The association of premorbid conditions with 6-month mortality in acutely admitted ICU patients over 80 years.

BACKGROUND: Premorbid conditions influence the outcome of acutely ill adult patients aged 80 years and over who are admitted to the ICU. The aim of this study was to determine the influence of such premorbid conditions on 6 month survival. METHODS: Prospective cohort study in 242 ICUs from 22 countries including patients 80 years or above, admitted over a 6 months period to an ICU between May 2018 and May 2019. Only emergency (acute) ICU admissions in adult patients ≥ 80 years of age were eligible. Patients who were admitted after planned/elective surgery were excluded. We measured the Clinical Frailty Scale (CFS), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), disability with the Katz activities of daily living (ADL) score, comorbidities and a Polypharmacy Score (CPS). RESULTS: Overall, the VIP2 study included 3920 patients. During ICU stay 1191 patients died (30.9%), and another 436 patients (11.1%) died after ICU discharge but within the first 30 days of admission, and an additional 895 patients died hereafter but within the first 6 months after admission (22.8%). The 6 months mortality was 64%. The median CFS was 4 (IQR 3-6). Frailty (CFS ≥ 5) was present in 26.6%. Cognitive decline (IQCODE above 3.5) was found in 30.2%. The median IQCODE was 3.19. A Katz ADL of 4 or less was present in 27.7%. Patients who surviving > 6 months were slightly younger (median age survivors 84 with IQR 81-86) than patients dying within the first 6 months (median age 84, IQR 82-87, p = 0.013), were less frequently frail (CFS > 5 in 19% versus 34%, p < 0.01) and were less dependent based on their Katz activities of daily living measurement (median Katz score 6, IQR 5-6 versus 6 points, IQR 3-6, p < 0.01). CONCLUSIONS: We found that Clinical Frailty Scale, age, and SOFA at admission were independent prognostic factors for 6 month mortality after ICU admission in patients age 80 and above. Adding other geriatric syndromes and scores did not improve the model. This information can be used in shared-decision making. CLINICALTRIALS: gov: NCT03370692.

Hypercapnia and its relationship with respiratory infections.

INTRODUCTION: Hypercapnia is developed in patients with acute and/or chronic respiratory conditions. Clinical data concerning hypercapnia and respiratory infections interaction is limited. AREAS COVERED: Currently, the relationship between hypercapnia and respiratory infections remains unclear. In this review, we summarize studies on the effects of hypercapnia on models of pulmonary infections to clarify the role of elevated CO2 in these pulmonary pathologies. Hypercapnia affects different cell types in the alveoli, leading to changes in the immune response. In vitro studies show that hypercapnia downregulates the NF-κß pathway, reduces inflammation and impairs epithelial wound healing. While in vivo models show a dual role between short- and long-term effects of hypercapnia on lung infection. However, it is still controversial whether the effects observed under hypercapnia are pH dependent or not. EXPERT OPINION: The role of hypercapnia is still a controversial debate. Hypercapnia could play a beneficial role in mechanically ventilated models, by lowering the inflammation produced by the stretch condition. But it could be detrimental in infectious scenarios, causing phagocyte dysfunction and lack of infection control. Further data concerning hypercapnia on respiratory infections is needed to elucidate this interaction.

30-day mortality among very old patients admitted to European intensive care units for major trauma.

INTRODUCTION: Cases of major trauma in the very old (over 80 years) are increasingly common in the intensive care unit. Predicting outcome is challenging in this group of patients as chronological age is a poor marker of health and poor predictor of outcome. Increasingly, decisions are guided with the use of organ dysfunction scores of both the acute condition (e.g. Sequential Organ Failure Assessment (SOFA) score) and chronic health issues (e.g. clinical frailty scale, (CFS)). Recent work suggests that increased CFS is associated with a worse outcome in elderly major trauma patients. We aimed to test whether this association held true in the very old (over 80) or whether SOFA had a stronger association with 30-day outcome. METHODS: Data from the VIP-1 and VIP-2 studies for patients over 80 years old with major trauma admissions were merged. These participants were recruited from 20 countries across Europe. Baseline characteristics, level of care provided and outcome (ICU and 30-day mortality) were summarised. Uni- and multi- variable regression analysis were undertaken to determine associations between CFS and SOFA score in the first 24-hours, type of major trauma and outcomes. RESULTS: Of the 8062 acute patients recruited to the two VIP studies, 498 patients were admitted to intensive care because of major trauma. Median age was 84 years; median SOFA score was 6 (IQR 3,9) and median CFS was 3 (IQR 2,5). Survival to 30-days was 54%. Median and inter-quartile range of CFS was the same in survivors and non-survivors. In the logistic regression analysis, CFS was not associated with increased mortality. SOFA score (p<0.001) and trauma with head injury (p<0.01) were associated with increased mortality. CONCLUSIONS: Major trauma admissions in the very old are not uncommon and 30-day mortality is high. We found that CFS was not a helpful predictor of mortality. SOFA and trauma with head injury were associated with worse outcomes in this patient group.

