Methylene blue in cardiogenic shock and cardiac arrest: A systematic review

Cardiogenic shock and cardiac arrest are associated with high risk of mortality despite advances in resuscitation techniques and supportive care. A growing body of evidence implicates a systemic inflammatory response syndrome (SIRS) in the pathogenesis of post-arrest vasoplegia and end-organ injury. Methylene blue (MB), a nitric oxide pathway inhibitor, has shown efficacy in vasoplegic and septic shock, yet its role in cardiogenic shock or cardiac arrest is not well established. We conducted a systematic review of peer-reviewed studies examining methylene blue in cardiogenic shock or cardiac arrest. Electronic databases MEDLINE, EMBASE, CENTRAL, Scopus, and Web of Science were searched in March 2025. Preclinical randomised trials and clinical studies in adult humans or animal models were included. Out of 676 screened records, seven studies met inclusion criteria: six preclinical randomised animal studies and one retrospective human cohort study. Early porcine studies using electrically induced ventricular fibrillation and continuous MB infusion during CPR demonstrated improved survival, haemodynamic profile, and neurologic outcomes. In contrast, more recent, well conducted bolus-only studies using infarct-induced models reported minimal or no benefit associated with MB administration. The single human study lacked a comparator group and provided limited cardiogenic shock-specific outcome data. This systematic review highlights the lack of data available for MB in cardiogenic shock and cardiac arrest, especially in humans. There was a potential therapeutic signal for methylene blue in some animal models of cardiogenic shock and cardiac arrest. Prospective studies with clinically relevant models of cardiac injury are warranted to determine whether MB can improve outcomes in this high-risk population.