• Praleene Sivapalan, Benjamin Skov Kaas-Hansen, Tine Sylvest Meyhoff, Peter Buhl Hjortrup, Maj-Brit N Kjær, Jon Henrik Laake, Maria Cronhjort, Stephan M Jakob, Maurizio Cecconi, Marek Nalos, Marlies Ostermann, MalbrainManu L N GMLNG0000-0002-1816-5255Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark.First Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland., MøllerMorten HylanderMH0000-0002-6378-9673Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark.Department of Clinical Medicine, Faculty of, Anders Perner, and Anders Granholm.
• Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
• Acta Anaesthesiol Scand. 2024 Apr 4.

BackgroundVariation in usual practice in fluid trials assessing lower versus higher volumes may affect overall comparisons. To address this, we will evaluate the effects of heterogeneity in treatment intensity in the Conservative versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care trial. This will reflect the effects of differences in site-specific intensities of standard fluid treatment due to local practice preferences while considering participant characteristics.MethodsWe will assess the effects of heterogeneity in treatment intensity across one primary (all-cause mortality) and three secondary outcomes (serious adverse events or reactions, days alive without life support and days alive out of hospital) after 90 days. We will classify sites based on the site-specific intensity of standard fluid treatment, defined as the mean differences in observed versus predicted intravenous fluid volumes in the first 24 h in the standard-fluid group while accounting for differences in participant characteristics. Predictions will be made using a machine learning model including 22 baseline predictors using the extreme gradient boosting algorithm. Subsequently, sites will be grouped into fluid treatment intensity subgroups containing at least 100 participants each. Subgroups differences will be assessed using hierarchical Bayesian regression models with weakly informative priors. We will present the full posterior distributions of relative (risk ratios and ratios of means) and absolute differences (risk differences and mean differences) in each subgroup.DiscussionThis study will provide data on the effects of heterogeneity in treatment intensity while accounting for patient characteristics in critically ill adult patients with septic shock.RegistrationsThe European Clinical Trials Database (EudraCT): 2018-000404-42, ClinicalTrials. gov: NCT03668236.© 2024 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.

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