The critically ill older patient with sepsis: a narrative review.

Sepsis is a significant public health concern, particularly affecting individuals above 70 years in developed countries. This is a crucial fact due to the increasing aging population, their heightened vulnerability to sepsis, and the associated high mortality rates. However, the morbidity and long-term outcomes are even more notable. While many patients respond well to timely and appropriate interventions, it is imperative to enhance efforts in identifying, documenting, preventing, and treating sepsis. Managing sepsis in older patients poses greater challenges and necessitates a comprehensive understanding of predisposing factors and a heightened suspicion for diagnosing infections and assessing the risk of sudden deterioration into sepsis. Despite age often being considered an independent risk factor for mortality and morbidity, recent research emphasizes the pivotal roles of frailty, disease severity, and comorbid conditions in influencing health outcomes. In addition, it is important to inquire about the patient's preferences and establish a personalized treatment plan that considers their potential for recovery with quality of life and functional outcomes. This review provides a summary of the most crucial aspects to consider when dealing with an old critically ill patient with sepsis.

Associations of Awake Prone Positioning-Induced Changes in Physiology with Intubation: An International Prospective Observational Study in Patients with Acute Hypoxemic Respiratory Failure Related to COVID-19.

INTRODUCTION: Awake prone positioning has the potential to improve oxygenation and decrease respiratory rate, potentially reducing the need for intubation in patients with acute hypoxemic respiratory failure. We investigated awake prone positioning-induced changes in oxygenation and respiratory rate, and the prognostic capacity for intubation in patients with COVID-19 pneumonia. METHODS: International multicenter prospective observation study in critically ill adult patients with COVID-19 receiving supplemental oxygen. We collected data on oxygenation and respiratory rate at baseline, and at 1 h after being placed in prone positioning. The combined primary outcome was oxygenation and respiratory rate at 1 h. The secondary endpoint was treatment failure, defined as need for intubation within 24 h of start of awake prone positioning. RESULTS: Between March 27th and November 2020, 101 patients were enrolled of which 99 were fully analyzable. Awake prone positioning lasted mean of 3 [2-4] h. In 77 patients (77.7%), awake prone positioning improved oxygenation, and in 37 patients (54.4%) it decreased respiratory rate. Twenty-nine patients (29.3%) were intubated within 24 h. An increase in SpO2/FiO2 of < 10 (OR 5.1, 95% CI 1.4-18.5, P = 0.01), a failure to increase PaO2/FiO2 to > 116 mmHg (OR 3.6, 95% CI 1.2-10.8, P = 0.02), and a decrease in respiratory rate of < 2 breaths/min (OR 3.6, 95% CI 1.3-9.5, P = 0.01) were independent variables associated with need for intubation. The AUC-ROC curve for intubation using a multivariable model was 0.73 (95% CI 0.62-0.84). CONCLUSIONS: Awake prone positioning improves oxygenation in the majority of patients, and decreases respiratory rate in more than half of patients with acute hypoxemic respiratory failure caused by COVID-19. One in three patients need intubation within 24 h. Awake prone position-induced changes in oxygenation and respiratory rate have prognostic capacity for intubation within 24 h.

