Awake Prone Positioning, High-Flow Nasal Oxygen and Non-Invasive Ventilation as Non-Invasive Respiratory Strategies in COVID-19 Acute Respiratory Failure: A Systematic Review and Meta-Analysis

Background: Acute respiratory failure is the most important organ dysfunction of COVID-19 patients. While non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) oxygen are frequently used, efficacy and safety remain uncertain. Benefits and harms of awake prone positioning (APP) in COVID-19 patients are unknown. Methods: We searched for randomized controlled trials (RCTs) comparing HFNC vs. NIV and APP vs. standard care. We meta-analyzed data for mortality, intubation rate, and safety. Results: Five RCTs (2182 patients) were identified. While it remains uncertain whether HFNC compared to NIV alters mortality (RR: 0.92, 95% CI 0.65–1.33), HFNC may increase rate of intubation or death (composite endpoint; RR 1.22, 1.03–1.45). We do not know if HFNC alters risk for harm. APP compared to standard care probably decreases intubation rate (RR 0.83, 0.71–0.96) but may have little or no effect on mortality (RR: 1.08, 0.51–2.31). Conclusions: Certainty of evidence is moderate to very low. There is no compelling evidence for either HFNC or NIV, but both carry substantial risk for harm. The use of APP probably has benefits although mortality appears unaffected.

Early Measurement of ROX Index in Intermediary Care Unit Is Associated with Mortality in Intubated COVID-19 Patients: A Retrospective Study

COVID-19 patients often present with rapidly progressing acute hypoxemic respiratory failure, requiring orotracheal intubation with different prognostic issues. However, ICU specialists lack predictive tools to stratify these patients. We conducted a single-center cross-sectional retrospective study to evaluate if the ROX index, measured under non-invasive oxygenation support, can predict ICU mortality in a COVID-19 intubated patient cohort. This study took place in the division of intensive care at the Geneva University Hospitals (Geneva, Switzerland). We included all consecutive adult patients treated by non-invasive oxygenation support and requiring intubation for acute respiratory failure due to COVID-19 between 9 September 2020 and 30 March 2021, corresponding to the second local surge of COVID-19 cases. Baseline demographic data, comorbidities, median ROX between H0 and H8, and clinical outcomes were collected. Overall, 82 patients were intubated after failing a non-invasive oxygenation procedure. Women represented 25.6% of the whole cohort. Median age and median BMI were 70 (60–75) years and 28 (25–33), respectively. Before intubation, the median ROX between H0 and H8 was 6.3 (5.0–8.2). In a multivariate analysis, the median ROX H0–H8 was associated with ICU mortality as a protective factor with an odds ratio (95% CI) = 0.77 (0.60–0.99); p < 0.05. In intubated COVID-19 patients treated initially by non-invasive oxygenation support for acute respiratory failure, the median ROX H0–H8 could be an interesting predictive factor associated with ICU mortality.

Cytokine Hemoadsorption as Rescue Therapy for Critically Ill Patients With SARS-CoV-2 Pneumonia With Severe Respiratory Failure and Hypercytokinemia

