Prevalence and Survival of Prolonged Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: An Analysis of the Extracorporeal Life Support Organization Registry.

OBJECTIVES: To examine trends in utilization and outcomes among patients with the acute respiratory distress syndrome (ARDS) requiring prolonged venovenous extracorporeal membrane oxygenation (VV ECMO) support. DESIGN: Retrospective observational cohort study. SETTING: Adult patients in the Extracorporeal Life Support Organization registry. PATIENTS: Thirteen thousand six hundred eighty-one patients that required ECMO for the support of ARDS between January 2012 and December 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mortality while supported with VV ECMO and survival to hospital discharge based on ECMO duration were examined utilizing multivariable logistic regression. Among the 13,681 patients supported with VV ECMO, 4,040 (29.5%) were supported for greater than or equal to 21 days and 975 (7.1%) for greater than or equal to 50 days. Patients supported with prolonged VV ECMO were less likely to be discharged alive from the hospital compared with those with short duration of support (46.5% vs. 59.7%; p < 0.001). However, among patients supported with VV ECMO greater than or equal to 21 days, duration of extracorporeal life support was not significantly associated with mortality (odds ratio [OR], 0.99; 95% CI, 0.98-1.01; p = 0.87 and adjusted OR, 0.99; 95% CI, 0.97-1.02; p = 0.48). Even in those supported with VV ECMO for at least 120 days (n = 113), 52 (46.0%) of these patients were ultimately discharged alive from the hospital. CONCLUSIONS: Prolonged VV ECMO support of ARDS has increased and accounts for a substantial portion of cases. Among patients that survive for greater than or equal to 21 days while receiving VV ECMO support, duration is not predictive of survival to hospital discharge and clinical recovery may occur even after very prolonged VV ECMO support.

Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS): study protocol for an international randomized clinical trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on "focal" or "non-focal" lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish "focal" from "non-focal" lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation. METHODS: The Personalized Mechanical Ventilation Guided by UltraSound in Patients with Acute Respiratory Distress Syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. Eligible patients will receive a LUS exam to classify lung morphology as "focal" or "non-focal". Thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for "non-focal" ARDS and lower PEEP and prone positioning for "focal" ARDS. The primary endpoint is all-cause mortality at day 90. Secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). After a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated. DISCUSSION: PEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach. TRIAL REGISTRATION: The PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344).

Comparison of limited driving pressure ventilation and low tidal volume strategies in adults with acute respiratory failure on mechanical ventilation: a randomized controlled trial.

BACKGROUND: Ventilator-induced lung injury (VILI) presents a grave risk to acute respiratory failure patients undergoing mechanical ventilation. Low tidal volume (LTV) ventilation has been advocated as a protective strategy against VILI. However, the effectiveness of limited driving pressure (plateau pressure minus positive end-expiratory pressure) remains unclear. OBJECTIVES: This study evaluated the efficacy of LTV against limited driving pressure in preventing VILI in adults with respiratory failure. DESIGN: A single-centre, prospective, open-labelled, randomized controlled trial. METHODS: This study was executed in medical intensive care units at Siriraj Hospital, Mahidol University, Bangkok, Thailand. We enrolled acute respiratory failure patients undergoing intubation and mechanical ventilation. They were randomized in a 1:1 allocation to limited driving pressure (LDP; ⩽15 cmH2O) or LTV (⩽8 mL/kg of predicted body weight). The primary outcome was the acute lung injury (ALI) score 7 days post-enrolment. RESULTS: From July 2019 to December 2020, 126 patients participated, with 63 each in the LDP and LTV groups. The cohorts had the mean (standard deviation) ages of 60.5 (17.6) and 60.9 (17.9) years, respectively, and they exhibited comparable baseline characteristics. The primary reasons for intubation were acute hypoxic respiratory failure (LDP 49.2%, LTV 63.5%) and shock-related respiratory failure (LDP 39.7%, LTV 30.2%). No significant difference emerged in the primary outcome: the median (interquartile range) ALI scores for LDP and LTV were 1.75 (1.00-2.67) and 1.75 (1.25-2.25), respectively (p = 0.713). Twenty-eight-day mortality rates were comparable: LDP 34.9% (22/63), LTV 31.7% (20/63), relative risk (RR) 1.08, 95% confidence interval (CI) 0.74-1.57, p = 0.705. Incidences of newly developed acute respiratory distress syndrome also aligned: LDP 14.3% (9/63), LTV 20.6% (13/63), RR 0.81, 95% CI 0.55-1.22, p = 0.348. CONCLUSIONS: In adults with acute respiratory failure, the efficacy of LDP and LTV in averting lung injury 7 days post-mechanical ventilation was indistinguishable. CLINICAL TRIAL REGISTRATION: The study was registered with the ClinicalTrials.gov database (identification number NCT04035915).