Evaluation of the Kinetics of Pancreatic Stone Protein as a Predictor of Ventilator-Associated Pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a severe condition. Early and adequate antibiotic treatment is the most important strategy for improving prognosis. Pancreatic Stone Protein (PSP) has been described as a biomarker that increases values 3-4 days before the clinical diagnosis of nosocomial sepsis in different clinical settings. We hypothesized that serial measures of PSP and its kinetics allow for an early diagnosis of VAP. METHODS: The BioVAP study was a prospective observational study designed to evaluate the role of biomarker dynamics in the diagnosis of VAP. To determine the association between repeatedly measured PSP and the risk of VAP, we used joint models for longitudinal and time-to-event data. RESULTS: Of 209 patients, 43 (20.6%) patients developed VAP, with a median time of 4 days. Multivariate joint models with PSP, CRP, and PCT did not show an association between biomarkers and VAP for the daily absolute value, with a hazard ratio (HR) for PSP of 1.01 (95% credible interval: 0.97 to 1.05), for CRP of 1.00 (0.83 to 1.22), and for PCT of 0.95 (0.82 to 1.08). The daily change of biomarkers provided similar results, with an HR for PSP of 1.15 (0.94 to 1.41), for CRP of 0.76 (0.35 to 1.58), and for PCT of 0.77 (0.40 to 1.45). CONCLUSION: Neither absolute PSP values nor PSP kinetics alone nor in combination with other biomarkers were useful in improving the prediction diagnosis accuracy in patients with VAP. CLINICAL TRIAL REGISTRATION: Registered retrospectively on August 3rd, 2012. NCT02078999.

Outcomes of patients aged ≥80 years with respiratory failure initially treated with non-invasive ventilation in European intensive care units before and during COVID-19 pandemic.

BACKGROUND: Non-invasive ventilation (NIV) has been commonly used to treat acute respiratory failure due to COVID-19. In this study we aimed to compare outcomes of older critically ill patients treated with NIV before and during the COVID-19 pandemic. METHODS: We analysed a merged cohort of older adults admitted to intensive care units (ICUs) due to respiratory failure. Patients were enrolled into one of two prospective observational studies: before COVID-19 (VIP2-2018 to 2019) and admitted due to COVID-19 (COVIP-March 2020 to January 2023). The outcomes included: 30-day mortality, intubation rate and NIV failure (death or intubation within 30 days). RESULTS: The final cohort included 1986 patients (1292 from VIP2, 694 from COVIP) with a median age of 83 years. NIV was used as a primary mode of respiratory support in 697 participants (35.1%). ICU admission due to COVID-19 was associated with an increased 30-day mortality (65.5% vs. 36.5%, HR 2.18, 95% CI 1.71 to 2.77), more frequent intubation (36.9% vs. 17.5%, OR 2.63, 95% CI 1.74 to 3.99) and NIV failure (76.2% vs. 45.3%, OR 4.21, 95% CI 2.84 to 6.34) compared to non-COVID causes of respiratory failure. Sensitivity analysis after exclusion of patients in whom life supporting treatment limitation was introduced during primary NIV confirmed higher 30-day mortality in patients with COVID-19 (52.5% vs. 23.4%, HR 2.64, 95% CI 1.83 to 3.80). CONCLUSION: The outcomes of patients aged ≥80 years treated with NIV during COVID-19 pandemic were worse compared then those treated with NIV in the pre-pandemic era.

A long-lasting porcine model of ARDS caused by pneumonia and ventilator-induced lung injury.

BACKGROUND: Animal models of acute respiratory distress syndrome (ARDS) do not completely resemble human ARDS, struggling translational research. We aimed to characterize a porcine model of ARDS induced by pneumonia-the most common risk factor in humans-and analyze the additional effect of ventilator-induced lung injury (VILI). METHODS: Bronchoscopy-guided instillation of a multidrug-resistant Pseudomonas aeruginosa strain was performed in ten healthy pigs. In six animals (pneumonia-with-VILI group), pulmonary damage was further increased by VILI applied 3 h before instillation and until ARDS was diagnosed by PaO2/FiO2 < 150 mmHg. Four animals (pneumonia-without-VILI group) were protectively ventilated 3 h before inoculum and thereafter. Gas exchange, respiratory mechanics, hemodynamics, microbiological studies and inflammatory markers were analyzed during the 96-h experiment. During necropsy, lobar samples were also analyzed. RESULTS: All animals from pneumonia-with-VILI group reached Berlin criteria for ARDS diagnosis until the end of experiment. The mean duration under ARDS diagnosis was 46.8 ± 7.7 h; the lowest PaO2/FiO2 was 83 ± 5.45 mmHg. The group of pigs that were not subjected to VILI did not meet ARDS criteria, even when presenting with bilateral pneumonia. Animals developing ARDS presented hemodynamic instability as well as severe hypercapnia despite high-minute ventilation. Unlike the pneumonia-without-VILI group, the ARDS animals presented lower static compliance (p = 0.011) and increased pulmonary permeability (p = 0.013). The highest burden of P. aeruginosa was found at pneumonia diagnosis in all animals, as well as a high inflammatory response shown by a release of interleukin (IL)-6 and IL-8. At histological examination, only animals comprising the pneumonia-with-VILI group presented signs consistent with diffuse alveolar damage. CONCLUSIONS: In conclusion, we established an accurate pulmonary sepsis-induced ARDS model.

