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

Efectos fisiológicos de diferentes estrategias ventilatorias empleadas en pacientes con insuficiencia respiratoria aguda severa

Los estudios realizados en la presente tesis están alineadas en determinar los efectos fisiológicos de dos estrategias utilizadas en pacientes en ventilación mecánica con insuficiencia respiratoria aguda severa. Las estrategias analizadas son habitualmente utilizadas en estos pacientes. El primer estudio presentado es sobre el alargamiento de la pausa inspiratoria. En este estudio se ha confirmado que el alargamiento de la pausa inspiratoria disminuye significativamente el espacio muerto y la PaCO2. Con este estudio, se proporciona una aplicación clínica de esta estrategia, ya que, la disminución de la PaCO2 permite disminuir el volumen corriente administrado y ayudar a la ventilación protectiva. El segundo estudio presentado es sobre la variación de los volúmenes pulmonares y el strain (deformación del tejido pulmonar causado por el cambio de volumen) con el cambio de posición de supino a prono. Este estudio ha permitido demostrar que los volúmenes pulmonares aumentan significativamente en la posición prono y disminuye significativamente el strain dinámico sobre el tejido pulmonar. Estos hallazgos pueden explicar la mejoría de los resultados clínicos con el uso de la posición prono en pacientes con síndrome de distres respiratorio agudo grave. La relativa sencillez e inocuidad de las estrategias estudiadas facilita su aplicación en el manejo clínico diario de estos pacientes y la información encontrada puede servir de base para futuros estudios y ampliar su uso en otro tipo de pacientes y patologías.The studies described in this thesis are about the physiological effects of two common strategies that are used in mechanically ventilated patients with acute severe respiratory failure. The first study was about the prolongation of inspiratory pause. This study confirmed that the prolongation of inspiratory pause significantly decreased dead space and PaCO2. Indeed, this study provides a clinical application of this strategy, because the decrease of the PaCO2 allows a significant decrease of tidal volume and helps to set the protective ventilation. The second study analysed the variation of lung volumes and strain with the change from supine position to prone position. This study showed a significant increase in lung volumes and a significant decrease of strain in prone position. These findings could explain the improvement of outcomes with prone position in severe acute respiratory distress syndrome patients. The relative simplicity and safety of these strategies facilitates its application at the bedside. These data could form the basis for future studies in other types of patients and pathologies

Efectos fisiológicos de diferentes estrategias ventilatorias empleadas en pacientes con insuficiencia respiratoria aguda severa

Los estudios realizados en la presente tesis están alineadas en determinar los efectos fisiológicos de dos estrategias utilizadas en pacientes en ventilación mecánica con insuficiencia respiratoria aguda severa. Las estrategias analizadas son habitualmente utilizadas en estos pacientes. El primer estudio presentado es sobre el alargamiento de la pausa inspiratoria. En este estudio se ha confirmado que el alargamiento de la pausa inspiratoria disminuye significativamente el espacio muerto y la PaCO2. Con este estudio, se proporciona una aplicación clínica de esta estrategia, ya que, la disminución de la PaCO2 permite disminuir el volumen corriente administrado y ayudar a la ventilación protectiva. El segundo estudio presentado es sobre la variación de los volúmenes pulmonares y el strain (deformación del tejido pulmonar causado por el cambio de volumen) con el cambio de posición de supino a prono. Este estudio ha permitido demostrar que los volúmenes pulmonares aumentan significativamente en la posición prono y disminuye significativamente el strain dinámico sobre el tejido pulmonar. Estos hallazgos pueden explicar la mejoría de los resultados clínicos con el uso de la posición prono en pacientes con síndrome de distres respiratorio agudo grave. La relativa sencillez e inocuidad de las estrategias estudiadas facilita su aplicación en el manejo clínico diario de estos pacientes y la información encontrada puede servir de base para futuros estudios y ampliar su uso en otro tipo de pacientes y patologías.The studies described in this thesis are about the physiological effects of two common strategies that are used in mechanically ventilated patients with acute severe respiratory failure. The first study was about the prolongation of inspiratory pause. This study confirmed that the prolongation of inspiratory pause significantly decreased dead space and PaCO2. Indeed, this study provides a clinical application of this strategy, because the decrease of the PaCO2 allows a significant decrease of tidal volume and helps to set the protective ventilation. The second study analysed the variation of lung volumes and strain with the change from supine position to prone position. This study showed a significant increase in lung volumes and a significant decrease of strain in prone position. These findings could explain the improvement of outcomes with prone position in severe acute respiratory distress syndrome patients. The relative simplicity and safety of these strategies facilitates its application at the bedside. These data could form the basis for future studies in other types of patients and pathologies