Introduction: A dysregulated inflammatory response, known as “cytokine storm”, plays an important role in the pathophysiology of coronavirus 2019 disease (COVID-19). Identifying patients with a dysregulated inflammatory response and at high risk for severe respiratory failure, organ dysfunction, and death is clinically relevant, as they could benefit from the specific therapies, such as cytokine removal by hemoadsorption. This study aimed to evaluate cytokine hemoadsorption as rescue therapy in critically ill patients with SARS-CoV-2 pneumonia, severe respiratory failure refractory to prone positioning, and hypercytokinemia.Methods: In this single center, observational and retrospective study, critically ill patients with SARS-CoV-2 pneumonia, severe acute respiratory failure, and hypercytokinemia were analyzed. All the patients underwent cytokine hemoadsorption using CytoSorb® (Cytosorbents Europe, Berlin, Germany). The indication for treatment was acute respiratory failure, inadequate clinical response to the prone position, and hypercytokinemia.Results: Among a total of 343 patients who were admitted to the intensive care unit (ICU) due to SARS-CoV-2 infection between March 3, 2020 and June 22, 2020, six patients received rescue therapy with cytokine hemoadsorption. All the patients needed invasive mechanical ventilation and prone positioning. A significant difference was found in the pre- and post-treatment D-dimer (17,868 mcg/ml [4,196–45,287] vs. 4,488 mcg/ml [3,166–17,076], p = 0.046), C-reactive protein (12.9 mg/dl [10.6] vs. 3.5 mg/dl [2.8], p = 0.028), ferritin (1,539 mcg/L [764–27,414] vs. 1,197 ng/ml [524–3,857], p = 0.04) and interleukin-6 (17,367 pg/ml [4,539–22,532] vs. 2,403 pg/ml [917–3,724], p = 0.043) levels. No significant differences in the pre- and post-treatment interleukin-10 levels (22.3 pg/ml [19.2–191] vs. 5.6 pg/ml [5.2–36.6], p = 0.068) were observed. Improvements in oxygenation (prehemoadsorption PaO2/FIO2 ratio 103 [18.4] vs. posthemoadsorption PaO2/FIO2 ratio 222 [20.9], p = 0.029) and in the organ dysfunction (prehemoadsorption SOFA score 9 [4.75] vs. posthemoadsorption SOFA score 7.7 [5.4], p = 0.046) were observed. ICU and in-hospital mortality was 33.7%.Conclusions: In this case series, critically ill patients with COVID-19 with severe acute respiratory failure refractory to prone positioning and hypercytokinemia who received adjuvant treatment with cytokine hemoadsorption showed a significant reduction in IL-6 plasma levels and other inflammatory biomarkers. Improvements in oxygenation and SOFA score were also observed.

Clinical impact of pneumothorax in patients with Pneumocystis jirovecii pneumonia and respiratory failure in an HIV-negative cohort

Background Pneumocystis jirovecii pneumonia (PCP) with acute respiratory failure can result in development of pneumothorax during treatment. This study aimed to identify the incidence and related factors of pneumothorax in patients with PCP and acute respiratory failure and to analyze their prognosis. Methods We retrospectively reviewed the occurrence of pneumothorax, including clinical characteristics and results of other examinations, in 119 non-human immunodeficiency virus patients with PCP and respiratory failure requiring mechanical ventilator treatment in a medical intensive care unit (ICU) at a tertiary-care center between July 2016 and April 2019. Results During follow up duration, twenty-two patients (18.5%) developed pneumothorax during ventilator treatment, with 45 (37.8%) eventually requiring a tracheostomy due to weaning failure. Cytomegalovirus co-infection (odds ratio 13.9; p = 0.013) was related with occurrence of pneumothorax in multivariate analysis. And development of pneumothorax was not associated with need for tracheostomy and mortality. Furthermore, analysis of survivor after 28 days in ICU, patients without pneumothorax were significantly more successful in weaning from mechanical ventilator than the patients with pneumothorax (44% vs. 13.3%, p = 0.037). PCP patients without pneumothorax showed successful home discharges compared to those who without pneumothorax (p = 0.010). Conclusions The development of pneumothorax increased in PCP patient with cytomegalovirus co-infection, pneumothorax might have difficulty in and prolonged weaning from mechanical ventilators, which clinicians should be aware of when planning treatment for such patients.

