce the spread of the virus, the development of a digital approach to implement in psychiatric and psychological consultations is needed. In this paper, we present the DigiCOVID protocol, a digital approach to offer remote, personalized psychological and psychiatric support to former or current patients with COVID-19 and their relatives. OBJECTIVE: The main goal of this project is to evaluate the feasibility, acceptability, and usability of the DigiCOVID protocol. Furthermore, we also aim to assess the impact of the abovementioned protocol by means of pre-post changes in psychological clinical variables. METHODS: Participants undergo an initial telephonic screening to ensure inclusion criteria are met. Secondly, participants complete a video-assisted neuropsychological IQ test as well as web-based self-reports of health and general well-being. Participants are then assigned to a psychotherapist who offers 8 teletherapy sessions. At the end of the therapy cycle, the web-based questionnaires are administered for a posttreatment evaluation. RESULTS: As of April 2022, we enrolled a total of 122 participants, of which 94 have completed neuropsychological tests and web-based questionnaires. CONCLUSIONS: Our study aims at testing the feasibility and preliminary efficacy of DigiCOVID, a remote telemedicine protocol for the improvement of psychological and psychiatric health in patients with COVID-19 and their relatives. To date, the approach used seems to be feasible and highly customizable to patients' needs, and therefore, the DigiCOVID protocol might pave the way for future telepsychiatry-based interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT05231018; https://clinicaltrials.gov/ct2/show/NCT05231018?term=NCT05231018 &draw=2&rank=1. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39080.

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.

Time to active sitting position: One-year findings from a temporary COVID-19 intensive care unit.

OBJECTIVE: To investigate the association between time to active sitting position and clinical features in people with COVID-19 admitted to intensive care unit (ICU) and referred to physiotherapists. METHOD: Prospective study conducted in the largest temporary ICU in Lombardy (Italy) between April 2020 and June 2021. All individuals with COVID-19 who received physiotherapy were included. Multivariable Cox proportional hazard model was fitted to explore the statistical association between active sitting position and characteristics of patients referred to physiotherapists, also accounting for the different multidisciplinary teams responsible for patients. RESULTS: 284 individuals over 478 (59.4%) had access to physiotherapy, which was performed for a median of 8 days, without difference between multidisciplinary teams (P = 0.446). The active sitting position was reached after a median of 18 (IQR: 10.0-32.0) days. Sex was the only characteristic associated with the time to active sitting position, with males showing a reduced hazard by a factor of 0.65 (95% CI: 0.48-0.87; P = 0.0042) compared to females. At ICU discharge, nearly 50% individuals increased Manchester Mobility Score by 3 points. During physiotherapy no major adverse event was recorded. CONCLUSION: Individuals with COVID-19 take long time to reach active sitting position in ICU, with males requiring longer rehabilitation than females.

Markers of blood-brain barrier disruption increase early and persistently in COVID-19 patients with neurological manifestations.

Background: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is associated with disorders affecting the peripheral and the central nervous system. A high number of patients develop post-COVID-19 syndrome with the persistence of a large spectrum of symptoms, including neurological, beyond 4 weeks after infection. Several potential mechanisms in the acute phase have been hypothesized, including damage of the blood-brain-barrier (BBB). We tested weather markers of BBB damage in association with markers of brain injury and systemic inflammation may help in identifying a blood signature for disease severity and neurological complications. Methods: Blood biomarkers of BBB disruption (MMP-9, GFAP), neuronal damage (NFL) and systemic inflammation (PPIA, IL-10, TNFα) were measured in two COVID-19 patient cohorts with high disease severity (ICUCovid; n=79) and with neurological complications (NeuroCovid; n=78), and in two control groups free from COVID-19 history, healthy subjects (n=20) and patients with amyotrophic lateral sclerosis (ALS; n=51). Samples from COVID-19 patients were collected during the first and the second wave of COVID-19 pandemic in Lombardy, Italy. Evaluations were done at acute and chronic phases of the COVID-19 infection. Results: Blood biomarkers of BBB disruption and neuronal damage are high in COVID-19 patients with levels similar to or higher than ALS. NeuroCovid patients display lower levels of the cytokine storm inducer PPIA but higher levels of MMP-9 than ICUCovid patients. There was evidence of different temporal dynamics in ICUCovid compared to NeuroCovid patients with PPIA and IL-10 showing the highest levels in ICUCovid patients at acute phase. On the contrary, MMP-9 was higher at acute phase in NeuroCovid patients, with a severity dependency in the long-term. We also found a clear severity dependency of NFL and GFAP levels, with deceased patients showing the highest levels. Discussion: The overall picture points to an increased risk for neurological complications in association with high levels of biomarkers of BBB disruption. Our observations may provide hints for therapeutic approaches mitigating BBB disruption to reduce the neurological damage in the acute phase and potential dysfunction in the long-term.

