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Background: This study aimed to assess a potential organ protective effect of volatile sedation in a scenario of severe inflammation with an early cytokine storm (in particular IL-6 elevation) in patients suffering from COVID-19-related lung injury with invasive mechanical ventilation and sedation. Methods: This is a small-scale pilot multicenter randomized controlled trial from four tertiary hospitals in Switzerland, conducted between April 2020 and May 2021. 60 patients requiring mechanical ventilation due to severe COVID-19-related lung injury were included and randomized to 48-hour sedation with sevoflurane vs. continuous intravenous sedation (= control) within 24 h after intubation. The primary composite outcome was determined as mortality or persistent organ dysfunction (POD), defined as the need for mechanical ventilation, vasopressors, or renal replacement therapy at day 28. Secondary outcomes were the length of ICU and hospital stay, adverse events, routine laboratory parameters (creatinine, urea), and plasma inflammatory mediators. Results: 28 patients were randomized to sevoflurane, 32 to the control arm. The intention-to-treat analysis revealed no difference in the primary endpoint with 11 (39%) sevoflurane and 13 (41%) control patients (p = 0.916) reaching the primary outcome. Five patients died within 28 days in each group (16% vs. 18%, p = 0.817). Of the 28-day survivors, 6 (26%) and 8 (30%) presented with POD (p = 0.781). There was a significant difference regarding the need for vasopressors (1 (4%) patient in the sevoflurane arm, 7 (26%) in the control one (p = 0.028)). Length of ICU stay, hospital stay, and registered adverse events within 28 days were comparable, except for acute kidney injury (AKI), with 11 (39%) sevoflurane vs. 2 (6%) control patients (p = 0.001). The blood levels of IL-6 in the first few days after the onset of the lung injury were less distinctly elevated than expected. Conclusions: No evident benefits were observed with short sevoflurane sedation on mortality and POD. Unexpectedly low blood levels of IL-6 might indicate a moderate injury with therefore limited improvement options of sevoflurane. Acute renal issues suggest caution in using sevoflurane for sedation in COVID-19. Trial registration: The trial was registered on ClinicalTrials.gov (NCT04355962) on 2020/04/21. [ABSTRACT FROM AUTHOR]

Background: Renal tubular acidosis (RTA) is an extremely rare cause of metabolic acidosis (10 in 100,000). RTA has been linked neither to pregnancy nor to severe coronavirus disease 2019 (COVID-19). The purpose of this study was to analyze the prevalence and clinical course of normal anion gap metabolic acidosis in critically ill pregnant COVID-19 patients and to compare them to an age-matched nonpregnant female patient cohort. Methods: Secondary analysis was conducted on a prospective observational cohort of critically ill patients suffering from COVID-19 consecutively admitted to a tertiary intensive care unit (ICU) between February 2020 and April 2021. Results: A total of 321 COVID-19 patients required admission to the ICU; 95 (30%) were female, and 18 (19%) were of childbearing age. Seven of eight (88%) pregnant women (all in the last trimester) required advanced respiratory support due to COVID-19. The estimated glomerular filtration rate was 135 (123–158) mL/min/m2 body surface area, and six pregnant women (86%) were diagnosed with a normal, respiratory compensated, anion gap metabolic acidosis (pHmin 7.3 (7.18–7.31), HCO3−min 14.8 (12.8–18.6) mmol/L, and paCO2 3.4 (3.3–4.5) kPa). Three (43%) acidotic pregnant women fulfilled diagnostic criteria for RTA. All women recovered spontaneously within less 7 days. Conclusions: Metabolic acidosis seems to be very common (85%) in pregnant critically ill COVID-19 patients, and the prevalence of RTA might be higher than normal. It remains to be demonstrated if this observation is an indirect epiphenomenon or due to a direct viral effect on the tubular epithelium. [ABSTRACT FROM AUTHOR]

First, despite older age and elevated risk profile, vaccinated ICU patients had less severe lung and systemic organ failure, need for mechanical ventilation and shorter ICU length-of-stay, yet still similar ICU mortality. ICU mortality estimates were modeled using a Cox proportional hazards model, with an underlying time scale of ICU admission until date of death or date of discharge which was defined as censoring event, with ICU mortality entered as event and ICU survival entered as censored event. [Extracted from the article]

