Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Adrenal insufficiency in neonates undergoing cardiopulmonary bypass and postoperative hypothalamic-pituitary-adrenal function after prophylactic glucocorticoids

Abstract

Objectives

Determine incidence of preoperative adrenal insufficiency in neonates >35 weeks gestation with congenital heart disease undergoing cardiothoracic surgery with bypass and effects of prophylactic methylprednisolone on postoperative hypothalamic-pituitary-adrenal function and hemodynamic stability.

Design

Prospective observational study in 36 neonates with preoperative adrenocorticotrophic hormone stimulation tests and serial total cortisol and adrenocorticotrophic hormone measurements before and after surgery. Data analyses: analysis of variance and regression.

Results

Baseline circulating adrenocorticotrophic hormone and cortisol were unchanged 4–20 days postnatal (P > 0.1); however, cortisol levels rose with increasing adrenocorticotrophic hormone, P = 0.02. Ten neonates (29%) demonstrated preoperative adrenal insufficiency (∆cortisol ≤9 µg/dl); one had postoperative hemodynamic instability. Growth-restricted neonates had lower baseline cortisol, but normal stimulation tests and responded well to surgical stresses. Seventy-five percent of neonates receiving perioperative methylprednisolone demonstrated postoperative hypothalamic-pituitary-adrenal inhibition.

Conclusion

Adrenal insufficiency appears common in neonates >35 weeks gestation with congenital heart disease, but did not contribute to postoperative hemodynamic instability despite hypothalamic-pituitary-adrenal inhibition.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

Similar content being viewed by others

References

  1. Prigent H, Maxime V, Annane D. Science review: mechanisms of impaired adrenal function in sepsis and molecular actions of glucocorticoids. Crit Care. 2004;8:243–52.

    Article  Google Scholar 

  2. Ishimoto H, Jaffe RB. Development and function of the human fetal adrenal cortex: a key component in the fetal–palcental unit. Endo Rev. 2011;32:317–55.

    Article  CAS  Google Scholar 

  3. Watterberg KL. Adrenocortical function and dysfunction in the fetus and neonate. Semin Neonatol. 2004;9:13–21.

    Article  Google Scholar 

  4. Ng PC, Lee CH, Lam CWK, Ma KC, Fok TF, Chan HIS, et al. Transient adrenocortical insufficiency of prematurity and systemic hypotension in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 2004;89:F119–F126.

    Article  CAS  Google Scholar 

  5. Fernandez E, Schrader R, Watterberg K. Prevalence of low cortisol values in term and near-term infants with vasopressor-resistant hypotension. J Perinatol. 2005;25:114–8.

    Article  CAS  Google Scholar 

  6. Fernandez EF, Montman R, Watterberg KL. ACTH and cortisol response to critical illness in term and late preterm newborns. J Perinatol. 2008;28:797–802.

    Article  CAS  Google Scholar 

  7. Waterhouse R. A case of suprarenal apoplexy. The Lancet. 1911;177:577–8.

    Article  Google Scholar 

  8. Friderichsen C. Nebennierenapoplexie bei kleinen Kindern. Jahrib Kinderh. 1918;87:109–25.

  9. Hatherill M, Tibby SM, Hilliard T, Turner C, Murdoch IA. Adrenal insufficiency in septic shock. Arch Dis Child. 1999;80:51–5.

    Article  CAS  Google Scholar 

  10. Pizarro CF, Troster EJ, Damiani D, Carcillo JA. Absolute and relative adrenal insufficiency in children with septic shock. Crit Care Med. 2005;33:855–9.

    Article  CAS  Google Scholar 

  11. Fernandez EF, Watterberg KL. Relative adrenal insufficiency in the preterm and term infant. J Perinatol. 2009;29:S44–9.

    Article  Google Scholar 

  12. Suominen PK, Keski-Nisula J, Ojala T, Rautianinen P, Jahnukainen T, Hastbacka J, et al. Stress-dose corticoposteroid versus placebo in neonatal cardiac operations: a randomized controlled trial. Ann Thorac Surg. 2017;104:1378–85.

    Article  Google Scholar 

  13. Langer M, Modi BP, Agus M. Adrenal insufficiency in the critically ill neonate and child. Curr Opin Pediatr. 2006;18:448–53.

