EPISYNC study : Predictors of patient-ventilator asynchrony in a prospective cohort of patients under invasive mechanical ventilation - Study protocol

Funding: The Episync study is supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grant number 2015/19122-4.Introduction: Patient-ventilator asynchrony is common during the entire period of invasive mechanical ventilation (MV) and is associated with worse clinical outcomes. However, risk factors associated with asynchrony are not completely understood. The main objectives of this study are to estimate the incidence of asynchrony during invasive MV and its association with respiratory mechanics and other baseline patient characteristics. Methods and analysis: We designed a prospective cohort study of patients admitted to the intensive care unit (ICU) of a university hospital. Inclusion criteria are adult patients under invasive MV initiated for less than 72 hours, and with expectation of remaining under MV for more than 24 hours. Exclusion criteria are high flow bronchopleural fistula, inability to measure respiratory mechanics and previous tracheostomy. Baseline assessment includes clinical characteristics of patients at ICU admission, including severity of illness, reason for initiation of MV, and measurement of static mechanics of the respiratory system. We will capture ventilator waveforms during the entire MV period that will be analysed with dedicated software (Better Care, Barcelona, Spain), which automatically identifies several types of asynchrony and calculates the asynchrony index (AI). We will use a linear regression model to identify risk factors associated with AI. To assess the relationship between survival and AI we will use Kaplan-Meier curves, log rank tests and Cox regression. The calculated sample size is 103 patients. The statistical analysis will be performed by the software R Programming (www.R-project.org) and will be considered statistically significant if the p value is less than 0.05. Ethics and dissemination: The study was approved by the Ethics Committee of Instituto do Coração, School of Medicine, University of São Paulo, Brazil, and informed consent was waived due to the observational nature of the study. We aim to disseminate the study findings through peer-reviewed publications and national and international conference presentations. Trial registration number: NCT02687802; Pre-results

Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study

Background: Awake prone positioning (awake-PP) in non-intubated coronavirus disease 2019 (COVID-19) patients could avoid endotracheal intubation, reduce the use of critical care resources, and improve survival. We aimed to examine whether the combination of high-flow nasal oxygen therapy (HFNO) with awake-PP prevents the need for intubation when compared to HFNO alone. Methods: Prospective, multicenter, adjusted observational cohort study in consecutive COVID-19 patients with acute respiratory failure (ARF) receiving respiratory support with HFNO from 12 March to 9 June 2020. Patients were classified as HFNO with or without awake-PP. Logistic models were fitted to predict treatment at baseline using the following variables: age, sex, obesity, non-respiratory Sequential Organ Failure Assessment score, APACHE-II, C-reactive protein, days from symptoms onset to HFNO initiation, respiratory rate, and peripheral oxyhemoglobin saturation. We compared data on demographics, vital signs, laboratory markers, need for invasive mechanical ventilation, days to intubation, ICU length of stay, and ICU mortality between HFNO patients with and without awake-PP. Results: A total of 1076 patients with COVID-19 ARF were admitted, of which 199 patients received HFNO and were analyzed. Fifty-five (27.6%) were pronated during HFNO; 60 (41/100) and 22 (40/100) patients from the HFNO and HFNO + awake-PP groups were intubated. The use of awake-PP as an adjunctive therapy to HFNO did not reduce the risk of intubation [RR 0.87 (95/100 CI 0.53–1.43), p equal 0.60]. Patients treated with HFNO + awake-PP showed a trend for delay in intubation compared to HFNO alone [median 1 (interquartile range, IQR 1.0–2.5) vs 2 IQR 1.0–3.0] days (p equal 0.055), but awake-PP did not affect 28-day mortality [RR 1.04 (95/100 CI 0.40–2.72), p equal 0.92].Conclusion: In patients with COVID-19 ARF treated with HFNO, the use of awake-PP did not reduce the need for intubation or affect mortality

Stratification for Identification of Prognostic Categories In the Acute RESpiratory Distress Syndrome (SPIRES) Score

OBJECTIVES: To develop a scoring model for stratifying patients with acute respiratory distress syndrome into risk categories (Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score) for early prediction of death in the ICU, independent of the underlying disease and cause of death. DESIGN: A development and validation study using clinical data from four prospective, multicenter, observational cohorts. SETTING: A network of multidisciplinary ICUs. PATIENTS: One-thousand three-hundred one patients with moderate-to-severe acute respiratory distress syndrome managed with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study followed Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines for prediction models. We performed logistic regression analysis, bootstrapping, and internal-external validation of prediction models with variables collected within 24 hours of acute respiratory distress syndrome diagnosis in 1,000 patients for model development. Primary outcome was ICU death. The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score was based on patient's age, number of extrapulmonary organ failures, values of end-inspiratory plateau pressure, and ratio of Pao(2) to Fio(2) assessed at 24 hours of acute respiratory distress syndrome diagnosis. The pooled area under the receiver operating characteristic curve across internal-external validations was 0.860 (95% CI, 0.831-0.890). External validation in a new cohort of 301 acute respiratory distress syndrome patients confirmed the accuracy and robustness of the scoring model (area under the receiver operating characteristic curve = 0.870; 95% CI, 0.829-0.911). The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score stratified patients in three distinct prognostic classes and achieved better prediction of ICU death than ratio of Pao(2) to Fio(2) at acute respiratory distress syndrome onset or at 24 hours, Acute Physiology and Chronic Health Evaluation II score, or Sequential Organ Failure Assessment scale. CONCLUSIONS: The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score represents a novel strategy for early stratification of acute respiratory distress syndrome patients into prognostic categories and for selecting patients for therapeutic trials.Analysis and support of clinical decision makingDevelopment and application of statistical models for medical scientific researc