Extracorporeal Co2 removal in hypercapnic patients at risk of noninvasive ventilation failure: a matched cohort study with historical control.

OBJECTIVES: To assess efficacy and safety of noninvasive ventilation-plus-extracorporeal Co2 removal in comparison to noninvasive ventilation-only to prevent endotracheal intubation patients with acute hypercapnic respiratory failure at risk of failing noninvasive ventilation. DESIGN: Matched cohort study with historical control. SETTING: Two academic Italian ICUs. PATIENTS: Patients treated with noninvasive ventilation for acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease (May 2011 to November 2013). INTERVENTIONS: Extracorporeal CO2 removal was added to noninvasive ventilation when noninvasive ventilation was at risk of failure (arterial pH ≤ 7.30 with arterial PCO2 > 20% of baseline, and respiratory rate ≥ 30 breaths/min or use of accessory muscles/paradoxical abdominal movements). The noninvasive ventilation-only group was created applying the genetic matching technique (GenMatch) on a dataset including patients enrolled in two previous studies. Exclusion criteria for both groups were mean arterial pressure less than 60 mm Hg, contraindications to anticoagulation, body weight greater than 120 kg, contraindication to continuation of active treatment, and failure to obtain consent. MEASUREMENTS AND MAIN RESULTS: Primary endpoint was the cumulative prevalence of endotracheal intubation. Twenty-five patients were included in the noninvasive ventilation-plus-extracorporeal CO2 removal group. The GenMatch identified 21 patients for the noninvasive ventilation-only group. Risk of being intubated was three times higher in patients treated with noninvasive ventilation-only than in patients treated with noninvasive ventilation-plus-extracorporeal CO2 removal (hazard ratio, 0.27; 95% CI, 0.07-0.98; p = 0.047). Intubation rate in noninvasive ventilation-plus-extracorporeal CO2 removal was 12% (95% CI, 2.5-31.2) and in noninvasive ventilation-only was 33% (95% CI, 14.6-57.0), but the difference was not statistically different (p = 0.1495). Thirteen patients (52%) experienced adverse events related to extracorporeal CO2 removal. Bleeding episodes were observed in three patients, and one patient experienced vein perforation. Malfunctioning of the system caused all other adverse events. CONCLUSIONS: These data provide the rationale for future randomized clinical trials that are required to validate extracorporeal CO2 removal in patients with hypercapnic respiratory failure and respiratory acidosis nonresponsive to noninvasive ventilation.

Outcomes and Impact of Pre-ECMO Clinical Course in Severe COVID-19-Related ARDS Treated with VV-ECMO: Data from an Italian Referral ECMO Center.

Background: The efficacy of veno-venous extracorporeal membrane oxygenation (VV-ECMO) as rescue therapy for refractory COVID-19-related ARDS (C-ARDS) is still debated. We describe the cohort of C-ARDS patients treated with VV-ECMO at our ECMO center, focusing on factors that may affect in-hospital mortality and describing the time course of lung mechanics to assess prognosis. Methods: We performed a prospective observational study in the intensive care unit at the "Città della Salute e della Scienza" University Hospital in Turin, Italy, between March 2020 and December 2021. Indications and management of ECMO followed the Extracorporeal Life Support Organization (ELSO) guidelines. Results: The 60-day in-hospital mortality was particularly high (85.4%). Non-survivor patients were more frequently treated with non-invasive ventilatory support and steroids before ECMO (95.1% vs. 57.1%, p = 0.018 and 73.2% vs. 28.6%, p = 0.033, respectively), while hypertension was the only pre-ECMO factor independently associated with in-hospital mortality (HR: 2.06, 95%CI: 1.06-4.00). High rates of bleeding (85.4%) and superinfections (91.7%) were recorded during ECMO, likely affecting the overall length of ECMO (18 days, IQR: 10-24) and the hospital stay (32 days, IQR: 24-47). Static lung compliance was lower in non-survivors (p = 0.031) and differed over time (p = 0.049), decreasing by 48% compared to initial values in non-survivors. Conclusions: Our data suggest the importance of considering NIS among the common ECMO eligibility criteria and changes in lung compliance during ECMO as a prognostic marker.

