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Current conceptCorticosteroid Insufficiency in
Acutely ill Patients
Mark S. Cooper, M.D., and Paul M. Stewart, M.D.
NEJM Volume 348:727-734
February 20, 2003 Number 8
By Ri 93-04-05
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Questions
How to make a diagnosis of adrenal
insufficiency in patient under stress?
Treatment?
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Hypothesis
The normal range of cortisol level (plasma,
morning: 6 ~ 30 g/dl)
But it should be adjust in patient with stress.
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Knowledge
Fight or Fright
The need of corticosteroid increases in patient
with stress
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Whats known or unknown
The s/s of adrenal insufficiency are usuallynonspecific.
Adrenal crisis can cause fetal outcome.
The role of using corticosteroid in pt withinfection is still unclear.
If the diagnosis of adrenal insufficiency is
established, how long should corticosteroid beused?
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The HypothalamicPituitaryAdrenal
Axis in Acute illness
The Hypothalamic-Pituitary-Adrenal Axis
A diurnal pattern cortisol secretion
corticotropin (pituitary gland)
hypothalamic corticotropin-releasinghormone
Negative feedback
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The HypothalamicPituitaryAdrenal Axis in
Acute illness
Stress: severe infection,trauma, burns, illness,
surgerycortisol
Roughlyproportional to the severity.
Diurnal variation: vanished.
Stimulation of the hypothalamicpituitary
adrenal
axis: elevated levels of circulating
cytokines and other factors.
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The HypothalamicPituitaryAdrenal Axis in
Acute illness
During severe illness, many factors can impair
the normal corticosteroidresponse.
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Head injury;CNS depressants
Pituitary infarction
Ketoconazole
Adrenal hemorrhage insepticemia orcoagulopathy
High level ofinflammatory cytokinesin sepsis pt directly
inhibit adrenal cortisolsynthesis
Extensivedestruction by
tumor orinfection
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The HypothalamicPituitaryAdrenal Axis in
Acute illness
The metabolism of cortisol: Liver, can be
enhanced by drugs such as rifampin or
phenytoin
Excessive inflammatory cytokines during
sepsis: systemic or tissue-specific resistance to
cortisol
The need of corticosteroid increases in
patient with stress
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The HypothalamicPituitaryAdrenal Axis in
Acute illness
Develop during an illness
Transient
Functional adrenal insufficiency
-- no obvious structral defects in HPA axis
Relative adrenal insufficiency
-- insufficient to control the inflammatoryresponse
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Diagnosis of Corticosteroid Insufficiency during
Acute illness
Corticosteroid insufficiency associated withacute illness
-- difficult to discern clinically, but there are
some featuresthat suggest the diagnosis.
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Diagnosis of Corticosteroid Insufficiency during
Acute illness
It still remains extremely difficult torecognizeadrenal insufficiency in the ICU.
Important diagnostic clues
Hemodynamic instability
despite adequate fluidresuscitation
Ongoing evidence of inflammation without an
obvious source that does not respond to empirical
treatment.
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Laboratory Investigations
Randomly measured cortisol levels
More usefulwould be the identification of aminimal threshold level and a maximal
thresholdlevel. 15 g/dl (10 g/dl to 34 g/dl) best identifies
persons with clinical featuresof corticosteroid
insufficiency or who would benefit fromcorticosteroid replacement
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Laboratory Investigations
Corticotropin stimulation test
IV or IM250 g of Cosyntropin
Check plasma cortisol levels
0, 30, ( 60 ) mins after administration
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Laboratory Investigations
Corticotropin stimulation test
Prognostic implications
-- < 9g /dl
increased risk of death.
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Laboratory Investigations
The authors opinion
> 34 g /dl:unlike.
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Methylprednisolone2 mg/kg/day
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Laboratory Investigations
When to recheck ?
Development of new clinical features
Deterioration in clinical condition
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Treatment of Acute Adrenal
Insufficiency
Critically ill patients with established
hypoadrenalism: IV or IM Hydrocortisone
(solu-cortef) 50 mg q6h.
Patients in shock: 5 percent dextrose in
normal saline shouldbe given IV initially.
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Treatment of
Acute Adrenal Insufficiency(in septic shock)
Evidence-based support the use of supplementalcorticosteroid in septic shock pt, esp. in ICU.
3 randomized,controlled trials of hydro-cortisonereplacement in patientswith septic shock
Improvements in hemodynamics
Reduction in the need for vasopressor therapy.
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Treatment of
Acute Adrenal Insufficiency(in septic shock)
In the largestrandomized, placebo-controlled
trial, treatment of300 medicaland surgical
patients with 200 mg of hydrocortisone per
dayand 50 g of fludrocortisone once daily for7 dayssignificantly reduced mortality and the
duration of vasopressortherapy.
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Treatment of
Acute Adrenal Insufficiency(in septic shock)
Supplemental corticosteroid treatment in
septic shock pt should be initiated ASAP.
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Treatment of
Acute Adrenal Insufficiency(in other critical illness)
It may be beneficial in patients with other
criticalillnesses such as trauma, burns, and
medical and surgical conditions.
But no evidence now
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Conclusions
Diagnose corticosteroid insufficiencyinpatients with critical illnesses: still difficult.
Recent trials confirmed corticosteroid
replacement in septic shock pt havesubstantial benefits.
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Conclusions
Treatment with physiologic levelsof cortico-
steroid appears to carry few risks.
low threshold to testing of the hypothalamic
pituitaryadrenalaxis and corticosteroid-
replacement therapyin acutely ill patients.
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Prospect
Further studies are needed to clarify
specific situations: in which corticosteroid
replacement is beneficial
optimal dose
optimal duration
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Take Home Message
Supplemental corticosteroid treatment in septic
shock pt should be initiated ASAP.
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Thanks for your attention !!