Stress Dose Steroids

Caring for patients is extremely rewarding… but it can also be rather Stressful. There are many complex math problems to solve and risk-benefit ratios to balance. Even the seemingly elementary problems can mentally taxing, especially in children who are prone to obscure their critical illness with “non-specific” symptoms (ex, Leukemia, Myocarditis). Additionally, you literally have to do arithmetic when ordering medications. One topic that combines both of these issues is Adrenal Insufficiency. Let us take a minute to digest a Morsel on Stress Dose Steroids:

Adrenal Insufficiency

  • Adrenal crisis is a potentially life-threatening condition! [Miller, 2019; El-Maouche, 2018]
    • Adrenal crisis can be first presentation of conditions associated with adrenal insufficiency.
    • Adrenal insufficiency is associated with substantial morbidity and mortality in children (~5-10 cases per 100 patient-years). [Miller, 2019]
  • Adrenal insufficiency is associated with numerous conditions.
    • Primary = defect in adrenal gland
      • Hyponatremia and Hyperkalemia can be seen.
    • Secondary (Central) = defect in the hypothalamus and/or pituitary
      • Deficient ACTH eventually creates reduced glucocorticoids.
      • Mineralocorticoid production is preserved via Renin-Angiotensin system.
      • Ex.: most common cause is Iatrogenic
  • Adrenal insufficiency can be exacerbated by acute physiologic stressors when endogenous steroids would normally increase to compensate:
    • Acute illness
      • Febrile Illness
      • Diarrhea
      • Vomiting
    • Physical injury / stress
    • Surgery
    • Anesthesia
  • Early recognition is imperative! [Miller, 2019]
    • Clinical Signs & Symptoms:
      • Fatigue, Weakness
      • Nausea, Vomiting, Abdominal Pain
      • Hypotension
      • Dizziness
      • Diaphoresis
      • Seizures
      • Coma
    • Laboratory Findings:
      • Hyponatremia is most consistent finding.
      • Hyperkalemia is present in primary adrenal insufficiency
      • Hypercalcemia
      • Hypoglycemia is frequent in neonates and infants.
    • Hypotension and hypoglycemia can develop suddenly, even after an initial normal triage assessment.

Stress Dose Steroids

  • Stress Dose Steroids = increased dose of exogenous steroids to account for physiologic stress requiring additional glucocorticoids.
  • There is limited evidence on the optimal stress dose regimen for children. [Miller, 2019]
  • Family and Patient Education is paramount! [Miller, 2019; El-Maouche, 2018; Dorr, 2018; Leblicq, 2011]
    • Since early recognition is important, families are empowered to help recognize possible exacerbating stressors and self-administer stress dose steroids.
    • There are Adrenal Insufficiency Action Plans that can help families and ED providers manage this difficult condition. [Miller, 2019]
  • Currently recommendations include: [Miller, 2019]
    • Oral Stress Dose = Triple TOTAL daily dose of Hydrocortisone and divide that into 4 doses (q 6 hrs).
    • Emergent Intramuscular Dosing can be given if child is not tolerating oral medications.
      • IM hydrocortisone sodium succinate (Solu-Cortef)
        • 25 mg for child 3 years and younger
        • 50 mg for children >3 yrs – 12 years
        • 100 mg for children 12 years and older.
      • This is 5-10 times the physiologic cortisol secretory rate. [Miller, 2019]
      • An auto-injector is being developed.
    • Intravenous hydrocortisone is preferred once in the Emergency Department.
      • If unable to administer within 15 minutes, give IM hydrocortisone.
      • Dexamethasone is NOT suitable for primary adrenal insufficiency, because it has no mineralocorticoid action.
      • Methylprednisolone can be used, but HYDORCORTISONE is PREFERRED.
    • After initial stress dose of hydrocortisone sodium succinate is given, it should be followed by 50-100 mg/m^2/Day divided every 6 hours for 24 – 48 hours.
  • Other Important Managements:
    • Volume resuscitation!
    • Monitor and supplement glucose as needed.
    • Evaluate and treat underlying exacerbating causes.
  • Helpful labs:
    • Chemistry panel for glucose and acid-base assessment
    • Serum cortisol
    • Plasma ACTH level
    • Treatment is based on clinical presentation, not laboratory studies!
    • Ideally, collect blood samples prior to giving hydrocortisone, but do NOT DELAY giving the stress dosing! [Miller, 2019]

Moral of the Morsel

  • Steroids don’t just make big muscles! Don’t overlook their importance!
  • Parents often know best! Ask the family if their child has a Adrenal Insufficiency Action Plan! If they have it… USE IT!
  • Fever, Vomiting, and Diarrhea… oh My! They are Stressors. If the child is on chronic steroids, help them to accommodate for the stress.
  • Initial vital signs may deceive! Hypotension and hypoglycemia can develop abruptly.
  • IV Hydrocortisone is preferred… but don’t wait! If you don’t have access after 15 minutes, give it IM!

References

Miller BS1, Spencer SP2, Geffner ME3, Gourgari E4, Lahoti A5, Kamboj MK2, Stanley TL6, Uli NK7, Wicklow BA8, Sarafoglou K1. Emergency management of adrenal insufficiency in children: advocating for treatment options in outpatient and field settings. J Investig Med. 2019 Feb 28. PMID: 30819831. [PubMed] [Read by QxMD]
Makaya T1, Gilbert J1, Ryan F1, Watts W1. Adrenal insufficiency, steroid sick day rules and the paediatric endocrine nurse. Nurs Child Young People. 2018 Mar 7;30(2):26-31. PMID: 29512963. [PubMed] [Read by QxMD]
Dörr HG1, Wollmann HA2, Hauffa BP3, Woelfle J4; German Society of Pediatric Endocrinology and Diabetology. Mortality in children with classic congenital adrenal hyperplasia and 21-hydroxylase deficiency (CAH) in Germany. BMC Endocr Disord. 2018 Jun 8;18(1):37. PMID: 29884168. [PubMed] [Read by QxMD]
El-Maouche D1, Hargreaves CJ1, Sinaii N2, Mallappa A1, Veeraraghavan P1, Merke DP1,3. Longitudinal Assessment of Illnesses, Stress Dosing, and Illness Sequelae in Patients With Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab. 2018 Jun 1;103(6):2336-2345. PMID: 29584889. [PubMed] [Read by QxMD]
Rensen N1, Gemke RJ, van Dalen EC, Rotteveel J, Kaspers GJ. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia. Cochrane Database Syst Rev. 2017 Nov 6;11:CD008727. PMID: 29106702. [PubMed] [Read by QxMD]
Leblicq C1, Rottembourg D, Deladoëy J, Van Vliet G, Deal C. Are guidelines for glucocorticoid coverage in adrenal insufficiency currently followed? J Pediatr. 2011 Mar;158(3):492-498. PMID: 21035819. [PubMed] [Read by QxMD]

Sean M. Fox

I enjoy taking care of patients and I finding it endlessly rewarding to help train others to do the same. I trained at the Combined Emergency Medicine and Pediatrics residency program at University of Maryland, where I had the tremendous fortune of learning from world renowned educators and clinicians. Now I have the unbelievable honor of working with an unbelievably gifted group of practitioners at Carolinas Medical Center. I strive every day to inspire my residents as much as they inspire me.

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