RESUMO
Objective: To describe a study protocol and statistical analysis plan (SAP) for the identification and treatment of hypoxemic respiratory failure (HRF) and acute respiratory distress syndrome (ARDS) with protection, paralysis, and proning (TheraPPP) study prior to completion of recruitment, electronic data retrieval, and analysis of any data. Design: TheraPPP is a stepped-wedge cluster randomised study evaluating a care pathway for HRF and ARDS patients. This is a type-1 hybrid effectiveness-implementation study design evaluating both intervention effectiveness and implementation; however primarily powered for the effectiveness outcome. Setting: Seventeen adult intensive care units (ICUs) across Alberta, Canada. Participants: We estimate a sample size of 18816 mechanically ventilated patients, with 11424 patients preimplementation and 7392 patients postimplementation. We estimate 2688 sustained ARDS patients within our study cohort. Intervention: An evidence-based, stakeholder-informed, multidisciplinary care pathway called Venting Wisely that standardises diagnosis and treatment of HRF and ARDS patients. Main outcome measures: The primary outcome is 28-day ventilator-free days (VFDs). The primary analysis will compare the mean 28-day VFDs preimplementation and postimplementation using a mixed-effects linear regression model. Prespecified subgroups include sex, age, HRF, ARDS, COVID-19, cardiac surgery, body mass index, height, illness acuity, and ICU volume. Results: This protocol and SAP are reported using the Standard Protocol Items: Recommendations for Interventional Trials guidance and the Guidelines for the Content of Statistical Analysis Plans in Clinical Trials. The study received ethics approval and was registered (ClinicalTrials.gov-NCT04744298) prior to patient enrolment. Conclusions: TheraPPP will evaluate the effectiveness and implementation of an HRF and ARDS care pathway.
RESUMO
BACKGROUND: Treatment of hypoxemic respiratory failure (HRF) and ARDS is complex. Standardized management of HRF and ARDS may improve adherence to evidence-informed practice and improve outcomes. RESEARCH QUESTION: What is the effect of standardized treatment compared with usual care on survival of patients with HRF and ARDS? STUDY DESIGN AND METHODS: MEDLINE, EMBASE, Cochrane, CINAHL, Scopus, and Web-of-Science were searched (inception to 2018). Included studies were randomized clinical trials or quasi-experimental studies that examined the effect of standardized treatment (care-protocol, care-pathway, or bundle) compared with usual treatment among mechanically ventilated adult patients admitted to an ICU with HRF or ARDS. Study characteristics, pathway components, and patient outcomes were abstracted independently by two reviewers. RESULTS: From 15,932 unique citations, 14 studies were included in the systematic review (three randomized clinical trials and 11 quasi-experimental studies). Twelve studies (including 5,767 patients) were included in the meta-analysis. Standardized management of HRF was associated with a 23% relative reduction in mortality (relative risk, 0.77; 95% CI, 0.65-0.91; I2, 70%; P = .002). In studies targeting patients with ARDS (n = 8), a 21% pooled mortality reduction was observed (relative risk, 0.79; 95% CI, 0.71-0.88; I2, 3.1%). Standardized management was associated with increased 28-day ventilator-free days (weighted mean difference, 3.48 days; 95% CI, 2.43-4.54 days; P < .001). Standardized management was also associated with a reduction in tidal volume (weighted mean difference, -1.80 mL/kg predicted body weight; 95% CI, -2.80 to -0.80 mL/kg predicted body weight; P < .001). Meta-regression demonstrated that the reduction in mortality was associated with provision of lower tidal volume (P = .045). INTERPRETATION: When compared with usual treatment, standardized treatment of patients with HRF and ARDS is associated with increased ventilator-free days, lower tidal volume ventilation, and lower mortality. ICUs should consider the use of standardized treatment to improve the processes and outcomes of care for patients with HRF and ARDS. CLINICAL TRIAL REGISTRATION: PROSPERO; No.: CRD42019099921; URL: www.crd.york.ac.uk/prospero/.