Anticoagulation Strategies in Critically Ill Patients With SARS-CoV-2 Infection: The Role of Direct Thrombin Inhibitors.

OBJECTIVES: To compare heparin-based anticoagulation and bivalirudin-based anticoagulation within the context of critically ill patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: An observational study. SETTING: At the intensive care unit of a university hospital. PARTICIPANTS AND INTERVENTIONS: Critically ill patients with a SARS-CoV-2 infection receiving full anticoagulation with heparin or bivalirudin. MEASUREMENTS AND MAIN RESULTS: Twenty-three patients received full anticoagulation with bivalirudin and 60 with heparin. Despite patients in the bivalirudin group having higher mortality risk scores (SAPS II 60 ± 16 v 39 ±7, p < 0.001) and a higher need for extracorporeal support compared to the heparin group, hospital mortality was comparable (57% v 45, p = 0.3). No difference in thromboembolic complications was observed, and bleeding events were more frequent in patients treated with bivalirudin (65% v 40%, p = 0.01). Similar results were confirmed in the subgroup analysis of patients undergoing intravenous anticoagulation; in addition to comparable thrombotic complications occurrence and thrombocytopenia rate, however, no difference in the bleeding rate was observed (65% v 35%, p = 0.08). CONCLUSIONS: Although heparin is the most used anticoagulant in the intensive care setting, bivalirudin-based anticoagulation was safe and effective in a cohort of critically ill patients with SARS-CoV-2. Bivalirudin may be given full consideration as an anticoagulation strategy for critically ill patients with SARS-CoV-2, especially in those with thrombocytopenia and on extracorporeal support.

CytoSorb purification in critically ill SARS-CoV-2 patients.

OBJECTIVE: To describe the experience with CytoSorb treatment in patients with refractory acute respiratory distress syndrome (ARDS) following SARS-CoV-2 infection. METHODS: Retrospective observational study on 15 patients treated in a University Hospital. RESULTS: All patients were male, with a mean age of 55 ± 14 years; eight patients (53%) were on venovenous extracorporeal membrane oxygenation (VV ECMO) due to refractory ARDS and all (100%) under mechanical ventilation at the time of CytoSorb use. We observed reduction in the level of C reactive protein (-52%, p = 0.002), total bilirubin (-46%, p = 0.03), direct bilirubin (-50%, p = 0.02), and D-dimers (-39%, p = 0.04) during CytoSorb treatment and a trend toward reduction in lactate dehydrogenase (-20%, p = 0.2), creatine phosphokinase (-38%, p = 0.1), and fibrinogen (-15%, p = 0.07). Eight patients died (53%) and seven (47%) were discharged from the ICU, of which five had recovery of the native lung function and two were successfully bridged to lung transplantation on VV ECMO support. No difference between survivors and non-survivors was present at baseline. Patients received three CytoSorb cycles on average: mean duration of CytoSorb cycle was 17 h 21 min, but premature circuit clotting despite appropriate level of systemic anticoagulation was frequently observed. CONCLUSIONS: CytoSorb treatment was effective in improving several laboratory parameters and inflammation in our experience and no treatment-related adverse effects were recorded. In the light of the unique pathophysiology of SARS-CoV-2 infection, CytoSorb treatment is extremely promising, since it might both reduce inflammation and activation of coagulation.

Eleven Years of Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: From H1N1 to SARS-CoV-2. Experience and Perspectives of a National Referral Center.

