Background: Interest in inhalational anesthesia in cardiac surgery has resurged as volatile anesthetics exert biological effects extending beyond hypnosis. Sevoflurane and desflurane activate mitochondrial cytoprotective signaling pathways, modulate inflammatory and endothelial responses and may attenuate ischemia–reperfusion injury during cardiopulmonary bypass, potentially influencing postoperative organ function and recovery. 

Methods: This narrative review critically examines experimental and clinical evidence on the use of volatile anesthetics in cardiac anesthesia. The current literature was analyzed to elucidate mechanistic foundations of myocardial and extracardiac organ protection, hemodynamic and metabolic effects, and the influence of patient-specific vulnerability profiles on perioperative outcomes. 

Results: Preclinical studies consistently demonstrate that volatile anesthetics trigger mitochondrial protective pathways, including K-ATP channel activation, controlled reactive oxygen species signaling and inhibition of the mitochondrial permeability transition pore. Clinical studies suggest potential benefits in myocardial protection and modulation of systemic inflammatory and microcirculatory responses. However, translation into consistent clinical outcome improvement remains heterogeneous, influenced by variability in surgical procedures, anesthetic protocols and patient risk stratification. 

Conclusions: Volatile anesthetics exhibit mechanistic properties supporting a potential role in organ protection during cardiac surgery. Nevertheless, clinical evidence remains inconclusive, underscoring the need for refined patient stratification and precision-based perioperative strategies. Identifying knowledge gaps and research priorities may facilitate rational, individualized integration of inhalational anesthesia into contemporary cardiac surgical practice.