Pulmonary volume-feedback and ventilatory pattern after bilateral lung transplantation using neurally adjusted ventilatory assist ventilation.

BACKGROUND: Bilateral lung transplantation results in pulmonary vagal denervation, which potentially alters respiratory drive, volume-feedback, and ventilatory pattern. We hypothesised that Neurally Adjusted Ventilatory Assist (NAVA) ventilation, which is driven by diaphragm electrical activity (EAdi), would reveal whether vagally mediated pulmonary-volume feedback is preserved in the early phases after bilateral lung transplantation. METHODS: We prospectively studied bilateral lung transplant recipients within 48 h of surgery. Subjects were ventilated with NAVA and randomised to receive 3 ventilatory modes (baseline NAVA, 50%, and 150% of baseline NAVA values) and 2 PEEP levels (6 and 12 cm H2O). We recorded airway pressure, flow, and EAdi. RESULTS: We studied 30 subjects (37% female; age: 37 (27-56) yr), of whom 19 (63%) had stable EAdi. The baseline NAVA level was 0.6 (0.2-1.0) cm H2O µV-1. Tripling NAVA level increased the ventilatory peak pressure over PEEP by 6.3 (1.8), 7.6 (2.4), and 8.7 (3.2) cm H2O, at 50%, 100%, and 150% of baseline NAVA level, respectively (P<0.001). EAdi peak decreased by 10.1 (9.0), 9.5 (9.4) and 8.8 µV (8.7) (P<0.001), accompanied by small increases in tidal volume, 8.3 (3.0), 8.7 (3.6), and 8.9 (3.3) ml kg-1 donor's predicted body weight at 50%, 100%, and 150% of baseline NAVA levels, respectively (P<0.001). Doubling PEEP did not affect tidal volume. CONCLUSIONS: NAVA ventilation was feasible in the majority of patients during the early postoperative period after bilateral lung transplantation. Despite surgical vagotomy distal to the bronchial anastomoses, bilateral lung transplant recipients maintained an unmodified respiratory pattern in response to variations in ventilatory assistance and PEEP. CLINICAL TRIAL REGISTRATION: NCT03367221.

Hospital-Acquired Infections in Critically Ill Patients With COVID-19.

BACKGROUND: Few small studies have described hospital-acquired infections (HAIs) occurring in patients with COVID-19. RESEARCH QUESTION: What characteristics in critically ill patients with COVID-19 are associated with HAIs and how are HAIs associated with outcomes in these patients? STUDY DESIGN AND METHODS: Multicenter retrospective analysis of prospectively collected data including adult patients with severe COVID-19 admitted to eight Italian hub hospitals from February 20, 2020, through May 20, 2020. Descriptive statistics and univariate and multivariate Weibull regression models were used to assess incidence, microbial cause, resistance patterns, risk factors (ie, demographics, comorbidities, exposure to medication), and impact on outcomes (ie, ICU discharge, length of ICU and hospital stays, and duration of mechanical ventilation) of microbiologically confirmed HAIs. RESULTS: Of the 774 included patients, 359 patients (46%) demonstrated 759 HAIs (44.7 infections/1,000 ICU patient-days; 35% multidrug-resistant [MDR] bacteria). Ventilator-associated pneumonia (VAP; n = 389 [50%]), bloodstream infections (BSIs; n = 183 [34%]), and catheter-related BSIs (n = 74 [10%]) were the most frequent HAIs, with 26.0 (95% CI, 23.6-28.8) VAPs per 1,000 intubation-days, 11.7 (95% CI, 10.1-13.5) BSIs per 1,000 ICU patient-days, and 4.7 (95% CI, 3.8-5.9) catheter-related BSIs per 1,000 ICU patient-days. Gram-negative bacteria (especially Enterobacterales) and Staphylococcus aureus caused 64% and 28% of cases of VAP, respectively. Variables independently associated with infection were age, positive end expiratory pressure, and treatment with broad-spectrum antibiotics at admission. Two hundred thirty-four patients (30%) died in the ICU (15.3 deaths/1,000 ICU patient-days). Patients with HAIs complicated by septic shock showed an almost doubled mortality rate (52% vs 29%), whereas noncomplicated infections did not affect mortality. HAIs prolonged mechanical ventilation (median, 24 days [interquartile range (IQR), 14-39 days] vs 9 days [IQR, 5-13 days]; P < .001), ICU stay (24 days [IQR, 16-41 days] vs 9 days [IQR, 6-14 days]; P = .003), and hospital stay (42 days [IQR, 25-59 days] vs 23 days [IQR, 13-34 days]; P < .001). INTERPRETATION: Critically ill patients with COVID-19 are at high risk for HAIs, especially VAPs and BSIs resulting from MDR organisms. HAIs prolong mechanical ventilation and hospitalization, and HAIs complicated by septic shock almost double mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04388670; URL: www.clinicaltrials.gov.

