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 ΔIL-6 (P = .485; P = .002), ΔIL-8 (P = .429; P = .008), and ΔIL-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.