Potentially modifiable ventilation factors associated with outcome in neurocritical care vs. non-neurocritical care patients: Rational and protocol for a patient-level analysis of PRoVENT, PRoVENT-iMiC and ENIO (PRIME).

Abstract

Introduction: Ventilator settings and ventilation variables and parameters vary between neurocritical care and non-neurocritical care patients. We aim to compare ventilation management in neurocritical care patients versus non-neurocritical care patients under invasive mechanical ventilation support, and to determine which factors related to ventilatory management have an independent association with outcome in neurocritical patients.

Methods and analysis: We meta-analyze harmonized individual patient data from three observational studies ('PRactice of VENTilation in critically ill patients without ARDS' [PRoVENT], 'PRactice of VENTilation in critically ill patients in Middle-income Countries' [PRoVENT-iMiC] and 'Extubation strategies and in neuro-intensive care unit patients and associations with outcomes' [ENIO]), pooled into a database named 'PRIME'. The primary endpoint is all cause ICU mortality. Secondary endpoints are key ventilator settings and ventilation variables and parameters. To identify potentially modifiable and non-modifiable factors contributing to ICU mortality, a multivariable model will be built using demographic factors, comorbidities, illness severities, and respiratory and laboratorial variables. In analyses examining the impact of ventilatory variables on outcome, we will estimate the relative risk of ICU mortality for neurocritical and non-neurocritical care patients by dividing the study population based on key ventilator variables and parameters.

Ethics and dissemination: This meta-analysis will address a clinically significant research question by comparing neurocritical care with non-neurocritical care patients. As this is a meta-analysis, additional ethical committee approval is not required. Findings will be disseminated to the scientific community through abstracts and original articles in peer-reviewed journals. Furthermore, the PRIME database will be made accessible for further post-hoc analyses.

Registration: PROVENT, PROVENT-iMiC and ENIO, and the pooled database PRIME are registered at clinicaltrials.gov (NCT01868321 for PRoVENT, NCT03188770 for PRoVENT-iMiC, and NCT03400904 for ENIO, and for PRIME is pending).