The Burden of Preoperative Stress: Biological Mechanisms and Postoperative Outcomes

Preoperative psychological stress is a highly prevalent but mostly underrecognized factor influencing perioperative physiology and postoperative outcomes. This narrative review synthesizes current evidence on the known mechanisms connecting preoperative stress to adverse surgical outcomes, with particular emphasis on HPA axis functioning, cortisol dynamics, inflammatory signaling and pain modulation. Elevated preoperative anxiety affects a substantial proportion of surgical patients and is consistently associated with increased analgesic and anesthetic requirements, higher postoperative pain intensity, greater risk of chronic postsurgical pain, neuropsychiatric complications, metabolic dysregulation and postoperative infections. Stress-related elevations in cortisol and pro-inflammatory cytokines, particularly interleukin-6, appear to mediate these effects through interactions with immune, metabolic, and central nervous system pathways. Stress-related pain modulation is reflected not only in experimental models but also in clinically measurable outcomes, underscoring its relevance for perioperative care. Despite growing recognition of these associations, standardized strategies for integrating stress assessment and biomarkers into perioperative risk stratification remain limited. Given that preoperative stress is potentially modifiable, targeted psychological, analgesic, and metabolic interventions may represent valuable opportunities to improve recovery, reduce complications, and prevent pain chronification.