Dysregulated cell death and inflammation in Perioperative Medicine: Mechanisms and therapeutic opportunities

Cell death is a fundamental process influencing tissue homeostasis and recovery following surgical trauma. In the perioperative context, regulated cell death aids in clearing damaged cells and initiating repair. However, excessive or dysregulated cell death-often exacerbated by ischemia-reperfusion injury, surgical stress, and anesthetic agents can trigger intense inflammatory responses, leading to complications such as postoperative organ dysfunction (e.g., acute lung injury, delirium, and myocardial injury), impaired wound healing, and increased risk of infections. Mitochondrial dysfunction, a key contributor to these processes, releases damage-associated molecular patterns, further amplifying perioperative inflammation. Emerging evidence suggests that modulating specific cell death pathways (e.g., apoptosis, pyroptosis, necroptosis) and associated inflammatory signaling (e.g., via NLRP3 inflammasome or TLR4 inhibition) may offer novel strategies to improve perioperative outcomes. This review explores the interplay between cell death and inflammation, with emphasis on perioperative relevance, and discusses emerging therapeutic targets that may facilitate precision medicine in surgical patients.