OBJECTIVE: Despite growing expertise and wide application of venovenous extracorporeal membrane oxygenation (VV ECMO) treatment for acute respiratory distress syndrome (ARDS) of different origin and during pandemics (H1N1 Influenza A virus and SARS-CoV-2), large reports are few and pertain mostly to multicenter registries, and randomized trials are difficult to perform. The aim of this study was to report outcomes, trends, and innovations of VV ECMO treatment over the last 11 years. DESIGN, SETTING, AND PARTICIPANTS: Observational study on 142 patients treated at the IRCCS San Raffaele Hospital in Milan from June 2009 (year of the H1N1 pandemic) to May 2020 (SARS-CoV-2 pandemic). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main causes of ARDS were H1N1 pneumonia in 36% of patients, bacterial pneumonia in 17%, and SARS-CoV-2 in 9%. Seventy-two percent of patients were centralized from remote hospitals, of whom 33% had implanted VV ECMO before transport. The most common cannulation strategy was the dual-lumen catheter cannulation system (55%), and anticoagulation was performed with bivalirudin in most patients (79%). Refractory hypoxia was treated with intravenous beta-blockers (64%), nitric oxide (20%), and pronation (8%). Almost one-third of patients (32%) were extubated while on ECMO. Forty-nine percent of patients were discharged from the intensive care unit, and hospital discharge was 46%; survival was lower in patients requiring VV ECMO for more than three weeks compared with shorter support duration (23% v 56%, p = 0.007). Anticoagulation with bivalirudin was associated with higher survival, compared with heparin (55% v 31%, p = 0.03), and lower thrombocytopenia incidence (69% v 35%, p = 0.003). CONCLUSION: VV ECMO is the pivotal rescue treatment for refractory ARDS-timely treatment and optimal care are needed to optimize therapy, as duration of support is associated with outcome. Anticoagulation with bivalirudin may improve outcome.

Trend and Pattern of 100 Acute Respiratory Distress Syndrome Patients Referred for Venovenous Extracorporeal Membrane Oxygenation Treatment in a National Referral Center in North Italy During the Last Decade.

OBJECTIVE: Current evidence supports centralization of patients with refractory acute respiratory distress syndrome (ARDS) to institutions with a high level of expertise and with extracorporeal membrane oxygenation (ECMO) capabilities. The aim of this study was to analyze and report the data of transferred refractory ARDS patients managed with venovenous (VV) ECMO at a national referral center over the last 11 years. DESIGN: Observational study. SETTING: Referral center in Italy. PARTICIPANTS: The study comprised 100 patients treated from May 2009-November 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean age was 54 ± 14 years, and 65% of patients were male. Patients were treated throughout the year, with seasonal peaks in the winter months. The majority of patients were referred from hospitals within the Lombardia region (81%), mainly from the city of Milan and surrounding area (36% of the total). The most common etiology of refractory ARDS was H1N1 influenza A (42 patients [42%]), followed by bacterial pneumonia (35 patients [35%]), and severe acute respiratory syndrome due to Sars-CoV-2 infection (five patients [5%]). All patients were severely hypoxic at the time of VV ECMO treatment. No transport-related complication was recorded. The most common configuration used in the authors' clinical practice was a bicaval dual-lumen configuration (61 patients [61%]), followed by a femoro-jugular configuration (38 patients [38%]). The intensive care unit survival rate was 55%. CONCLUSIONS: Referral to a specialized center for VV ECMO treatment should be considered expeditiously in case of refractory ARDS, which often is lethal. Transport of patients with an unstable condition, although challenging, is feasible, and centralization of patient care is associated with good outcomes.

Immunosuppressive strategies in invasively ventilated ARDS COVID-19 patients.

BACKGROUND: COVID-19 is associated with elevated levels of inflammatory cytokines. We present the characteristics and outcomes of patients treated in the Intensive Care Unit (ICU) with immunosuppressive drugs, either tocilizumab or anakinra compared with controls. METHODS: A single-center observational prospective study on ICU invasively ventilated COVID-19 patients. The primary outcome was the clinical improvement at day 28. A Bayesian framework was employed, and all analyses were adjusted for confounders. RESULTS: Sixty-one consecutive invasively ventilated patients were included, nine (14.7%) received tocilizumab and 15 (24.6%) received anakinra. Over the first seven days, tocilizumab was associated with a greater decrease in C-reactive protein (P<0.001). After adjusting for confounders, the probability of clinical improvement at day 28 compared to control was 7∙6% (OR=0.36 [95% CrI: 0.09-1.46]) for tocilizumab and 40.9% (OR=0.89 [95% CrI: 0.32-2.43]) for anakinra. At day 28, the probability of being in a better clinical category was 2.5% (OR=2.98 [95% CrI: 1.00-8.88]) for tocilizumab, and 49.5% (OR=1.00 [95% CrI: 0.42-2.42]) for anakinra. CONCLUSIONS: In invasively ventilated COVID-19 patients, treatment with anakinra was associated with a higher probability of clinical improvement compared to tocilizumab; however, treatment with either drug did not result in clinically meaningful improvements compared with controls.