Impact of exposure time in awake prone positioning on clinical outcomes of patients with COVID-19-related acute respiratory failure treated with high-flow nasal oxygen: a multicenter cohort study

Background In patients with COVID-19-related acute respiratory failure (ARF), awake prone positioning (AW-PP) reduces the need for intubation in patients treated with high-flow nasal oxygen (HFNO). However, the effects of different exposure times on clinical outcomes remain unclear. We evaluated the effect of AW-PP on the risk of endotracheal intubation and in-hospital mortality in patients with COVID-19-related ARF treated with HFNO and analyzed the effects of different exposure times to AW-PP. Methods This multicenter prospective cohort study in six ICUs of 6 centers in Argentine consecutively included patients > 18 years of age with confirmed COVID-19-related ARF requiring HFNO from June 2020 to January 2021. In the primary analysis, the main exposure was awake prone positioning for at least 6 h/day, compared to non-prone positioning (NON-PP). In the sensitivity analysis, exposure was based on the number of hours receiving AW-PP. Inverse probability weighting–propensity score (IPW-PS) was used to adjust the conditional probability of treatment assignment. The primary outcome was endotracheal intubation (ETI); and the secondary outcome was hospital mortality. Results During the study period, 580 patients were screened and 335 were included; 187 (56%) tolerated AW-PP for [median (p25–75)] 12 (9–16) h/day and 148 (44%) served as controls. The IPW–propensity analysis showed standardized differences < 0.1 in all the variables assessed. After adjusting for other confounders, the OR (95% CI) for ETI in the AW-PP group was 0.36 (0.2–0.7), with a progressive reduction in OR as the exposure to AW-PP increased. The adjusted OR (95% CI) for hospital mortality in the AW-PP group ≥ 6 h/day was 0.47 (0.19–1.31). The exposure to prone positioning ≥ 8 h/d resulted in a further reduction in OR [0.37 (0.17–0.8)]. Conclusion In the study population, AW-PP for ≥ 6 h/day reduced the risk of endotracheal intubation, and exposure ≥ 8 h/d reduced the risk of hospital mortality.

Association between unmet medication needs after hospital discharge and readmission or death among acute respiratory failure survivors: the addressing post-intensive care syndrome (APICS-01) multicenter prospective cohort study

Introduction Survivors of acute respiratory failure (ARF) commonly experience long-lasting physical, cognitive, and/or mental health impairments. Unmet medication needs occurring immediately after hospital discharge may have an important effect on subsequent recovery. Methods and analysis In this multicenter prospective cohort study, we enrolled ARF survivors who were discharged directly home from their acute care hospitalization. The primary exposure was unmet medication needs. The primary outcome was hospital readmission or death within 3 months after discharge. We performed a propensity score analysis, using inverse probability weighting for the primary exposure, to evaluate the exposure–outcome association, with an a priori sample size of 200 ARF survivors. Results We enrolled 200 ARF survivors, of whom 107 (53%) were female and 77 (39%) were people of color. Median (IQR) age was 55 (43–66) years, APACHE II score 20 (15–26) points, and hospital length of stay 14 (9–21) days. Of the 200 participants, 195 (98%) were in the analytic cohort. One hundred fourteen (57%) patients had at least one unmet medication need; the proportion of medication needs that were unmet was 6% (0–15%). Fifty-six (29%) patients were readmitted or died by 3 months; 10 (5%) died within 3 months. Unmet needs were not associated (risk ratio 1.25; 95% CI 0.75–2.1) with hospital readmission or death, although a higher proportion of unmet needs may have been associated with increased hospital readmission (risk ratio 1.7; 95% CI 0.96–3.1) and decreased mortality (risk ratio 0.13; 95% CI 0.02–0.99). Discussion Unmet medication needs are common among survivors of acute respiratory failure shortly after discharge home. The association of unmet medication needs with 3-month readmission and mortality is complex and requires additional investigation to inform clinical trials of interventions to reduce unmet medication needs. Study registration number: NCT03738774. The study was prospectively registered before enrollment of the first patient.