    Article  Google Scholar 

  14. Rothwell PM, Udwadia ZF, Lawler PG. Cortisol response to corticotropin and survival in septic shock. Lancet. 1991;337:582–3.

    Article  CAS  Google Scholar 

  15. Plumpton KR, Anderson BJ, Beca J. Thyroid hormone and cortisol concentrations after congenital heart surgery in infants younger than 3 months of age. Intens Care Med. 2010;36:321–8.

    Article  CAS  Google Scholar 

  16. Mackie AS, Gauvreau K, Booth KL, Newburger JW, Laussen PC, Roth SJ. Hemodynamic correlates of serum cortisol in neonates after cardiopulmonary bypass. Pediatr Crit Care Med. 2011;12:297–303.

    Article  Google Scholar 

  17. Wald EL, Preze E, Eickhoff JC, Backer CL. The effect of cardiopulmonary bypass on the hypothalamic-pituitary-adrenal axis in children. Pediatr Crit Care Med. 2011;12:190–6.

    Article  Google Scholar 

  18. Scrascia G, Rotunno C, Guida P, Amorese L, Polieri D, Codazzi D, et al. Perioperative steroids administration in pediatric cardiac surgery: a meta-analysis of randomized controlled trials*. Pediatr Crit Care Med. 2014;15:435–42.

    Article  Google Scholar 

  19. Graham EM, Atz AM, Butts RJ, Baker NL, Zyblewski SC, Deardorff RL, et al. Standardized preoperative corticosteroid treatment in neonates undergoing cardiac surgery: results from a randomized trial. J Thorac Cardiovasc Surg. 2011;142:1523–9.

    Article  CAS  Google Scholar 

  20. Graham EM, Atz AM, McHugh KE, Butts RJ, Baker NL, Stroud RE, et al. Preoperative steroid treatment does not improve markers of inflammation after cardiac surgery in neonates:results from a randomized trial. J Thorac Cardiovasc Surg. 2014;147:902–8.

    Article  CAS  Google Scholar 

  21. Bronicki RA, Backer CL, Baden HP, Mavroudis C, Crawford SE, Green TP. Dexamethasone reduces the inflammatory response to cardiopulmonary bypass in children. Ann Thorac Surg. 2000;69:1490–5.

    Article  CAS  Google Scholar 

  22. Checchia PA, Bronicki RA, Costello JM, Neslon DP. Steroid use before pediatric operations using cardiopulmonary bypass: an international survey of 36 centers. Pediatr Crit Care Med. 2005;6:441–4.

    Article  Google Scholar 

  23. Gaies MG, Gurney JG, Yen AH, Napoli ML, Gajarski RJ, Ohye RG, et al. Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med. 2010;11:234–8.

    Article  Google Scholar 

  24. Leteurtre S, Martinot A, Duhamel A, Gauvin F, Grandbastien B, Nam TV, et al. Development of a pediatric multiple organ dysfunction score: use of two strategies. Med Decis Making. 1999;19:399–410.

    Article  CAS  Google Scholar 

  25. Leteurtre S, Martinot A, Duhamel A, Proulx F, Grandbastien B, Cotting J, et al. Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study. Lancet. 2003;362:192–7.

    Article  Google Scholar 

  26. Olsen IE, Groveman SA, Lawson ML, Clark RH, Zemel BS. New intrauterine growth curves based on United States data. Pediatrics. 2010;125:e214–24.

    Article  Google Scholar 

  27. Gajarski RJ, Stefanelli CB, Graziano JN, Kaciroti N, Charpie JR, Vazquez D. Adrenocortical response in infants undergoing cardiac surgery with cardiopulmonary bypass and circulatory arrest. Pediatr Crit Care Med. 2010;11:44–51.

    Article  Google Scholar 

  28. Clyman RI, Wickremasinhe A, Merritt TA, Solomon T, McNamara P, Jain A, et al. Hypotension following patent ductus arteriosus ligation: the role of adrenal hormones. J Pediatr. 2014;164:1449–55.

    Article  CAS  Google Scholar 

  29. Mastropietro CW, Miletic K, Chen H, Rossi NF. Effects of corticosteroids on arginine vasopressin after pediatric cardiac surgery. J Crit Care. 2014;29:982–6.

