Epidemiology, ventilation management and outcomes of COVID-19 ARDS patients versus patients with ARDS due to pneumonia in the Pre-COVID era.

BACKGROUND: Ventilation management may differ between COVID-19 ARDS (COVID-ARDS) patients and patients with pre-COVID ARDS (CLASSIC-ARDS); it is uncertain whether associations of ventilation management with outcomes for CLASSIC-ARDS also exist in COVID-ARDS. METHODS: Individual patient data analysis of COVID-ARDS and CLASSIC-ARDS patients in six observational studies of ventilation, four in the COVID-19 pandemic and two pre-pandemic. Descriptive statistics were used to compare epidemiology and ventilation characteristics. The primary endpoint were key ventilation parameters; other outcomes included mortality and ventilator-free days and alive (VFD-60) at day 60. RESULTS: This analysis included 6702 COVID-ARDS patients and 1415 CLASSIC-ARDS patients. COVID-ARDS patients received lower median VT (6.6 [6.0 to 7.4] vs 7.3 [6.4 to 8.5] ml/kg PBW; p < 0.001) and higher median PEEP (12.0 [10.0 to 14.0] vs 8.0 [6.0 to 10.0] cm H2O; p < 0.001), at lower median ΔP (13.0 [10.0 to 15.0] vs 16.0 [IQR 12.0 to 20.0] cm H2O; p < 0.001) and higher median Crs (33.5 [26.6 to 42.1] vs 28.1 [21.6 to 38.4] mL/cm H2O; p < 0.001). Following multivariable adjustment, higher ΔP had an independent association with higher 60-day mortality and less VFD-60 in both groups. Higher PEEP had an association with less VFD-60, but only in COVID-ARDS patients. CONCLUSIONS: Our findings show important differences in key ventilation parameters and associations thereof with outcomes between COVID-ARDS and CLASSIC-ARDS. TRIAL REGISTRATION: Clinicaltrials.gov (identifier NCT05650957), December 14, 2022.

Association between early cumulative fluid balance and successful liberation from invasive ventilation in COVID-19 ARDS patients - insights from the PRoVENT-COVID study: a national, multicenter, observational cohort analysis.

BACKGROUND: Increasing evidence indicates the potential benefits of restricted fluid management in critically ill patients. Evidence lacks on the optimal fluid management strategy for invasively ventilated COVID-19 patients. We hypothesized that the cumulative fluid balance would affect the successful liberation of invasive ventilation in COVID-19 patients with acute respiratory distress syndrome (ARDS). METHODS: We analyzed data from the multicenter observational 'PRactice of VENTilation in COVID-19 patients' study. Patients with confirmed COVID-19 and ARDS who required invasive ventilation during the first 3 months of the international outbreak (March 1, 2020, to June 2020) across 22 hospitals in the Netherlands were included. The primary outcome was successful liberation of invasive ventilation, modeled as a function of day 3 cumulative fluid balance using Cox proportional hazards models, using the crude and the adjusted association. Sensitivity analyses without missing data and modeling ARDS severity were performed. RESULTS: Among 650 patients, three groups were identified. Patients in the higher, intermediate, and lower groups had a median cumulative fluid balance of 1.98 L (1.27-7.72 L), 0.78 L (0.26-1.27 L), and - 0.35 L (- 6.52-0.26 L), respectively. Higher day 3 cumulative fluid balance was significantly associated with a lower probability of successful ventilation liberation (adjusted hazard ratio 0.86, 95% CI 0.77-0.95, P = 0.0047). Sensitivity analyses showed similar results. CONCLUSIONS: In a cohort of invasively ventilated patients with COVID-19 and ARDS, a higher cumulative fluid balance was associated with a longer ventilation duration, indicating that restricted fluid management in these patients may be beneficial. Trial registration Clinicaltrials.gov ( NCT04346342 ); Date of registration: April 15, 2020.

Observational Research for Therapies Titrated to Effect and Associated With Severity of Illness: Misleading Results From Commonly Used Statistical Methods.