Hiệu quả của phương pháp oxy hóa qua màng ngoài cơ thể (ECMO) trong hỗ trợ điều trị hội chứng suy hô hấp cấp nguy kịch trên bệnh nhân Covid

TÓM TẮT Sự bùng phát của hội chứng viêm đường hô hấp cấp do coronavirus 2 (SARS-CoV-2) nhanh chóng trở thành đại dịch trên toàn thế giới với hơn 40 triệu người mắc và hơn 1 triệu người chết tính đến ngày 17 tháng 10 năm 2020. Nhiều bệnh nhân COVID-19 được báo cáo cho thấy rằng có thể dẫn đến suy hô hấp cấp cần chăm sóc đặc biệt (ICU) và thiết bị hỗ trợ thở và bệnh cảnh có thể nhanh chóng tiến triển thành chứng suy hô hấp cấp (ARDS) với thiếu oxy ở mức độ nặng và gây ra tử vong dù đã có sự hỗ trợ của thiết bị hỗ trợ thở, cả 2 khả năng này thậm chí có thể cùng xảy ra. Các tổ chức quốc tế và các chuyên gia trong lĩnh vực này khuyến nghị sử dụng ECMO cho những bệnh nhân ARDS bị bệnh nặng có COVID-19. Tuy nhiên, tỷ lệ sống sót là rất thấp trong những trường hợp được sử dụng ECMO với COVID-19 trong đợt đầu tiên. Nghiên cứu của chúng tôi nhằm đánh giá kết quả bước đầu ứng dụng kỹ thuật ECMO trong hỗ trợ điều trị hội chứng suy hô hấp cấp nguy kịch trên bệnh nhân COVID-19 tại trung tâm hồi sức bệnh viện Trung ương Huế. ABSTRACT EFFECTIVENESS OF EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO) IN THE TREATMENT OF ACUTE RESPIRATORY DISTRESS SYNDROME IN PATIENTS WITH COVID-19 The outbreak of acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) quickly developed into a worldwide pandemic with more than 40 million people infected and more than 1 million dead as of October 17, 2020. Numerous patient reports COVID-19 can lead to acute respiratory failure requiring intensive care (ICU) and ventilators, and it can rapidly evolve into a certificate of acute respiratory failure (ARDS) with red oxygen in the heavy and death, despite the protective ventilator, even both. International organizations and experts in the field recommend ECMO for critically ill ARDS patients with COVID-19. However, survival is very low in the ECMO - corrected case series with COVID-19 during the first COVID-19 wave. Our study aimed to evaluate the results of the initial application of transmembrane oxygenation (ECMO) technique in the support of critical acute respiratory distress syndrome on COVID-19 patients at the hospital resuscitation center of Hue central hospital. Keywords: ECMO, ARDS, COVID-19.

In-hospital mortality in the emergency department: clinical and etiological differences between early and late deaths among patients awaiting admission

Objective Given that there are no studies on diseases that occur by waiting for hospitalization, we aimed to evaluate the main causes of death in the emergency room (ER) and their relationship with overcrowding.Methods Patients who died in the ER in the past 2 years (pediatrics and trauma victims excluded) were divided into two groups: patients who died within 6 hours of arrival (emergency department [ED] group) and patients who died later (LD group). We compared the causes of death, total vital signs, diagnostic tests performed, and therapy between the groups. We assessed for possible correlation between the number of monthly deaths per group and four variables of overcrowding: number of patients treated per month, waiting time before medical visit (W-Time), mean intervention time (I-Time), and number of patients admitted to the ward per month (NPA).Results During the two years, 175 patients had died in our ER (52% in ED group and 48% in LD group). The total time spent in the ER was, respectively, 2.9±0.2 hours for ED group and 17.9± 1.5 hours for LD group. The more frequent cause of death was cardiovascular syndrome (30%) in ED group and sepsis (27%) and acute respiratory failure (27%) in LD group. Positive correlations between number of monthly deaths and W-Time (R2 0.51, P<0.001), I-Time (R2 0.73, P< 0.0001), and NPA (R2 0.37, P<0.01) were found only in LD group.Conclusion Patients with sepsis and acute respiratory failure die after a long stay in the ER, and the risk increases with overcrowding. A fast-track pathway should be considered for hospital admission of critical patients.