Increased duration and similar outcomes of V-V ECLS in patients with COVID-19 ARDS compared to non-COVID ARDS: Single center experience.

BACKGROUND: Veno-venous extracorporeal life support (V-V ECLS or V-V ECMO) has been adopted as a rescue support in severe cases of COVID-19 ARDS. Initial reports on the use of V-V ECLS in COVID-19 patients reported very high mortality rates (57%-94%), but subsequent studies showed much lower rates (30%-40%). The aim of this study is to analyze demographic features, clinical course and outcomes of COVID-19 treated with V-V ECLS during the Italian 'third wave', in which the alpha variant was prevalent in the country. METHODS: Single-center, retrospective observational study conducted at the ECLS referral center of a teaching hospital in Italy from January 1st, 2021 and October 31st, 2021. RESULTS: Between January and October 2021, 18 consecutive adult patients who underwent V-V ECLS for severe ARDS due to COVID-19 were enrolled. Thirteen patients (72.2%) were male, and their median age was 50 years; the median P/F ratio before V-V ECLS initiation was 43 mm Hg (IQR, 40; 56), and the median RESP score was 0.5 (IQR, -2.25; 1.0). The mortality rate at 90 days was 55.6, compared to 55.7% in non-COVID patients in our center (p > 0.05); the median duration of ECLS was 29 days (IQR, 11; 32), compared to 10 days (IQR, 8; 15), in non-COVID patients (p = 0.004). Incidence of complications was high. CONCLUSIONS: In patients with COVID-19 ARDS receiving V-V ECLS, unadjusted mortality was similar to pre-pandemic V-V ECLS cases, while the duration of ECLS was almost three times longer and with frequent complications. This could be partly explained by the selection of very sick patients at the baseline that evolved to multiorgan failure during the course of ECLS.

High-Flow Nasal Oxygen for Severe Hypoxemia: Oxygenation Response and Outcome in Patients with COVID-19.

Rationale: The "Berlin definition" of acute respiratory distress syndrome (ARDS) does not allow inclusion of patients receiving high-flow nasal oxygen (HFNO). However, several articles have proposed that criteria for defining ARDS should be broadened to allow inclusion of patients receiving HFNO. Objectives: To compare the proportion of patients fulfilling ARDS criteria during HFNO and soon after intubation, and 28-day mortality between patients treated exclusively with HFNO and patients transitioned from HFNO to invasive mechanical ventilation (IMV). Methods: From previously published studies, we analyzed patients with coronavirus disease (COVID-19) who had PaO2/FiO2 of ⩽300 while treated with ⩾40 L/min HFNO, or noninvasive ventilation (NIV) with positive end-expiratory pressure of ⩾5 cm H2O (comparator). In patients transitioned from HFNO/NIV to invasive mechanical ventilation (IMV), we compared ARDS severity during HFNO/NIV and soon after IMV. We compared 28-day mortality in patients treated exclusively with HFNO/NIV versus patients transitioned to IMV. Measurements and Main Results: We analyzed 184 and 131 patients receiving HFNO or NIV, respectively. A total of 112 HFNO and 69 NIV patients transitioned to IMV. Of those, 104 (92.9%) patients on HFNO and 66 (95.7%) on NIV continued to have PaO2/FiO2 ⩽300 under IMV. Twenty-eight-day mortality in patients who remained on HFNO was 4.2% (3/72), whereas in patients transitioned from HFNO to IMV, it was 28.6% (32/112) (P < 0.001). Twenty-eight-day mortality in patients who remained on NIV was 1.6% (1/62), whereas in patients who transitioned from NIV to IMV, it was 44.9% (31/69) (P < 0.001). Overall mortality was 19.0% (35/184) and 24.4% (32/131) for HFNO and NIV, respectively (P = 0.2479). Conclusions: Broadening the ARDS definition to include patients on HFNO with PaO2/FiO2 ⩽300 may identify patients at earlier stages of disease but with lower mortality.

Environmental Contamination by SARS-CoV-2 During Noninvasive Ventilation in COVID-19.