Effect of a low versus intermediate tidal volume strategy on pulmonary complications in patients at risk of acute respiratory distress syndrome-a randomized clinical trial.

Introduction: There is no consensus on whether invasive ventilation should use low tidal volumes (VT) to prevent lung complications in patients at risk of acute respiratory distress syndrome (ARDS). The purpose of this study is to determine if a low VT strategy is more effective than an intermediate VT strategy in preventing pulmonary complications. Methods: A randomized clinical trial was conducted in invasively ventilated patients with a lung injury prediction score (LIPS) of >4 performed in the intensive care units of 10 hospitals in Spain and one in the United States of America (USA) from 3 November 2014 to 30 August 2016. Patients were randomized to invasive ventilation using low VT (≤ 6 mL/kg predicted body weight, PBW) (N = 50) or intermediate VT (> 8 mL/kg PBW) (N = 48). The primary endpoint was the development of ARDS during the first 7 days after the initiation of invasive ventilation. Secondary endpoints included the development of pneumonia and severe atelectases; the length of intensive care unit (ICU) and hospital stay; and ICU, hospital, 28- and 90-day mortality. Results: In total, 98 patients [67.3% male], with a median age of 65.5 years [interquartile range 55-73], were enrolled until the study was prematurely stopped because of slow recruitment and loss of equipoise caused by recent study reports. On day 7, five (11.9%) patients in the low VT group and four (9.1%) patients in the intermediate VT group had developed ARDS (risk ratio, 1.16 [95% CI, 0.62-2.17]; p = 0.735). The incidence of pneumonia and severe atelectasis was also not different between the two groups. The use of a low VT strategy did neither affect the length of ICU and hospital stay nor mortality rates. Conclusions: In patients at risk for ARDS, a low VT strategy did not result in a lower incidence of ARDS than an intermediate VT strategy.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02070666.

Associations of anemia and blood transfusions with mortality in old, critically ill COVID-19 patients - Results from the prospective COVIP Study.

AIMS: Anemia is common in the old and often observed in critically ill patients. Increased age is associated with higher mortality following a COVID-19 infection, making old patients prone to poor outcomes. We investigated whether anemia at admission to the ICU or the need for blood transfusion was associated with 90-day mortality in older, critically ill COVID-19 patients. METHODS: In this prospective multicenter study, the 90-day mortality of COVID-19 patients≥70 years treated in 138 intensive care units (ICU) was analyzed. Associations between anemia (WHO definition) at admission and discharge from ICU and the use of red blood cell (RBC) transfusions with mortality were assessed. Hemoglobin thresholds of RBC transfusions in old, critically ill COVID-19 patients were recorded. RESULTS: In 493 patients (350 anemic, 143 non-anemic), anemia (WHO definition) at the time of ICU admission was not associated with impaired overall survival. Transfusion and severe anemia (hemoglobin≤10 g/dL) at ICU discharge were independently associated with a higher risk of 90-day mortality. CONCLUSION: The need for red blood cell transfusions and severe anemia at ICU discharge, but not at the timepoint of admission, were independently associated with 90-day mortality in critically-ill old COVID-19 patients.

Bioengineered extracellular vesicles: future of precision medicine for sepsis.

Sepsis is a syndromic response to infection and is frequently a final common pathway to death from many infectious diseases worldwide. The complexity and high heterogeneity of sepsis hinder the possibility to treat all patients with the same protocol, requiring personalized management. The versatility of extracellular vesicles (EVs) and their contribution to sepsis progression bring along promises for one-to-one tailoring sepsis treatment and diagnosis. In this article, we critically review the endogenous role of EVs in sepsis progression and how current advancements have improved EVs-based therapies toward their translational future clinical application, with innovative strategies to enhance EVs effect. More complex approaches, including hybrid and fully synthetic nanocarriers that mimic EVs, are also discussed. Several pre-clinical and clinical studies are examined through the review to offer a general outlook of the current and future perspectives of EV-based sepsis diagnosis and treatment.