OBJECTIVES: In critically ill patients, treatment dose or intensity is often related to severity of illness and mortality risk, whereas overtreatment or undertreatment (relative to the individual need) may further increase the odds of death. We aimed to investigate how these relationships affect the results of common statistical methods used in observational studies. DESIGN: Using Monte Carlo simulation, we generated data for 5,000 patients with a treatment dose related to the pretreatment mortality risk but with randomly distributed overtreatment or undertreatment. Significant overtreatment or undertreatment (relative to the optimal dose) further increased the mortality risk. A prognostic score that reflects the mortality risk and an outcome of death or survival was then generated. The study was analyzed: 1) using logistic regression to estimate the effect of treatment dose on outcome while controlling for prognostic score and 2) using propensity score matching and inverse probability weighting of the effect of high treatment dose on outcome. The data generation and analyses were repeated 1,500 times over sample sizes between 200 and 30,000 patients, with an increasing accuracy of the prognostic score and with different underlying assumptions. SETTING: Computer-simulated studies. MEASUREMENTS AND MAIN RESULTS: In the simulated 5,000-patient observational study, higher treatment dose was found to be associated with increased odds of death (p = 0.00001) while controlling for the prognostic score with logistic regression. Propensity-matched analysis led to similar results. Larger sample sizes led to equally biased estimates with narrower CIs. A perfect risk predictor negated the bias only under artificially perfect assumptions. CONCLUSIONS: When a treatment dose is associated with severity of illness and should be dosed "enough," logistic regression, propensity score matching, and inverse probability weighting to adjust for confounding by severity of illness lead to biased results. Larger sample sizes lead to more precisely wrong estimates.

Nursing Practice of Airway Care Interventions and Prone Positioning in ICU Patients with COVID-19-A Dutch National Survey.

Background: Airway care interventions and prone positioning are used in critically ill patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU) to improve oxygenation and facilitate mucus removal. At the onset of the COVID-19 pandemic, the decision-making process regarding the practice of airway care interventions and prone positioning was challenging. Objective: To provide an overview of the practice of airway care interventions and prone positioning during the second wave of the pandemic in the Netherlands. Method: Web-based survey design. Seventy ICU nurses, each representing one intensive care in the Netherlands, were contacted for participation. Potential items were generated based on a literature search and formulated by a multidisciplinary team. Questions were pilot tested for face and construct validity by four intensive care nurses from four different hospitals. Results: The response rate was 53/77 (69%). This survey revealed widespread use of airway care interventions in the Netherlands in COVID-19 patients, despite questionable benefits. Additionally, prone positioning was used in invasively and non-invasively ventilated patients. Conclusions: The use of airway care interventions and prone positioning is time consuming and comes with the production of waste. Further research is needed to assess the effectiveness, workload, and environmental impact of airway care interventions and prone positioning.

Broadening the Berlin definition of ARDS to patients receiving high-flow nasal oxygen: an observational study in patients with acute hypoxemic respiratory failure due to COVID-19.

BACKGROUND: High-flow nasal oxygen (HFNO) is increasingly used in patients with acute hypoxemic respiratory failure. It is uncertain whether a broadened Berlin definition of acute respiratory distress syndrome (ARDS), in which ARDS can be diagnosed in patients who are not receiving ventilation, results in similar groups of patients receiving HFNO as in patients receiving ventilation. METHODS: We applied a broadened definition of ARDS in a multicenter, observational study in adult critically ill patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19), wherein the requirement for a minimal level of 5 cm H2O PEEP with ventilation is replaced by a minimal level of airflow rate with HFNO, and compared baseline characteristics and outcomes between patients receiving HFNO and patients receiving ventilation. The primary endpoint was ICU mortality. We also compared outcomes in risk for death groups using the PaO2/FiO2 cutoffs as used successfully in the original definition of ARDS. Secondary endpoints were hospital mortality; mortality on days 28 and 90; need for ventilation within 7 days in patients that started with HFNO; the number of days free from HFNO or ventilation; and ICU and hospital length of stay. RESULTS: Of 728 included patients, 229 patients started with HFNO and 499 patients with ventilation. All patients fulfilled the broadened Berlin definition of ARDS. Patients receiving HFNO had lower disease severity scores and lower PaO2/FiO2 than patients receiving ventilation. ICU mortality was lower in receiving HFNO (22.7 vs 35.6%; p = 0.001). Using PaO2/FiO2 cutoffs for mild, moderate and severe arterial hypoxemia created groups with an ICU mortality of 16.7%, 22.0%, and 23.5% (p = 0.906) versus 19.1%, 37.9% and 41.4% (p = 0.002), in patients receiving HFNO versus patients receiving ventilation, respectively. CONCLUSIONS: Using a broadened definition of ARDS may facilitate an earlier diagnosis of ARDS in patients receiving HFNO; however, ARDS patients receiving HFNO and ARDS patients receiving ventilation have distinct baseline characteristics and mortality rates. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov (identifier NCT04719182).

Effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients (CONFIDENCE): protocol for a multicentre randomised controlled trial.

