1) The document discusses adrenal insufficiency in intensive care unit patients, including the incidence, types, diagnosis, and treatment. 2) There is no agreed-upon standard for confirming adrenal insufficiency in ICU patients. Relative adrenal insufficiency is the most common type seen. 3) The use of adrenal stimulation tests in critically ill patients is controversial, and stress-dose steroids are only recommended for patients with septic shock not responding to fluids and vasopressors.

1. ADRENAL INSUFFICIENCY IN THE
INTENSIVE CARE UNIT
SAMIR EL ANSARY
ICU PROFESSOR
AIN SHAMS
CAIRO

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3. The incidence of adrenal insufficiency
in the ICU population is 1 % to 6% and
may be as high as 74% for patients
with septic shock.
However, no gold standard is agreed
on for confirming adrenal insufficiency
among ICU patients, and, in many
cases, uncertainty exists on how to
respond to this diagnosis.

4. Relative adrenal insufficiency
This is the most common and
perplexing type of adrenal
insufficiency seen in patients in the
ICU.
Patients with relative adrenal insufficiency may
present with vasopressor dependency, acute
multiple organ dysfunction, hypothermia, or an
inability to wean from mechanical ventilation.

5. Relative adrenal insufficiency
These patients can be identified
by their limited response to
adrenal stimulation tests or lower-
than-expected basal cortisol
levels despite critical illness.

6. Acute adrenal crisis or insufficiency
The acute clinical presentation typically
includes profound
hypotension, fever, and hypovolemia.
These patients will have very low
cortisol levels
(< 3 mcg/dL).
Chronic adrenal insufficiency

7. Primary adrenal insufficiency
(Addison disease)
The most common causes are
autoimmune diseases (70%) and
tuberculosis (10%).
Rare causes include adrenal
hemorrhage, adrenal metastasis,
cytomegalo virus, human
immunodeficiency virus (HIV) disease,
amyloidosis, and sarcoidosis.

8. Secondary adrenal insufficiency
This condition is caused by inadequate
production of
Adrenocorticotropic hormone (ACTH)
due to long-term use of exogenous
steroids (most common cause),
hypopituitary state, or isolated ACTH
deficiency.

9. Controversy
Etomidate, an anesthetic agent often used
for rapid-sequence intubation in critically ill
patients, increases the relative risk of
adrenal insufficiency by more than 60%.
Whether this increased risk of adrenal
insufficiency increases the risk of mortality
for adult ICU patients remains controversial.

10. Clinical markers of acute
adrenal insufficiency
Acute adrenal insufficiency presents
with various combinations of
Hypotension, tachycardia, severe
hypovolemia, respiratory failure,
nausea, vomiting, diarrhea, lethargy,
and weakness.

11. Clinical markers of acute
adrenal insufficiency
Patients with acute adrenal insufficiency
due to chronic exogenous replacement
May not initially exhibit
Hypotension
because mineralocorticoid secretion
can be intact until late-stage illness.

12. laboratory abnormalities associated
with adrenal insufficiency.
Decreased Na , Cl , HCO3 ---- Increased
K
Hyponatremia is most common.
Low levels of chloride and bicarbonate and
high levels of potassium occur
frequently.
Also seen are moderate
eosinophilia, lymphocytosis,
hypercalcemia, and hypoglycemia.

13. Diagnosis of adrenal
insufficiency
In ICU patients

14. The use of provocative adrenal stimulation
tests in critically ill patients remains
controversial.
Perhaps the most widely used protocol
identifies
patients with septic shock as having relative
adrenal insufficiency if their baseline
cortisol level is < 35 mcg/dL and they
respond to an ACTH stimulation test (250
mcg corticotropin) with a
bump in cortisol of < I0 mcgIdL .

15. The patients identified as nonresponders
appeared to have a reduction in mortality
when given stress-dose steroids.
However, in a large subsequent study, no
mortality benefit with stress-dose steroids
was observed for patients with or without
evidence of relative adrenal insufficiency.
Steroid use for "late acute respiratory
distress syndrome"
is controversial.

