Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial.

Importance: Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial. Objective: To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023. Interventions: Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days. Results: Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital. Conclusion and Relevance: In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg. Trial Registration: ClinicalTrials.gov Identifier: NCT04425031.

Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020.

BackgroundWomen are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown.AimWe assessed the impact of sex and gender on PASC in a Swiss population.MethodOur multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030).ConclusionSpecific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident.

Enhancement of the haemostatic effect of platelets in the presence of high normal concentrations of von Willebrand factor for critically ill patients needing platelet transfusion-a protocol for the will-plate randomised controlled trial.

INTRODUCTION: von Willebrand Factor (vWF) is a key protein mediating platelet adhesion on the surface of damaged endothelia. To the best of our knowledge, no trial exists that investigated the effect of platelet transfusion in combination with the administration of balanced vWF in severe blood loss, despite being widely used in clinical practice. The Basel Will-Plate study will investigate the impact of the timely administration of balanced vWF (1:1 vWF and FVIII) in addition to platelet transfusion on the need for blood and coagulation factor transfusion in patients admitted to the intensive care unit (ICU) who suffer from severe bleeding. The study hypothesis is based on the assumption that adding balanced vWF to platelets will reduce the overall need for transfusion of blood products compared to the transfusion of platelets alone. METHODS AND ANALYSIS: The Will-Plate study is an investigator-initiated, single-centre, double-blinded randomised controlled clinical trial in 120 critically ill patients needing platelet transfusion. The primary outcome measure will be the number of fresh frozen plasma (FFP) and red blood cell (RBC) transfusions according to groups. Secondary outcome measures include the number of platelet concentrates transfused within the first 48 h after treatment of study medication, quantity of blood loss in the first 48 h after treatment with the study medication, length of stay in ICU and hospital, number of revision surgeries for haemorrhage control, ICU mortality, hospital mortality, 30-day mortality and 1-year mortality. Patients will be followed after 30 days and 1 year for activities of daily living and mortality assessment. The sample size was calculated to detect a 50% reduction in the number of blood products subsequently transfused within 2 days in patients with Wilate® compared to placebo. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Northwestern and Central Switzerland and will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the ICH-GCP or ISO EN 14155 (as far as applicable) and all national legal and regulatory requirements. The study results will be presented at international conferences and published in a peer-reviewed journal. TRIALS REGISTRATION: ClinicalTrials.gov NCT04555785. PROTOCOL VERSION: Clinical Study Protocol Version 2, 01.11.2020. Registered on Sept. 21, 2020.

Inverse relationship between IL-6 and sodium levels in patients with COVID-19 and other respiratory tract infections: data from the COVIVA study.

Objective: Hyponatremia in COVID-19 is often due to the syndrome of inadequate antidiuresis (SIAD), possibly mediated by interleukin-6 (IL-6)-induced non-osmotic arginine vasopressin (AVP) secretion. We hypothesized an inverse association between IL-6 and plasma sodium concentration, stronger in COVID-19 compared to other respiratory infections. Design: Secondary analysis of a prospective cohort study including patients with COVID-19 suspicion admitted to the Emergency Department, University Hospital of Basel, Switzerland, between March and July 2020. Methods: We included patients with PCR-confirmed COVID-19 and patients with similar symptoms, further subclassified into bacterial and other viral respiratory infections. The primary objective was to investigate the association between plasma sodium and IL-6 levels. Results: A total of 500 patients were included, 184 (37%) with COVID-19, 92 (18%) with bacterial respiratory infections, and 224 (45%) with other viral respiratory infections. In all groups, median (IQR) IL-6 levels were significantly higher in hyponatremic compared to normonatremic patients (COVID-19: 43.4 (28.4, 59.8) vs 9.2 (2.8, 32.7) pg/mL, P < 0.001; bacterial: 122.1 (63.0, 282.0) vs 67.1 (24.9, 252.0) pg/mL, P < 0.05; viral: 14.1 (6.9, 84.7) vs 4.3 (2.1, 14.4) pg/mL, P < 0.05). IL-6 levels were negatively correlated with plasma sodium levels in COVID-19, whereas the correlation in bacterial and other viral infections was weaker (COVID-19: R = -0.48, P < 0.001; bacterial: R = -0.25, P = 0.05, viral: R = -0.27, P < 0.001). Conclusions: IL-6 levels were inversely correlated with plasma sodium levels, with a stronger correlation in COVID-19 compared to bacterial and other viral infections. IL-6 might stimulate AVP secretion and lead to higher rates of hyponatremia due to the SIAD in these patients.

