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Background: The continuous exposure of blood to a non-biological surface during extracorporeal membrane oxygenation (ECMO) may lead to progressive thrombus formation in the oxygenator, hemolysis and consequently impaired gas exchange. In most centers oxygenator performance is monitored only on a once daily basis. Carboxyhemoglobin (COHb) is generated upon red cell lysis and is routinely measured with any co-oximetry performed to surveille gas exchange and acid–base homeostasis every couple of hours. This retrospective cohort study aims to evaluate COHb in the arterial blood gas as a novel marker of oxygenator dysfunction and its predictive value for imminent oxygenator change. Results: Out of the 484 screened patients on ECMO 89, cumulatively requiring 116 oxygenator changes within 1833 patient days, including 19,692 arterial COHb measurements were analyzed. Higher COHb levels were associated with lower post-oxygenator pO2 (estimate for log(COHb): − 2.176 [95% CI − 2.927, − 1.427], p < 0.0001) and with a shorter time to oxygenator change (estimate for log(COHb): − 67.895 [95% CI − 74.209, − 61.542] hours, p < 0.0001). COHb was predictive of oxygenator change within 6 h (estimate for log(COHb): 5.027 [95% CI 1.670, 15.126], p = 0.004). Conclusion: COHb correlates with oxygenator performance and can be predictive of imminent oxygenator change. Therefore, longitudinal measurements of COHb in clinical routine might be a cheap and more granular candidate for ECMO surveillance that should be further analyzed in a controlled prospective trial design. [ABSTRACT FROM AUTHOR]

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: Clogging is characterized by a progressive impairment of transmembrane patency in renal replacement devices and occurs due to obstruction of pores by unknown molecules. If citrate-based anti-coagulation is used, clogging can manifest as a metabolic alkalosis accompanied by hypernatremia and hypercalcemia, primarily a consequence of Na3Citrate infusion. An increased incidence of clogging has been observed during the COVID-19 pandemic. However, precise factors contributing to the formation remain uncertain. This investigation aimed to analyze its incidence and assessed time-varying trajectories of associated factors in critically ill patients on continuous renal replacement therapy (CRRT). Methods: In this retrospective, single-center data analysis, we evaluated COVID-19 patients undergoing CRRT and admitted to critical care between March 2020 and December 2021. We assessed the proportional incidence of clogging surrogates in the overall population and subgroups based on the specific CRRT devices employed at our institution, including multiFiltrate (Fresenius Medical Care) and Prismaflex System (Baxter). Moderate and severe clogging were defined as Na > 145 or ≥ 150 mmol/l and HCO3− > 28.0 or ≥ 30 mmol/l, respectively, with a total albumin-corrected calcium > 2.54 mmol/l. A mixed effect model was introduced to investigate factors associated with development of clogging. Results: Fifty-three patients with 240 CRRT runs were analyzed. Moderate and severe clogging occurred in 15% (8/53) and 19% (10/53) of patients, respectively. Twenty-seven percent (37/136) of CRRTs conducted with a multiFiltrate device met the criteria for clogging, whereas no clogging could be observed in patients dialyzed with the Prismaflex System. Occurrence of clogging was associated with elevated triglyceride plasma levels at filter start (p = 0.013), amount of enteral nutrition (p = 0.002) and an increasing white blood cell count over time (p = 0.002). Conclusions: Clogging seems to be a frequently observed phenomenon in critically ill COVID-19 patients. The presence of hypertriglyceridemia, combined with systemic inflammation, may facilitate the development of an impermeable secondary membrane within filters, thereby contributing to compromised membrane patency. [ABSTRACT FROM AUTHOR]