Prone Positioning during Venovenous Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome. A Multicenter Cohort Study and Propensity-matched Analysis.

Rationale: Prone positioning reduces mortality in patients with severe acute respiratory distress syndrome (ARDS). To date, no evidence supports the use of prone positioning (PP) during venovenous extracorporeal oxygenation (ECMO).Objectives: The aim of the study was to assess the feasibility, safety, and effect on oxygenation and lung mechanics of PP 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 PP during ECMO support (prone group; four centers) and patients managed in the supine position (control group; two centers). Physiological variables were analyzed at four time points (supine before PP, start of PP, end of PP, and supine after PP). The association between PP and hospital mortality was assessed by multivariate analysis and propensity score-matching.Results: A total of 240 patients were included, with 107 in the prone group and 133 in the supine group. The median duration of the 326 pronation cycles was 15 (12-18) hours. Minor reversible complications were reported in 6% of PP maneuvers. PP 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, PP remained significantly associated with a reduction of hospital mortality (odds ratio, 0.50; 95% confidence interval, 0.29-0.87). Sixty-six propensity score-matched patients were identified in each group. In this matched sample, patients who underwent pronation had higher ECMO duration (16 vs. 10 d; P = 0.0344) but lower hospital mortality (30% vs. 53%; P = 0.0241).Conclusions: PP during ECMO improved oxygenation and was associated with a reduction of hospital mortality.

Concurrent Thoracic Endovascular Aortic Repair and Liver Transplant: Multidisciplinary Management of Multiple Posttraumatic Lesions.

Association of thoracic and abdominal injuries in patients with major trauma is common. Under emergency conditions, it is often difficult to promptly perform a certain diagnosis and identify treatment priorities of life-threatening lesions. We present the case of a young man with combined thoracic and abdominal injuries after a motorcycle accident. Primary evaluation through echography and X-ray showed fluid within the hepatorenal recess and an enlarged mediastinum. Volume load, blood transfusions, and vasoactive agents were initiated to sustain circulation. Despite hemodynamic instability, we decided to perform computed tomographic angiography (CTA) scan that revealed a high-grade traumatic aortic pseudoaneurysm, multiple and severe areas of liver contusion, and a small amount of hemoperitoneum, without active bleeding spots. The patient was successfully submitted to thoracic endovascular aortic repair (TEVAR). Immediately after the end of the successful TEVAR, signs of massive abdominal bleeding revealed. Immediate explorative laparotomy was performed showing massive hepatic hemorrhage. After liver packing and Pringle's maneuver, control of bleeding was lastly obtained with hemostatic devices and selective cross-clamping of the right hepatic artery. The patient was then transferred to intensive care unit where, despite absence of further hemorrhage, hemodynamic instability, anuria, severe lactic acidosis together with liver necrosis indices appeared. A new CTA demonstrated massive parenchymal disruption within the right lobe of the liver and multiple hematomas in the left lobe. Considering the high-grade lesions of the hepatic vascular tree and liver failure, patient was listed for emergency liver transplantation (LT). LT occurred few hours later, and patient's clinical conditions rapidly improved even if the subsequent clinical course was characterized by a severe fungal infection because of immunosuppression. Evaluation of life-threatening lesions and treatment priorities, availability of different excellence skills, and multidisciplinary collaboration have a key role to achieve clinical success in such severe cases.

