Anesthesia and mitochondria: balancing toxicity and protection through emerging therapeutic strategies.

Anesthesia is a cornerstone of modern surgical practice, enabling interventions by deliberately modulating nociception and consciousness-from localized analgesia and mild sedation to deep unconsciousness. Yet the molecular and cellular mechanisms that produce these reversible states remain only partly defined, constraining our ability to predict interpatient variability, prevent mitochondrial- and neurotoxicity-related adverse effects, and optimize agent selection, dosing, and timing across perioperative care. Beyond their intended effects, anesthetics and their adjuvants impose substantial physiological stress on the brain, metabolism, and immune system, with particularly pronounced risks in vulnerable populations such as pediatric and elderly patients with developing and otherwise fragile neural networks. Recent studies have highlighted mitochondria, the cell's energy processing unit and key regulator of homeostasis, as especially susceptible to anesthetic exposure. Evidence indicates that agents used in the perioperative period may disrupt mitochondrial function by altering oxidative phosphorylation, increasing reactive oxygen species (ROS) production, and impairing mitochondrial dynamics. Such disruptions can contribute to neurotoxicity, metabolic dysregulation, and immune suppression, potentially affecting postoperative recovery and long-term cognitive outcomes. This review critically examines emerging data on the interplay between anesthesia agents and mitochondrial function. We discuss the implications of mitochondrial dysfunction for neural health and postoperative recovery, and we highlight current and prospective strategies to possibly refine anesthesia drug protocols through targeted mitochondrial therapeutics. Ultimately, a deeper understanding of these mitochondrial interactions is imperative for developing safer, more effective anesthesia practices, especially for pediatric and other high-risk patient populations.