Serial Urinary C-C Motif Chemokine Ligand 14 and Risk of Persistent Severe Acute Kidney Injury.

To assess the added prognostic value of serial monitoring of urinary C-C motif chemokine ligand 14 (uCCL14) over that of single measurements, which have been shown to be prognostic for development of persistent severe acute kidney injury (AKI) in critically ill patients. DESIGN: Retrospective observational study. SETTING: Data derived from two multinational ICU studies (Ruby and Sapphire). PATIENTS: Critically ill patients with early stage 2-3 AKI. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed three consecutive uCCL14 measurements at 12-hour intervals after diagnosis of stage 2-3 AKI by Kidney Disease Improving Global Outcomes criteria. Primary outcome was persistent severe AKI, defined as 72 consecutive hours of stage 3 AKI, death, or receipt of dialysis prior to 72 hours. uCCL14 was measured using the NEPHROCLEAR uCCL14 Test on the Astute 140 Meter (Astute Medical, San Diego, CA). Based on predefined, validated cutoffs, we categorized uCCL14 as: low (≤ 1.3 ng/mL), medium (> 1.3 to ≤ 13 ng/mL), or high (> 13 ng/mL). Seventy-five of 417 patients with three consecutive uCCL14 measurements developed persistent severe AKI. Initial uCCL14 category strongly correlated with primary endpoint and, in most cases (66%), uCCL14 category was unchanged over the first 24 hours. Compared with no change and accounting for baseline category, decrease in category was associated with decreased odds of persistent severe AKI (odds ratio [OR], 0.20; 95% CI, 0.08-0.45; p < 0.001) and an increase in category with increased odds (OR, 4.04; 95% CI, 1.75-9.46; p = 0.001). CONCLUSIONS: In one-third of patients with moderate to severe AKI uCCL14 risk category altered over three serial measurements and such changes were associated with altered risk for persistent severe AKI. Serial CCL-14 measurement may detect progression or resolution of underlying kidney pathology and help refine AKI prognosis.

Diabetes mellitus is associated with 90-day mortality in old critically ill COVID-19 patients: a multicenter prospective observational cohort study.

BACKGROUND: Several studies have found an association between diabetes mellitus, disease severity and outcome in COVID-19 patients. Old critically ill patients are particularly at risk. This study aimed to investigate the impact of diabetes mellitus on 90-day mortality in a high-risk cohort of critically ill patients over 70 years of age. METHODS: This multicentre international prospective cohort study was performed in 151 ICUs across 26 countries. We included patients ≥ 70 years of age with a confirmed SARS-CoV-2 infection admitted to the intensive care unit from 19th March 2020 through 15th July 2021. Patients were categorized into two groups according to the presence of diabetes mellitus. Primary outcome was 90-day mortality. Kaplan-Meier overall survival curves until day 90 were analysed and compared using the log-rank test. Mixed-effect Weibull regression models were computed to investigate the influence of diabetes mellitus on 90-day mortality. RESULTS: This study included 3420 patients with a median age of 76 years were included. Among these, 37.3% (n = 1277) had a history of diabetes mellitus. Patients with diabetes showed higher rates of frailty (32% vs. 18%) and several comorbidities including chronic heart failure (20% vs. 11%), hypertension (79% vs. 59%) and chronic kidney disease (25% vs. 11%), but not of pulmonary comorbidities (22% vs. 22%). The 90-day mortality was significantly higher in patients with diabetes than those without diabetes (64% vs. 56%, p < 0.001). The association of diabetes and 90-day mortality remained significant (HR 1.18 [1.06-1.31], p = 0.003) after adjustment for age, sex, SOFA-score and other comorbidities in a Weibull regression analysis. CONCLUSION: Diabetes mellitus was a relevant risk factor for 90-day mortality in old critically ill patients with COVID-19. STUDY REGISTRATION: NCT04321265, registered March 19th, 2020.

Inhaled amikacin for pneumonia treatment and dissemination prevention: an experimental model of severe monolateral Pseudomonas aeruginosa pneumonia.