Limited breathing pressure or low amount of air given to the lung; which one is better for adults who need breathing help by ventilator machineWe conducted this research at Siriraj Hospital in Bangkok, Thailand, aiming to compare two ways of helping patients with breathing problems. We studied 126 patients who were randomly put into two groups. One group received a method where the pressure during breathing was limited (limited driving pressure: LDP), and the other group got a method where the amount of air given to the lungs was kept low (low tidal volume: LTV). We checked how bad the lung injury was at seven days later. The results showed that there was no difference between the two methods. Both ways of helping patients breathe had similar outcomes, and neither was significantly better than the other in preventing lung problems. The study suggests that both approaches work about the same for patients who need help with breathing using a machine.

Prone positioning does not improve outcomes of intubated patients with pneumocystis pneumonia and moderate-severe acute respiratory distress syndrome: a single-center, retrospective, observational, cohort study.

BACKGROUND: Pneumocystis pneumonia is an uncommon precipitant of acute respiratory distress syndrome and is associated with high mortality. Prone positioning ventilation has been proven to reduce mortality in patients with moderate-severe acute respiratory distress syndrome. We investigated the effect of prone positioning on oxygenation and mortality in intubated patients with pneumocystis pneumonia comorbid with moderate-severe acute respiratory distress syndrome. METHODS: In this single-center, retrospective, observational, cohort study, eligible patients were enrolled at West China Hospital of Sichuan University from January 1, 2017, to December 31, 2021. Data on demographics, clinical features, ventilation parameters, arterial blood gas, and outcomes were collected. Patients were assigned to the prone cohort or supine cohort according to whether they received prone positioning ventilation. The main outcome was 28-day mortality. FINDINGS: A total of 79 patients were included in the study. Sixty-three patients were enrolled in the prone cohort, and 16 patients were enrolled in the supine cohort. The 28-day mortality was 61.9% in the prone cohort and 68.8% in the supine cohort (P = 0.26), and 90-day mortality was 66.7% in the prone cohort and 68.8% in the supine cohort (P = 0.55). Patients in the supine cohort had fewer invasive mechanical ventilation days and more ventilator-free days. The incidence of complications was higher in the prone cohort than in the supine cohort. CONCLUSIONS: In patients with pneumocystis pneumonia and moderate-severe acute respiratory distress syndrome, prone positioning did not decrease 28-day or 90-day mortality. Trial registration ClinicalTrials.gov number, ChiCTR2200063889. Registered on 20 September 2022, https://www.chictr.org.cn/showproj.html?proj=174886 .

Inflammatory subphenotypes previously identified in ARDS are associated with mortality at intensive care unit discharge: a secondary analysis of a prospective observational study.