BACKGROUND: Environmental contamination by SARS-CoV-2 from patients with COVID-19 undergoing noninvasive ventilation (NIV) in the ICU is still under investigation. This study set out to investigate the presence of SARS-CoV-2 on surfaces near subjects receiving NIV in the ICU under controlled conditions (ie, use of dual-limb circuits, filters, adequate room ventilation). METHODS: This was a single-center, prospective, observational study in the ICU of a tertiary teaching hospital. Four surface sampling areas, at increasing distance from subject's face, were identified; and each one was sampled at fixed intervals: 6, 12, and 24 h. The presence of SARS-CoV-2 was detected with real-time reverse transcriptase-polymerase-chain-reaction (RT-PCR) test on environmental swabs; the RT-PCR assay targeted the SARS-CoV-2 virus nucleocapsid N1 and N2 genes and the human RNase P gene as internal control. RESULTS: In a total of 256 collected samples, none were positive for SARS-CoV-2 genetic material, whereas 21 samples (8.2%) tested positive for RNase P, thus demonstrating the presence of genetic material unrelated to SARS-CoV-2. CONCLUSIONS: Our data show that application of NIV in an appropriate environment and with correct precautions leads to no sign of surface environmental contamination. Accordingly, our data support the idea that use of NIV in the ICU is safe both for health care workers and for other patients.

Assessment of a PK/PD Target of Continuous Infusion Beta-Lactams Useful for Preventing Microbiological Failure and/or Resistance Development in Critically Ill Patients Affected by Documented Gram-Negative Infections.

BACKGROUND: Emerging data suggest that more aggressive beta-lactam PK/PD targets could minimize the occurrence of microbiological failure and/or resistance development. This study aims to assess whether a PK/PD target threshold of continuous infusion (CI) beta-lactams may be useful in preventing microbiological failure and/or resistance development in critically ill patients affected by documented Gram-negative infections. METHODS: Patients admitted to intensive care units from December 2020 to July 2021 receiving continuous infusion beta-lactams for documented Gram-negative infections and having at least one therapeutic drug monitoring in the first 72 h of treatment were included. A receiver operating characteristic (ROC) curve analysis was performed using the ratio between steady-state concentration and minimum inhibitory concentration (Css/MIC) ratio as the test variable and occurrence of microbiological failure as the state variable. Area under the curve (AUC) and 95% confidence interval (CI) were calculated. Independent risk factors for the occurrence of microbiological failure were investigated using logistic regression. RESULTS: Overall, 116 patients were included. Microbiological failure occurred in 26 cases (22.4%). A Css/MIC ratio ≤ 5 was identified as PK/PD target cut-off with sensitivity of 80.8% (CI 60.6-93.4%) and specificity of 90.5% (CI 74.2-94.4%), and with an AUC of 0.868 (95%CI 0.793-0.924; p < 0.001). At multivariate regression, independent predictors of microbiological failure were Css/MIC ratio ≤ 5 (odds ratio [OR] 34.54; 95%CI 7.45-160.11; p < 0.001) and Pseudomonas aeruginosa infection (OR 4.79; 95%CI 1.11-20.79; p = 0.036). CONCLUSIONS: Early targeting of CI beta-lactams at Css/MIC ratio > 5 during the treatment of documented Gram-negative infections may be helpful in preventing microbiological failure and/or resistance development in critically ill patients.

Synergistic Effect of Static Compliance and D-dimers to Predict Outcome of Patients with COVID-19-ARDS: A Prospective Multicenter Study.

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A "training sample" (March-June 2020) and a "testing sample" (September 2020-January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO2/FiO2 ratio, and sample (training/testing). "Training" and "testing" samples amounted to 347 and 296 patients, respectively. Three groups were identified: D-dimer ≤ 1880 ng/mL (LD); D-dimer > 1880 ng/mL and compliance > 41 mL/cmH2O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH2O (HD-LC). 28-days mortality progressively increased in the three groups (from 24% to 35% and 57% (training) and from 27% to 39% and 60% (testing), respectively; p < 0.01). Adjusted mortality was significantly higher in HD-LC group compared with LD (HR = 0.479, p < 0.001) and HD-HC (HR = 0.542, p < 0.01); no difference was found between LD and HD-HC. In conclusion, combination of high D-dimer and low static compliance identifies a clinical phenotype with high mortality in COVID-19-ARDS.