Practice of ventilation in middle-Income countries (PRoVENT-iMIC): Rationale and protocol for a prospective international multicentre observational study in intensive care units in Asia

Introduction: Current evidence on epidemiology and outcomes of invasively mechanically ventilated intensive care unit (ICU) patients is predominantly gathered in resource-rich settings. Patient casemix and patterns of critical illnesses, and probably also ventilation practices are likely to be different in resource-limited settings. We aim to investigate the epidemiological characteristics, ventilation practices and clinical outcomes of patients receiving mechanical ventilation in ICUs in Asia.Methods and Analysis: PRoVENT-iMIC (study of PRactice of VENTilation in Middle-Income Countries) is an international multicentre observational study to be undertaken in approximately 60 ICUs in 11 Asian countries. Consecutive patients aged 18 years or older who are receiving invasive ventilation in participating ICUs during a predefined 28-day period are to be enrolled, with a daily follow-up of 7 days. The primary outcome is ventilatory management (including tidal volume expressed as mL/kg predicted body weight and positive end-expiratory pressure expressed as cm H2O) during the first 3 days of mechanical ventilation-compared between patients at no risk for acute respiratory distress syndrome (ARDS), patients at risk for ARDS and in patients with ARDS (in case the diagnosis of ARDS can be made on admission). Secondary outcomes include occurrence of pulmonary complications and all-cause ICU mortality.Ethics and Dissemination: PRoVENT-iMIC will be the first international study that prospectively assesses ventilation practices, outcomes and epidemiology of invasively ventilated patients in ICUs in Asia. The results of this large study, to be disseminated through conference presentations and publications in international peer-reviewed journals, are of ultimate importance when designing trials of invasive ventilation in resource-limited ICUs. Access to source data will be made available through national or international anonymised datasets on request and after agreement of the PRoVENT-iMIC steering committee

Epidemiological characteristics, ventilator management, and clinical outcome in patients receiving invasive ventilation in intensive care units from 10 Asian middle-income countries (PRoVENT-iMiC): An International, multicenter, prospective study

Epidemiology, ventilator management, and outcome in patients receiving invasive ventilation in intensive care units (ICUs) in middle-income countries are largely unknown. PRactice of VENTilation in Middle-income Countries is an international multicenter 4-week observational study of invasively ventilated adult patients in 54 ICUs from 10 Asian countries conducted in 2017/18. Study outcomes included major ventilator settings (including tidal volume [V T] and positive end-expiratory pressure [PEEP]); the proportion of patients at risk for acute respiratory distress syndrome (ARDS), according to the lung injury prediction score (LIPS), or with ARDS; the incidence of pulmonary complications; and ICU mortality. In 1,315 patients included, median V T was similar in patients with LIPS \u3c 4 and patients with LIPS ≥ 4, but lower in patients with ARDS (7.90 [6.8-8.9], 8.0 [6.8-9.2], and 7.0 [5.8-8.4] mL/kg Predicted body weight; P = 0.0001). Median PEEP was similar in patients with LIPS \u3c 4 and LIPS ≥ 4, but higher in patients with ARDS (five [5-7], five [5-8], and 10 [5-12] cmH2O; P \u3c 0.0001). The proportions of patients with LIPS ≥ 4 or with ARDS were 68% (95% CI: 66-71) and 7% (95% CI: 6-8), respectively. Pulmonary complications increased stepwise from patients with LIPS \u3c 4 to patients with LIPS ≥ 4 and patients with ARDS (19%, 21%, and 38% respectively; P = 0.0002), with a similar trend in ICU mortality (17%, 34%, and 45% respectively; P \u3c 0.0001). The capacity of the LIPS to predict development of ARDS was poor (ROC AUC of 0.62, 95% CI: 0.54-0.70). In Asian middle-income countries, where two-thirds of ventilated patients are at risk for ARDS according to the LIPS and pulmonary complications are frequent, setting of V T is globally in line with current recommendations

Abnormal Right Ventricular Myocardial Performance Index Is Not Associated With Outcomes in Invasively Ventilated Intensive Care Unit Patients Without Acute Respiratory Distress Syndrome—Post hoc Analysis of Two RCTs

