Fibrinolytic therapy in patients with COVID-19 and ARDS: protocol for a systematic review and meta-analysis.

INTRODUCTION: In COVID-19-related acute respiratory distress syndrome (ARDS), the clot play a role in gas exchange abnormalities. Fibrinolytic therapy can improve alveolar ventilation by restoring blood flow. In this systematic review and meta-analysis protocol, we aim to assess the safety and efficacy of fibrinolytic therapy in such a population. METHODS: We will perform a systematic search in MEDLINE, EMBASE, Cochrane CENTRAL and LILACS databases without language restrictions for relevant randomised controlled trials (RCTs) and quasi-RCTs. Two review authors will independently perform data extraction and quality assessments of data from included studies. In case of divergence, a third author will be contacted. The Cochrane handbook will be used for guidance. If the results are not appropriate for a meta-analysis, a descriptive analysis will be performed. DISCUSSION: This systematic review and meta-analysis protocol will provide current evidence about the safety and efficacy of fibrinolytic therapy in patients with COVID-19 and ARDS. These findings will provide if fibrinolytic therapy might be an option for a desperate clinical setting, where all medical efforts have been used. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020187482. ETHICS AND DISSEMINATION: Ethics committee approval is not necessary. We intend to update the public registry, report any protocol amendments and publish the results in a widely accessible journal.

Effectiveness of a quality improvement strategy with implementation of a specific visual tool to promote ICU early mobilization.

Early progressive mobilization is a safe strategy in the intensive care unit (ICU), however, it is still considered challenging by the inherent barriers and poor adherence to early mobilization protocol. The aim of this study was to evaluate the effectiveness of a quality improvement (QI) multifaceted strategy with implementation of a specific visual tool, the "mobility clock", in reducing non-compliance with the institutional early mobilization (EM) protocol in adult ICUs. A single-center QI with a retrospective before-after comparison study was conducted using data from medical records and hospital electronic databases. Patients from different periods presented similar baseline characteristics. After the QI strategy, a decline in "non-compliance" with the protocol was observed compared to the previous period (10.11% vs. 26.97%, p < 0.004). The proportion of patients walking was significantly higher (49.44% vs. 29.21%, p < 0.006) and the ICU readmission rate was lower in the "after" period (2.25% vs. 11.24%; p = 0.017). The multifaceted strategy specifically designed considering institutional barriers was effective to increase out of bed mobilization, to reduce the "non-compliance" rate with the protocol and to achieve a higher level of mobility in adult ICUs of a tertiary hospital.

COVID-19 convalescent plasma cohort study: Evaluation of the association between both donor and recipient neutralizing antibody titers and patient outcomes.

BACKGROUND: Current evidence regarding COVID-19 convalescent plasma (CCP) transfusion practices is limited and heterogeneous. We aimed to determine the impact of the use of CCP transfusion in patients with previous circulating neutralizing antibodies (nAbs) in COVID-19. METHODS: Prospective cohort including 102 patients with COVID-19 transfused with ABO compatible CCP on days 0-2 after enrollment. Clinical status of patients was assessed using the adapted World Health Organization (WHO) ordinal scale on days 0, 5, and 14. The nAbs titration was performed using the cytopathic effect-based virus neutralization test with SARS-CoV-2 (GenBank MT126808.1). The primary outcome was clinical improvement on day 14, defined as a reduction of at least two points on the adapted WHO ordinal scale. Secondary outcomes were the number of intensive care unit (ICU)-free days and the number of invasive mechanical ventilation-free days. RESULTS: Both nAbs of CCP units transfused (p < 0.001) and nAbs of patients before CCP transfusions (p = 0.028) were associated with clinical improvements by day 14. No significant associations between nAbs of patients or CCP units transfused were observed in the number of ICU or mechanical ventilation-free days. Administration of CCP units after 10 days of symptom onset resulted in a decrease in ICU-free days (p < 0.001) and mechanical ventilation-free days (p < 0.001). CONCLUSION: Transfusion of high titer nAbs CCP units may be a determinant in clinical strategies against COVID-19. We consider these data as useful parameters to guide future CCP transfusion practices.