BACKGROUND: Fluid therapy is a common intervention in critically ill patients. It is increasingly recognised that deresuscitation is an essential part of fluid therapy and delayed deresuscitation is associated with longer invasive ventilation and length of intensive care unit (ICU) stay. However, optimal timing and rate of deresuscitation remain unclear. Lung ultrasound (LUS) may be used to identify fluid overload. We hypothesise that daily LUS-guided deresuscitation is superior to deresuscitation without LUS in critically ill patients expected to undergo invasive ventilation for more than 24 h in terms of ventilator free-days and being alive at day 28. METHODS: The "effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients" (CONFIDENCE) is a national, multicentre, open-label, randomised controlled trial (RCT) in adult critically ill patients that are expected to be invasively ventilated for at least 24 h. Patients with conditions that preclude a negative fluid balance or LUS examination are excluded. CONFIDENCE will operate in 10 ICUs in the Netherlands and enrol 1000 patients. After hemodynamic stabilisation, patients assigned to the intervention will receive daily LUS with fluid balance recommendations. Subjects in the control arm are deresuscitated at the physician's discretion without the use of LUS. The primary endpoint is the number of ventilator-free days and being alive at day 28. Secondary endpoints include the duration of invasive ventilation; 28-day mortality; 90-day mortality; ICU, in hospital and total length of stay; cumulative fluid balance on days 1-7 after randomisation and on days 1-7 after start of LUS examination; mean serum lactate on days 1-7; the incidence of reintubations, chest drain placement, atrial fibrillation, kidney injury (KDIGO stadium ≥ 2) and hypernatremia; the use of invasive hemodynamic monitoring, and chest-X-ray; and quality of life at day 28. DISCUSSION: The CONFIDENCE trial is the first RCT comparing the effect of LUS-guided deresuscitation to routine care in invasively ventilated ICU patients. If proven effective, LUS-guided deresuscitation could improve outcomes in some of the most vulnerable and resource-intensive patients in a manner that is non-invasive, easy to perform, and well-implementable. TRIAL REGISTRATION: ClinicalTrials.gov NCT05188092. Registered since January 12, 2022.

Prone Positioning Decreases Inhomogeneity and Improves Dorsal Compliance in Invasively Ventilated Spontaneously Breathing COVID-19 Patients-A Study Using Electrical Impedance Tomography.

BACKGROUND: We studied prone positioning effects on lung aeration in spontaneously breathing invasively ventilated patients with coronavirus disease 2019 (COVID-19). METHODS: changes in lung aeration were studied prospectively by electrical impedance tomography (EIT) from before to after placing the patient prone, and back to supine. Mixed effect models with a random intercept and only fixed effects were used to evaluate changes in lung aeration. RESULTS: fifteen spontaneously breathing invasively ventilated patients were enrolled, and remained prone for a median of 19 [17 to 21] hours. At 16 h the global inhomogeneity index was lower. At 2 h, there were neither changes in dorsal nor in ventral compliance; after 16 h, only dorsal compliance (ßFe +18.9 [95% Confidence interval (CI): 9.1 to 28.8]) and dorsal end-expiratory lung impedance (EELI) were increased (ßFe, +252 [95% CI: 13 to 496]); at 2 and 16 h, dorsal silent spaces was unchanged (ßFe, -4.6 [95% CI: -12.3 to +3.2]). The observed changes induced by prone positioning disappeared after turning patients back to supine. CONCLUSIONS: in this cohort of spontaneously breathing invasively ventilated COVID-19 patients, prone positioning decreased inhomogeneity, increased lung volumes, and improved dorsal compliance.

Improvement of an interobserver agreement of ARDS diagnosis by adding additional imaging and a confidence scale.

Acute respiratory distress syndrome (ARDS) often is not recognized in clinical practice, largely due to variation in the interpretation of chest x-ray (CXR) leading to poor interobserver reliability. We hypothesized that the agreement in the interpretation of chest imaging for the diagnosis of ARDS in invasively ventilated intensive care unit patients between experts improves when using an 8-grade confidence scale compared to using a dichotomous assessment and that the agreement increases after adding chest computed tomography (CT) or lung ultrasound (LUS) to CXR. Three experts scored ARDS according to the Berlin definition based on case records from an observational cohort study using a dichotomous assessment and an 8-grade confidence scale. The intraclass correlation (ICC), imaging modality, and the scoring method were calculated per day and compared using bootstrapping. A consensus judgement on the presence of ARDS was based on the combined confidence grades of the experts, followed by a consensus meeting for conflicting scores. In total, 401 patients were included in the analysis. The best ICC was found using an 8-grade confidence scale for LUS (ICC: 0.49; 95%-CI: 0.29-0.63) and CT evaluation (ICC: 0.49; 95%-CI: 0.34-0.61). The ICC of CXR increased by 0.022 and of CT by 0.065 when 8-grade scoring was used instead of the dichotomous assessment. Adding information from LUS or chest CT increased the ICC by 0.25 when using the 8-grade confidence assessment. An agreement on the diagnosis of ARDS can increase substantially by adapting the scoring system from a dichotomous assessment to an 8-grade confidence scale and by adding additional imaging modalities such as LUS or chest CT. This suggests that a simple assessment of the diagnosis of ARDS with a chart review by one assessor is insufficient to define ARDS in future studies. Clinical trial registration: Trialregister.nl (identifier NL8226).