Effectiveness of mid-regional pro-adrenomedullin, compared to other biomarkers (including lymphocyte subpopulations and immunoglobulins), as a prognostic biomarker in COVID-19 critically ill patients: New evidence from a 15-month observational prospective study.

Background: Mid-regional pro-adrenomedullin (MR-proADM), an endothelium-related peptide, is a predictor of death and multi-organ failure in respiratory infections and sepsis and seems to be effective in identifying COVID-19 severe forms. The study aims to evaluate the effectiveness of MR-proADM in comparison to routine inflammatory biomarkers, lymphocyte subpopulations, and immunoglobulin (Ig) at an intensive care unit (ICU) admission and over time in predicting mortality in patients with severe COVID-19. Methods: All adult patients with COVID-19 pneumonia admitted between March 2020 and June 2021 in the ICUs of a university hospital in Italy were enrolled. MR-proADM, lymphocyte subpopulations, Ig, and routine laboratory tests were measured within 48 h and on days 3 and 7. The log-rank test was used to compare survival curves with MR-proADM cutoff value of >1.5 nmol/L. Predictive ability was compared using the area under the curve (AUC) and 95% confidence interval (CI) of different receiver-operating characteristic curves. Results: A total of 209 patients, with high clinical severity [SOFA 7, IQR 4-9; SAPS II 52, IQR 41-59; median viral pneumonia mortality score (MuLBSTA)-11, IQR 9-13] were enrolled. ICU and overall mortality were 55.5 and 60.8%, respectively. Procalcitonin, lactate dehydrogenase, D-dimer, the N-terminal prohormone of brain natriuretic peptide, myoglobin, troponin, neutrophil count, lymphocyte count, and natural killer lymphocyte count were significantly different between survivors and non-survivors, while lymphocyte subpopulations and Ig were not different in the two groups. MR-proADM was significantly higher in non-survivors (1.17 ± 0.73 vs. 2.31 ± 2.63, p < 0.0001). A value of >1.5 nmol/L was an independent risk factor for mortality at day 28 [odds ratio of 1.9 (95% CI: 1.220-3.060)] after adjusting for age, lactate at admission, SOFA, MuLBSTA, superinfections, cardiovascular disease, and respiratory disease. On days 3 and 7 of the ICU stay, the MR-proADM trend evaluated within 48 h of admission maintained a correlation with mortality (p < 0.0001). Compared to all other biomarkers considered, the MR-proADM value within 48 h had the best accuracy in predicting mortality at day 28 [AUC = 0.695 (95% CI: 0.624-0.759)]. Conclusion: MR-proADM seems to be the best biomarker for the stratification of mortality risk in critically ill patients with COVID-19. The Ig levels and lymphocyte subpopulations (except for natural killers) seem not to be correlated with mortality. Larger, multicentric studies are needed to confirm these findings.

ECMO Support and Operator Safety in the Context of COVID-19 Outbreak: A Regional Center Experience.

Since the beginning of the COVID-19 emergency, the referral Intensive Care Unit for the Extracorporeal Membrane Oxygenation (ECMO) support of Piedmont Region (Italy), in cooperation with infectious disease specialists, perfusionists and cardiac surgeons, developed a protocol to guarantee operator safety during invasive procedures, among which the ECMO positioning or inter-hospital transport. The use of powered air-purifying respirators, filtering facepiece particles (FFP) 2-3 masks, protective suits, disposable sterile surgical gowns, and two pairs of sterile gloves as a part of a protocol seemed effective and feasible for trained healthcare workers and allow all the complex activities connected with the positioning of the ECMO support to be completed effectively. The simulation training on donning and doffing procedures and the presence of a dedicated team member to verify the compliance with the safety procedure effectively reassured operators and likely reduced the risk of self-contamination. From 1 March to 31 December 2020, we used the procedure in 35 severe acute respiratory distress syndrome (ARDS) patients and one acute respiratory failure caused by neoplastic total tracheal obstruction, all positive to COVID-19, to be connected to veno-venous ECMO in peripheral hospitals and centralized for ECMO management. This preliminary experience seems to confirm that the use of ECMO during COVID-19 outbreaks is feasible and the risks associated with its positioning and management are sustainable for the health-care workers and safe for patients.