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry.

BACKGROUND: It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS: Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS: Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION: Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.

Clinical utility of inflammatory biomarkers in COVID-19 in direct comparison to other respiratory infections-A prospective cohort study.

BACKGROUND: Inflammatory biomarkers are associated with severity of coronavirus disease 2019 (COVID-19). However, direct comparisons of their utility in COVID-19 versus other respiratory infections are largely missing. OBJECTIVE: We aimed to investigate the prognostic utility of various inflammatory biomarkers in COVID-19 compared to patients with other respiratory infections. MATERIALS AND METHODS: Patients presenting to the emergency department with symptoms suggestive of COVID-19 were prospectively enrolled. Levels of Interleukin-6 (IL-6), c-reactive protein (CRP), procalcitonin, ferritin, and leukocytes were compared between COVID-19, other viral respiratory infections, and bacterial pneumonia. Primary outcome was the need for hospitalisation, secondary outcome was the composite of intensive care unit (ICU) admission or death at 30 days. RESULTS: Among 514 patients with confirmed respiratory infections, 191 (37%) were diagnosed with COVID-19, 227 (44%) with another viral respiratory infection (viral controls), and 96 (19%) with bacterial pneumonia (bacterial controls). All inflammatory biomarkers differed significantly between diagnoses and were numerically higher in hospitalized patients, regardless of diagnoses. Discriminative accuracy for hospitalisation was highest for IL-6 and CRP in all three diagnoses (in COVID-19, area under the curve (AUC) for IL-6 0.899 [95%CI 0.850-0.948]; AUC for CRP 0.922 [95%CI 0.879-0.964]). Similarly, IL-6 and CRP ranged among the strongest predictors for ICU admission or death at 30 days in COVID-19 (AUC for IL-6 0.794 [95%CI 0.694-0.894]; AUC for CRP 0.807 [95%CI 0.721-0.893]) and both controls. Predictive values of inflammatory biomarkers were generally higher in COVID-19 than in controls. CONCLUSION: In patients with COVID-19 and other respiratory infections, inflammatory biomarkers harbour strong prognostic information, particularly IL-6 and CRP. Their routine use may support early management decisions.

Sex disparities in patients with suspected COVID-19 presenting at an emergency department in Switzerland.

AIMS OF THE STUDY: In the global COVID-19 pandemic, female sex is associated with comparable infection rates but better outcome. However, most studies lacked appropriate controls. We investigated whether these sex disparity findings are specific to patients with COVID-19 or generalizable to patients presenting to the emergency room (ER) with similar symptoms but no COVID-19. METHODS: In this prospective cohort study, consecutive patients presenting with symptoms suggestive of COVID-19 were recruited at the ER of the University Hospital Basel, Switzerland from March to June 2020. Patients were categorized as SARS-CoV-2 positive (cases) or negative (controls) based on nasopharyngeal PCR swab tests. The final clinical diagnosis was determined for all patients. The primary outcome was a composite of intensive care admission, rehospitalization for respiratory distress and all-cause death within 30 days. We used Kaplan-Meier curves and Cox proportional hazards models to explore associations between sex and outcomes. RESULTS: Among 1,081 consecutive ER patients, 191 (18%) tested positive for SARS-CoV-2, with an even sex distribution (17.9% female vs. 17.5% male, p = 0.855). In COVID-19 patients, female sex was associated with lower risk of hospitalization (51% vs. 66%, p = 0.034), lower necessity of haemodynamic support (8% vs. 20%, p = 0.029), lower rates of intubation (10% vs. 21%, p = 0.037) and the primary outcome (18% vs. 31%, p = 0.045; age-adjusted HR 0.536, 95%CI 0.290-0.989, p = 0.046) compared with male sex. Sex disparities were most prominent in patients ≥55 years (HR for composite primary outcome in women 0.415, 95%CI 0.201-0.855, p = 0.017). In contrast to the COVID-19 patients, no sex-specific differences in outcomes were observed in the unselected overall control group (age-adjusted HR 0.844, 95%CI 0.560-1.273, p = 0.419) or in a subgroup of controls with upper respiratory tract infections or pneumonia (age-adjusted HR 0.840, 95%CI 0.418-1.688, p = 0.624). CONCLUSION: In this unselected, consecutive cohort study at a tertiary hospital in Switzerland, female sex is associated with better outcome in patients presenting to the ER with COVID-19. These sex disparities seem to be at least partly specific to COVID-19, as they were not observed in comparable controls.