Two-months quality of life of COVID-19 invasively ventilated survivors; an Italian single-center study.

BACKGROUND: COVID-19 disease can lead to severe functional impairments after discharge. We assessed the quality of life of invasively ventilated COVID-19 ARDS survivors. METHODS: We carried out a prospective follow-up study of the patients admitted to the Intensive Care Units (ICUs) of a teaching hospital. Patients affected by COVID-19 ARDS who required invasive ventilation and were successfully discharged home were assessed through the telephone administration of validated tests. We explored survival, functional outcomes, return to work, quality of life, cognitive and psychological sequelae. The main variables of interest were the following: demographics, severity scores, laboratory values, comorbidities, schooling, working status, treatments received during ICU stay, complications, and psychological, cognitive, functional outcomes. RESULTS: Out of 116 consecutive invasively ventilated patients, overall survival was 65/116 (56%) with no death occurring after hospital discharge. Forty-two patients were already discharged home with a median follow-up time of 61 (51-71) days after ICU discharge and 39 of them accepted to be interviewed. Only one patient (1/39) experienced cognitive decline. The vast majority of patients reported no difficulty in walking (32/35:82%), self-care (33/39:85%), and usual activities (30/39:78%). All patients were either malnourished (15/39:38%) or at risk for malnutrition (24/39:62%). Exertional dyspnea was present in 20/39 (51%) patients. 19/39 (49%) reported alterations in senses of smell and/or taste either before or after hospitalization. CONCLUSIONS: Invasively ventilated COVID-19 ARDS survivors have an overall good recovery at a 2-months follow-up which is better than what was previously reported in non-COVID-19 ARDS patients.

Venovenous ECMO treatment, outcomes, and complications in adults according to large case series: A systematic review.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV ECMO) has gained popularity for the treatment of refractory respiratory failure during and after the 2009 influenza pandemic, and still represents a precious therapeutic resource for severe novel coronavirus 2019 infection. However, most of the published studies are small case series, and only two randomized trials exist in literature. AIM: Aim of this systematic review is to describe trends in VV ECMO treatment outcomes according to large studies only. METHODS: We searched and included studies with more than 100 VV ECMO cases dated up to August 1st, 2019. RESULTS: Thirty-three studies published in the period 2011-2019 met inclusion criteria, for a total of 12,860 patients (age 46.3 ± 17.4 years). ARDS was mainly by pneumonia, in 3126 (37%) cases; further 401(7%) patients had H1N1 Influenza A infection. Cannulation-related complications occurred in 502 (7%) cases. Weighted mean (95% confidence interval) of VV ECMO duration was 8.9 (8.7-9.1) days, and ICU stay was 23.6 (22.4-24.8) days. Mortality at the longest follow up available was 40%. Data collection in 70% of the studies had a duration of >5 years. CONCLUSION: This study reveals the characteristics of large case VV ECMO studies.

Prevalence, Characteristics, Risk Factors, and Outcomes of Invasively Ventilated COVID-19 Patients with Acute Kidney Injury and Renal Replacement Therapy.

BACKGROUND: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems. OBJECTIVE: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients. METHODS: Observational study in a tertiary care hospital in Milan, Italy. RESULTS: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients. CONCLUSIONS: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality.