The STEPCARE-trial is designed with three major arms of interventions; targeted temperature management (TTM), mean arterial pressure (MAP) and sedation.
Blood pressure is one of the main determinants of perfusion to the brain, heart and kidneys. Current guidelines recommend targeting a mean arterial blood pressure higher than 65 mmHg. This is based on observational data alone. Smaller pilot trials have suggested feasibility and safety of a target of 85-100 mmHg in cardiac arrest patients, and preliminary data suggest organ protective effects from a higher blood pressure.
Multiple publications have indicated the pathophysiological importance of inadequate cerebral perfusion and increasing brain injury in patients after cardiac arrest. Studies focusing on the pathophysiology have reported a decrease in cerebral blood flow and cerebral vasoconstriction occurring in the early phase after the arrest. It follows that targeting a higher MAP may lower the risk of inadequate CBF related to low MAP. Whether this translates into improved outcome in patients with and without chronic hypertension is unknown.
In myocardial infarction reduced cardiac output results in a cascade of neurohormonal activation and vasoconstriction which is the target of subsequent therapy for heart failure. Although increasing blood pressure in the acute phase of myocardial infarction complicated by cardiac arrest is at odds with the concept of acute unloading to limit infarct size, results from the COMACARE trial showed lower levels of troponin among patients who were assigned to a higher MAP-target. Taken together with the neutral results of the BOX-trial, in which almost half of the participants had an ST-elevation myocardial infarction, this supports the safety of a higher MAP-target among patients with cardiac arrest and acute coronary ischemia.
The large sample size of the STEPCARE trial will allow for hypothesis-generating subgroup analyses based on pre-randomization parameters such as previous coronary vascular disease and heart failure.
The evidence which forms the basis for Current Guidelines on post-cardiac arrest management is limited. MAP is one easily modifiable physiological variable in all critically ill patients. The majority of OHCA patients need treatment for low blood pressure during the first 48 hours after a cardiac arrest. Pilot data suggest that by using slightly higher doses of vasopressor the higher MAP target is achievable in most OHCA patients. The intervention is cheap and applicable in ICUs all over the world. While the BOX-trial has provided evidence that any effect of a modestly increased MAP target is likely small, it remains to be determined if larger increases in the MAP-target are beneficial. The BOX-trial also leaves an evidence gap among patients who have a non-cardiac cause of arrest. Only a large trial will help in informing clinicians on whether a higher MAP target improves outcome in OHCA patients.