Hemodynamic Effects of Methylene Blue in Pediatric Cardiac Critical Care Patients: A Descriptive Study of Causal Inference and Cluster Analysis Using High-Fidelity Data

Methylene blue inhibits the nitric oxide-soluble guanylyl cyclase-cyclic GMP pathway and is used to restore vascular tone in vasoplegic circulatory failure. Its hemodynamic and oxygenation effects in children, however, remain incompletely defined. A single-center retrospective, mechanistic, physiology-focused analysis of pediatric cardiac intensive care unit patients who received methylene blue for vasoplegia was conducted. High-fidelity physiologic data were extracted from Sickbay. Percent change in vasoactive score, mean arterial blood pressure, cerebral near infrared spectroscopy, and renal near infrared spectroscopy within four hours after administration were calculated relative pre-dose baseline. Unsupervised cluster analysis identified physiologic response phenotypes, and random forest regression models were used to determine which pre-administration variables predicted response magnitude. Independent variables included vasoactive medications, fluid balance, sedation, and patient characteristics. 19 administrations across 15 unique patients were analyzed. Cluster analysis revealed 3 distinct response phenotypes including a group with significant improvement in adequacy of oxygen delivery and a group without such increase. Random forest modeling identified methylene blue dose, vasopressin dose, and epinephrine dose as important response prediction features. Calcium chloride augmented response while vasopressin blunted it. Data from this descriptive study suggest that methylene blue may improve arterial blood pressure, and adequacy of oxygen delivery in critically ill pediatric patients with vasoplegia. The greatest response occurred in patients with higher catecholamine but lower vasopressin doses, consistent with a catecholamine-responsive, nitric oxide-mediated phenotype. Calcium appeared to augment methylene blue response while vasopressin blunted it. These findings provide a physiologic framework for targeted methylene blue use in pediatric circulatory failure.