Adverse Events of Percutaneous Microaxial Left Ventricular Assist Devices-A Retrospective, Single-Centre Cohort Study.

Worldwide, the left ventricular assist device Impella® (Abiomed, Danvers, MA, USA) is increasingly implanted in patients with acute cardiogenic shock or undergoing high-risk cardiac interventions. Despite its long history of use, few studies have assessed its safety and possible complications associated with its use. All patients treated with a left-sided Impella® device at the University Hospital of Basel from 1 January 2011 to 31 December 2019 were enrolled. The primary endpoint was the composite rate of mortality and adverse events (bleeding, acute kidney injury, and limb ischemia). Out of 281 included patients, at least one adverse event was present in 262 patients (93%). Rates of in-hospital, 90-day, and one-year mortality were 48%, 47%, and 50%, respectively. BARC type 3 bleeding (62%) and hemolysis (41.6%) were the most common complications. AKI was observed in 50% of all patients. Renal replacement therapy was required in 97 (35%) of all patients. Limb ischemia occurred in 13% of cases. Bleeding and hemolysis are common Impella®-associated complications. Additionally, we found a high rate of AKI. A careful selection of patients receiving microaxial LV support and defining the indication for its use are essential measures to be taken for the benefits to outweigh potential complications.

Direct Comparison of Clinical Characteristics, Outcomes, and Risk Prediction in Patients with COVID-19 and Controls-A Prospective Cohort Study.

Most studies investigating early risk predictors in coronavirus disease 19 (COVID-19) lacked comparison with controls. We aimed to assess and directly compare outcomes and risk predictors at time of emergency department (ED) presentation in COVID-19 and controls. Consecutive patients presenting to the ED with suspected COVID-19 were prospectively enrolled. COVID-19-patients were compared with (i) patients tested negative (overall controls) and (ii) patients tested negative, who had a respiratory infection (respiratory controls). Primary outcome was the composite of intensive care unit (ICU) admission and death at 30 days. Among 1081 consecutive cases, 191 (18%) were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 890 (82%) were tested negative (overall controls), of which 323 (30%) had a respiratory infection (respiratory controls). Incidence of the composite outcome was significantly higher in COVID-19 (23%) as compared with the overall control group (10%, adjusted-HR 2.45 (95%CI, 1.61-3.74), p < 0.001) or the respiratory control group (10%, adjusted-HR 2.93 (95%CI, 1.66-5.17), p < 0.001). Blood oxygen saturation, age, high-sensitivity troponin, c-reactive protein, and lactate dehydrogenase were identified as the strongest predictors of poor outcome available at time of ED presentation in COVID-19 with highly comparable prognostic utility in overall and respiratory controls. In conclusion, patients presenting to the ED with COVID-19 have a worse outcome than controls, even after adjustment for differences in baseline characteristics. Most predictors of poor outcome in COVID-19 were not restricted to COVID-19, but of comparable prognostic utility in controls and therefore generalizable to unselected patients with suspected COVID-19.

Use of crystalloids and colloids in Europe per year from 2010 to 2019: Protocol for an international descriptive study.

INTRODUCTION: Intravenous (IV) fluids are widely used in everyday clinical practice. In the last two decades, several trials and clinical practice guidelines have been published on the use of different types and dosages of IV fluid. This may have led to a change in clinical practice. Thus, we aim to describe the use of IV crystalloids and colloids in Europe over a 10-year period. METHODS AND ANALYSIS: We will collect national or regional data on the use of IV crystalloids and colloids in European hospitals through companies and/or federal medical agencies that provide pharmaceutical data concerning the type and amount of fluids used from January 1st, 2010 to December 31st, 2019. We will use run charts to describe time trends in the use of fluids. CONCLUSION: This study will provide insight into the use of IV fluids in Europe between 2010 and 2019. It will enable the observation of changes over time and among the different European countries and regions. This will provide information on the extent to which landmark trials and clinical practice guidelines on fluids have affected clinical practice in Europe regarding the use of IV fluids.

Low dose radiation therapy for severe COVID-19 pneumonia: a randomized double-blind study.

