Corticosteroid Replacement in Critically Ill Patients

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Corticosteroid Replacement in Critically Ill
Patients

• Deepika Nehra, MSIV
• Trauma Conference
• July 10th 2006

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Steroid Physiology
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• Basal Cortisol Production 8-25 mg in 24hrs
• Production can be increased 6-fold in stress
• Diurnal pattern of cortisol production lost in
  stress situations
• Cortisol T1/2 70-120 minutes
• Bound to circulating CBG, albumin, ?1-acid
  glycoprotein
• 10 free biologically active
• CBG decreases rapidly in critically ill pts ?
  increased free cortisol

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Adrenal Insufficiency (AI)

• 1. Primary Adrenal Insufficiency (Addisons)
• gt90 destruction of adrenal cortex
• Causes thrombosis, hemorrhage (septic shock with
  DIC), necrosis from ischemia
• Sxs truncal pain, fever, shaking chills,
  hypotension, shock, abdominal rigidity or
  rebound, dehydration, hyponatremia, hyperkalemia,
  elevated BUN
• Failure to recognize and tx severe adrenal
  insufficiency (addisonian crisis) can be fatal
  within 6-48 hours

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Adrenal Insufficiency (AI)

• 2. Secondary Adrenal Insufficiency
• Pituitary or hypothalamic abnormalities
• Causes empty sella syndrome, tumors,
  hypopituitarism, head trauma, postpartum
  pituitary necrosis, exogenous glucocorticoid use
• Sxs similar to primary AI but with preserved
  aldosterone (no Na, K abnormalities)

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Adrenal Insufficiency (AI)

• 3. Relative or Functional AI (1)
• Reported in critically ill pts
• Subnormal adrenal corticosteroid production
• Hypoadrenal state without clearly defined defects
  in hypothalamic-pituitary-adrenal axis
• Difficult to define based on serum cortisol
  concentrations as cortisol production may be
  inadequate to control inflammatory response or
  meet an elevated metabolic demand
• Characteristic rapid improvement on HC thx

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Diagnosis of Adrenal Insufficiency

• High-dose corticotropin stimulation test
• Can be done at any time of day
• Baseline cortisol ? 250?g cosyntropin ? measure
  cortisol at 30 and 60 minutes
• Nonstressed pt increase to ?18 ?g /dL r/o AI
• Hi sensitivity specificity for primary AI using
  threshold value of 15 ?g /dL
• Less sensitive for secondary AI

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Diagnostic Clues in Critically Ill Patients

• Persistent hypotension despite adequate volume
  resuscitation
• Hyperdynamic circulation and low SVR
• Ongoing e/o inflammation w/o obvious source that
  does not respond to empiric treatment

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Lab test difficulties in critical illness

• Cortisol level interpretation complicated by
• Hard to define normal ranges as expected levels
  vary based on disease severity
• Reduced CBG
• Changes in tissue resistance to cortisol
• Local release of free cortisol
• Etomidate use for intubation

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Random Cortisol Level

• Poor prognosis in septic shock patients (4)
• extremely HIGH (gt34?g/dL) total cortisol
• extremely LOW (lt25?g/dL) total cortisol
• Interpretation of Baseline Cortisol
  Controversial
• Cortisol level lt15?g/dL suggested to ID pts with
  clinical features of AI or who would benefit from
  replacement (2)
• Others suggest that a pt w/ septic shock on
  vasopressors should have baseline cortisol of
  gt25 ?g/dL if measured w/i 48 hrs of admit (3)

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Cosyntropin Stimulation

• Advocated as standard of diagnosis of AI in
  critically ill pts (5)
• Failure to increase cortisol concentration at
  least 9 ?g/dL to value gt20 ?g/dL associated w/
• Increased mortality
• Lack response to catecholamines
• Disagreement on threshold of basal concentration
  and change in cortisol with stimulation necessary
  to diagnose relative AI

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Outcome of steroid replacement

• Cochrane Database Meta-analysis in 2004 (6)
• 15 trials ? no significant reduction in all-cause
  mortality at 28 days w/ steroid replacement in
  septic shock
• 4 trials ? reduced mortality increased shock
  reversal with long courses of low dose steroids
• Another Meta-analysis in 2004 (7)
• Short courses of high-dose steroids decreased
  survival during sepsis
• But a 5- to 7-day course of physiologic
  hydrocortisone doses with subsequent tapering
  increased survival rate and shock reversal in
  patients with vasopressor-dependent septic shock

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Conclusion

• Patients with septic shock should have
• Baseline cortisol measured
• Undergo corticotropin-stimulation testing
• Patients with inadequate cortisol response
  (baseline lt15-25?g/dL and failure to increase by
  ?9?g/dL) benefit from glucocorticoid replacement
• HC at 200-300 mg/d recommended with intermittent
  or continuous IV infusion
• Steroids tx for 5-7days followed by taper (total
  treatment time of 10days)

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References

• Bollaert PE. 2000. Stress doses of
  glucocorticoids in catecholamine dependency a
  new therapy for a new syndrome?. Intensive care
  medicine 26 (1) 3-5.
• Cooper MS, Stewart PM. 2003. Corticosteroid
  insufficiency in acutely ill patients. The New
  England journal of medicine 348 (8) 727-734.
• Marik PE, Zaloga GP. 2003. Adrenal insufficiency
  during septic shock. Critical care medicine 31
  (1) 141-145.
• Marik PE, Zaloga GP. 2002. Adrenal insufficiency
  in the critically ill a new look at an old
  problem. Chest 122 (5) 1784-1796.
• Jacobi J. 2006. Corticosteroid replacement in
  critically ill patients. Critical care clinics 22
  (2) 245-53, vi.
• Annane D, Bellissant E, Bollaert PE, Briegel J,
  Keh D, Kupfer Y. 2004. Corticosteroids for severe
  sepsis and septic shock a systematic review and
  meta-analysis. BMJ 329 (7464) 480-480.
• Minneci PC, Deans KJ, Banks SM, Eichacker PQ,
  Natanson C. 2004. Meta-analysis the effect of
  steroids on survival and shock during sepsis
  depends on the dose. Annals of internal medicine
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