Molecular Hydrogen Reverses Sepsis-Induced Immunoparalysis in Severe Trauma Patient with Refractory Septic Shock

Refractory septic shock and post-cardiac arrest syndrome (PCAS) are critical conditions often leading to lethal immunoparalysis, a state of immune suppression that leaves patients vulnerable to secondary infections and organ dysfunction. Current standard-of-care treatments often fall short in addressing this profound immune depletion. Molecular hydrogen has emerged as a potential therapeutic agent due to its antioxidant and anti-inflammatory properties, but its specific effects on deep human immunophenotyping in such severe contexts, particularly longitudinally, remain poorly understood.

This case report details a 49-year-old man with severe tricuspid regurgitation and Child-Pugh class B alcoholic cirrhosis who developed severe pneumonia, refractory septic shock, and PCAS after high-energy thoracic trauma. Facing a therapeutic impasse with NT-proBNP levels exceeding 35,000 pg/ml and profound immune depletion, adjuvant hydrogen inhalation was initiated. The patient's clinical and immunological status was monitored longitudinally using deep flow cytometry to assess various immune cell compartments, including T-cells and B-cells.

Adjuvant hydrogen inhalation led to a 64% reduction in myocardial stress, evidenced by a significant drop in NT-proBNP levels, and temporary clinical stabilization. Deep longitudinal flow cytometry revealed system-wide immunological reprogramming. In the T-cell compartment, hydrogen induced a biphasic resolution of exhaustion in T-helper cells, marked by an immediate decline in expression of FAS (also known as CD95) and asynchronous normalization of PD1 and TIM3 expression. This was accompanied by bidirectional restoration of physiological immune checkpoints in cytotoxic T-cells. Furthermore, a sequential, compensatory recovery of the regulatory T-cell (Treg)/type 1 regulatory T-cell (Tr1) immune-braking system was observed. In the humoral compartment, despite prolonged bone marrow suppression and loss of transitional/regulatory B-cells, hydrogen therapy was associated with a V-shaped recovery of plasma and double-negative (CD27-/IgD-) B-cells. > It also appeared to protect switched memory B-cells by markedly reducing FAS expression, suggesting an anti-apoptotic effect.