BACKGROUND: Intensive care unit (ICU)-survivors have an increased risk of mortality after discharge compared to the general population. On ICU admission subphenotypes based on the plasma biomarker levels of interleukin-8, protein C and bicarbonate have been identified in patients admitted with acute respiratory distress syndrome (ARDS) that are prognostic of outcome and predictive of treatment response. We hypothesized that if these inflammatory subphenotypes previously identified among ARDS patients are assigned at ICU discharge in a more general critically ill population, they are associated with short- and long-term outcome. METHODS: A secondary analysis of a prospective observational cohort study conducted in two Dutch ICUs between 2011 and 2014 was performed. All patients discharged alive from the ICU were at ICU discharge adjudicated to the previously identified inflammatory subphenotypes applying a validated parsimonious model using variables measured median 10.6 h [IQR, 8.0-31.4] prior to ICU discharge. Subphenotype distribution at ICU discharge, clinical characteristics and outcomes were analyzed. As a sensitivity analysis, a latent class analysis (LCA) was executed for subphenotype identification based on plasma protein biomarkers at ICU discharge reflective of coagulation activation, endothelial cell activation and inflammation. Concordance between the subphenotyping strategies was studied. RESULTS: Of the 8332 patients included in the original cohort, 1483 ICU-survivors had plasma biomarkers available and could be assigned to the inflammatory subphenotypes. At ICU discharge 6% (n = 86) was assigned to the hyperinflammatory and 94% (n = 1397) to the hypoinflammatory subphenotype. Patients assigned to the hyperinflammatory subphenotype were discharged with signs of more severe organ dysfunction (SOFA scores 7 [IQR 5-9] vs. 4 [IQR 2-6], p < 0.001). Mortality was higher in patients assigned to the hyperinflammatory subphenotype (30-day mortality 21% vs. 11%, p = 0.005; one-year mortality 48% vs. 28%, p < 0.001). LCA deemed 2 subphenotypes most suitable. ICU-survivors from class 1 had significantly higher mortality compared to class 2. Patients belonging to the hyperinflammatory subphenotype were mainly in class 1. CONCLUSIONS: Patients assigned to the hyperinflammatory subphenotype at ICU discharge showed significantly stronger anomalies in coagulation activation, endothelial cell activation and inflammation pathways implicated in the pathogenesis of critical disease and increased mortality until one-year follow up.

Causes and attributable fraction of death from ARDS in inflammatory phenotypes of sepsis.

BACKGROUND: Hypoinflammatory and hyperinflammatory phenotypes have been identified in both Acute Respiratory Distress Syndrome (ARDS) and sepsis. Attributable mortality of ARDS in each phenotype of sepsis is yet to be determined. We aimed to estimate the population attributable fraction of death from ARDS (PAFARDS) in hypoinflammatory and hyperinflammatory sepsis, and to determine the primary cause of death within each phenotype. METHODS: We studied 1737 patients with sepsis from two prospective cohorts. Patients were previously assigned to the hyperinflammatory or hypoinflammatory phenotype using latent class analysis. The PAFARDS in patients with sepsis was estimated separately in the hypo and hyperinflammatory phenotypes. Organ dysfunction, severe comorbidities, and withdrawal of life support were abstracted from the medical record in a subset of patients from the EARLI cohort who died (n = 130/179). Primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support. RESULTS: The PAFARDS was 19% (95%CI 10,28%) in hypoinflammatory sepsis and, 14% (95%CI 6,20%) in hyperinflammatory sepsis. Cause of death differed between the two phenotypes (p < 0.001). Respiratory failure was the most common cause of death in hypoinflammatory sepsis, whereas circulatory shock was the most common cause in hyperinflammatory sepsis. Death with severe underlying comorbidities was more frequent in hypoinflammatory sepsis (81% vs. 67%, p = 0.004). CONCLUSIONS: The PAFARDS is modest in both phenotypes whereas primary cause of death among patients with sepsis differed substantially by phenotype. This study identifies challenges in powering future clinical trials to detect changes in mortality outcomes among patients with sepsis and ARDS.

Endotyping in ARDS: one step forward in precision medicine.

BACKGROUND: The Berlin definition of acute respiratory distress syndrome (ARDS) includes only clinical characteristics. Understanding unique patient pathobiology may allow personalized treatment. We aimed to define and describe ARDS phenotypes/endotypes combining clinical and pathophysiologic parameters from a Canadian ARDS cohort. METHODS: A cohort of adult ARDS patients from multiple sites in Calgary, Canada, had plasma cytokine levels and clinical parameters measured in the first 24 h of ICU admission. We used a latent class model (LCM) to group the patients into several ARDS subgroups and identified the features differentiating those subgroups. We then discuss the subgroup effect on 30 day mortality. RESULTS: The LCM suggested three subgroups (n1 = 64, n2 = 86, and n3 = 30), and 23 out of 69 features made these subgroups distinct. The top five discriminating features were IL-8, IL-6, IL-10, TNF-a, and serum lactate. Mortality distinctively varied between subgroups. Individual clinical characteristics within the subgroup associated with mortality included mean PaO2/FiO2 ratio, pneumonia, platelet count, and bicarbonate negatively associated with mortality, while lactate, creatinine, shock, chronic kidney disease, vasopressor/ionotropic use, low GCS at admission, and sepsis were positively associated. IL-8 and Apache II were individual markers strongly associated with mortality (Area Under the Curve = 0.84). PERSPECTIVE: ARDS subgrouping using biomarkers and clinical characteristics is useful for categorizing a heterogeneous condition into several homogenous patient groups. This study found three ARDS subgroups using LCM; each subgroup has a different level of mortality. This model may also apply to developing further trial design, prognostication, and treatment selection.

