title: The stress response to surgery and postoperative delirium: evidence of hypothalamic-pituitary-adrenal axis hyperresponsiveness and decreased suppression of the GH/IGF-1 Axis.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Psychiatry, Centro Hospitalar Universitário de Coimbra, Portugal. jcerejeira@netcabo.pt
authors.forename: Joaquim
authors.initials: J
authors.lastname: Cerejeira
authors.forename: Pedro
authors.initials: P
authors.lastname: Batista
authors.forename: Vasco
authors.initials: V
authors.lastname: Nogueira
authors.forename: Adriano
authors.initials: A
authors.lastname: Vaz-Serra
authors.forename: Elizabeta B
authors.initials: EB
authors.lastname: Mukaetova-Ladinska
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000758:Anesthesia; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects / Q000523:psychology; D003071:Cognition / Q000502:physiology; D003627:Data Interpretation, Statistical; D003693:Delirium / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007107:Immune System / Q000502:physiology; D018836:Inflammation Mediators / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000502:physiology; D019990:Perioperative Care; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011183:Postoperative Complications / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D011184:Postoperative Period; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D018836:Inflammation Mediators; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D006854:Hydrocortisone
keywords: C-reactive protein; cortisol; delirium; inflammation; insulin-like growth factor 1; interleukins