Background: The objective of the study was to determine the association between right ventricular (RV) myocardial performance index (MPI) and successful liberation from the ventilator and death within 28 days. Methods: Post hoc analysis of 2 ventilation studies in invasively ventilated patients not having ARDS. RV-MPI was collected through transthoracic echocardiography within 24–48 h from the start of invasive ventilation according to the study protocols. RV-MPI ≤ 0.54 was considered normal. The primary endpoint was successful liberation from the ventilator < 28 days; the secondary endpoint was 28-day mortality. Results: A total of 81 patients underwent transthoracic echocardiography at median 30 (24–42) h after the start of ventilation—in 73 (90%) patients, the RV-MPI could be collected. A total of 56 (77%) patients were successfully liberated from the ventilator < 28 days; A total of 22 (30%) patients had died before or at day 28. A total of 18 (25%) patients had an abnormal RV-MPI. RV-MPI was neither associated with successful liberation from the ventilator within 28 days [HR, 2.2 (95% CI 0.47–10.6); p = 0.31] nor with 28-day mortality [HR, 1.56 (95% CI 0.07–34.27); p = 0.7]. Conclusion: In invasively ventilated critically ill patients without ARDS, an abnormal RV-MPI indicative of RV dysfunction was not associated with time to liberation from invasive ventilation

Accuracy of the Radiographic Assessment of Lung Edema Score for the Diagnosis of ARDS

Background: Bilateral opacities on chest radiographs are part of the Berlin Definition for Acute Respiratory Distress Syndrome (ARDS) but have poor interobserver reliability. The “Radiographic Assessment of Lung Edema” (RALE) score was recently proposed for evaluation of the extent and density of alveolar opacities on chest radiographs of ARDS patients. The current study determined the accuracy of the RALE score for the diagnosis and the prognosis of ARDS. Methods: Post-hoc analysis of a cohort of invasively ventilated intensive care unit (ICU) patients expected to need invasive ventilation for >24 h. The Berlin Definition was used as the gold standard. The RALE score was calculated for the first available chest radiograph after start of ventilation in the ICU. The primary endpoint was the diagnostic accuracy for ARDS of the RALE score. Secondary endpoints included the prognostic value of the RALE score for ICU and hospital mortality, and the association with ARDS severity, and the PaO 2/FiO 2. Receiver operating characteristic (ROC) curves were constructed, and the optimal cutoff was used to determine sensitivity, specificity and the negative and positive predictive value of the RALE score for ARDS. Results: The study included 131 patients, of whom 30 had ARDS (11 mild, 15 moderate, and 4 severe ARDS). The first available chest radiograph was obtained median 0 [0 to 1] days after start of invasive ventilation in ICU. Compared to patients without ARDS, a higher RALE score was found in patients with ARDS (24 [interquartile range (IQR) 16–30] vs. 6 [IQR 3–11]; P < 0.001), with RALE scores of 20 [IQR 14–24], 26 [IQR 16–32], and 32 [IQR 19–36] for mild, moderate and severe ARDS, respectively, (P = 0.166). The area under the ROC for ARDS was excellent (0.91 [0.86–0.96]). The best cutoff for ARDS diagnosis was 10 with 100% sensitivity, 71% specificity, 51% positive predictive value and 100% negative predictive value. The RALE score was not associated with ICU or hospital mortality, and weakly correlated with the PaO 2/FiO 2. Conclusion: In this cohort of invasively ventilated ICU patients, the RALE score had excellent diagnostic accuracy for ARDS

Lung Ultrasound to Determine the Effect of Lower vs. Higher PEEP on Lung Aeration in Patients without ARDS—A Substudy of a Randomized Clinical Trial

Background: Ventilation with lower positive end–expiratory pressure (PEEP) may cause loss of lung aeration in critically ill invasively ventilated patients. This study investigated whether a systematic lung ultrasound (LUS) scoring system can detect such changes in lung aeration in a study comparing lower versus higher PEEP in invasively ventilated patients without acute respiratory distress syndrome (ARDS). Methods: Single center substudy of a national, multicenter, randomized clinical trial comparing lower versus higher PEEP ventilation strategy. Fifty–seven patients underwent a systematic 12–region LUS examination within 12 h and between 24 to 48 h after start of invasive ventilation, according to randomization. The primary endpoint was a change in the global LUS aeration score, where a higher value indicates a greater impairment in lung aeration. Results: Thirty–three and twenty–four patients received ventilation with lower PEEP (median PEEP 1 (0–5) cm H2O) or higher PEEP (median PEEP 8 (8–8) cm H2O), respectively. Median global LUS aeration scores within 12 h and between 24 and 48 h were 8 (4 to 14) and 9 (4 to 12) (difference 1 (–2 to 3)) in the lower PEEP group, and 7 (2–11) and 6 (1–12) (difference 0 (–2 to 3)) in the higher PEEP group. Neither differences in changes over time nor differences in absolute scores reached statistical significance. Conclusions: In this substudy of a randomized clinical trial comparing lower PEEP versus higher PEEP in patients without ARDS, LUS was unable to detect changes in lung aeration

