Total and free cortisol responses and their relation to outcomes after cardiopulmonary bypass in infants

J Thorac Cardiovasc Surg. 2017 May;153(5):1155-1163. doi: 10.1016/j.jtcvs.2016.11.030. Epub 2016 Nov 21.

Abstract

Background: Hypothalamic-pituitary-adrenal (HPA) axis dysfunction may be partially responsible for the hemodynamic instability experienced by infants after cardiopulmonary bypass (CPB). We report the full spectrum of the HPA response surrounding CPB for infant congenital cardiac surgery.

Methods: We enrolled 84 infants who received 1 mg/kg of dexamethasone before initiation of CPB. Total cortisol (TC), free cortisol (FC), adrenocorticotropic hormone (ACTH), and corticosteroid-binding globulin (CBG) were measured at 3 time points: immediately before CPB (TP1), on intensive care unit arrival (TP2), and at 24 hours after surgery (TP3). A 1-μg ACTH stimulation test was performed at each time point to evaluate adrenal responsiveness.

Results: Sixty-eight infants completed all study procedures. Levels of TC, FC, CBG, and ACTH decreased significantly between the preoperative and 24-hour postoperative measurements. There were no significant associations between preoperative FC responses and clinical outcomes after adjusting for weight and Risk-Adjusted Scores for Congenital Heart Surgery. Infants with subnormal TC responses to ACTH stimulation (<9 μg/dL) at TP2 had greater fluid requirements (P < .001) and greater chest tube output (P < .001) during the first 24 hours, as well as longer length of stay (LOS) (P = .007). Except for LOS, these differences persisted for infants with subnormal stimulation tests at TP3.

Conclusions: We observed a significant decline in all aspects of the HPA axis throughout the first 24 hours after infant CPB. TC and FC levels were not associated with clinical outcomes. Subnormal (Δ <9 μg/dL) TC response to cosyntropin stimulation during the postoperative period was associated with increased fluid resuscitation and greater LOS.

Keywords: adrenal insufficiency; cardiopulmonary bypass; clinical outcomes; congenital heart surgery; cortisol.

Publication types

  • Multicenter Study
  • Observational Study
  • Video-Audio Media

MeSH terms

  • Adrenal Cortex / drug effects
  • Adrenal Cortex / metabolism*
  • Adrenal Cortex / physiopathology
  • Adrenal Cortex Function Tests
  • Adrenocorticotropic Hormone / blood
  • Age Factors
  • Biomarkers / blood
  • Cardiac Surgical Procedures / adverse effects*
  • Cardiopulmonary Bypass / adverse effects*
  • Child, Preschool
  • Cosyntropin / administration & dosage
  • Dexamethasone / administration & dosage
  • Female
  • Heart Defects, Congenital / physiopathology
  • Heart Defects, Congenital / surgery*
  • Humans
  • Hydrocortisone / blood*
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Infant
  • Infant, Newborn
  • Male
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / metabolism*
  • Pituitary-Adrenal System / physiopathology
  • Prospective Studies
  • Time Factors
  • Transcortin / metabolism
  • Treatment Outcome
  • United States

Substances

  • Biomarkers
  • SERPINA6 protein, human
  • Cosyntropin
  • Dexamethasone
  • Adrenocorticotropic Hormone
  • Transcortin
  • Hydrocortisone