Effects of hyperoxemia in patients with sepsis - A post-hoc analysis of a multicentre randomized clinical trial.

BACKGROUND: Administration of supplemental oxygen is a life-saving treatment in critically ill patients. Still, optimal dosing remains unclear during sepsis. The aim of this post-hoc analysis was to assess the association between hyperoxemia and 90-day mortality in a large cohort of septic patients. METHODS: This is a post-hoc analysis of the Albumin Italian Outcome Sepsis (ALBIOS) randomized controlled trial (RCT). Patients with sepsis who survived the first 48 h since randomization were included and stratified into two groups according to their average PaO2 levels during the first 48 h (PaO2 0-48 h). The cut-off value was established at 100 mmHg (average PaO2 0-48 h >100 mmHg: hyperoxemia group; PaO2 0-48h≤100: normoxemia group). The primary outcome was 90-day mortality. RESULTS: 1632 patients were included in this analysis (661 patients in the hyperoxemia group, 971 patients in the normoxemia group). Concerning the primary outcome, 344 (35.4%) patients in the hyperoxemia group vs. 236 (35.7%) in the normoxemia group had died within 90 days from randomization (p = 0.909). No association was found after adjusting for confounders (HR 0.87; CI [95%] 0.736-1.028, p = 0.102) or after excluding patients with hypoxemia at enrollment, patients with lung infection or including post-surgical patients only. Conversely, we found an association between lower risk of 90-day mortality and hyperoxemia in the subgroup including patients who had the lung as primary site of infection (HR 0.72; CI [95%] 0.565-0.918). Mortality at 28 days, ICU mortality, incidence of acute kidney injury, use of renal replacement therapy, days to suspension of vasopressor or inotropic agents, and resolution of primary and secondary infections did not differ significantly. Duration of mechanical ventilation and length of stay in ICU were significantly longer in patients with hyperoxemia. CONCLUSIONS: In a post-hoc analysis of a RCT enrolling septic patients, hyperoxemia as average PaO2>100 mmHg during the first 48 h was not associated with patients' survival.

Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review.

BACKGROUND: Tocilizumab is an IL-6 receptor-blocking agent proposed for the treatment of severe COVID-19. The aim of this systematic review was to describe the rationale for the use of tocilizumab for the treatment of COVID-19 and to summarize the available evidence regarding its efficacy and safety. METHODS: MEDLINE, PubMed, EMBASE, pre-print repositories (bioRxiv and medRxiv) and two trial Registries were searched for studies on the use of tocilizumab in COVID-19 or SARS-CoV-2 infection, viral pneumonia, and/or sepsis until 20th June 2020. RESULTS: We identified 3 indirect pre-clinical studies and 28 clinical studies including 5776 patients with COVID-19 (13 with a comparison group, 15 single-arm). To date, no randomized trials have been published. We retrieved no studies at low risk of bias. Forty-five ongoing studies were retrieved from trial registries. CONCLUSIONS: There is insufficient evidence regarding the clinical efficacy and safety of tocilizumab in patients with COVID-19. Its use should be considered experimental, requiring ethical approval and clinical trial oversight.

Sufentanil Sublingual Tablet System: from rationale of use to clinical practice.

The control of post-operative pain in Italy and other western countries is still suboptimal. In recent years, the Sufentanil Sublingual Tablet System (SSTS; Zalviso; AcelRx Pharmaceuticals, Redwood City, CA, USA), which is designed for patient-controlled analgesia (PCA), has entered clinical practice. SSTS enables patients to manage moderate-to-severe acute pain during the first 72 postoperative hours directly in the hospital setting. However, the role of SSTS within the current framework of options for the management of post-operative pain needs to be better established. This paper presents the position on the use of SSTS of a multidisciplinary group of Italian Experts and provides protocols for the use of this device.

The role of antithrombin III in critical patients in obstetrics.

A preliminary study was conducted to detect significant differences between the inflammatory cytokines network recorded in mild and severe preeclampsia compared with normal pregnancy. 36 patients were divided in two groups: (NP) normal pregnancy and (SPH) Severe Preeclampsia and HELLP syndrome. Inflammatory cytokines (IL 6, TNF, IL 10), Antithrombin III (AT III), Protein C (PC) and Tissue Factor Pathway Inhibitor (TFPI) plasma level and Organ Disfunction modified Score (ODS) were recorded. Results shows a difference (P<0,05 ) for AT III and other markers levels in the two groups and, inside of the SPH group, between Severe preeclampsia patients and HELLP syndrome patients. A correlation was found between coagulation natural inhibitors, specially antithrombin III, and the clinical scores. Performing a Caesarean section did not change these results. Based on results of the study we have designed a monitoring and a treatment protocol in our obstetric and general ICU. A multicentric study is now ongoing to validate the preliminary data on the substitutive treatment with AT III.