Effect of mechanical power on mortality in invasively ventilated ICU patients without the acute respiratory distress syndrome: An analysis of three randomised clinical trials

BACKGROUNDThe mechanical power of ventilation (MP) has an association with outcome in invasively ventilated patients with the acute respiratory distress syndrome (ARDS). Whether a similar association exists in invasively ventilated patients without ARDS is less certain.OBJECTIVETo investigate the association of mechanical power with mortality in ICU patients without ARDS.DESIGNThis was an individual patient data analysis that uses the data of three multicentre randomised trials.SETTINGThis study was performed in academic and nonacademic ICUs in the Netherlands.PATIENTSOne thousand nine hundred and sixty-Two invasively ventilated patients without ARDS were included in this analysis. The median [IQR] age was 67 [57 to 75] years, 706 (36%) were women.MAIN OUTCOME MEASURESThe primary outcome was the all-cause mortality at day 28. Secondary outcomes were the all-cause mortality at day 90, and length of stay in ICU and hospital.RESULTSAt day 28, 644 patients (33%) had died. Hazard ratios for mortality at day 28 were higher with an increasing MP, even when stratified for its individual components (driving pressure (P<0.001), tidal volume (P<0.001), respiratory rate (P<0.001) and maximum airway pressure (P=0.001). Similar associations of mechanical power (MP) were found with mortality at day 90, lengths of stay in ICU and hospital. Hazard ratios for mortality at day 28 were not significantly different if patients were stratified for MP, with increasing levels of each individual component.CONCLUSIONIn ICU patients receiving invasive ventilation for reasons other than ARDS, MP had an independent association with mortality. This finding suggests that MP holds an added predictive value over its individual components, making MP an attractive measure to monitor and possibly target in these patients.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT02159196, ClinicalTrials.gov Identifier: NCT02153294, ClinicalTrials.gov Identifier: NCT03167580

PRactice of VENTilation in Patients with Novel Coronavirus Disease (PRoVENT-COVID): rationale and protocol for a national multicenter observational study in The Netherlands

Background: The coronavirus disease 2019 (COVID-19) pandemic is rapidly expanding across the world, with more than 100,000 new cases each day as of end-June 2020. Healthcare workers are struggling to provide the best care for COVID-19 patients. Approaches for invasive ventilation vary widely between and within countries and new insights are acquired rapidly. We aim to investigate invasive ventilation practices and outcome in COVID-19 patients in the Netherlands. Methods: PRoVENT-COVID ('study of PRactice of VENTilation in COVID-19') is an investigator-initiated national, multicenter observational study to be undertaken in intensive care units (ICUs) in The Netherlands. Consecutive COVID-19 patients aged 18 years or older, who are receiving invasive ventilation in the participating ICUs, are to be enrolled during a 10-week period, with a daily follow-up of 7 days. The primary outcome is ventilatory management (including tidal volume expressed as mL/kg predicted body weight and positive end-expiratory pressure expressed as cmH2O) during the first 3 days of ventilation. Secondary outcomes include other ventilatory variables, use of rescue therapies for refractory hypoxemia such as prone positioning and extracorporeal membrane oxygenation, use of sedatives, vasopressors and inotropes; daily cumulative fluid balances; acute kidney injury; ventilator-free days and alive at day 28 (VFD-28), duration of ICU and hospital stay, and ICU, hospital and 90-day mortality. Discussion: PRoVENT-COVID will be the largest observational study to date, with high density ventilatory data and major outcomes. There is urgent need for a better understanding of ventilation practices, and the effects of ventilator settings on outcomes in COVID-19 patients. The results of PRoVENT-COVID will be rapidly disseminated through electronic presentations, such as webinars and electronic conferences, and publications in international peer-reviewed journals. Access to source data will be made available through local, regional and national anonymized datasets on request, and after agreement of the PRoVENT-COVID steering committee. Trial Registration: PRoVENT-COVID is registered at clinicaltrials.gov (identifier NCT04346342)