Driving pressure, as opposed to tidal volume based on predicted body weight, is associated with mortality: results from a prospective cohort of COVID-19 acute respiratory distress syndrome patients.

OBJECTIVE: To evaluate the association between driving pressure and tidal volume based on predicted body weight and mortality in a cohort of patients with acute respiratory distress syndrome caused by COVID-19. METHODS: This was a prospective, observational study that included patients with acute respiratory distress syndrome due to COVID-19 admitted to two intensive care units. We performed multivariable analyses to determine whether driving pressure and tidal volume/kg predicted body weight on the first day of mechanical ventilation, as independent variables, are associated with hospital mortality. RESULTS: We included 231 patients. The mean age was 64 (53 - 74) years, and the mean Simplified Acute and Physiology Score 3 score was 45 (39 - 54). The hospital mortality rate was 51.9%. Driving pressure was independently associated with hospital mortality (odds ratio 1.21, 95%CI 1.04 - 1.41 for each cm H2O increase in driving pressure, p = 0.01). Based on a double stratification analysis, we found that for the same level of tidal volume/kg predicted body weight, the risk of hospital death increased with increasing driving pressure. However, changes in tidal volume/kg predicted body weight were not associated with mortality when they did not lead to an increase in driving pressure. CONCLUSION: In patients with acute respiratory distress syndrome caused by COVID-19, exposure to higher driving pressure, as opposed to higher tidal volume/kg predicted body weight, is associated with greater mortality. These results suggest that driving pressure might be a primary target for lung-protective mechanical ventilation in these patients.

Accuracy of the Verbal Autopsy questionnaire in the diagnosis of COVID-19 deaths in a Brazilian capital.

The Verbal Autopsy (VA) is a questionnaire about the circumstances surrounding a death. It was widely used in Brazil to assist in postmortem diagnoses and investigate excess mortality during the Coronavirus Disease 2019 (COVID-19) pandemic. This study aimed to determine the accuracy of investigating acute respiratory distress syndrome (ARDS) using VA. This is a cross-sectional study with prospective data collected from January 2020 to August 2021 at the Death Verification Service of Sao Luis city, Brazil. VA was performed for suspected COVID-19 deaths, and one day of the week was randomly chosen to collect samples from patients without suspected COVID-19. Two swabs were collected after death and subjected to reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection. Of the 250 cases included, the VA questionnaire identified COVID-19-related ARDS in 67.2% (52.98% were positive for COVID-19). The sensitivity of the VA questionnaire was 0.53 (0.45-0.61), the specificity was 0.75 (0.64-0.84), the positive predictive value was 0.81 (0.72-0.88), and the negative predictive value was 0.44 (0.36-0.53). The VA had a lower-than-expected accuracy for detecting COVID-19 deaths; however, because it is an easily accessible and cost-effective tool, it can be combined with more accurate methods to improve its performance.

Use of CPAP Ventilation in Non-ICU Wards May Influence Outcomes in Patients with Severe Respiratory COVID-19.

