2.corticosteroid replacement in critically ill patients

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Corticosteroid Replacementin Critically Ill Patients

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Steroid Physiology



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-acidglycoprotein

10% free = biologically active CBG decreases rapidly in critically ill pts increased

free cortisol



Adrenal Insufficiency (AI)

1. Primary Adrenal Insufficiency (Addison’s)

– >90% 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 adrenalinsufficiency (addisonian crisis) can be fatal within6-48 hours




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 preservedaldosterone (no Na, K abnormalities)




3. Relative or Functional AI (1)

– Reported in critically ill pts

– Subnormal adrenal corticosteroid production

– Hypoadrenal state without clearly defined defects inhypothalamic-pituitary-adrenal axis

– Difficult to define based on serum cortisol concentrations as

cortisol production may be inadequate to controlinflammatory response or meet an elevated metabolic

demand

– Characteristic rapid improvement on HC thx



Diagnosis of Adrenal

Insufficiency High-dose corticotropin stimulation test

– Can be done at any time of day

– Baseline cortisol 250g cosyntropinmeasure cortisol at 30 and 60 minutes

– Nonstressed pt: increase to 18 g /dL r/o AI

– Hi sensitivity & specificity for primary AIusing threshold value of 15 g /dL

– Less sensitive for secondary AI



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 empirictreatment



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



Random Cortisol Level

Poor prognosis in septic shock patients: (4)

– extremely HIGH (>34g/dL) total cortisol

– extremely LOW (<25g/dL) total cortisol

Interpretation of Baseline Cortisol = Controversial

– Cortisol level <15g/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 >25 g/dL if measured w/i

48 hrs of admit (3)



Cosyntropin Stimulation

Advocated as standard of diagnosis of AI incritically ill pts (5)

– Failure to increase cortisol concentration at least 9g/dL to value >20 g/dL associated w/

Increased mortality

Lack response to catecholamines

Disagreement on threshold of basalconcentration and change in cortisol withstimulation necessary to diagnose relative AI



Outcome of steroid replacement Cochrane Database Meta-analysis in 2004 (6)

– 15 trials no significant reduction in all-cause mortality at28 days w/ steroid replacement in septic shock

– 4 trials reduced mortality & increased shock reversalwith long courses of low dose steroids

Another Meta-analysis in 2004 (7)

– Short courses of high-dose steroids decreased survivalduring sepsis

– But a 5- to 7-day course of physiologic hydrocortisonedoses with subsequent tapering increased survival rateand shock reversal in patients with vasopressor-dependent septic shock



Conclusion

Patients with septic shock should have: – Baseline cortisol measured

– Undergo corticotropin-stimulation testing

Patients with inadequate cortisol response(baseline <15-25g/dL and failure to increase by9g/dL) benefit from glucocorticoid replacement

HC at 200-300 mg/d recommended withintermittent or continuous IV infusion

Steroids tx for 5-7days followed by taper (total

treatment time of 10days)



References

1. Bollaert PE. 2000. Stress doses of glucocorticoids in catecholamine dependency: a

new therapy for a new syndrome?. Intensive care medicine 26 (1): 3-5.

2. Cooper MS, Stewart PM. 2003. Corticosteroid insufficiency in acutely ill patients. The New

England journal of medicine 348 (8): 727-734.

3. Marik PE, Zaloga GP. 2003. Adrenal insufficiency during septic shock. Critical care

medicine 31 (1): 141-145.

4. Marik PE, Zaloga GP. 2002. Adrenal insufficiency in the critically ill: a new look at an old

problem. Chest 122 (5): 1784-1796.

5. Jacobi J. 2006. Corticosteroid replacement in critically ill patients. Critical care clinics 22

(2): 245-53, vi.

6. 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.

7. 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 141 (1): 47-56.

2.corticosteroid replacement in critically ill patients

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