Management of critically ill patients with COVID-19: suggestions and instructions from the coordination of intensive care units of Lombardy.

With 63,098 confirmed cases on 17 April 2020 and 11,384 deaths, Lombardy has been the most affected region in Italy by coronavirus disease 2019 (COVID-19). To cope with this emergency, the COVID-19 Lombardy intensive care units (ICU) network was created. The network identified the need of defining a list of clinical recommendations to standardize treatment of patients with COVID-19 admitted to Intensive Care Unit (ICU). Three core topics were identified: 1) rational use of intensive care resources; 2) ventilation strategies; 3) non-ventilatory interventions. Identification of patients who may benefit from ICU treatment is challenging. Clinicians should consider baseline performance and frailty status and they should adopt disease-specific staging tools. Continuous positive airway pressure, mainly delivered through a helmet as elective method, should be considered as initial treatment for all patients with respiratory failure associated with COVID-19. In case of persisting dyspnea and/or desaturation despite 4-6 hours of noninvasive ventilation, endotracheal intubation and invasive mechanical ventilation should be considered. In the early phase, muscle relaxant use and volume-controlled ventilation is recommended. Prone position should be performed in patients with PaO2/FiO2≤100 mmHg. For patients admitted to ICU with COVID-19 interstitial pneumonia, we do not recommend empiric antibiotic therapy for community-acquired pneumonia. Consultation of an infectious disease specialist is suggested before start of any antiviral therapy. In conclusion, the COVID-19 Lombardy ICU Network identified a list of best practice statements supported by the available evidence and clinical experience or identified as panel members expert opinions for the management of critically ill patients with COVID-19.

Key Role of Respiratory Quotient to Reduce the Occurrence of Hypoxemia During Extracorporeal Gas Exchange: A Theoretical Analysis.

OBJECTIVES: Extracorporeal respiratory support, including low blood flow systems providing mainly extracorporeal CO2 removal, are increasingly applied in clinical practice. Gas exchange physiology during extracorporeal respiratory support is complex and differs between full extracorporeal membrane oxygenation and extracorporeal CO2 removal. Aim of the present article is to review pathophysiological aspects which are relevant for the understanding of hypoxemia development during extracorporeal CO2 removal. We will describe the mathematical and physiologic background underlying changes in respiratory quotient and alveolar oxygen tension during venovenous extracorporeal gas exchange and highlight the clinical implications. DESIGN: Theoretical analysis of venovenous extracorporeal gas exchange. SETTING: Italian university research hospital. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: While the effect of extracorporeal CO2 removal on the respiratory quotient of the native lung has long been known, the role of extracorporeal oxygenation in dictating changes in the respiratory quotient has been less addressed. Indeed, both extracorporeal CO2 removal and extracorporeal oxygen delivery affect the respiratory quotient of the native lung and thus influence the alveolar PO2. Indeed, for the same amount of extracorporeal CO2 extraction, it is possible to reduce the FIO2, reduce the risk of absorption atelectasis, and maintain the same alveolar PO2, by increasing the extracorporeal oxygen delivery. CONCLUSIONS: Worsening of hypoxemia is frequent during low-flow extracorporeal CO2 removal combined with ultraprotective mechanical ventilation. In this context, increasing extracorporeal oxygen delivery, increases the respiratory quotient of the native lung and could reduce both the occurrence of alveolar hypoxia and absorption atelectasis, thus optimizing the residual lung function.

Preparation of a radiology department in an Italian hospital dedicated to COVID-19 patients.

Preparedness for the ongoing coronavirus disease 2019 (COVID-19) and its spread in Italy called for setting up of adequately equipped and dedicated health facilities to manage sick patients while protecting healthcare workers, uninfected patients, and the community. In our country, in a short time span, the demand for critical care beds exceeded supply. A new sequestered hospital completely dedicated to intensive care (IC) for isolated COVID-19 patients needed to be designed, constructed, and deployed. Along with this new initiative, the new concept of "Pandemic Radiology Unit" was implemented as a practical solution to the emerging crisis, born out of a critical and urgent acute need. The present article describes logistics, planning, and practical design issues for such a pandemic radiology and critical care unit (e.g., space, infection control, safety of healthcare workers, etc.) adopted in the IC Hospital Unit for the care and management of COVID-19 patients.