Background and Objectives: The COVID-19 disease has significantly burdened the healthcare system, including all units of severe patient treatment. Non-intensive care units were established to rationalize the capacity within the Intensive Care Unit (ICU) and to create a unit where patients with Acute Respiratory Distress Syndrome (ARDS) could be treated with non-invasive Continuous Positive Air Pressure (CPAP) outside the ICU. This unicentric retrospective study aimed to assess the efficacy of NIV Treatment in Patients of the fourth pandemic wave and how its application affects the frequency and mortality of ICU-treated patients at University Hospital Rijeka compared to earlier waves of the COVID-19 pandemic. Furthermore, the study showcases the effect of the Patient/Nurse ratio (P/N ratio) on overall mortality in the ICU. Materials and Methods: The study was conducted on two groups of patients with respiratory insufficiency in the second and third pandemic waves, treated in the COVID Respiratory Centre (CRC) (153 patients). We also reviewed a cohort of patients from the fourth pandemic wave who were initially hospitalized in a COVID-6 non-intensive unit from 1 October 2021 to 1 November 2022 (102 patients), and some of them escalated to CRC. Results: The introduction of the CPAP non-invasive ventilation method as a means of hypoxic respiratory failure treatment in non-intensive care units has decreased the strain, overall number of admissions, and CRC patient mortality. The overall fourth wave mortality was 29.4%, compared to the 58.2% overall mortality of the second and third waves. Conclusions: As a result, this has decreased CRC patient admissions and, by itself, overall mortality.

Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome.

BACKGROUNDThe molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes to outcomes is unknown. Therefore, we profiled inflammation and tissue injury dynamics over the first 7 days of ARDS, and associated specific biomarkers with mortality, persistent ARDS, and persistent multiple organ dysfunction syndrome (MODS).METHODSIn a single-center prospective cohort of intubated pediatric patients with ARDS, we collected plasma on days 0, 3, and 7. Nineteen biomarkers reflecting inflammation, tissue injury, and damage-associated molecular patterns (DAMPs) were measured. We assessed the relationship between biomarkers and trajectories with mortality, persistent ARDS, or persistent MODS using multivariable mixed effect models.RESULTSIn 279 patients (64 [23%] nonsurvivors), hyperinflammatory cytokines, tissue injury markers, and DAMPs were higher in nonsurvivors. Survivors and nonsurvivors showed different biomarker trajectories. IL-1α, soluble tumor necrosis factor receptor 1, angiopoietin 2 (ANG2), and surfactant protein D increased in nonsurvivors, while DAMPs remained persistently elevated. ANG2 and procollagen type III N-terminal peptide were associated with persistent ARDS, whereas multiple cytokines, tissue injury markers, and DAMPs were associated with persistent MODS. Corticosteroid use did not impact the association of biomarker levels or trajectory with mortality.CONCLUSIONSPediatric ARDS survivors and nonsurvivors had distinct biomarker trajectories, with cytokines, endothelial and alveolar epithelial injury, and DAMPs elevated in nonsurvivors. Mortality markers overlapped with markers associated with persistent MODS, rather than persistent ARDS.FUNDINGNIH (K23HL-136688, R01-HL148054).

Association between a low-risk COVID-19 extracorporeal membrane oxygenation criteria and mortality: A retrospective study.

OBJECTIVE: Our study aimed to compare the outcomes of COVID-19 patients who met a low-risk inclusion criteria for veno-venous extra corporeal membrane oxygenation (VV ECMO) with those who did not meet criteria due to higher risk but were subsequently cannulated. METHODS: This was a retrospective observational cohort study that included adult patients who were placed on VV ECMO for COVID-19 related acute respiratory distress syndrome (ARDS) at a tertiary care academic medical center. The primary outcome was the association between the low-risk criteria and mortality. The patients met the criteria if they met EOLIA severe ARDS criteria, no absolute contraindications (age > 60 years, BMI > 55 kg/m2, mechanical ventilation (MV) duration >7 days, irreversible neurologic damage, chronic lung disease, active malignancy, or advanced multiorgan dysfunction), and had three or less relative contraindications (age > 50 years, BMI > 45 kg/m2, comorbidities, MV duration > 4 days, acute kidney injury, receiving vasopressors, hospital LOS > 14 days, or COVID-19 diagnosis > 4 weeks). RESULTS: Sixty-five patients were included from March 2020 through March 2022. Patients were stratified into low-risk or high-risk categories. The median Sequential Organ Failure Assessment score was 7 and the median PaO2/FiO2 ratio was 44 at the time of ECMO cannulation. The in-hospital mortality was 47.8% in the low-risk group and 69.0% in the high-risk group (p = 0.096). CONCLUSION: There was not a statistically significant difference in survival between low-risk patients and high-risk patients; however, there was a trend toward higher survival in the lower-risk group.