PRactice of VENTilation in Patients with Novel Coronavirus Disease (PRoVENT-COVID): rationale and protocol for a national multicenter observational study in The Netherlands

Background: The coronavirus disease 2019 (COVID-19) pandemic is rapidly expanding across the world, with more than 100,000 new cases each day as of end-June 2020. Healthcare workers are struggling to provide the best care for COVID-19 patients. Approaches for invasive ventilation vary widely between and within countries and new insights are acquired rapidly. We aim to investigate invasive ventilation practices and outcome in COVID-19 patients in the Netherlands. Methods: PRoVENT-COVID ('study of PRactice of VENTilation in COVID-19') is an investigatorinitiated national, multicenter observational study to be undertaken in intensive care units (ICUs) in The Netherlands. Consecutive COVID-19 patients aged 18 years or older, who are receiving invasive ventilation in the participating ICUs, are to be enrolled during a 10-week period, with a daily follow-up of 7 days. The primary outcome is ventilatory management (including tidal volume expressed as mL/kg predicted body weight and positive end-expiratory pressure expressed as cmH(2)O) during the first 3 days of ventilation. Secondary outcomes include other ventilatory variables, use of rescue therapies for refractory hypoxemia such as prone positioning and extracorporeal membrane oxygenation, use of sedatives, vasopressors and inotropes; daily cumulative fluid balances; acute kidney injury; ventilator-free days and alive at day 28 (VFD-28), duration of ICU and hospital stay, and ICU, hospital and 90-day mortality. Discussion: PRoVENT-COVID will be the largest observational study to date, with high density ventilatory data and major outcomes. There is urgent need for a better understanding of ventilation practices, and the effects of ventilator settings on outcomes in COVID-19 patients. The results of PRoVENT-COVID will be rapidly disseminated through electronic presentations, such as webinars and electronic conferences, and publications in international peer-reviewed journals. Access to source data will be made available through local, regional and national anonymized datasets on request, and after agreement of the PRoVENT-COVID steering committee

PRactice of VENTilation in Patients with Novel Coronavirus Disease (PRoVENT-COVID): rationale and protocol for a national multicenter observational study in The Netherlands

Background: The coronavirus disease 2019 (COVID-19) pandemic is rapidly expanding across the world, with more than 100,000 new cases each day as of end-June 2020. Healthcare workers are struggling to provide the best care for COVID-19 patients. Approaches for invasive ventilation vary widely between and within countries and new insights are acquired rapidly. We aim to investigate invasive ventilation practices and outcome in COVID-19 patients in the Netherlands. Methods: PRoVENT-COVID ('study of PRactice of VENTilation in COVID-19') is an investigator-initiated national, multicenter observational study to be undertaken in intensive care units (ICUs) in The Netherlands. Consecutive COVID-19 patients aged 18 years or older, who are receiving invasive ventilation in the participating ICUs, are to be enrolled during a 10-week period, with a daily follow-up of 7 days. The primary outcome is ventilatory management (including tidal volume expressed as mL/kg predicted body weight and positive end-expiratory pressure expressed as cmH2O) during the first 3 days of ventilation. Secondary outcomes include other ventilatory variables, use of rescue therapies for refractory hypoxemia such as prone positioning and extracorporeal membrane oxygenation, use of sedatives, vasopressors and inotropes; daily cumulative fluid balances; acute kidney injury; ventilator-free days and alive at day 28 (VFD-28), duration of ICU and hospital stay, and ICU, hospital and 90-day mortality. Discussion: PRoVENT-COVID will be the largest observational study to date, with high density ventilatory data and major outcomes. There is urgent need for a better understanding of ventilation practices, and the effects of ventilator settings on outcomes in COVID-19 patients. The results of PRoVENT-COVID will be rapidly disseminated through electronic presentations, such as webinars and electronic conferences, and publications in international peer-reviewed journals. Access to source data will be made available through local, regional and national anonymized datasets on request, and after agreement of the PRoVENT-COVID steering committee. Trial Registration: PRoVENT-COVID is registered at clinicaltrials.gov (identifier NCT04346342)