The Stress Response to Surgery and Postoperative Delirium: Evidence of Hypothalamic-Pituitary-Adrenal Axis Hyperresponsiveness and Decreased Suppression of the GH/IGF-1 Axis

Introduction: The aim of this study is to determine whether postoperative delirium is associated with dysregulation of hypothalamic-pituitary-adrenal and growth hormone/insulin-like growth factor 1 (GH/IGF-1) responses following acute systemic inflammation. Methods: Plasma levels of cortisol, IGF-1, C-reactive protein, interleukin (IL)-6, IL-8, and IL-10 were measured before and after surgery in 101 patients 60 years without dementia undergoing elective hip arthroplasty. Participants were assessed with confusion assessment method and Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision; DSM-IV-TR) postoperatively and 37 patients fulfilled the DSM-IV-TR criteria for delirium. Results: Preoperative plasma cortisol levels were similar in delirium and nondelirium groups (405.37 +/- 189.04 vs 461.83 +/- 219.39; P = .22). Participants with delirium had higher postoperative cortisol levels (821.67 +/- 367.17 vs 599.58 +/- 214.94; P = .002) with enhanced postoperative elevation in relation to baseline (1.9- vs 1.5-fold; P = .004). The plasma levels of IGF1 did not differ in delirium and nondelirium groups before (18.12 +/- 7.58 vs 16.8 +/- 7.86; P = .477) and following surgery (13.39 +/- 5.94 vs 11.12 +/- 6.2; P = .639), but the levels increased in relation to baseline more frequently in patients who developed delirium (24.3% vs 7.8%; P = .034). The magnitude of postoperative cortisol elevation correlated with IL-6 (P = .485; P = .002), IL-8 (P = .429; P = .008), and IL-10 (P = .544; P < .001) only in patients with delirium. Conclusions: Hypothalamic-pituitary-adrenal axis hyperresponsiveness and a less frequent suppression of the GH/IGF-1 axis in response to acute stress are possibly involved in delirium pathophysiology.