Corticosteroid Therapy in Cardiac Arrest: Evidence, Guidelines, and Future Directions

Cardiac arrest causes circulatory collapse, stress-related adrenal insufficiency, and a strong inflammatory response, creating a plausible rationale for corticosteroid therapy. Glucocorticoids can restore adrenergic responsiveness, raise vascular tone and blood pressure, correct inadequate cortisol activity during critical stress, and attenuate ischemia-reperfusion inflammation. Across randomized trials, the most consistent finding is a higher rate of return of spontaneous circulation (ROSC) with steroid-containing regimens, particularly in in-hospital cardiac arrest and when steroids are combined with vasopressin. Results for survival to discharge and favorable neurological recovery are mixed, and benefits in out-of-hospital cardiac arrest are less consistent. Meta-analyses generally confirm an ROSC advantage and suggest a potential dose-response, with higher intra-arrest methylprednisolone doses associated with improved survival to discharge. Safety findings are reassuring overall, with no clear increase in hyperglycemia, infection, or bleeding, although most trials were not powered for rare adverse effects. Major guideline bodies acknowledge physiologic plausibility and ROSC gains but do not recommend steroids as standard therapy during resuscitation. Priorities for future work include adequately powered multicenter trials that use survival with favorable neurological recovery as primary outcomes, prospectively test dose and timing (intra-arrest and post-ROSC), separate the effect of steroids from coadministered vasopressin, standardize postresuscitation care targets, and incorporate early endocrine and inflammatory biomarkers to focus enrollment on patients most likely to benefit.