PURPOSE: The morbidity and mortality of patients requiring mechanical ventilation for coronavirus disease 2019 (COVID-19) pneumonia is considerable. We studied the use of whole-lung low dose radiation therapy (LDRT) in this patient cohort. METHODS AND MATERIALS: Patients admitted to the intensive care unit (ICU) and requiring mechanical ventilation for COVID-19 pneumonia were included in this randomized double-blind study. Patients were randomized to 1 Gy whole-lung LDRT or sham irradiation (sham-RT). Treatment group allocation was concealed from patients and ICU clinicians, who treated patients according to the current standard of care. Patients were followed for the primary endpoint of ventilator-free days (VFDs) at day 15 post-intervention. Secondary endpoints included overall survival, as well as changes in oxygenation and inflammatory markers. RESULTS: Twenty-two patients were randomized to either whole-lung LDRT or sham-RT between November and December 2020. Patients were generally elderly and comorbid, with a median age of 75 years in both arms. No difference in 15-day VFDs was observed between groups (p = 1.00), with a median of 0 days (range, 0-9) in the LDRT arm, and 0 days (range, 0-13) in the sham-RT arm. Overall survival at 28 days was identical at 63.6% (95%CI, 40.7-99.5%) in both arms (p = 0.69). Apart from a more pronounced reduction in lymphocyte counts following LDRT (p < 0.01), analyses of secondary endpoints revealed no significant differences between the groups. CONCLUSIONS: Whole-lung LDRT failed to improve clinical outcomes in critically ill patients requiring mechanical ventilation for COVID-19 pneumonia.

Gender differences in the provision of intensive care: a Bayesian approach.

PURPOSE: It is currently unclear whether management and outcomes of critically ill patients differ between men and women. We sought to assess the influence of age, sex and diagnoses on the probability of intensive care provision in critically ill cardio- and neurovascular patients in a large nationwide cohort in Switzerland. METHODS: Retrospective analysis of 450,948 adult patients with neuro- and cardiovascular disease admitted to all hospitals in Switzerland between 01/2012 and 12/2016 using Bayesian modeling. RESULTS: For all diagnoses and populations, median ages at admission were consistently higher for women than for men [75 (64;82) years in women vs. 68 (58;77) years in men, p < 0.001]. Overall, women had a lower likelihood to be admitted to an intensive care unit (ICU) than men, despite being more severely ill [odds ratio (OR) 0.78 (0.76-0.79)]. ICU admission probability was lowest in women aged > 65 years (OR women:men 0.94 (0.89-0.99), p < 0.001). Women < 45 years had a similar ICU admission probability as men in the same age category [OR women:men 1.03 (0.94-1.13)], in spite of more severe illness. The odds to die were significantly higher in women than in men per unit increase in Simplified Acute Physiology Score (SAPS) II (OR 1.008 [1.004-1.012]). CONCLUSION: In the care of the critically ill, our study suggests that women are less likely to receive ICU treatment regardless of disease severity. Underuse of ICU care was most prominent in younger women < 45 years. Although our study has several limitations that are imposed by the limited data available from the registries, our findings suggest that current ICU triage algorithms could benefit from careful reassessment. Further, and ideally prospective, studies are needed to confirm our findings.

Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia: A Randomized Double-Blind Study.

PURPOSE: The morbidity and mortality of patients requiring mechanical ventilation for coronavirus disease 2019 (COVID-19) pneumonia is considerable. We studied the use of whole-lung low-dose radiation therapy (LDRT) in this patient cohort. METHODS AND MATERIALS: Patients admitted to the intensive care unit and requiring mechanical ventilation for COVID-19 pneumonia were included in this randomized double-blind study. Patients were randomized to 1 Gy whole-lung LDRT or sham irradiation (sham-RT). Treatment group allocation was concealed from patients and intensive care unit clinicians, who treated patients according to the current standard of care. Patients were followed for the primary endpoint of ventilator-free days at day 15 postintervention. Secondary endpoints included overall survival, as well as changes in oxygenation and inflammatory markers. RESULTS: Twenty-two patients were randomized to either whole-lung LDRT or sham-RT between November and December 2020. Patients were generally elderly and comorbid, with a median age of 75 years in both arms. No difference in 15-day ventilator-free days was observed between groups (P = 1.00), with a median of 0 days (range, 0-9) in the LDRT arm and 0 days (range, 0-13) in the sham-RT arm. Overall survival at 28 days was identical at 63.6% (95% confidence interval, 40.7%-99.5%) in both arms (P = .69). Apart from a more pronounced reduction in lymphocyte counts after LDRT (P < .01), analyses of secondary endpoints revealed no significant differences between the groups. CONCLUSIONS: Whole-lung LDRT failed to improve clinical outcomes in critically ill patients requiring mechanical ventilation for COVID-19 pneumonia.