16. In non-ICU patients
In a nonstressed patient, a random
cortisol level >20 mcg/dL may rule
out the diagnosis of adrenal
insufficiency.
A random cortisol level < 3
mcg/dL confirms the
diagnosis of adrenal
insufficiency.

17. How should one use the ACTH
stimulation test?
Cortisol levels are measured before and 30
to 60 minutes after a supraphysiologic dose
of ACTH
(250 mcg corticotropin given
intravenously).
In patients who are not critically ill, a normal
response generates a poststimulation
cortisol level of > 20 mcg/dL.

18. How should one use the ACTH
stimulation test?
It isrecommended that
ACTH stimulation tests should not be
used to determine whether adult
patients with septic shock should
receive steroids.

19. Corticotropin-releasing hormone (CHR)
stimulation
CHR is given to stimulate cortisol levels.
Unlike the ACTH stimulation test, CHR
stimulation can rule out central adrenal
insufficiency.
A normal response generates a
poststimulation cortisol level > 20 mcg/dL or
a 30- to 60-minute rise in cortisol 27 mcg/dL.

20. Should the low-dose
ACTH (1 mcg)
stimulation test be used?
This test may detect adrenal atrophy
associated with adrenal insufficiency.
No consensus exists on how to
determine the lower level that equates
with a normal cortisol response.

21. How does one distinguish
between acute adrenal
insufficiency and other illness
states in the ICU?
The clinical findings and laboratory findings
among patients with acute adrenal
insufficiency are also common in the ICU
population.

22. Distinguishing between adrenal
insufficiency and other illnesses in
critically ill patients requires clinical
suspicion and at least one of the
following:
Failure to respond adequately to an
adrenal stimulation test .
Inappropriately low basal cortisol
levels .
An unequivocal clinical response to
empiric exogenous steroids .

23. Should steroids be administered
to ICU patients with a history of
long-term steroid use?
Patients' adrenals may become
insufficient after taking the equivalent
of 20 mg/day of prednisone for just 5
days, but adrenal insufficiency is rare
among patients taking steroids for <7
days.

24. Patients' adrenals
may become insufficient
after taking very-low-dose steroids
for months to years
> 5 mg/day
prednisone equivalent.

25. Fearing life-threatening adrenal
impairment, many physicians give
stress doses
(hydrocortisone 300-400 mglday
or equivalent)
to critically ill ICU patients who
have received a course of steroids
in the weeks or months before
their admission to the ICU.

26. Patient groups are at high risk
for adrenal insufficiency
Patients with septic shock
Patients taking chronic steroids.
Patients with HIV disease
The adrenal gland may be involved in >50%
of patients infected with HIV.
However, because adrenal function requires <20%
of the gland to function, adrenal
insufficiency in this population is uncommon (3%).

27. Patient groups are at high risk
for adrenal insufficiency
Patients with cancer
Even when cancers metastasize to
the adrenal gland, adrenal
dysfunction is uncommon.

28. Patient groups are at high risk
for adrenal insufficiency
High-risk postoperative patients
Patients >55 years old, patients undergoing
major operations (e.g., coronary artery
bypass grafting, abdominal aortic aneurysm
repair, Whipple procedure), patients with
multiple trauma, and postoperative patients
requiring vasopressors or failing to wean
from mechanical ventilation appear to be at
higher risk for adrenal insufficiency.

29. Do neurotrauma patients have
special problems with adrenal
insufficiency?
Fifty percent of patients with moderate
to severe traumatic head injury have
cortisol levels less than15 mcg/dL.
This is especially true among patients
receiving pentobarbital or propofol.

30. Do neurotrauma patients have
special problems with adrenal
insufficiency?
These patients often require vasopressors.
Thus monitoring cortisol levels in patients
with moderate to severe head injury may be
warranted.
Steroid supplementation can be
considered in patients with head trauma
who have relative adrenal insufficiency
and sustained hypotension.

31. stress-dose steroids be used
only among patients with
septic shock whose blood
pressure is poorly responsive
to both fluid resuscitation and
vasopressor therapy.

