Effects of Sedation, TEmperature and Pressure After Cardiac Arrest and REsuscitation on Major Adverse Kidney Events (STEPCARE-MAKE): A Protocol for a Pre-Planned Sub-Study of a Randomized Clinical Trial

Abstract

Background: Acute kidney injury (AKI) is a common and serious complication after cardiac arrest, affecting more than 30% of initially successfully resuscitated patients, with around 10% receiving Kidney Replacement Therapy (KRT). Currently, treatment options to prevent renal complications are limited. In this predefined sub-study of the Sedation, TEmperature and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial, we evaluate the effects of sedation depth, fever management strategies, and mean arterial pressure (MAP) targets on the risk of major adverse kidney events (MAKE) in post-cardiac arrest patients. Methods: STEPCARE-MAKE is a predefined prospective sub-study of the international, randomized clinical STEPCARE trial. The main trial will enroll 3500 patients and employs a 2 × 2 × 2 factorial design, randomizing participants across three interventions: (1) deep sedation for 36 h or minimal sedation, (2) fever management with or without a feedback-controlled device, and (3) MAP target ≥ 65 mmHg or ≥ 85 mmHg. The primary outcome is the composite outcome MAKE, which includes death from any cause by day 30, initiation of KRT, or persistent renal dysfunction, defined as the final creatinine value ≥ 200% of the baseline at the time of discharge from the primary hospital or at day 30, whichever occurs first. Differences between baseline and the highest in-hospital creatinine, baseline and the last measured in-hospital creatinine, baseline and 72-h creatinine, and baseline and the highest creatinine within 72 h will be reported as secondary outcomes. Conclusion: The findings of this sub-study will provide new evidence on the renal effects of the STEPCARE trial interventions and may inform the future of individualized kidney-protective treatment approaches.