Advanced Respiratory Support Days as a Novel Marker of Mortality in COVID-19 Acute Respiratory Distress Syndrome Requiring Extracorporeal Membrane Oxygenation.

Emerging evidence suggests prolonged use of noninvasive respiratory support may increase mortality of patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome who require extracorporeal membrane oxygenation (ECMO). Using a database of adults receiving ECMO for COVID-19, we calculated survival curves and multivariable Cox regression to determine the risk of death associated with pre-ECMO use of high-flow nasal oxygen (HFNO), noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) days. We investigated the performance of a novel variable, advanced respiratory support days (composite of HFNO, NIV, and IMV days), on Respiratory ECMO Survival Prediction (RESP) score. Subjects (N = 146) with increasing advanced respiratory support days (<5, 5-9, and ≥10) had a stepwise increase in 90 day mortality (32.2%, 57.7%, and 75.4%, respectively; p = 0.002). Ninety-day mortality was significantly higher in subjects (N = 121) receiving NIV >4 days (81.8% vs. 52.4%, p < 0.001). Each additional pre-ECMO advanced respiratory support day increased the odds of right ventricular failure (odds ratio [OR]: 1.066, 95% confidence interval [CI]: 1.002-1.135) and in-hospital mortality (1.17, 95% CI: 1.08-1.27). Substituting advanced respiratory support days for IMV days improved RESP score mortality prediction (area under the curve (AUC) or: 0.64 vs. 0.71). Pre-ECMO advanced respiratory support days were associated with increased 90 day mortality compared with IMV days alone. Adjusting the RESP score for advanced respiratory support days improved mortality prediction.

Novel Oxygenation and Saturation Indices for Mortality Prediction in COVID-19 ARDS Patients: The Impact of Driving Pressure and Mechanical Power.

Background: The oxygenation index (OI) and oxygen saturation index (OSI) are proven mortality predictors in pediatric and adult patients, traditionally using mean airway pressure (Pmean). We introduce novel indices, replacing Pmean with DP (ΔPinsp), MPdyn, and MPtot, assessing their potential for predicting COVID-19 acute respiratory distress syndrome (ARDS) mortality, comparing them to traditional indices. Methods: We studied 361 adult COVID-19 ARDS patients for 7 days, collecting ΔPinsp, MPdyn, and MPtot, OI-ΔPinsp, OI-MPdyn, OI-MPtot, OSI-ΔPinsp, OSI-MPdyn, and OSI-MPtot. We compared these in surviving and non-surviving patients over the first 7 intensive care unit (ICU) days using Mann-Whitney U test. Logistic regression receiver operating characteristic (ROC) analysis assessed AUC and CI values for ICU mortality on day three. We determined cut-off values using Youden's method and conducted multivariate Cox regression on parameter limits. Results: All indices showed significant differences between surviving and non-surviving patients on the third day of ICU care. The AUC values of OI-ΔPinsp were significantly higher than those of P/F and OI-Pmean (P values .0002 and <.0001, respectively). Similarly, AUC and CI values of OSI-ΔPinsp and OSI-MPdyn were significantly higher than those of SpO2/FiO2 and OSI-Pmean values (OSI-ΔPinsp: P < .0001, OSI-MPdyn: P values .047 and .028, respectively). OI-ΔPinsp, OSI-ΔPinsp, OI-MPdyn, OSI-MPdyn, OI-MPtot, and OSI-MPtot had AUC values of 0.72, 0.71, 0.69, 0.68, 0.66, and 0.64, respectively, with cut-off values associated with hazard ratios and P values of 7.06 (HR = 1.84, P = .002), 8.04 (HR = 2.00, P ≤ .0001), 7.12 (HR = 1.68, P = .001), 5.76 (HR = 1.70, P ≤ .0001), 10.43 (HR = 1.52, P = .006), and 10.68 (HR = 1.66, P = .001), respectively. Conclusions: Critical values of all indices were associated to higher ICU mortality rates and extended mechanical ventilation durations. The OI-ΔPinsp, OSI-ΔPinsp, and OSI-MPdyn indices displayed the strongest predictive capabilities for ICU mortality. These novel indices offer valuable insights for intensivists in the clinical management and decision-making process for ARDS patients.

