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).

ObjectiveThe aim of the study is to evaluate the clinical and economic impact of introducing a rocuronium–neostigmine–sugammadex strategy into a cisatracurium–neostigmine regimen for neuromuscular block (NMB) management.MethodsWe conducted a retrospective analysis of clinical outcomes and cost-effectiveness in five operating rooms at University Hospital of Padova. A clinical outcome evaluation after sugammadex administration as first-choice reversal drug in selected patients (rocuronium–sugammadex) and as rescue therapy after neostigmine reversal (rocuronium–neostigmine–sugammadex) compared to control was performed. A cost-analysis of NMB management accompanying the introduction of a rocuronium–neostigmine–sugammadex strategy into a cisatracurium–neostigmine regimen was carried out. To such purpose, two periods were compared: 2011–2012, without sugammadex available; 2013–2014, with sugammadex available. A subsequent analysis was performed to evaluate if sugammadex replacing neostigmine as first choice reversal drug is cost-effective.ResultsThe introduction of a rocuronium–neostigmine–sugammadex strategy into a cisatracurium–neostigmine regimen reduced the average cost of NMB management by 36%, from €20.8/case to €13.3/case. Patients receiving sugammadex as a first-choice reversal drug (3%) exhibited significantly better train-of-four ratios at extubation (P<0.001) and were discharged to the surgical ward (P<0.001) more rapidly than controls. The cost-saving of sugammadex as first-choice reversal drug has been estimated to be €2.9/case. Patients receiving sugammadex as rescue therapy after neostigmine reversal (3.2%) showed no difference in time to discharge to the surgical ward (P=0.44) compared to controls. No unplanned intensive care unit (ICU) admissions with rocuronium–neostigmine–sugammadex strategy were observed. The potential economic benefit in avoiding postoperative residual curarization (PORC)-related ICU admission in the 2013–2014 period was estimated at an average value of €13,548 (€9,316–€23,845).ConclusionSugammadex eliminated PORC and associated morbidities. In our center, sugammadex reduced the costs of NMB management and promoted rapid turnover of patients in operating rooms, with total cost-effectiveness that counteracts the disadvantages of its high cost.

Background The indications and timing for tracheostomy in patients with SARS CoV2-related are controversial. Purpose In a recent issue published in the European Archives of Otorhinolaryngology, Mattioli et al. published a short communication about tracheostomy timing in patients with COVID-19 (Coronavirus Disease 2019); they reported that the tracheostomy could allow early Intensive Care Units discharge and, in the context of prolonged Invasive Mechanical Ventilation, should be suggested within 7 and 14 days to avoid potential tracheal damages. In this Letter to the Editor we would like to present our experience with tracheostomy in a Hub Covid Hospital. Methods 8 patients underwent open tracheostomy in case of intubation prolonged over 14 days, bronchopulmonary overlap infections, and patients undergoing weaning. They were followed up and the number and timing of death were recorded. Results Two patients died after tracheostomy; the median time between tracheostomy and death was 3 days. A negative prognostic trend was observed for a shorter duration of intubation. Conclusion In our experience, tracheostomy does not seem to influence the clinical course and prognosis of the disease, in the face of possible risks of contagion for healthcare workers. The indication for tracheostomy in COVID-19 patients should be carefully evaluated and reserved for selected patients. Although it is not possible to define an optimal timing, it is our opinion that tracheostomy in a stable or clinically improved COVID-19 patient should not be proposed before the 20th day after orotracheal intubation.

BackgroundThe aims of this prospective study were to analyze the predictors of postoperative sleep disturbance after esophagectomy for cancer and to identify patients at risk for postoperative hypnotic administration.MethodsSixty two consecutive patients who underwent cancer-related esophagectomy were enrolled in this study from May 2011 to February 2012. Data about perioperative management, postoperative complications, ICU stay, and vasopressor, hypnotic, and painkiller administration were retrieved. The EORTC QLQ-C30 was used and global quality of life (QL2 item) and sleep disturbance (SL item) were the primary endpoints. Univariate and multivariate analyses were performed.ResultsPostoperative request of hypnotics independently predicted bad quality of life outcome. Sleep disturbance after esophagectomy was independently predicted by the duration of dopamine infusion in the ICU and the daily request of benzodiazepines. Even in this case, only sleep disturbance at diagnosis revealed to be an independent predictor of hypnotic administration need. ROC curve analysis showed that sleep disturbance at diagnosis was a good predictor of benzodiazepine request (AUC = 73%, P = 0.02).ConclusionsThe use of vasopressors in the ICU affects sleep in the following postoperative period and the use of hypnotics is neither completely successful nor lacking in possible consequences. Sleep disturbance at diagnosis can successfully predict patients who can develop sleep disturbance during the postoperative period.

Our results confirm the reliability of SPECT in the diagnosis of BD. A problem arises about its effectiveness in brain-dead children, but this seems to be a matter of definition of BD and cerebral viability, rather than a limit of SPECT.