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Adrenal Dysfunction following
Cardiac Surgery
JM CO, MD, FPCP, FPSEM
ENDOCRINOLOGY, DIABETES AND METABOLISM
UERMMMCI
ST LUKE’S MEDICAL CENTER QC
CARDINAL SANTOS MEDICAL CENTER
MAY 24, 2012
Should I be concerned re adrenal
dysfunction?
Hypotension post-cardiac
surgery? Probably cardiac.
Why is my patient still
Does
he
have
Am
I
missing
hypotensive several days
adrenal
aftersomething?!
cardiac
surgery?
dysfunction?
I’m just here for
the sugars!
Consider adrenal dysfunction in your
post-cardiac surgery patient whom you have
difficulty weaning off vasopressors.
WHY? IS THIS
CONDITION A
COMMON
OCCURRENCE?
Incidence in surgical ICU
Incidence of adrenal insufficiency among
surgical ICU patients > 55 years of age
with postoperative hypotension
requiring vasopressors was as high as
32.7%
Rivers EP, Gaspari M, Saad GA et al. Chest 2001; 119:889-896
120 elective CABG patients
 93 had relative adrenal insufficiency (77.5%)
 Of the 78 patients who received etomidate, 69 had
developed relative adrenal insufficiency (88%)
 Of the 42 patients who did not receive etomidate, 24
developed relative Adrenal insufficiency (57.1%)
Iribarren et al. Journal of Cardiothoracic Surgery 2010, 5:26
Diagnostic criteria still needs work
 ACTH-stimulation tests in CABG patients
 38.5% of the clinically euadrenal and maximally
stressed surgical patients with an uneventful clinical
course showed an inadequate rise of cortisol levels
after the 250 ug ACTH-stimulation, when using the 9
ug/dL criterion.
J Clin Endocrinol Metab 90: 4579–4586, 2005
The adrenal gland
Mineralocorticoids
(eg Aldosterone)
Glucocorticoids
(eg Cortisol)
Androgens
Catecholamines
(eg Epinephrine)
Cortisol affects the transcription of thousands of genes in
every cell of the body.
 Effects
 Increases glucose
 Activation of lipolysis
 Increases sensitivity to vasopressor agents such as
catecholamines and angiotensin II
 Anti-inflammatory actions


Reduction in the number and function of various immune cells at
sites of inflammation
Decreases the production of cytokines, chemokines, and
eicosanoids
Marik PE et al. Crit Care Med 2008 Vol. 36, No. 6
Adrenal response to stress
 With severe infection, trauma, burns, illness, or
surgery, there is an increase in cortisol production by
as much as a factor of six that is roughly proportional
to the severity of the illness.
 Diurnal variation in cortisol secretion is also lost.
 These effects are due to increased production of CRH
and ACTH and a reduction in negative feedback from
cortisol.
Cooper M, Stewart P. N Engl J Med 2003. 348;8
Adrenal response to surgery
 Surgery is one of the most potent activators of the
hypothalamic-pituitary-adrenal axis
 Maximum cortisol levels are reached in the early
postoperative period, especially following
anaesthesia reversal and endotracheal extubation
 In CABG


Peak cortisol levels achieved 30 minutes after extubation
Cortisol levels have high normal values about 48-72 hours
after surgical procedure
Marik PE et al. Crit Care Med 2008 Vol. 36, No. 6
Why would the adrenal fail?
 Strong inflammatory signals, such as cytokines (TNF-α)
or other peptides, known as corticostatins, compete with
ACTH for binding on its receptor, thus resulting in
decreased cortisol production and secretion
 Other neuropeptides, signaling molecules, components
of oxidative stress and the impaired adrenal blood flow
contribute to adrenal insufficiency.
 Some inflammatory factors may cause glucocorticoid
resistance at the level of target cell, affecting vital steps of
the glucocorticoid receptor signaling.
http://www.endotext.org accessed 23 May 2012
Now that you are considering adrenal dysfunction..
What should I do?
Was adrenal dysfunction present before surgery?
 Ask for symptoms
 Weakness and fatigue
 Anorexia, nausea,
vomiting
 Abdominal pain
 Myalgia or arthralgia
 History of pituitary
 History of steroid use?
 Prednisone, Medrol,
Decilone
 Celestamine, Claricort
 Nasal sprays (?)
 Look for:
 Decreased body hair
 Vitiligo
 Increased pigmentation
dysfunction?


