In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825 .).

BACKGROUNDVolatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). METHODSWe conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. RESULTSA total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. CONCLUSIONSAmong patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia.

Introduction In addition to the directly attributed mortality, COVID-19 is also likely to increase mortality indirectly. In this systematic review, we investigate the direct and indirect effects of COVID-19 on out-of-hospital cardiac arrests. Methods We searched PubMed, BioMedCentral, Embase and the Cochrane Central Register of Controlled Trials for studies comparing out-of-hospital cardiac arrests occurring during the pandemic and a non-pandemic period. Risk of bias was assessed with the ROBINS-I tool. The primary endpoint was return of spontaneous circulation. Secondary endpoints were bystander-initiated cardiopulmonary resuscitation, survival to hospital discharge, and survival with favourable neurological outcome. Results We identified six studies. In two studies, rates of return of spontaneous circulation and survival to hospital discharge decreased significantly during the pandemic. Especially in Europe, bystander-witnessed cases, bystander-initiated cardiopulmonary resuscitation and resuscitation attempted by emergency medical services were reduced during the pandemic. Also, ambulance response times were significantly delayed across all studies and patients presenting with non-shockable rhythms increased in two studies. In 2020, 3.9-5.9% of tested patients were SARS-CoV-2 positive and 4.8-26% had suggestive symptoms (fever and cough or dyspnoea). Conclusions Out-of-hospital cardiac arrests had worse short-term outcomes during the pandemic than a non-pandemic period suggesting direct effects of COVID-19 infection and indirect effects from lockdown and disruption of healthcare systems. Patients at high risk of deterioration should be identified outside the hospital to promptly initiate treatment and reduce fatalities. Study registration PROSPERO CRD42020195794.

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Received the first dose of study drug 4612 (97.0) (96.7) Received the second dose of the study drug 4586 (96.4) (96.5) Received both doses of the study drug 4581 (96.3) (96.3) no. = number; % = percentage

Conclusions: Corticosteroids may be considered in severe critically ill patients with COVID-19 but must be discouraged in patients not requiring oxygen therapy. Urgently, further trials are warranted before implementing this treatment worldwide.

Severe COVID-19 cases have a detrimental hyper-inflammatory host response and different cytokine-blocking biologic agents were explored to improve outcomes. Anakinra blocks the activity of both IL-1α and IL-1β and is approved for different autoinflammatory disorders, but it is used off-label for conditions characterized by an excess of cytokine production. Several studies on anakinra in COVID-19 patients reported positive effects. We performed a meta-analysis of all published evidence on the use of anakinra in COVID19 to investigate its effect on survival and need for mechanical ventilation. Methods: We searched for any study performed on adult patients with acute hypoxemic failure related to 2019-nCoV infection, receiving anakinra versus any comparator. Primary endpoint was mortality at the longest available follow-up. Adverse effects, need for mechanical ventilation and discharge at home with no limitations were also analysed. Results: Four observational studies involving 184 patients were included. Overall mortality of patients treated with anakinra was significantly lower than mortality in the control group (95% CI 0.14-0.48, p<0.0001). Moreover, patients treated with anakinra had a significantly lower risk of need for mechanical ventilation than controls (95% CI 0.250.74, p=0.002). No difference in adverse events and discharge at home with no limitations was observed. The Trial Sequential Analysis z-cumulative line reached the monitoring boundary for benefit and the required sample size. Conclusions: Administration of anakinra in COVID-19 patients was safe and might be associated with reductions in both mortality and need for mechanical ventilation. Randomized clinical trials are warranted to confirm these findings.

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