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Background: Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated. Methods: A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS). Results: Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations. Conclusion: Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.

Abstract Background Ventilation during cardiopulmonary resuscitation (CPR) has long been a part of the standard treatment during cardiac arrests. Ventilation is usually given either during continuous chest compressions (CCC) or during a short pause after every 30 chest compressions (30:2). There is limited knowledge of how ventilation is delivered if it effects the hemodynamics and if it plays a role in the occurrence of lung injuries. The aim of this study was to compare ventilation parameters, hemodynamics, blood gases and lung injuries during experimental CPR given with CCC and 30:2 in a porcine model. Methods Sixteen pigs weighing approximately 33 kg were randomized to either receive CPR with CCC or 30:2. Ventricular fibrillation was induced by passing an electrical current through the heart. CPR was started after 3 min and given for 20 min. Chest compressions were provided mechanically with a chest compression device and ventilations were delivered manually with a self-inflating bag and 12 l/min of oxygen. During the experiment, ventilation parameters and hemodynamics were sampled continuously, and arterial blood gases were taken every five minutes. After euthanasia and cessation of CPR, the lungs and heart were removed in block and visually examined followed by sampling of lung tissue which were examined using microscopy. Results In the CCC group and the 30:2 group, peak inspiratory pressure (PIP) was 58.6 and 35.1 cmH2O (p

Abstract Background The COVID-19 pandemic, which has a prominent social and economic impact worldwide, shows a largely unexplained male bias for the severity and mortality of the disease. Loss of chromosome Y (LOY) is a risk factor candidate in COVID-19 due to its prior association with many chronic age-related diseases, and its impact on immune gene transcription. Methods Publicly available scRNA-seq data of PBMC samples derived from male patients critically ill with COVID-19 were reanalyzed, and LOY status was added to the annotated cells. We further studied LOY in whole blood for 211 COVID-19 patients treated at intensive care units (ICU) from the first and second waves of the pandemic. Of these, 139 patients were subject to cell sorting for LOY analysis in granulocytes, low-density neutrophils (LDNs), monocytes, and PBMCs. Results Reanalysis of available scRNA-seq data revealed LDNs and monocytes as the cell types most affected by LOY. Subsequently, DNA analysis indicated that 46%, 32%, and 29% of critically ill patients showed LOY above 5% cut-off in LDNs, granulocytes, and monocytes, respectively. Hence, the myeloid lineage that is crucial for the development of severe COVID-19 phenotype is affected by LOY. Moreover, LOY correlated with increasing WHO score (median difference 1.59%, 95% HDI 0.46% to 2.71%, p=0.025), death during ICU treatment (median difference 1.46%, 95% HDI 0.47% to 2.43%, p=0.0036), and history of vessel disease (median difference 2.16%, 95% HDI 0.74% to 3.7%, p=0.004), among other variables. In 16 recovered patients, sampled during ICU stay and 93–143 days later, LOY decreased significantly in whole blood and PBMCs. Furthermore, the number of LDNs at the recovery stage decreased dramatically (median difference 76.4 per 10,000 cell sorting events, 95% HDI 55.5 to 104, p=6e−11). Conclusions We present a link between LOY and an acute, life-threatening infectious disease. Furthermore, this study highlights LOY as the most prominent clonal mutation affecting the myeloid cell lineage during emergency myelopoiesis. The correlation between LOY level and COVID-19 severity might suggest that this mutation affects the functions of monocytes and neutrophils, which could have consequences for male innate immunity.

Introduction: The presented study aimed to investigate whether a mechanical chest compression piston device with a suction cup assisting chest recoil could impact the hemodynamic status when compared to a bare piston during cardiopulmonary resuscitation. Methods: 16 piglets were anesthetized and randomized into 2 groups. After 3 minutes of induced ventricular fibrillation, a LUCAS 3 device was used to perform chest compressions, in one group a suction cup was mounted on the device’s piston, while in the other group, compressions were performed by the bare piston. The device was used in 30:2 mode and the animals were manually ventilated. Endpoints of the study were: end tidal carbon dioxide, coronary and cerebral perfusion pressures, and brain oxygenation (measured using near infrared spectroscopy). At the end of the protocol, the animals that got a return to spontaneous circulation were observed for 60 minutes, then euthanized. Results: No difference was found in end tidal carbon dioxide or tidal volumes. Coronary perfusion pressure and cerebral oxygenation were higher in the Suction cup group over the entire experiment time, while cerebral perfusion pressure was higher only in the last 5 minutes of CPR. A passive tidal volume (air going in and out the airways during compressions) was detected and found correlated to end tidal carbon dioxide. Conclusions: The use of a suction cup on a piston-based chest compression device did not increase end tidal carbon dioxide, but it was associated to a higher coronary perfusion pressure.

Background: Immediate coronary angiography with subsequent percutaneous coronary intervention (PCI) has the potential to reduce post-resuscitation myocardial dysfunction in out-of-hospital cardiac arrest (OHCA) patients. The aim of this study was to see if immediate coronary angiography, with potential PCI, in patients without ST-elevation on the ECG, influenced post-resuscitation myocardial function and cardiac biomarkers. Methods: A secondary analysis of the Direct or Subacute Coronary Angiography in Out-of-Hospital Cardiac Arrest (DISCO) trial (ClinicalTrials.gov ID: NCT02309151). Patients with bystander-witnessed OHCA, without ST-elevations on the ECG were randomly assigned to immediate coronary angiography within two hours of cardiac arrest (n = 38) versus standard-of-care with deferred angiography (n = 40). Outcome measures included left ventricle ejection fraction (LVEF) at 24 h, peak Troponin T levels, lactate clearance and NT-proBNP at 72 h. Results: In the immediate-angiography group, median LVEF at 24 h was 47% (Q1-Q3; 30–55) vs. 46% (Q1-Q3; 35–55) in the standard-of-care group. Peak Troponin-T levels during the first 24 h were 362 ng/L (Q1-Q3; 174–2020) in the immediate angiography group and 377 ng/L (Q1-Q3; 205–1078) in the standard-of-care group. NT-proBNP levels at 72 h were 931 ng/L (Q1-Q3; 396–2845) in the immediate-angiography group and 1913 ng/L (Q1-Q3; 489–3140) in the standard-of-care group. Conclusion: In this analysis of OHCA patients without ST-elevation on the ECG randomized to immediate coronary angiography or standard-of-care, no differences in post-resuscitation myocardial dysfunction parameters between the two groups were found. This finding was consistent also in patients randomized to immediate coronary angiography where PCI was performed compared to those where PCI was not performed. Keywords: Out-of-hospital cardiac arrest, Coronary angiography, Troponin, Echocardiography

Amyloid β (Aβ) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aβ accumulation in familial AD, less is known about the cause(s) of brain amyloidosis in sporadic disease. Animal and postmortem studies suggest that Aβ secretion can be up-regulated in response to hypoxia. We employed a new technology (Single Molecule Arrays, SiMoA) capable of ultrasensitive protein measurements and developed a novel assay to look for changes in serum Aβ42 concentration in 25 resuscitated patients with severe hypoxia due to cardiac arrest. After a lag period of 10 or more hours, very clear serum Aβ42 elevations were observed in all patients. Elevations ranged from approximately 80% to over 70-fold, with most elevations in the range of 3-10-fold (average approximately 7-fold). The magnitude of the increase correlated with clinical outcome. These data provide the first direct evidence in living humans that ischemia acutely increases Aβ levels in blood. The results point to the possibility that hypoxia may play a role in the amyloidogenic process of AD.