Intensive Care Medicine

, Volume 37, Issue 3, pp 518–524 | Cite as

Clinical effects of adding fludrocortisone to a hydrocortisone-based shock protocol in hypotensive critically ill children

  • Kiran B. Hebbar
  • Jana A. Stockwell
  • James D. Fortenberry
Pediatric Original



Adult studies evaluating corticosteroids have found varied efficacy. One study showing mortality benefit utilized fludrocortisone (FLU) and hydrocortisone (HC) (Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871, 2002). Use of FLU in children has not been described. We developed a protocol using HC for systemic inflammatory response syndrome (SIRS) and shock with optional addition of FLU.


Addition of FLU to a HC-based steroid protocol is associated with decreased vasopressor duration without adverse effects in hypotensive children with SIRS.


Retrospective review of low-dose HC and FLU supplementation in children with SIRS and fluid refractory shock. Patients receiving FLU in addition to HC were compared with patients receiving HC alone.


Ninety-seven children with SIRS and shock received steroids. Sixty of 97 (62%) received FLU in addition to HC. Seventy-three children required dopamine (DA) infusion, and 56 received norepinephrine (NE). Overall mortality was 7/97 (7%), with 5/7 (71%) nonsurvivors receiving HC + FLU. Fifty of 97 (52%) children with SIRS met definition for sepsis. Septic children who received HC + FLU required NE for significantly shorter duration than those receiving HC alone (p = 0.011). Nineteen of 60 HC + FLU patients (32%) developed nonsymptomatic hypokalemia. Hypokalemia was significantly more common in HC + FLU patients compared with those receiving HC alone (p = 0.05).


Overall, addition of FLU in children with SIRS was not associated with decreased vasopressor duration or vasopressor score. However, HC + FLU was associated with shorter duration of NE support in the septic subgroup. Hypokalemia was a frequent adverse finding with HC + FLU (p = 0.05). Use of FLU should be considered in further studies evaluating the role of steroids in refractory pediatric septic shock.


Adrenal insufficiency Pediatric Critical care Cortisol 



Financial support was provided by a grant from the Friends Research Fund, Children’s Healthcare of Atlanta.

Conflict of interest

The authors have declared no conflicts of interest.