BACKGROUND: Pseudomonas aeruginosa pneumonia is commonly treated with systemic antibiotics to ensure adequate treatment of multidrug resistant (MDR) bacteria. However, intravenous (IV) antibiotics often achieve suboptimal pulmonary concentrations. We therefore aimed to evaluate the effect of inhaled amikacin (AMK) plus IV meropenem (MEM) on bactericidal efficacy in a swine model of monolateral MDR P. aeruginosa pneumonia. METHODS: We ventilated 18 pigs with monolateral MDR P. aeruginosa pneumonia for up to 102 h. At 24 h after the bacterial challenge, the animals were randomized to receive 72 h of treatment with either inhaled saline (control), IV MEM only, or IV-MEM plus inhaled AMK (MEM + AMK). We dosed IV MEM at 25 mg/kg every 8 h and inhaled AMK at 400 mg every 12 h. The primary outcomes were the P. aeruginosa burden and histopathological injury in lung tissue. Secondary outcomes included the P. aeruginosa burden in tracheal secretions and bronchoalveolar lavage fluid, the development of antibiotic resistance, the antibiotic distribution, and the levels of inflammatory markers. RESULTS: The median (25-75th percentile) P. aeruginosa lung burden for animals in the control, MEM only, and MEM + AMK groups was 2.91 (1.75-5.69), 0.72 (0.12-3.35), and 0.90 (0-4.55) log10 CFU/g (p = 0.009). Inhaled therapy had no effect on preventing dissemination compared to systemic monotherapy, but it did have significantly higher bactericidal efficacy in tracheal secretions only. Remarkably, the minimum inhibitory concentration of MEM increased to > 32 mg/L after 72-h exposure to monotherapy in 83% of animals, while the addition of AMK prevented this increase (p = 0.037). Adjunctive therapy also slightly affected interleukin-1ß downregulation. Despite finding high AMK concentrations in pulmonary samples, we found no paired differences in the epithelial lining fluid concentration between infected and non-infected lungs. Finally, a non-significant trend was observed for higher amikacin penetration in low-affected lung areas. CONCLUSIONS: In a swine model of monolateral MDR P. aeruginosa pneumonia, resistant to the inhaled AMK and susceptible to the IV antibiotic, the use of AMK as an adjuvant treatment offered no benefits for either the colonization of pulmonary tissue or the prevention of pathogen dissemination. However, inhaled AMK improved bacterial eradication in the proximal airways and hindered antibiotic resistance.

SEVERE CORONAVIRUS DISEASE 2019: FROM PATHOGENESIS TO THERAPY.

ABSTRACT: The COVID-19 pandemic has been a challenge to propose efficient therapies. Because severe SARS-CoV2 infection is a viral sepsis eventually followed by an immunological autoinflammatory phenomenon, many approaches have been inspired by the previous attempts made in bacterial sepsis, while specific antiviral strategies (use of interferon or specific drugs) have been additionally investigated. We summarize our current thinking on the use of SARS-CoV-2 antivirals, corticosteroids, anti-IL-1, anti-IL-6, anti-C5a, as well as stem cell therapy in severe COVID-19. Patient stratification and appropriate time window will be important to be defined to guide successful treatment.

Practice of Awake Prone Positioning in Critically Ill COVID-19 Patients-Insights from the PRoAcT-COVID Study.

We describe the incidence, practice and associations with outcomes of awake prone positioning in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) in a national multicenter observational cohort study performed in 16 intensive care units in the Netherlands (PRoAcT−COVID-study). Patients were categorized in two groups, based on received treatment of awake prone positioning. The primary endpoint was practice of prone positioning. Secondary endpoint was 'treatment failure', a composite of intubation for invasive ventilation and death before day 28. We used propensity matching to control for observed confounding factors. In 546 patients, awake prone positioning was used in 88 (16.1%) patients. Prone positioning started within median 1 (0 to 2) days after ICU admission, sessions summed up to median 12.0 (8.4−14.5) hours for median 1.0 day. In the unmatched analysis (HR, 1.80 (1.41−2.31); p < 0.001), but not in the matched analysis (HR, 1.17 (0.87−1.59); p = 0.30), treatment failure occurred more often in patients that received prone positioning. The findings of this study are that awake prone positioning was used in one in six COVID-19 patients. Prone positioning started early, and sessions lasted long but were often discontinued because of need for intubation.