32. No randomized trials have been done
to guide clinicians when confronted
with critically ill patients without septic
shock who show evidence of relative
adrenal insufficiency, such as
postoperative surgical patients,
patients with severe pancreatitis, and
patients with moderate to severe
traumatic head injury.

33. The indicated therapies
for ICU patients with
septic shock
who may or may not have
adrenal insufficiency

34. Fluid resuscitation
Patients with septic shock typically require
multiple large boluses of intravenous fluids
and often vasopressors to maintain effective
arterial circulation.
If the patient's blood pressure
responds poorly to fluids and
vasopressors, the administration
of stress-dose steroids should be
initiated.

35. Steroid dosing
Administration of hydrocortisone,
300 to 400 mg/day given
intravenously in three or four
divided doses
with or without fludrocortisone (50
mcg enterally every day), is
accepted practice.

36. Steroid duration
For adult patients with septic shock whose
blood pressure is poorly responsive to
multiple intravenous fluid boluses for >1 to 2
hours, the author recommends
administration of stress-dose hydrocortisone
(300 mg/day) for 4 days.
If the
patient shows rapid clinical improvement,
the steroids may be stopped or tapered over
1 to 2 days. If significant hypotension recurs,
steroid dosing should return to the initial
dose, and a

37. Steroid duration
For adult patients with septic shock whose
blood pressure is poorly responsive to
multiple intravenous fluid boluses for >1 to 2
hours, the author recommends
administration of stress-dose hydrocortisone
(300 mg/day) for 4 days.

38. If the
patient shows rapid clinical
improvement, the steroids may be
stopped or tapered over 1 to 2 days.
If significant hypotension recurs,
steroid dosing should return to the
initial dose, and a
rapid taper can be undertaken after
7 days.

39. Should stress-dose steroid
supplementation be strongly considered
in all patients with septic shock?
Because of conflicting studies, opinions on
this point differ.
Yes, of course
A majority of patients with septic shock have
relative adrenal insufficiency.
The mortality rate for such patients is 30% to
60%.

40. A landmark randomized control trial
found an
absolute mortality reduction of 10%
among patients with severe sepsis
or septic shock and relative adrenal
insufficiency who received stress-
dose steroids versus placebo.

41. This finding is supported by a recent
systematic review that concluded that
prolonged low-dose steroid use reduces all-
cause mortality among adult patients with
septic shock.
Steroid supplementation for most ICU
patients with septic shock makes sense given
the modest risk of a short course of low-dose
steroids.

42. No
The data are too mixed
The Annane trial did not demonstrate across-
the-board mortality reduction in the steroid
group with severe sepsis and septic shock.
The subsequent CORTICUS
study showed no mortality benefit after
hydrocortisone therapy in patients with septic
shock.

43. No mortality benefit of steroids was
seen even among patients who
met criteria for relative adrenal
insufficiency.
In addition, the steroid arm of the
CORTICUS trial had significantly
more superinfections.

44. Early, smaller studies indicated
a survival benefit from using
steroids in septic shock.
However, this benefit was not
seen in meta-analysis of later
and
larger studies.

45. The Surviving Sepsis Campaign International
Guidelines recommend using steroids for
patients with septic shock unresponsive to
fluids and vasopressors.
This is largely a consensus-based
recommendation rather than an evidence-
based conclusion.
The scientific evidence to support even
this limited use of steroids in patients with
septic shock is modest.

46. SUMMARY

47. Relative adrenal insufficiency is common
in ICU patients with septic shock, but its
clinical importance remains
controversial.
2. To decide if and when a patient should
receive hydrocortisone therapy for septic
shock, there is no need to evaluate the
patient for relative adrenal insufficiency.

48. 3. ICU patients with septic shock whose
blood pressure does not respond to fluid
boluses and vasopressors should
receive stress-dose steroids.
4. Critically ill ICU patients who recently
received a prednisone equivalent to 25
mg/day for > 7 days should probably
receive stress-dose steroid coverage.

49. GOOD LUCK
SAMIR EL ANSARY
ICU PROFESSOR
AIN SHAMS
CAIRO
elansarysamir@yahoo.com
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Wellcome in our new group ..... Dr.SAMIR EL ANSARY