Epidemiology, outcomes, and the use of intensive care unit resources of critically ill patients diagnosed with COVID-19 in Sao Paulo, Brazil: A cohort study.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has brought significant challenges worldwide, with high mortality, increased use of hospital resources, and the collapse of healthcare systems. We aimed to describe the clinical outcomes of critically ill COVID-19 patients and assess the impact on the use of hospital resources and compare with critically ill medical patients without COVID-19. METHODS AND FINDINGS: In this retrospective cohort study, we included patients diagnosed with COVID-19 admitted to a private ICU in Sao Paulo, Brazil from March to June 2020. We compared these patients with those admitted to the unit in the same period of the previous year. A total of 212 consecutive patients with a confirmed diagnosis of COVID-19 were compared with 185 medical patients from the previous year. Patients with COVID-19 were more frequently males (76% vs. 56%, p<0.001) and morbidly obese (7.5% vs. 2.2%, p = 0.027), and had lower SAPS 3 (49.65 (12.19) vs. 55.63 (11.94), p<0.001) and SOFA scores (3.78 (3.53) vs. 4.48 (3.11), p = 0.039). COVID-19 patients had a longer ICU stay (median of 7 vs. 3 days, p<0.001), longer duration of mechanical ventilation (median of 9 vs. 4 days, p = 0.003), and more frequent tracheostomies (10.8 vs. 1.1%, p<0.001). Survival rates until 28 days were not statistically different (91% vs. 85.4%, p = 0.111). After multivariable adjustment for age, gender, SAPS 3, and Charlson Comorbidity Index, COVID-19 remained not associated with survival at 28 days (HR 0.59, 95% CI 0.33-1.06, p = 0.076). Among patients who underwent invasive mechanical ventilation, the observed mortality at 28-days was 16.2% in COVID-19 patients compared to 34.6% in the previous year. CONCLUSIONS: COVID-19 required more hospital resources, including invasive and non-invasive ventilation, had a longer duration of mechanical ventilation, and a more prolonged ICU and hospital length of stay. There was no difference in all-cause mortality at 28 and 60 days, suggesting that health systems preparedness be an important determinant of clinical outcomes.

Performance of a qualitative rapid chromatographic immunoassay to diagnose COVID-19 in patients in a middle-income country.

OBJECTIVES: We evaluated a rapid chromatographic immunoassay (IgG/IgM antibodies) and an ELISA assay to diagnose COVID-19 in patient sat two Brazilian hospitals. METHODS: A total of 122 subjects with COVID-19 were included: 106 SARS-COV-2 RT-PCR-positive patients and 16 RT-PCR-negative patients with symptoms and chest computed tomography (CT) consistent with COVID-19. Ninety-six historical blood donation samples were used as controls. Demographic and clinical characteristics were retrieved from electronic records. Sensitivity and specificity were calculated, as were their 95% binomial confidence intervals using the Clopper-Pearson method. All analyses were performed in R version 3.6.3. RESULTS: The sensitivity of the chromatographic immunoassay in all RT-PCR-positive patients, irrespective of the timing of symptom onset, was 85.8% (95% binomial CI 77.7% to 91.9%). This increased with time after symptom onset, and at >14 days was 94.9% (85.9% to 98.9%). The specificity was 100% (96.4% to 100%). 15/16 (94%) RT- PCR-negative cases tested positive. The most frequent comorbidities were hypertension and diabetes mellitus and the most frequent symptoms were fever, cough, and dyspnea. All RT-PCR-negative patients had pneumonia. The most frequent thoracic CT findings were ground glass changes (n = 11, 68%), which were bilateral in 9 (56%) patients, and diffuse reticulonodular infiltrates (n = 5, 31%). CONCLUSIONS: The COVID-19 rapid chromatographic immunoassay evaluated in this study had a high sensitivity and specificity using plasma, particularly after 14 days from symptom onset. ELISA and qualitative rapid chromatographic immunoassays can be used for the diagnosis of RT-PCR-negative patients.

Shortening ventilatory support with a protocol based on daily extubation screening and noninvasive ventilation in selected patients.

BACKGROUND: Prolonged invasive mechanical ventilation and reintubation are associated with adverse outcomes and increased mortality. Daily screening to identify patients able to breathe without support is recommended to reduce the length of mechanical ventilation. Noninvasive positive-pressure ventilation has been proposed as a technique to shorten the time that patients remain on invasive ventilation. METHODS: We conducted a before-and-after study to evaluate the efficacy of an intervention that combined daily screening with the use of noninvasive ventilation immediately after extubation in selected patients. The population consisted of patients who had been intubated for at least 2 days. RESULTS: The baseline characteristics were similar between the groups. The intervention group had a lower length of invasive ventilation (6 [4;9] vs. 7 [4;11.5] days, p = 0.04) and total (invasive plus noninvasive) ventilator support (7 [4;11] vs. 9 [6;8], p = 0.01). Similar reintubation rates within 72 hours were observed for both groups. In addition, a lower ICU mortality was found in the intervention group (10.8% vs. 24.3%, p = 0.03), with a higher cumulative survival probability at 60 days (p = 0.05). Multivariate analysis showed that the intervention was an independent factor associated with survival (RR: 2.77; CI 1.14-6.65; p = 0.03), whereas the opposite was found for reintubation at 72 hours (RR: 0.27; CI 0.11-0.65; p = 0.01). CONCLUSION: The intervention reduced the length of invasive ventilation and total ventilatory support without increasing the risk of reintubation and was identified as an independent factor associated with survival.

