Ventilation management and outcomes in out-of-hospital cardiac arrest: a protocol for a preplanned secondary analysis of the TTM2 trial.

INTRODUCTION: Mechanical ventilation is a fundamental component in the management of patients post cardiac arrest. However, the ventilator settings and the gas-exchange targets used after cardiac arrest may not be optimal to minimise post-anoxic secondary brain injury. Therefore, questions remain regarding the best ventilator management in such patients. METHODS AND ANALYSIS: This is a preplanned analysis of the international randomised controlled trial, targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (OHCA)-target temperature management 2 (TTM2). The primary objective is to describe ventilatory settings and gas exchange in patients who required invasive mechanical ventilation and included in the TTM2 trial. Secondary objectives include evaluating the association of ventilator settings and gas-exchange values with 6 months mortality and neurological outcome. Adult patients after an OHCA who were included in the TTM2 trial and who received invasive mechanical ventilation will be eligible for this analysis. Data collected in the TTM2 trial that will be analysed include patients' prehospital characteristics, clinical examination, ventilator settings and arterial blood gases recorded at hospital and intensive care unit (ICU) admission and daily during ICU stay. ETHICS AND DISSEMINATION: The TTM2 study has been approved by the regional ethics committee at Lund University and by all relevant ethics boards in participating countries. No further ethical committee approval is required for this secondary analysis. Data will be disseminated to the scientific community by abstracts and by original articles submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02908308.

Sex- and Gender-specific Risk Factors of Post-COVID-19 Syndrome: A Population-based Cohort Study in Switzerland

BackgroundWomen are overrepresented amongst individuals suffering from post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown. Methods and FindingsBy using Bayesian models comprising >200 co-variates, we assessed the impact of social context in addition to biological data on PASC in a multi-centre prospective cohort study of 2927 (46% women) individuals in Switzerland. Women more often reported at least one persistent symptom than men (43.5% vs 32.0% of men, p<0.001) six (IQR 5-9) months after SARS-CoV-2 infection. Adjusted models showed that women with personality traits stereotypically attributed to women were most often affected by PASC (OR 2.50[1.25-4.98], p<0.001), in particular when they were living alone (OR 1.84[1.25-2.74]), had an increased stress level (OR 1.06[1.03-1.09]), had undergone higher education (OR 1.30[1.08-1.54]), preferred pre-pandemic physical greeting over verbal greeting (OR 1.71[1.44-2.03]), and had experienced an increased number of symptoms during index infection (OR 1.27[1.22-1.33]). ConclusionBesides gender- and sex-sensitive biological parameters, sociocultural variables play an important role in producing sex differences in PASC. Our results indicate that predictor variables of PASC can be easily identified without extensive diagnostic testing and are targets of interventions aiming at stress coping and social support.

Bacterial pulmonary superinfections are associated with unfavourable outcomes in critically ill COVID-19 patients

Objectives While superinfections are associated with unfavourable disease course, their impact on clinical outcomes in critically ill COVID-19 patients remains largely unknown. We aimed to investigate the burden of superinfections in COVID-19 patients. Methods In this prospective single centre cohort study in an intensive care setting patients aged [≥] 18 years with COVID-19 acute respiratory distress syndrome were assessed for concomitant microbial infections by longitudinal analysis of tracheobronchial secretions, bronchoalveolar lavages and blood. Our primary outcome was ventilator-free survival on day 28 in patients with and without clinically relevant superinfection. Further outcomes included the association of superinfection with ICU length of stay, incidence of bacteremia, viral reactivations, and fungal colonization. Results In 45 critically ill COVID-19 patients, we identified 19 patients with superinfections (42.2%) by longitudinal analysis of 433 TBS, 35 BAL and 455 blood samples, respectively. On average, superinfections were detected on day 10 after ICU admission. The most frequently isolated clinically relevant bacteria were Enterobacteriaceae, Streptococcus pneumoniae, and Pseudomonas aeruginosa. Ventilator-free survival was substantially lower in patients with superinfection (subhazard ratio 0.37, 95%-CI 0.15-0.90, p=0.028). Patients with pulmonary superinfections more often had bacteraemia, virus reactivations, yeast colonization, and needed ICU treatment for a significantly longer time. Conclusions The detection of superinfections was frequent and associated with reduced ventilator-free survival. Despite empirical antibiotic therapy, superinfections lead to an extended ICU stay in COVID 19 patients. Longitudinal microbiological sampling in COVID-19 patients could allow targeted antimicrobial therapy, and therefore minimize the use of broad-spectrum and reserve antibiotics.