Effects of Steroids and Tocilizumab on the Immune Response Profile of Patients with COVID-19-Associated ARDS Requiring or Not Veno-Venous Extracorporeal Membrane Oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a life-saving rescue therapy in patients with Acute Respiratory Distress Syndrome (ARDS). ECMO has been associated with development of lymphocytopenia that is also common in COVID-19. Hyperinflammation may complicate SARS-CoV-2 pneumonia, prompting therapy with steroids and immunomodulatory drugs. We aimed to evaluate the association of therapies such as steroids and Tocilizumab with trajectories of the total leukocytes, lymphocyte subpopulation count, and inflammatory and fibrinolysis markers in COVID-19-related ARDS, requiring or not VV-ECMO support. The association of the trajectories of the leukocytes, lymphocyte subpopulation count, and inflammatory and fibrinolysis markers with treatment with steroids (Steroids), Tocilizumab (Tocilizumab), both drugs (Steroids + Tocilizumab), and absence of treatment (No Treatment) were analyzed using mixed effects regression models, where ECMO was considered as a potential effect modifier. One hundred and thirty-nine leukocyte and eighty-one lymphocyte subpopulation counts were obtained from thirty-one patients who required (VV-ECMO, N = 13) or not (no VV-ECMO, N = 18) extracorporeal support. In both groups, treatment with Steroids + Tocilizumab was independently associated with a significant reduction of 46% and 67% in total lymphocytes, 22% and 60% in CD3+, and 61% and 91% in CD19+ (B lymphocytes) compared to those obtained without treatment, respectively. In the no VV-ECMO group, Tocilizumab was associated with a 79% increase in total lymphocytes and with a reduction in procalcitonin compared to no treatment. CD45+, CD3+CD4+ (Th cell), CD3+CD8+, CD4+/CD8+, the NK cell subpopulation, neutrophils, monocytes, and basophils were significantly reduced by Steroids + Tocilizumab without an effect modification by VV-ECMO support. In critically ill COVID-19 patients with ARDS, concomitant therapies with steroids and Tocilizumab, beside mitigating the inflammation and fibrinolysis, could reduce the total leukocyte, lymphocyte, and subpopulation count. Moreover, the effect of Tocilizumab in increasing the total lymphocytes and reducing procalcitonin might be blunted by VV-ECMO.

The European accreditation of Istituto Tumori Giovanni Paolo II of Bari.

The National Cancer Institute of Bari (Istituto di Ricovero e Cura a Carattere Scientifico, IRCCS) has been involved since the conception of the project of the Italian Ministry for Health aimed to validate the applicability of the Organisation of European Cancer Institutes (OECI) accreditation and designation (A&D) model to the Network of Italian Cancer Centers, IRCCS, of Alleanza Contro il Cancro. The self-assessment phase of the Institute started in September 2013 and ended in June 2014. All documents and tools were transferred to the OECI A&D Board in June 2014 and a 2-day peer review visit was conducted in October 2014 by an international qualified audit team. The Institute received its final designation and certification in June 2015. The OECI A&D Board, in its final report, came to the conclusion that Istituto Tumori "Giovanni Paolo II" of Bari has a strong research component with some essential elements of comprehensive cancer care still under development; the lack of a system for using outcome data for the strategic management approach to decision-making and missing a regular internal audit system eventually helping further quality improvement were reported as examples of areas with opportunities for improvement. The OECI A&D process represented a great opportunity for the cancer center to benchmark the quality of its performance according to standard parameters in comparison with other international centers and to further develop a participatory group identity. The common goal of accreditation was real and participatory with long-lasting positive effects. We agree with the OECI comments about the next areas of work in which the Institute could produce future further efforts: the use of its powerful IT system as a means for outcome analysis and empowerment projects for its cancer patients.

Acute respiratory distress syndrome: new definition, current and future therapeutic options.

Since acute respiratory distress syndrome (ARDS) was first described in 1967 there has been large number of studies addressing its pathogenesis and therapies. Despite this intense research activity, there are very few effective therapies for ARDS other than the use of lung protection strategies. This lack of therapeutic modalities is not only related to the complex pathogenesis of this syndrome but also the insensitive and nonspecific diagnostic criteria to diagnose ARDS. This review article will summarize the key features of the new definition of ARDS, and provide a brief overview of innovative therapeutic options that are being assessed in the management of ARDS.