Background: Optimal anticoagulation strategies for COVID-19 patients with the acute respiratory distress syndrome (ARDS) on venovenous extracorporeal membrane oxygenation (VV ECMO) remain uncertain. A higher incidence of intracerebral hemorrhage (ICH) during VV ECMO support compared to non-COVID-19 viral ARDS patients has been reported, with increased bleeding rates in COVID-19 attributed to both intensified anticoagulation and a disease-specific endotheliopathy. We hypothesized that lower intensity of anticoagulation during VV ECMO would be associated with a lower risk of ICH. In a retrospective, multicenter study from three academic tertiary intensive care units, we included patients with confirmed COVID-19 ARDS requiring VV ECMO support from March 2020 to January 2022. Patients were grouped by anticoagulation exposure into higher intensity, targeting anti-factor Xa activity (anti-Xa) of 0.3–0.4 U/mL, versus lower intensity, targeting anti-Xa 0.15–0.3 U/mL, cohorts. Mean daily doses of unfractionated heparin (UFH) per kg bodyweight and effectively measured daily anti-factor Xa activities were compared between the groups over the first 7 days on ECMO support. The primary outcome was the rate of ICH during VV ECMO support. Results: 141 critically ill COVID-19 patients were included in the study. Patients with lower anticoagulation targets had consistently lower anti-Xa activity values over the first 7 ECMO days (p < 0.001). ICH incidence was lower in patients in the lower anti-Xa group: 4 (8%) vs 32 (34%) events. Accounting for death as a competing event, the adjusted subhazard ratio for the occurrence of ICH was 0.295 (97.5% CI 0.1–0.9, p = 0.044) for the lower anti-Xa compared to the higher anti-Xa group. 90-day ICU survival was higher in patients in the lower anti-Xa group, and ICH was the strongest risk factor associated with mortality (odds ratio [OR] 6.8 [CI 2.1–22.1], p = 0.001). Conclusions: For COVID-19 patients on VV ECMO support anticoagulated with heparin, a lower anticoagulation target was associated with a significant reduction in ICH incidence and increased survival. [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]

Patient safety is a priority in healthcare, yet it is unclear how sources of errors should best be analyzed. Eye tracking is a tool used to monitor gaze patterns in medicine. The aim of this study was to analyze the distribution of visual attention among critical care nurses performing non-simulated, routine patient care on invasively ventilated patients in an ICU. ICU nurses were tracked bedside in daily practice. Eight specific areas of interest were pre-defined (respirator, drug preparation, medication, patient data management system, patient, monitor, communication and equipment/perfusors). Main independent variable and primary outcome was dwell time, secondary outcomes were hit ratio, revisits, fixation count and average fixation time on areas of interest in a targeted tracking-time of 60 min. 28 ICU nurses were analyzed and the average tracking time was 65.5 min. Dwell time was significantly higher for the respirator (12.7% of total dwell time), patient data management system (23.7% of total dwell time) and patient (33.4% of total dwell time) compared to the other areas of interest. A similar distribution was observed for fixation count (respirator 13.3%, patient data management system 25.8% and patient 31.3%). Average fixation time and revisits of the respirator were markedly elevated. Apart from the respirator, average fixation time was highest for the patient data management system, communication and equipment/perfusors. Eye tracking is helpful to analyze the distribution of visual attention of critical care nurses. It demonstrates that the respirator, the patient data management system and the patient form cornerstones in the treatment of critically ill patients. This offers insights into complex work patterns in critical care and the possibility of improving work flows, avoiding human error and maximizing patient safety. [ABSTRACT FROM AUTHOR]

Group A Streptococcus (GAS) is a human pathogen causing a wide range of mild to severe and life-threatening diseases. The GAS M1 protein is a major virulence factor promoting GAS invasiveness and resistance to host innate immune clearance. M1 displays an irregular coiled-coil structure, including the B-repeats that bind fibrinogen. Previously, we found that B-repeat stabilisation generates an idealised version of M1 (M1*) characterised by decreased fibrinogen binding in vitro. To extend these findings based on a soluble truncated version of M1, we now studied the importance of the B-repeat coiled-coil irregularities in full length M1 and M1* expressed in live GAS and tested whether the modulation of M1-fibrinogen interactions would open up novel therapeutic approaches. We found that altering either the M1 structure on the GAS cell surface or removing its target host protein fibrinogen blunted GAS virulence. GAS expressing M1* showed an impaired ability to adhere to and to invade human endothelial cells, was more readily killed by whole blood or neutrophils and most importantly was less virulent in a murine necrotising fasciitis model. M1-mediated virulence of wild-type GAS was strictly dependent on the presence and concentration of fibrinogen complementing our finding that M1-fibrinogen interactions are crucial for GAS virulence. Consistently blocking M1-fibrinogen interactions by fragment D reduced GAS virulence in vitro and in vivo. This supports our conclusion that M1-fibrinogen interactions are crucial for GAS virulence and that interference may open up novel complementary treatment options for GAS infections caused by the leading invasive GAS strain M1. [ABSTRACT FROM AUTHOR]