Prone Positioning During Extracorporeal Membrane Oxygenation in Patients With Severe ARDS: The PRONECMO Randomized Clinical Trial.

Importance: Prone positioning may improve outcomes in patients with severe acute respiratory distress syndrome (ARDS), but it is unknown whether prone positioning improves clinical outcomes among patients with ARDS who are undergoing venovenous extracorporeal membrane oxygenation (VV-ECMO) compared with supine positioning. Objective: To test whether prone positioning vs supine positioning decreases the time to successful ECMO weaning in patients with severe ARDS supported by VV-ECMO. Design, Setting, and Participants: Randomized clinical trial of patients with severe ARDS undergoing VV-ECMO for less than 48 hours at 14 intensive care units (ICUs) in France between March 3, 2021, and December 7, 2021. Interventions: Patients were randomized 1:1 to prone positioning (at least 4 sessions of 16 hours) (n = 86) or to supine positioning (n = 84). Main Outcomes and Measures: The primary outcome was time to successful ECMO weaning within 60 days following randomization. Secondary outcomes included ECMO and mechanical ventilation-free days, ICU and hospital length of stay, skin pressure injury, serious adverse events, and all-cause mortality at 90-day follow-up. Results: Among 170 randomized patients (median age, 51 [IQR, 43-59] years; n = 60 women [35%]), median respiratory system compliance was 15.0 (IQR, 10.7-20.6) mL/cm H2O; 159 patients (94%) had COVID-19-related ARDS; and 164 (96%) were in prone position before ECMO initiation. Within 60 days of enrollment, 38 of 86 patients (44%) had successful ECMO weaning in the prone ECMO group compared with 37 of 84 (44%) in the supine ECMO group (risk difference, 0.1% [95% CI, -14.9% to 15.2%]; subdistribution hazard ratio, 1.11 [95% CI, 0.71-1.75]; P = .64). Within 90 days, no significant difference was observed in ECMO duration (28 vs 32 days; difference, -4.9 [95% CI, -11.2 to 1.5] days; P = .13), ICU length of stay, or 90-day mortality (51% vs 48%; risk difference, 2.4% [95% CI, -13.9% to 18.6%]; P = .62). No serious adverse events were reported during the prone position procedure. Conclusions and Relevance: Among patients with severe ARDS supported by VV-ECMO, prone positioning compared with supine positioning did not significantly reduce time to successful weaning of ECMO. Trial Registration: ClinicalTrials.gov Identifier: NCT04607551.

Lung morphology impacts the association between ventilatory variables and mortality in patients with acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) patients with different lung morphology have distinct pulmonary mechanical dysfunction and outcomes. Whether lung morphology impacts the association between ventilatory variables and mortality remains unclear. Moreover, the impact of a novel combined ventilator variable [(4×DP) + RR] on morality in ARDS patients needs external validation. METHODS: We obtained data from the Chinese Database in Intensive Care (CDIC), which included adult ARDS patients who received invasive mechanical ventilation for at least 24 h. Patients were further classified into two groups based on lung morphology (focal and non-focal). Ventilatory variables were collected longitudinally within the first four days of ventilation. The primary outcome was 28-day mortality. Extended Cox regression models were employed to explore the interaction between lung morphology and longitudinal ventilatory variables on mortality. FINDINGS: We included 396 ARDS patients with different lung morphology (64.1% non-focal). The overall 28-day mortality was 34.4%. Patients with non-focal lung morphology have more severe and persistent pulmonary mechanical dysfunction and higher mortality than those with focal lung morphology. Time-varying driving pressure (DP) was more significantly associated with 28-day mortality in patients with non-focal lung morphology compared to focal lung morphology patients (P for interaction = 0.0039). The impact of DP on mortality was more significant than that of respiratory rate (RR) only in patients with non-focal lung morphology. The hazard ratio (HR) of mortality for [(4×DP) + RR] was significant in patients with non-focal lung morphology (HR 1.036, 95% CI 1.027-1.045), not in patients with focal lung morphology (HR 1.019, 95% CI 0.999-1.039). INTERPRETATION: The association between ventilator variables and mortality varied among patients with different lung morphology. [(4×DP) + RR] was only associated with mortality in patients with non-focal lung morphology. Further validation is needed.

