The stress response to surgery and postoperative delirium: evidence of hypothalamic-pituitary-adrenal axis hyperresponsiveness and decreased suppression of the GH/IGF-1 Axis

J Geriatr Psychiatry Neurol. 2013 Sep;26(3):185-94. doi: 10.1177/0891988713495449. Epub 2013 Jul 17.

Abstract

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.

Keywords: C-reactive protein; cortisol; delirium; inflammation; insulin-like growth factor 1; interleukins.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anesthesia
  • Arthroplasty, Replacement, Hip / adverse effects
  • Arthroplasty, Replacement, Hip / psychology
  • Cognition / physiology
  • Data Interpretation, Statistical
  • Delirium / etiology*
  • Delirium / physiopathology
  • Delirium / psychology
  • Female
  • Growth Hormone / blood
  • Growth Hormone / physiology*
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Immune System / physiology
  • Inflammation Mediators / blood
  • Insulin-Like Growth Factor I / physiology*
  • Male
  • Middle Aged
  • Neurosecretory Systems / physiology
  • Perioperative Care
  • Pituitary-Adrenal System / physiopathology*
  • Postoperative Complications / etiology*
  • Postoperative Complications / physiopathology
  • Postoperative Complications / psychology
  • Postoperative Period
  • Stress, Physiological / physiology*

Substances

  • Inflammation Mediators
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • Hydrocortisone