title: The effect of cardiopulmonary bypass on the hypothalamic-pituitary-adrenal axis in children.
abstract: OBJECTIVE
  The pathophysiology of low-cardiac-output syndrome after cardiopulmonary bypass is incompletely understood, but adrenal insufficiency has been proposed as a contributing factor. Our objective was to examine the effect of cardiopulmonary bypass on the hypothalamic-pituitary-adrenal axis, specifically adrenal responsiveness, in patients with congenital heart disease undergoing surgery. We hoped to correlate bound and free cortisol values both postoperatively and after adrenocorticotropic hormone stimulation, in conjunction with corticosteroid-binding globulin levels, with clinical outcomes to determine whether these variables are sensitive indicators of adrenal axis function.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  A children's hospital.
  
  
  METHODS
  Fifty-two pediatric heart surgery patients undergoing cardiopulmonary bypass.
  
  
  METHODS
  Total cortisol and corticosteroid-binding globulin levels were obtained pre- and postoperatively and after a postoperative cosyntropin stimulation test. Free cortisol was calculated by using Coolens' method.
  
  
  RESULTS
  Nine of 51 (17.6%) patients had low (<3 μg/dL) baseline postoperative total cortisol, median 1.6 μg/dL, yet all nine had normal (>9 μg/dL increase from postoperative baseline) stimulation tests. The corticosteroid-binding globulin levels declined from a mean of 29 mg/L preoperatively to 22 mg/L postoperatively (p < .001) and showed marked variability between patients. Patients with free cortisol δ >6 μg/dL (n = 18, 35%) had a longer length of stay (median 9 vs. 5 days; p = .002), higher inotrope scores (median 13.3 vs. 10.8; p = .05), greater fluid requirement (median 73.5 vs. 55.6 mL/kg; p = .007), and longer ventilator times (median 41.5 vs. 20 hrs; p = .013).
  
  
  CONCLUSIONS
  Although hypothalamic-pituitary-adrenal axis dysfunction may play a role in low-cardiac-output syndrome among children undergoing congenital heart surgery, using total cortisol to investigate such dysfunction may be inadequate. Decreased corticosteroid-binding globulin levels and marked free cortisol increase after stimulation were associated with worse clinical outcomes. Further investigation into the cortisol-corticosteroid-binding globulin complex and its relationship to free cortisol is necessary to examine the problem of adrenal insufficiency from a more integrated perspective.
authors.affiliation: Department of Surgery, Northwestern University Medical School, Children's Memorial Hospital, Chicago, IL, USA. ewaldchildrensmemorial.org
authors.forename: Eric L
authors.initials: EL
authors.lastname: Wald
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Preze
authors.forename: Jens C
authors.initials: JC
authors.lastname: Eickhoff
authors.forename: Carl L
authors.initials: CL
authors.lastname: Backer
mesh_terms: D000302:Adrenal Cortex / Q000503:physiopathology; D000305:Adrenal Cortex Hormones; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006776:Hospitals, Pediatric; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007223:Infant; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011446:Prospective Studies; D014156:Transcortin / Q000032:analysis
chemical_list: D000305:Adrenal Cortex Hormones; D014156:Transcortin; D006854:Hydrocortisone