Shortening ventilatory support with a protocol based on daily extubation screening and noninvasive ventilation in selected patients

BACKGROUND: Prolonged invasive mechanical ventilation and reintubation are associated with adverse outcomes and increased mortality. Daily screening to identify patients able to breathe without support is recommended to reduce the length of mechanical ventilation. Noninvasive positive-pressure ventilation has been proposed as a technique to shorten the time that patients remain on invasive ventilation. METHODS: We conducted a before-and-after study to evaluate the efficacy of an intervention that combined daily screening with the use of noninvasive ventilation immediately after extubation in selected patients. The population consisted of patients who had been intubated for at least 2 days. RESULTS: The baseline characteristics were similar between the groups. The intervention group had a lower length of invasive ventilation (6 [4;9] vs. 7 [4;11.5] days, p = 0.04) and total (invasive plus noninvasive) ventilator support (7 [4;11] vs. 9 [6;8], p = 0.01). Similar reintubation rates within 72 hours were observed for both groups. In addition, a lower ICU mortality was found in the intervention group (10.8 percent vs. 24.3 percent, p = 0.03), with a higher cumulative survival probability at 60 days (p = 0.05). Multivariate analysis showed that the intervention was an independent factor associated with survival (RR: 2.77; CI 1.14-6.65; p = 0.03), whereas the opposite was found for reintubation at 72 hours (RR: 0.27; CI 0.11-0.65; p = 0.01). CONCLUSION: The intervention reduced the length of invasive ventilation and total ventilatory support without increasing the risk of reintubation and was identified as an independent factor associated with survival.

Effect of acute kidney injury on weaning from mechanical ventilation in critically ill patients.

OBJECTIVES: Acute kidney injury (AKI) worsens outcome in various scenarios. We sought to investigate whether the occurrence of AKI has any effect on weaning from mechanical ventilation. DESIGN AND SETTING: Observational, retrospective study in a 23-bed medical/surgical intensive care unit (ICU) in a cancer hospital from January to December 2003. PATIENTS: The inclusion criterion was invasive mechanical ventilation for > or =48 hrs. AKI was defined as at least one measurement of serum creatinine of > or =1.5 mg/dL during the ICU stay. Patients were then separated into AKI and non-AKI patients (control group). The criterion for weaning was the combination of positive end-expiratory pressure of < or =8 cm H2O, pressure support of < or =10 cm H2O, and Fio2 of < or =0.4, with spontaneous breathing. The primary end point was duration of weaning and the secondary end points were rate of weaning failure, total length of mechanical ventilation, length of stay in the ICU, and ICU mortality. RESULTS: A total of 140 patients were studied: 93 with AKI and 47 controls. The groups were similar in regard to age, sex, and type of tumor. Diagnosis of acute lung injury/acute respiratory distress syndrome as cause of respiratory failure and Simplified Acute Physiology Score II at admission did not differ between groups. During ICU stay, AKI patients had markers of more severe disease: increased occurrence of severe sepsis or septic shock, higher number of antibiotics, and longer use of vasoactive drugs. The median (interquartile range) duration of mechanical ventilation (10 [6-17] vs. 7 [2-12] days, p = .017) and duration of weaning from mechanical ventilation (41 [16-97] vs. 21 [7-33.5] hrs, p = .018) were longer in AKI patients compared with control patients. Cox regression analysis demonstrated that a > or =85% increase in baseline serum creatinine (hazard rate, 2.30; 95% confidence interval, 1.30-4.08), oliguria (hazard rate, 2.51; 95% confidence interval, 1.24-5.08), and the number of antibiotics (hazard rate, 2.64; 95% confidence interval, 1.51-4.63) predicted longer duration of weaning. The length of ICU stay and ICU mortality rate were significantly greater in the AKI patients. After adjusting for Simplified Acute Physiology Score II, oliguria (odds ratio, 30.8; 95% confidence interval, 7.7-123.0) remained as a strong risk factor for mortality. CONCLUSION: This study shows that renal dysfunction has serious consequences in the duration of mechanical ventilation, weaning from mechanical ventilation, and mortality in critically ill cancer patients.