ADRENAL INSUFFICIENCY IN THEINTENSIVE CARE UNIT

SAMIR EL ANSARYICU PROFESSOR

AIN SHAMSCAIRO

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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.

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.

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.

Acute adrenal crisis or insufficiency The acute clinical presentation typically

includes profoundhypotension, fever, and hypovolemia.

These patients will have very low

cortisol levels(< 3 mcg/dL).

Chronic adrenal insufficiency

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.

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.

ControversyEtomidate, 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.

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.

Clinical markers of acute adrenal insufficiency

Patients with acute adrenal insufficiency due to chronic exogenous replacement

May not initially exhibitHypotension

because mineralocorticoid secretion can be intact until late-stage illness.

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 moderateeosinophilia, lymphocytosis,

hypercalcemia, and hypoglycemia.

Diagnosis of adrenal insufficiency

In ICU patients

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 .

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.

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 thediagnosis of adrenal

insufficiency.

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.

How should one use the ACTH stimulation test?

It isrecommended thatACTH stimulation tests should not be

used to determine whether adult patients with septic shock should

receive steroids.

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.

Should the low-doseACTH (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.

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.

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 .

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.

Patients' adrenalsmay become insufficient

after taking very-low-dose steroids for months to years

> 5 mg/dayprednisone equivalent.

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.

Patient groups are at high risk for adrenal insufficiency

Patients with septic shockPatients taking chronic steroids.

Patients with HIV diseaseThe adrenal gland may be involved in >50%

of patients infected with HIV. However, because adrenal function requires <20%

of the gland to function, adrenalinsufficiency in this population is uncommon (3%).

Patient groups are at high risk for adrenal insufficiency

Patients with cancerEven when cancers metastasize to

the adrenal gland, adrenal dysfunction is uncommon.

Patient groups are at high risk for adrenal insufficiency

High-risk postoperative patientsPatients >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.

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.

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.

stress-dose steroids be used only among patients with septic shock whose blood

pressure is poorly responsive to both fluid resuscitation and

vasopressor therapy.

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.

The indicated therapies for ICU patients with

septic shock who may or may not have

adrenal insufficiency

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.

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.

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 thepatient 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.

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 thepatient 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 arapid taper can be undertaken after

7 days.

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 courseA majority of patients with septic shock have

relative adrenal insufficiency. The mortality rate for such patients is 30% to

60%.

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.

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.

NoThe 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 CORTICUSstudy showed no mortality benefit after

hydrocortisone therapy in patients with septic shock.

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.

Early, smaller studies indicated a survival benefit from using

steroids in septic shock.

However, this benefit was not seen in meta-analysis of later

andlarger studies.

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.

SUMMARY

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.

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.

GOOD LUCK

SAMIR EL ANSARYICU PROFESSOR

AIN SHAMSCAIRO

elansarysamir@yahoo.com

https://www.facebook.com/groups/1451610115129555/#!/groups/1451610115129555/

Wellcome in our new group ..... Dr.SAMIR EL ANSARY