Changes in shunt, ventilation/perfusion mismatch, and lung aeration with PEEP in patients with ARDS: a prospective single-arm interventional study.

BACKGROUND: Several studies have found only a weak to moderate correlation between oxygenation and lung aeration in response to changes in PEEP. This study aimed to investigate the association between changes in shunt, low and high ventilation/perfusion (V/Q) mismatch, and computed tomography-measured lung aeration following an increase in PEEP in patients with ARDS. METHODS: In this preliminary study, 12 ARDS patients were subjected to recruitment maneuvers followed by setting PEEP at 5 and then either 15 or 20 cmH2O. Lung aeration was measured by computed tomography. Values of pulmonary shunt and low and high V/Q mismatch were calculated by a model-based method from measurements of oxygenation, ventilation, and metabolism taken at different inspired oxygen levels and an arterial blood gas sample. RESULTS: Increasing PEEP resulted in reduced values of pulmonary shunt and the percentage of non-aerated tissue, and an increased percentage of normally aerated tissue (p < 0.05). Changes in shunt and normally aerated tissue were significantly correlated (r = - 0.665, p = 0.018). Three distinct responses to increase in PEEP were observed in values of shunt and V/Q mismatch: a beneficial response in seven patients, where shunt decreased without increasing high V/Q; a detrimental response in four patients where both shunt and high V/Q increased; and a detrimental response in a patient with reduced shunt but increased high V/Q mismatch. Non-aerated tissue decreased with increased PEEP in all patients, and hyperinflated tissue increased only in patients with a detrimental response in shunt and V/Q mismatch. CONCLUSIONS: The results show that improved lung aeration following an increase in PEEP is not always consistent with reduced shunt and V/Q mismatch. Poorly matched redistribution of ventilation and perfusion, between dependent and non-dependent regions of the lung, may explain why patients showed detrimental changes in shunt and V/Q mismatch on increase in PEEP, despite improved aeration. TRIAL REGISTRATION: ClinicalTrails.gov, NCT04067154. Retrospectively registered on August 26, 2019.

Hypercoagulability of COVID-19 patients in intensive care unit: A report of thromboelastography findings and other parameters of hemostasis.

BACKGROUND: The severe inflammatory state secondary to COVID-19 leads to a severe derangement of hemostasis that has been recently described as a state of disseminated intravascular coagulation (DIC) and consumption coagulopathy, defined as decreased platelet count, increased fibrin(ogen) degradation products such as D-dimer, as well as low fibrinogen. AIMS: Whole blood from 24 patients admitted at the intensive care unit because of COVID-19 was collected and evaluated with thromboelastography by the TEG point-of-care device on a single occasion and six underwent repeated measurements on two consecutive days for a total of 30 observations. Plasma was evaluated for the other parameters of hemostasis. RESULTS: TEG parameters are consistent with a state of hypercoagulability as shown by decreased values, and increased values of K angle and MA. Platelet count was normal or increased, prothrombin time and activated partial thromboplastin time were near(normal). Fibrinogen was increased and D-dimer was dramatically increased. C-reactive protein was increased. Factor VIII and von Willebrand factor (n = 11) were increased. Antithrombin (n = 11) was marginally decreased and protein C (n = 11) was increased. CONCLUSION: The results of this cohort of patients with COVID-19 are not consistent with acute DIC, rather they support hypercoagulability together with a severe inflammatory state. These findings may explain the events of venous thromboembolism observed in some of these patients and support antithrombotic prophylaxis/treatment. Clinical trials are urgently needed to establish the type of drug, dosage, and optimal duration of prophylaxis.

Time-Course of Physiologic Variables During Extracorporeal Membrane Oxygenation and Outcome of Severe Acute Respiratory Distress Syndrome.