  1. 1.
    Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaud P, Bellissant E (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871CrossRefPubMedGoogle Scholar
  2. 2.
    Sprung CL, Caralis PV, Marcial EH, Pierce M, Gelbard MA, Long WM, Duncan RC, Tendler MD, Karpf M (1984) The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study. N Engl J Med 311:1137–1143CrossRefPubMedGoogle Scholar
  3. 3.
    Bone RC, Fisher CJ Jr, Clemmer TP, Slotman GJ, Metz CA, Balk RA (1987) A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 317:653–658CrossRefPubMedGoogle Scholar
  4. 4.
    Sjolin J (1991) High-dose corticosteroid therapy in human septic shock: has the jury reached a correct verdict? Circ Shock 35:139–151PubMedGoogle Scholar
  5. 5.
    Ligtenberg JJ, Zijlstra JG (2006) Diagnosis and treatment of relative adrenal insufficiency: confusing but at a higher level? J Crit Care 21:77–78CrossRefPubMedGoogle Scholar
  6. 6.
    Jalloul A (2005) Hydrocortisone infusion for severe community-acquired pneumonia: the role of relative adrenal insufficiency. Am J Respir Crit Care Med 172:781 (author reply 782–783)Google Scholar
  7. 7.
    Nieboer P, van der Werf TS, Beentjes JA, Tulleken JE, Zijlstra JG, Ligtenberg JJ (2000) Catecholamine dependency in a polytrauma patient: relative adrenal insufficiency? Intensive Care Med 26:125–127CrossRefPubMedGoogle Scholar
  8. 8.
    Fleseriu M, Loriaux DL (2009) “Relative” adrenal insufficiency in critical illness. Endocr Pract 15:632–640CrossRefPubMedGoogle Scholar
  9. 9.
    Ligtenberg JJ, Zijlstra JG (2004) The relative adrenal insufficiency syndrome revisited: which patients will benefit from low-dose steroids? Curr Opin Crit Care 10:456–460CrossRefPubMedGoogle Scholar
  10. 10.
    Annetta M, Maviglia R, Proietti R, Antonelli M (2009) Use of corticosteroids in critically ill septic patients : a review of mechanisms of adrenal insufficiency in sepsis and treatment. Curr Drug Targets 10:887–894CrossRefPubMedGoogle Scholar
  11. 11.
    Karir V, Cooke CR, Andersson L, Caldwell E, Rubenfeld GD (2009) Practice variability in the assessment and treatment of critical illness-related corticosteroid insufficiency. J Crit CareGoogle Scholar
  12. 12.
    Druce LA, Thorpe CM, Wilton A (2008) Mineralocorticoid effects due to cortisol inactivation overload explain the beneficial use of hydrocortisone in septic shock. Med Hypotheses 70:56–60CrossRefPubMedGoogle Scholar
  13. 13.
    Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J (2008) Hydrocortisone therapy for patients with septic shock. N Engl J Med 358:111–124CrossRefPubMedGoogle Scholar
  14. 14.
    Burry LD, Wax RS (2004) Role of corticosteroids in septic shock. Ann Pharmacother 38:464–472CrossRefPubMedGoogle Scholar
  15. 15.
    Maxime V, Lesur O, Annane D (2009) Adrenal insufficiency in septic shock. Clin Chest Med 30:17–27, viiGoogle Scholar
  16. 16.
    Goldstein B, Giroir B, Randolph A (2005) International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 6:2–8CrossRefPubMedGoogle Scholar
  17. 17.
    Brierley J, Carcillo JA, Choong K, Cornell T, Decaen A, Deymann A, Doctor A, Davis A, Duff J, Dugas MA, Duncan A, Evans B, Feldman J, Felmet K, Fisher G, Frankel L, Jeffries H, Greenwald B, Gutierrez J, Hall M, Han YY, Hanson J, Hazelzet J, Hernan L, Kiff J, Kissoon N, Kon A, Irazuzta J, Lin J, Lorts A, Mariscalco M, Mehta R, Nadel S, Nguyen T, Nicholson C, Peters M, Okhuysen-Cawley R, Poulton T, Relves M, Rodriguez A, Rozenfeld R, Schnitzler E, Shanley T, Kache S, Skippen P, Torres A, von Dessauer B, Weingarten J, Yeh T, Zaritsky A, Stojadinovic B, Zimmerman J, Zuckerberg A (2009) Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock:2007 update from the American College of Critical Care Medicine. Crit Care Med 37:666–688CrossRefPubMedGoogle Scholar
  18. 18.
    Taketomo CK (1999) Fludrocortisone. In: Hodding JH, Kraus DM (eds) Pediatric dosage hand-book. Lexi-Comp Inc., Cleveland, p 2000Google Scholar
  19. 19.
    Wernovsky G, Wypij D, Jonas RA, Mayer JE Jr, Hanley FL, Hickey PR, Walsh AZ, Chang AC, Castaneda AR, Newburger JW et al (1995) Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation 92:2226–2235PubMedGoogle Scholar
  20. 20.
    du Cheyron D, Lesage A, Daubin C, Ramakers M, Charbonneau P (2003) Hyperreninemic hypoaldosteronism: a possible etiological factor of septic shock-induced acute renal failure. Intensive Care Med 29:1703–1709CrossRefPubMedGoogle Scholar
  21. 21.
    Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34:17–60CrossRefPubMedGoogle Scholar
  22. 22.
    Venkatesh B, Cohen J, Hickman I, Nisbet J, Thomas P, Ward G, Hall J, Prins J (2007) Evidence of altered cortisol metabolism in critically ill patients: a prospective study. Intensive Care Med 33:1746–1753CrossRefPubMedGoogle Scholar
  23. 23.
    Amato MB, Carvalho CR (2006) Severe acute respiratory distress syndrome, leptospirosis, and lung protective strategies. Crit Care Med 34:2703–2704; author reply 2704CrossRefPubMedGoogle Scholar
  24. 24.
    Annane D, Cariou A, Maxime V, Azoulay E, D’Honneur G, Timsit JF, Cohen Y, Wolf M, Fartoukh M, Adrie C, Santre C, Bollaert PE, Mathonet A, Amathieu R, Tabah A, Clec’h C, Mayaud J, Lejeune J, Chevret S (2010) Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA 303:341–348CrossRefPubMedGoogle Scholar
  25. 25.
    (2009) Abstracts of the Society of Critical Care Medicine’s 39th Critical Care Congress. January 9–13, 2010. Miami Beach, Florida, USA. Crit Care Med 37: A1–A542Google Scholar
  26. 26.
    Ceneviva G, Paschall JA, Maffei F, Carcillo JA (1998) Hemodynamic support in fluid-refractory pediatric septic shock. Pediatrics 102:e19CrossRefPubMedGoogle Scholar
  27. 27.
    Trimarchi T (2006) Endocrine problems in critically ill children: an overview. AACN Clin Issues 17:66–78CrossRefPubMedGoogle Scholar
  28. 28.
    Carcillo JA, Fields AI (2002) Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock. Crit Care Med 30:1365–1378CrossRefPubMedGoogle Scholar
  29. 29.
    Carcillo JA, Fields AI (2002) Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock. J Pediatr (Rio J) 78:449–466CrossRefGoogle Scholar

Copyright information

© Copyright jointly held by Springer and ESICM 2010

Authors and Affiliations

  • Kiran B. Hebbar
    • 1
  • Jana A. Stockwell
    • 1
  • James D. Fortenberry
    • 1
  1. 1.Division of Critical Care, Department of PediatricsEmory University School of Medicine and Children’s Healthcare of Atlanta at EglestonAtlantaUSA

Personalised recommendations