Objectives: Critically ill coronavirus disease 2019 (COVID‐19) patients are characterised by a severely dysregulated cytokine profile and elevated neutrophil counts, impacting disease severity. However, it remains unclear how neutrophils contribute to pathophysiology during COVID‐19. Here, we assessed the impact of the dysregulated cytokine profile on the regulated cell death (RCD) programme of neutrophils. Methods: Regulated cell death phenotype of neutrophils isolated from critically ill COVID‐19 patients or healthy donors and stimulated with COVID‐19 or healthy plasma ex vivo was assessed by flow cytometry, time‐lapse microscopy and cytokine multiplex analysis. Immunohistochemistry of COVID‐19 patients and control biopsies were performed to assess the in situ neutrophil RCD phenotype. Plasma cytokine levels of COVID‐19 patients and healthy donors were measured by multiplex analysis. Clinical parameters were correlated to cytokine levels of COVID‐19 patients. Results: COVID‐19 plasma induced a necroptosis‐sensitive neutrophil phenotype, characterised by cell lysis, elevated release of damage‐associated molecular patterns (DAMPs), increased receptor‐interacting serine/threonine‐protein kinase (RIPK) 1 levels and mixed lineage kinase domain‐like pseudokinase (MLKL) involvement. The occurrence of neutrophil necroptosis MLKL axis was further confirmed in COVID‐19 thrombus and lung biopsies. Necroptosis was induced by the tumor necrosis factor receptor 1 (TNFRI)/TNF‐α axis. Moreover, reduction of soluble Fas ligand (sFasL) levels in COVID‐19 patients and hence decreased signalling to Fas directly increased RIPK1 levels, exacerbated TNF‐driven necroptosis and correlated with disease severity, which was abolished in patients treated with glucocorticoids. Conclusion: Our results suggest a novel role for sFasL signalling in the TNF‐α‐induced RCD programme in neutrophils during COVID‐19 and a potential therapeutic target to curb inflammation and thus influence disease severity and outcome. [ABSTRACT FROM AUTHOR]

Purpose: Estimation of cardiac output (CO) and evaluation of change in CO as a result of therapeutic interventions are essential in critical care medicine. Whether noninvasive tools estimating CO, such as continuous cardiac output (esCCOTM) methods, are sufficiently accurate and precise to guide therapy needs further evaluation. We compared esCCOTM with an established method, namely, transpulmonary thermodilution (TPTD). Patients and Methods. In a single center mixed ICU, esCCOTM was compared with the TPTD method in 38 patients. The primary endpoint was accuracy and precision. The cardiac output was assessed by two investigators at baseline and after eight hours.Results: In 38 critically ill patients, the two methods correlated significantly (r = 0.742). The Bland-Altman analysis showed a bias of 1.6 l/min with limits of agreement of -1.76 l/min and +4.98 l/min. The percentage error for COesCCO was 47%. The correlation of trends in cardiac output after eight hours was significant (r = 0.442), with a concordance of 74%. The performance of COesCCO could not be linked to the patient's condition.Conclusion: The accuracy and precision of the esCCOTM method were not clinically acceptable for our critical patients. EsCCOTM also failed to reliably detect changes in cardiac output. [ABSTRACT FROM AUTHOR]

• The role of circulating Angiopoietin-2 has never been assessed in burns. • The Angiopoietin-2/-1 ratio increases in the first 48 h after burn insult. • An increased Angiopoietin-2/-1 ratio is associated with higher mortality. Angiopoietin-2 (Angpt-2) is involved in the pathogenesis of the capillary leak syndrome in sepsis and has been shown to be associated with worse outcomes in diverse critical illnesses. It is however unclear whether Angpt-2 plays a similar role in severely burned patients during the early phase characterized by massive capillary leakage. Our aim was to analyze the Angiopoietin-2/Angiopoietin-1 ratio (Angpt-2/Angpt-1 ratio) over the first two days in critically ill burn patients and examine its association with survival and further clinical parameters. Adult burn patients with a total burn surface area (TBSA) ≥ 20% treated in the burn intensive care unit (ICU) of the University Hospital of Zurich, Switzerland, were included. Serum samples were collected prospectively and serum Angpt-1 and Angpt-2 were measured by enzyme-linked immunosorbent assay (ELISA) over the first two days after burn insult and stratified according to survival status, TBSA and the abbreviated burn severity index (ABSI). Due to hemodilution in the initial resuscitation phase, the Angpt-2/Angpt-1 ratio was normalized to albumin. Fifty-six patients were included with a median age of 51.5 years. Overall mortality was 14.3% (8/56 patients). The total amount of infused crystalloids was 12́902 ml (IQR 9́362–16́770 ml) at 24 h and 18́461 ml (IQR 13́024–23́766 ml) at 48 h. The amount of substituted albumin was 20 g (IQR 10–50 g) at 24 h and 50 g (IQR 20–60 g) at 48 h. The albumin-corrected Angpt-2/Angpt-1 ratios increased over the first 48 h after the burn insult (d0: 0.5 pg*l/ml*g [IQR 0.24 – 0.80 pg*l/ml*g]; d1: 0.83 pg*l/ml*g [IQR 0.29 – 1.98 pg*l/ml*g]; d2: 1.76 pg*l/ml*g [IQR 0.70 – 3.23 pg*l/ml*g]; p < 0.001) and were significantly higher in eventual ICU non-survivors (p = 0.005), in patients with a higher TBSA (p = 0.001) and in patients with a higher ABSI (p = 0.001). In analogy to the pathological host response in sepsis, the Angpt-2/Angpt-1 ratio steadily increases in the first two days in critically ill burn patients, suggesting a putative involvement in the pathogenesis of capillary leakage in burns. A higher Angpt-2/Angpt-1 ratio is associated with mortality, total burn surface area and burn scores. [ABSTRACT FROM AUTHOR]