+ Adrenal Insufficiency (AI) in the Septic Patient Fady Youssef, MD PGY-2 2014

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Adrenal Insufficiency (AI) in
the Septic Patient
Fady Youssef, MD PGY-2 2014
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Objectives

Define adrenal insufficiency

Understand who gets Relative adrenal insufficiency

Review the current evidence

Understand how to manage “Relative adrenal insufficiency” in the
setting of sepsis.
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Case Problem
68 yo male with PMH of HTN, HL and COPD presents to ER with AMS
and cough with productive sputum for 1 day. T 39 degrees C, BP 70/35,
HR 121, RR 21. He has been given 4L of NS and has been started on
norepinephrine, with no improvement in his vitals. Which of the
following next steps is most appropriate?
A: Draw a
B:
random cortisol level
Perform a high dose ACTH stimulation test
C: Administer
hydrocortisone
D: Administer
hydrocortisone with fludrocortisone
E:
None of the above
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Definition

Acute reversible dysfunction of the HPA axis in the setting of
physiologic stress (e.g. sepsis, intra/post operative state)

It is estimated that ___ % of critically ill patients suffer from
HPA axis dysfunction


30%
Symptoms of AI

shock, abdominal pain, fever, nausea and vomiting, electrolyte
disturbances and, occasionally, hypoglycemia
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Who gets AI?

Any patient in the setting of physiologic stress

Etiology:

Adrenal ACTH resistance

Decreased responsiveness of the target tissue to
glucocorticoids (GC)

Secondary AI: 2/2 chronic steroid therapy (dose dependent)

Certain meds: Etomidate, Phenytoin, Ketoconazole
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HPA Axis
2ry AI
Where is the dysfunction occurring in secondary AI?
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Diagnosing Relative Adrenal
Insufficiency

Diurnal variation is LOST during physiological stress

Lab assays of plasma cortisol concentration and ACTH stimulation test
are unreliable in critically ill patients

Random serum cortisol: Varies widely in critically ill patients.


Increased mortality with both very low and very high cortisol levels
There is are no reliable tests for diagnosing relative adrenal
insufficiency.
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So when to start steroid therapy?

Low MAP or SBP: requiring vasopressors


All meta-analyses confirmed improved shock reversal with
low-dose corticosteroid use (trials listed below for further
reference)


Response to vasopressors is irrelevant to whether steroids should be
started or not
Responsiveness is defined as: maintaining MAP > 65 mmHg
without vasopressor use within 1 day of starting hydrocortisone
Don’t delay treatment for ACTH stim test
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Treatment in sepsis


Hydrocortisone: total of 200 – 300 mg over 24 hrs

50 – 100 mg q6-8h for 5-7 days with taper

Patients receiving higher doses of steroids had worse outcomes (citation
below)
Fludrocortisone (a mineralocorticoid) has not been shown to help in
relative adrenal insufficiency.

Hydrocortisone seems to have sufficient mineralocorticoid activity

COIITSS trial
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Case Problem
68 yo male with pmxh of HTN, HL and COPD presents to ER with AMS
and cough with productive sputum for 1 day. T 39 degrees C, BP 70/35,
HR 121, RR 21. He has been given 4L of NS and has been started on
norepinephrine, with no improvement in his vitals. Which of the
following next steps is most appropriate?
A: Draw a
B:
random cortisol level
Perform a high dose ACTH stimulation test
C: Administer
hydrocortisone
D: Administer
hydrocortisone with fludrocortisone
E:
None of the above
+
Summary

No diagnostic test is reliable for relative adrenal insufficiency.

Low threshold to treat relative adrenal insufficiency in patients with
septic shock

Use low dose hydrocortisone/physiologic dosing for a limited time

Fludrocortisone has not been shown to help in relative AI
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Interested? Here is more …
HPA axis – Normal response

Physiological stress activates the HPA axis which in turn increases
serum cortisol levels

Serum Cortisol levels remain elevated during stress due to several
factors:

Reduced activity of cortisol metabolizing enzymes

Renal dysfunction prolonging the half life

Decrease in cortisol-binding globulin and albumin which brings > 90% of
cortisol

Inflammatory cytokines: Increase GC receptor affinity and increase the
peripheral conversion of precursors to cortisol
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