Haemophagocytic lymphohistiocytosis and liver failure-induced massive hyperferritinaemia in a male COVID-19 patient.

The authors present the case of a 58-year-old man with the unique combination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and, later on, haemophagocytic lymphohistiocytosis admitted to the intensive care unit. During his ICU stay the patient developed a variety of complications including acute respiratory distress syndrome, pulmonary embolism, right heart failure and suspected HLH leading to multiorgan failure and death. Despite the proven diagnosis of haemophagocytic lymphohistiocytosis, the excessively high ferritin levels of the patient did not seem fully explained by this diagnosis. Therefore, the authors want to highlight different causes of hyperferritinaemia in critically ill patients and underline the importance of differential diagnoses when interpreting continuously rising ferritin levels.

Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure.

BACKGROUND: Patients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are treated with supplemental oxygen, but the benefits and harms of different oxygenation targets are unclear. We hypothesized that using a lower target for partial pressure of arterial oxygen (Pao2) would result in lower mortality than using a higher target. METHODS: In this multicenter trial, we randomly assigned 2928 adult patients who had recently been admitted to the ICU (≤12 hours before randomization) and who were receiving at least 10 liters of oxygen per minute in an open system or had a fraction of inspired oxygen of at least 0.50 in a closed system to receive oxygen therapy targeting a Pao2 of either 60 mm Hg (lower-oxygenation group) or 90 mm Hg (higher-oxygenation group) for a maximum of 90 days. The primary outcome was death within 90 days. RESULTS: At 90 days, 618 of 1441 patients (42.9%) in the lower-oxygenation group and 613 of 1447 patients (42.4%) in the higher-oxygenation group had died (adjusted risk ratio, 1.02; 95% confidence interval, 0.94 to 1.11; P = 0.64). At 90 days, there was no significant between-group difference in the percentage of days that patients were alive without life support or in the percentage of days they were alive after hospital discharge. The percentages of patients who had new episodes of shock, myocardial ischemia, ischemic stroke, or intestinal ischemia were similar in the two groups (P = 0.24). CONCLUSIONS: Among adult patients with acute hypoxemic respiratory failure in the ICU, a lower oxygenation target did not result in lower mortality than a higher target at 90 days. (Funded by the Innovation Fund Denmark and others; HOT-ICU ClinicalTrials.gov number, NCT03174002.).

Prone Positioning as a Potential Risk Factor for Deep Vein Thrombosis in COVID-19 Patients: A Hypothesis Generating Observation.

AIMS OF THE STUDY: Virchow's triad with stasis, activated coagulation, and endothelial damage is common in SARS-CoV2. Therefore, we sought to retrospectively assess whether the duration of prone position may serve as a risk factor for deep vein thrombosis in critically ill patients. METHODS: In this single center retrospective study of a tertiary referral hospital, patients with acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia admitted to critical care underwent venous ultrasound screening for deep vein thrombosis (DVT). Data on DVT diagnosis, duration of prone positioning, demographic, respiratory, and laboratory parameters were retrospectively collected and compared between DVT and non-DVT patients. RESULTS: 21 patients with ARDS from COVID-19 pneumonia were analyzed. DVT was detected in 11 (52%) patients (76.2% male, median age 64 (58; 68.5) years, median body mass index 31 (27; 33.8) kg/m2). In patients diagnosed with DVT, median prone ventilation had been maintained twice as long as compared to patients without DVT (57 (19; 72) versus 28 (0; 56.3) h, p = 0.227) on ICU day 5 with a trend towards longer prone position time (71 (19; 104) versus 28 (0; 73) h, p = 0.06) on ICU day 7. CONCLUSIONS: Prone ventilation and constitutional factors may constitute an additional risk factor for DVT in COVID-19 patients. Since recent studies have shown that therapeutic anticoagulation does not impact the occurrence of thromboembolic events, it may be worthwhile to consider mechanical factors potentially affecting blood flow stasis in this high-risk population. However, due to the limited number of patients, our observations should only be considered as hypothesis-generating. Future studies, sufficiently powered and preferably prospective, will be needed to confirm our hypothesis.