Estudio clínico, observacional, de una nueva modalidad ventilatoria; Ventilación Asistida Proporcional. Hospital de la Santa Creu i Sant Pau, Barcelona, 2010

La ventilació assistida proporcional és una modalitat en la que el respirador genera una assistència proporcional a l'esforç muscular del pacient. En aquest estudi s'han inclòs vuit malalts en "weaning" de la ventilació mecànica. Es descriu la tolerància clínica i es quantifica l'esforç muscular dels pacients. L'esforç muscular va estar sempre dintre de límits predefinits de confort. Concloem que la ventilació assistida proporcional dóna una ventilació mecànica similar a altres modalitats i és probablement més fisiològica.La Ventilación Asistida Proporcional es una modalidad en la que el respirador genera una asistencia proporcional al esfuerzo muscular del paciente. En el estudio se incluyeron ocho pacientes en "weaning" de ventilación mecánica. Se describe la tolerancia clínica y analiza el esfuerzo muscular que los pacientes realizan. El esfuerzo muscular se mantuvo dentro de los niveles predefinidos de confort durante toda la ventilación. Concluimos que la ventilación asistida proporcional brinda una ventilación mecánica similar a otras modalidades ventilatorias y probablemente más fisiológica

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort

BACKGROUND Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. METHODS Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. RESULTS Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). CONCLUSION In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.

BACKGROUND Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. METHODS Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. RESULTS Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). CONCLUSION In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort

Background: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is wide‑ spread. While the risks and benefts of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefts of diferent respiratory sup‑ port strategies, employed in intensive care units during the frst months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. Methods: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclas‑ sifed into standard oxygen therapy ≥10 L/min (SOT), high-fow oxygen therapy (HFNC), noninvasive positive-pressur

Machine learning using the extreme gradient boosting (XGBoost) algorithm predicts 5-day delta of SOFA score at ICU admission in COVID-19 patients

Background: Accurate risk stratification of critically ill patients with coronavirus disease 2019 (COVID-19) is essential for optimizing resource allocation, delivering targeted interventions, and maximizing patient survival probability. Machine learning (ML) techniques are attracting increased interest for the development of prediction models as they excel in the analysis of complex signals in data-rich environments such as critical care. Methods: We retrieved data on patients with COVID-19 admitted to an intensive care unit (ICU) between March and October 2020 from the RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry. We applied the Extreme Gradient Boosting (XGBoost) algorithm to the data to predict as a binary out- come the increase or decrease in patients’ Sequential Organ Failure Assessment (SOFA) score on day 5 after ICU admission. The model was iteratively cross-validated in different subsets of the study cohort. Results: The final study population consisted of 675 patients. The XGBoost model correctly predicted a decrease in SOFA score in 320/385 (83%) critically ill COVID-19 patients, and an increase in the score in 210/290 (72%) patients. The area under the mean receiver operating characteristic curve for XGBoost was significantly higher than that for the logistic regression model (0.86 vs . 0.69, P < 0.01 [paired t -test with 95% confidence interval]). Conclusions: The XGBoost model predicted the change in SOFA score in critically ill COVID-19 patients admitted to the ICU and can guide clinical decision support systems (CDSSs) aimed at optimizing available resources

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort

Background: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is wide‑ spread. While the risks and benefts of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefts of diferent respiratory sup‑ port strategies, employed in intensive care units during the frst months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. Methods: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclas‑ sifed into standard oxygen therapy ≥10 L/min (SOT), high-fow oxygen therapy (HFNC), noninvasive positive-pressureBackground: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. Methods: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. Results: Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). Conclusion: In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

International audienceBackground: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society