In patients undergoing extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS), it is unknown which clinical physiologic variables should be monitored to follow the evolution of lung injury and extrapulmonary organ dysfunction and to differentiate patients according to their course. We analyzed the time-course of prospectively collected clinical physiologic variables in 83 consecutive ARDS patients undergoing ECMO at a single referral center. Selected variables-including ventilator settings, respiratory system compliance, intrapulmonary shunt, arterial blood gases, central hemodynamics, and sequential organ failure assessment (SOFA) score-were compared according to outcome at time-points corresponding to 0%, 25%, 50%, 75%, and 100% of the entire ECMO duration and daily during the first 7 days. A logistic regression analysis was performed to identify changes between ECMO start and end that independently predicted hospital mortality. Tidal volume, intrapulmonary shunt, arterial lactate, and SOFA score differentiated survivors and nonsurvivors early during the first 7 days and over the entire ECMO duration. Respiratory system compliance, PaO2/FiO2 ratio, arterial pH, and mean pulmonary arterial pressure showed distinct temporal course according to outcome over the entire ECMO duration. Lack of improvement of SOFA score independently predicted hospital mortality. In ARDS patients on ECMO, temporal trends of specific physiologic parameters differentiate survivors from non-survivors and could be used to monitor the evolution of lung injury. Progressive worsening of extrapulmonary organ dysfunction is associated with worse outcome.

Practical Clinical Application of an Extracorporeal Carbon Dioxide Removal System in Acute Respiratory Distress Syndrome and Acute on Chronic Respiratory Failure.

We retrospectively reviewed the medical records of 11 patients supported with a veno-venous low-flow extracorporeal carbon dioxide (CO2) removal (ECCO2R) device featuring a large gas exchange surface membrane lung (ML) (i.e., 1.8 m). Seven patients suffered from exacerbation of a chronic pulmonary disease, while four subjects were affected by acute respiratory distress syndrome (ARDS). Twenty-four hours of ECCO2R treatment reduced arterial PCO2 from 63 ± 12 to 54 ± 11 mm Hg (p < 0.01), increased arterial pH from 7.29 ± 0.07 to 7.39 ± 0.06 (p < 0.01), and decreased respiratory rate from 32 ± 10 to 21 ± 8 bpm (p < 0.05). Extracorporeal blood flow and CO2 removal were 333 ± 37 and 94 ± 18 ml/min, respectively. The median duration of ECCO2R treatment was 7 days (6.5-9.5). All four ARDS patients were invasively ventilated at the time of treatment start, no one was extubated and they all died. Among the seven patients with exacerbation of chronic pulmonary diseases, four were managed with noninvasive ventilation at ECCO2R institution, while three were extubated after starting the extracorporeal treatment. No one of these seven patients was intubated or re-intubated after ECCO2R institution and five (71%) survived to hospital discharge. A low-flow ECCO2R device with a large surface ML removes a relevant amount of CO2 resulting in a decreased arterial PCO2, an increased arterial pH, and in a reduced ventilatory load.

Spontaneous breathing during veno-venous extracorporeal membrane oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) has started to be applied in awake spontaneously breathing patients as an alternative to invasive mechanical ventilation. As the physiologic cardiorespiratory variability is increased in this condition, the dynamic interaction between patient respiratory activity and extracorporeal system function affects the clinical management. The effect of extracorporeal CO2 removal on patient respiratory drive is variable and not always predictable, with some patients responding to CO2 removal with a decrease in respiratory rate and effort and other patients demonstrating a persistently high work of breathing independent on CO2 unload. While the pathophysiological mechanisms of this different interactions are still to be clarified, improved monitoring ability is needed both to titrate the support in responders and to avoid the risk of ventilation injury in non-responders. Acute changes in patient respiratory patterns may also occur during spontaneous breathing, making it difficult to maintain constant levels of extracorporeal respiratory support, also because changes in the distribution of venous blood volume due to lung-heart interactions affect extracorporeal blood flow. Assessment of native lung function and of its evolution over time is challenging while respiratory gas exchanges are provided by the extracorporeal system, since both oxygenation and decarboxylation capabilities can be fully evaluated only when alveolar ventilation is restored reducing extracorporeal CO2 removal. The rationale for using "awake ECMO" varies across different types of acute respiratory failure: the pathophysiological mechanisms of the underlying disease affect the patient-ECMO interaction and the goal of support. In this review we discuss the pathophysiology, technical challenges and monitoring issues of the use of ECMO in awake spontaneously breathing patients with acute respiratory failure of different etiologies.