Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

BackgroundExtracorporeal membrane oxygenation (ECMO) supplies systemic blood perfusion and gas exchange in patients with cardiopulmonary failure. The current literature lacks of papers reporting the possible risks of microembolism among the complications of this treatment.In this study we present our preliminary experience on brain blood flow velocity and emboli detection through the transcranial Doppler monitoring during ECMO.MethodsSix patients suffering of heart failure, four after cardiac surgery and two after cardiopulmonary resuscitation were treated with ECMO and submitted to transcranial doppler monitoring to accomplish the neurophysiological evaluation for coma.Four patients had a full extracorporeal flow supply while in the remaining two patients the support was maintained 50% in respect to normal demand.All patients had a bilateral transcranial brain blood flow monitoring for 15 minutes during the first clinical evaluation.ResultsMicroembolic signals were detected only in patients with the full extracorporeal blood flow supply due to air embolism.ConclusionsWe established that the microembolic load depends on gas embolism from the central venous lines and on the level of blood flow assistance.The gas microemboli that enter in the blood circulation and in the extracorporeal circuits are not removed by the membrane oxygenator filter.Maximum care is required in drugs and fluid infusion of this kind of patients as a possible source of microemboli. This harmful phenomenon may be overcome adding an air filter device to the intravenous catheters.

The efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the intensive care unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: (1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and (2) assessing whether the length of NIV application affects patient survival. This observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February–April 2020), who underwent endotracheal intubation after NIV failure. Among the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60–76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06–4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04–1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. In-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality.

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Background A Covid-19 outbreak developed in Lombardy, Veneto and Emilia-Romagna (Italy) at the end of February 2020. Fear of an imminent saturation of available ICU beds generated the notion that rationing of intensive care resources could have been necessary. Results In order to evaluate the impact of Covid-19 on the ICU capacity to manage critically ill patients, we performed a retrospective analysis of the first 2 weeks of the outbreak (February 24–March 8). Data were collected from regional registries and from a case report form sent to participating sites. ICU beds increased from 1545 to 1989 (28.7%), and patients receiving respiratory support outside the ICU increased from 4 (0.6%) to 260 (37.0%). Patients receiving respiratory support outside the ICU were significantly older [65 vs. 77 years], had more cerebrovascular (5.8 vs. 13.1%) and renal (5.3 vs. 10.0%) comorbidities and less obesity (31.4 vs. 15.5%) than patients admitted to the ICU. PaO2/FiO2 ratio, respiratory rate and arterial pH were higher [165 vs. 244; 20 vs. 24 breath/min; 7.40 vs. 7.46] and PaCO2 and base excess were lower [34 vs. 42 mmHg; 0.60 vs. 1.30] in patients receiving respiratory support outside the ICU than in patients admitted to the ICU, respectively. Conclusions Increase in ICU beds and use of out-of-ICU respiratory support allowed effective management of the first 14 days of the Covid-19 outbreak, avoiding resource rationing.