History of low TSH and
FT4?
Brain surgery / trauma /
irradiation / Sheehan’s?
Cooper M, Stewart P. N Engl J Med 2003. 348;8
Features suggesting corticosteroid insufficiency
Clinical problems
 Hemodynamic instability
 Ongoing inflammation
with no obvious source
 Multiple-organ dysfunction
Laboratory findings
 Hyponatremia
 Hyperkalemia
 Hypoglycemia
 Eosinophilia
Rarely seen in
ICU patients
Cooper M, Stewart P. N Engl J Med 2003. 348;8
Before you test for cortisol..
Septic shock and ARDS should be treated with
glucocorticoids
 Septic shock




SIRS
Infection
End-organ damage
Refractory hypotension
 ARDS




Hypoxia
Chest X-Ray: Bilateral diffuse infiltrates of the lungs
No cardiovascular lesion
PaO2/FiO2 ratio less than 200
Marik PE et al. Crit Care Med 2008 Vol. 36, No. 6
Cooper M, Stewart P. N Engl J Med 2003. 348;8
Cooper M, Stewart P. N Engl J Med 2003. 348;8
Corticotropin test / ACTH stimulation test
 Baseline cortisol
 Administer synthetic ACTH (synacthen) 250g IV over 2
minutes (do not use 1 g)
 Get cortisol at 30 and 60 mins
 Adequate response:  Cortisol ≥ 9g/dl
 Where can I get ACTH (synacthen)?



Makati Medical Center (clinic of Dra. Crisostomo or Dra. Isidro):
Php500
St. Luke’s Medical Center QC DTEC (7230101 local 5210): Php4,350
The Medical City and UST: in-hospital use only
American College of Critical Care Medicine
At this time, adrenal insufficiency in critical illness is
best diagnosed by:
  cortisol (after 250 µg cosyntropin) of <9 µg/dL
 Random total cortisol of <10 µg/dL
Marik PE et al. Crit Care Med 2008 Vol. 36, No. 6
ACTH is not available in my area, can’t I
just do a random cortisol assay?
Yes but if your result is between 15-34 µg/dL,
still better to do corticotropin test.
My patient is hypotensive! Isn’t that stress
enough to stimulated the adrenals?
It may sound plausible, but I can’t give you
any evidence to recommend such at this time.
Can I do an insulin tolerance test instead
of giving ACTH?
No, this is contraindicated in patients with
ischemic heart disease.
My lab doesn’t do cortisol. Can I just go
clinical and treat?
No evidence that treatment may be harmful,
so maybe could be acceptable.
Corticosteroid-replacement doses
Cooper M, Stewart P. N Engl J Med 2003. 348;8
Glucocorticoid supplementation
 For severe surgical stress, including cardiothoracic
surgery:


IV hydrocortisone 150mg/day (eg 50mg q8h)
Taper over next 2-3 days post-surgery
 For myocardial infarction:
 Same dose as above
 Taper once clinical condition stabilizes
 Septic shock / major trauma / life-threatening
complication

Maximum 200mg/day IV hydrocortisone (eg 50mg q6h)
Jung C et al. Med J Aust 2008 188:409-413
Are glucocorticoids beneficial?
 69% of patients with functional hypoadrenalism
(Cortisol < 30 g/dL or  cortisol ≤ 9 g/dL) could
be weaned from treatment with vasopressors within
24 h (p<0.031)

This benefit was not seen in patients with normal adrenal
response
 Mortality was also lower in the hydrocortisone-
treated Adrenal Insufficiency patients: 21% vs 45%
(p < 0.01)
Rivers EP, Gaspari M, Saad GA et al. Chest 2001; 119:889-896
More data is needed re the benefits of treatment
 The role of glucocorticoids in the management of
patients with community-acquired pneumonia, liver
failure, pancreatitis, those undergoing cardiac
surgery, and other groups of critically ill patients
requires further investigation.
 Please contribute to our knowledge through research
Marik PE et al. Crit Care Med 2008 Vol. 36, No. 6
Wow, this cardiologist
really takes everything
into consideration!
Let’s work this patient
up for adrenal
dysfunction and give
steroids if warranted
Hey I should
have thought of
that earlier!
Adrenal Dysfunction following
Cardiac Surgery
JM CO, MD, FPCP, FPSEM
ENDOCRINOLOGY, DIABETES AND METABOLISM
FOR SLIDE REQUESTS:
[email protected]

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