    Article  CAS  Google Scholar 

  30. Wallenstein MB, Harper LM, Odibo AO, Roehl KA, Longman RE, Macones GA, et al. Fetal congenital heart disease and intrauterine growth restriction: a retrospective cohort study. J Matern Fetal Neonatal Med. 2012;25:662–5.

    Article  Google Scholar 

  31. Gardner DS, Poore KR. Do not turn to the hypothalamus for feedback on stress if you are growth restricted. Endocrinology. 2013;154:2257–9.

    Article  CAS  Google Scholar 

  32. Cottrell EC, Seckl JR, Holmes MC, Wyrwoll CS. Foetal and placental 11βHSD2: a hub for developmental programming. Acta Physiol. 2014;210:288–95.

    Article  CAS  Google Scholar 

  33. Pasquali SK, Li JS, He X, Jacobs ML, O’Brien SM, Hall M. et al. Perioperative methylprednisolone and outcome in neonates undergoing heart surgery. Pediatrics. 2012;129:e385–91.

    Article  Google Scholar 

  34. Fudulu D, Schadenberg A, Angelini G, Stoica S. Perioperative use of steroids in neonatal heart surgery: evidence based practice or tradition? Ann Med Surg. 2016;9:67–71.

    Article  Google Scholar 

  35. Schroeder VA, Pearl JM, Schwartz SM, Shanley TP, Manning PB, Nelson DP. Combined steroid treatment for congenital heart surgery improves oxygen delivery and reduces postbypass inflammatory mediator expression. Circulation. 2003;107:2823–8.

    Article  CAS  Google Scholar 

  36. Dreher M, Glatz AC, Kennedy A, Rosenthal T, Gaynor JW. A single-center analysis of methylprednisolone use during pediatric cardiopulmonary bypass. JECT. 2015;47:155–9.

    Google Scholar 

  37. Al-Habet SMH, Rogers HJ. Methylprednisolone pharmacokinetics after intravenous and oral administration. Br J Clin Pharmacol. 1989;27:285–90.

    Article  CAS  Google Scholar 

  38. Jacqz-Aigrain E, Burton P, Azevedo I, Cavaillon JM, Cezard JP, Czernichow P, et al. Les corticoids: pharmacologie et indications des cure courtes en pédiatrie. Arch Pediatr. 1995;2:353–64.

    Article  CAS  Google Scholar 

  39. Keski-Nisula J, Pesonen E, Olkkola KT, Peltola K, Neuvonen PJ, Touminen N, et al. Methylprednisolone in neonatal cardiac surgery: reduced inflammation without improved clinical outcome. Ann Thorac Surg. 2013;95:2126–32.

    Article  Google Scholar 

  40. Wald EL, Backer CL, Dearani JA, Li Z, Oliver WC, Crow SS. Total and free cortisol responses and their relation to outcomes after cardiopulmonary bypass in infants. J Thorac Cardiovasc Surg. 2017;153:1155–63.

    Article  CAS  Google Scholar 

  41. Wiriyathian S, Rosenfeld CR, Arant BS Jr, Porter JC, Faucher DJ, Engle WD. Urinary arginine vasopressin pattern of excretion in the neonatal period. Pediatr Res. 1986;20:103–8.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank the nursing staff in the CVICU who facilitated the collection of the blood samples and Dr. Joseph Forbess for access to his patients. Support for the study was provided by the Children’s Clinical Research Advisory Committee, Children’s Medical Center Foundation, and the George L MacGregor Professorship was awarded to CRR.

Funding

Research grant from the Children’s Clinical Research Advisory Committee, Children’s Medical Center Foundation to Michel Mikhael and the George L. MacGregor Professorship awarded to Charles Rosenfeld.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Charles R. Rosenfeld.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tang, A., Rosenfeld, C.R., Mikhael, M. et al. Adrenal insufficiency in neonates undergoing cardiopulmonary bypass and postoperative hypothalamic-pituitary-adrenal function after prophylactic glucocorticoids. J Perinatol 39, 640–647 (2019). https://doi.org/10.1038/s41372-019-0344-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-019-0344-7

Search

Quick links