The relationship between immature granulocyte count and mortality in ARDS Due to COVID-19.

Background: Acute phase reactants and inflammation biomarkers such as ferritin, procalcitonin, C-reactive protein (CRP), and complete blood count parameters (White blood cell, platelet count) are usually used to evaluate and monitor the disease severity and treatment response of systemic inflammatory diseases. In addition to these parameters, Immature granulocytes (IG) that increase during systemic infection, hematological malignancy, and drug treatments (such as chemotherapy and glucocorticoids) are important parameters for evaluating systemic inflammation. The sensitivity and specificity of IG are as high as the abovementioned inflammatory biomarkers for monitoring disease severity and treatment response. Aim: The aim of the study is to evaluate the relationship between IG count and the need for mechanical ventilation and mortality in patients hospitalized in the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). Patients and Methods: The medical records of the 401 patients who were followed up in the ICU due to COVID-19-related acute respiratory distress syndrome between October 2020 and February 2021 were retrospectively reviewed. On the day of admission to the ICU complete blood count (CBC), arterial blood gas analysis, coagulation parameters (fibrinogen, D-dimer) are recorded. CRP, procalcitonin, and ferritin levels are also recorded at the day of admission. During the follow-up period, the survival status and mechanical ventilation status of the patients were recorded and the relation between IG count and these parameters was evaluated. Results: The mean IG at the admission was 0.2 ± 0.4 109/L. The IG level of the intubated patients at the time of intubation was 0.3 ± 0.5 109/L. There was a significant positive correlation between mortality and IG levels at admission and at the time of intubation (IG admission; P = 0.001, r = 0.347 and IG at intubation; P = 0.001, r = 0.228). Conclusion: IG levels in CBC data could be a potential practical biomarker. This issue requires further research and the development of therapies targeting IG cells is needed.

Predictors of in-hospital mortality of COVID-19 patients and the role of telemetry in an internal medicine ward during the third phase of the pandemic.

OBJECTIVE: The first pandemic phase of COVID-19 in Italy was characterized by high in-hospital mortality ranging from 23% to 38%. During the third pandemic phase there has been an improvement in the management and treatment of COVID-19, so mortality and predictors may have changed. A prospective study was planned to identify predictors of mortality during the third pandemic phase. PATIENTS AND METHODS: From 15 December 2020 to 15 May 2021, 208 patients were hospitalized (median age: 64 years; males: 58.6%); 83% had a median of 2 (IQR,1-4) comorbidities; pneumonia was present in 89.8%. Patients were monitored remotely for respiratory function and ECG trace for 24 hours/day. Management and treatment were done following the timing and dosage recommended by international guidelines. RESULTS: 79.2% of patients necessitated O2-therapy. ARDS was present in 46.1% of patients and 45.4% received non-invasive ventilation and 11.1% required ICU treatment. 38% developed arrhythmias which were identified early by telemetry and promptly treated. The in-hospital mortality rate was 10%. At multivariate analysis independent predictors of mortality were: older age (R-R for≥70 years: 5.44), number of comorbidities ≥3 (R-R 2.72), eGFR ≤60 ml/min (RR 2.91), high d-Dimer (R-R for≥1,000 ng/ml:7.53), and low PaO2/FiO2 (R-R for <200: 3.21). CONCLUSIONS: Management and treatment adherence to recommendations, use of telemetry, and no overcrowding appear to reduce mortality. Advanced age, number of comorbidities, severe renal failure, high d-Dimer and low P/F remain predictors of poor outcome. The data help to identify current high-risk COVID-19 patients in whom management has yet to be optimized, who require the greatest therapeutic effort, and subjects in whom vaccination is mandatory.