A 48-year-old man with a history of asthma treated with intermittent steroids, and a history of kidney stones, is admitted to the ICU with urosepsis. He is intubated, started on antibiotics, and fluid resuscitated with 30 mL/kg of normal saline. Despite this therapy he becomes increasingly hypotensive requiring escalating vasopressor doses. An ACTH stimulation test is performed revealing a baseline cortisol of 10 µg/dL and a 30-minute peak of 16 µg/dL.
Which of the following interventions is most appropriate given the ACTH test results?
Correct Answer: A
Administering ACTH (cosyntropin) is a way of interrogating the hypothalamic-pituitary-adrenal axis to determine its function in response to systemic stress. The ACTH stimulation test involves measuring a baseline (random) cortisol level, administering 250 µg of ACTH, and measuring the rise in serum cortisol after 30 to 60 minutes. A peak cortisol of 18 to 20 µg/dL is considered a normal response to ACTH stimulation and excludes primary and nearly all cases of secondary adrenal insufficiency. In critical illness an incremental increase of less than 9 µg/dL is the most sensitive and specific cutoff of identify nonresponders. Thus, in this patient a peak level of 16 µg/dL and rise of only 6 µg/dL indicate adrenal insufficiency, and she would likely benefit from corticosteroids. There is no indication that repeat testing is necessary as long as the peak levels are drawn at the appropriate time. The 250 µg cosyntropin stimulation tests raised the ACTH concentration to 60,000 pg/mL, which dwarfs the physiologic 100 pg/mL of ACTH needed to maximally stimulate the adrenal cortex. However, it is possible that patients who respond to these supra-maximal doses may still be adrenally insufficient when this stimulus is removed. Corticosteroid administration has been shown to be useful in shock reversal in patients with critical illness–related corticosteroid insufficiency.
A 75-year-old man is admitted to the ICU with septic shock. Broad spectrum antibiotics are initiated, and he undergoes fluid resuscitation. Despite receiving 5 L of lactated ringers, he remains hypotensive requiring high-dose norepinephrine and vasopressin infusions. Cardiac ultrasound reveals hyperdynamic ventricular function without other abnormalities.
Which of the following statements regarding administration of systemic corticosteroids is most appropriate for this patient?
Correct Answer: C
The surviving sepsis guidelines recommend low-dose steroids in patients who are fluid-resuscitated in vasopressor-dependent shock who are unable to reach their target MAP goal. It is not necessary to perform an ACTH stimulation test. Steroid use is associated with improved MAP and shorter duration of vasopressor use. This is a low-strength recommendation, but steroids may be warranted in this decompensating patient.
Early research using high-dose methylprednisolone (supra-physiologic) did not show improved survival and possible harm. Subsequent trials using physiologic doses arrived at conflicting results. The study by Annane and colleagues (2002) and the APROCCHSS trial (2018) showed that patients with septic shock had faster reversal of shock and decreased mortality after receiving low-dose hydrocortisone and fludrocortisone. On the other hand, the CORTICUS trial in 2008 and the ADRENAL trial in 2018 found a faster resolution of shock, but no difference in 28-day mortality with hydrocortisone administration. Thus, evidence is mixed against recommending routine use in patients who are adrenally insufficient. Guidelines do not recommend routine ACTH testing as it may be unreliable in critical illness and may be affected by numerous medications.
A 56-year-old woman with hypertension, rheumatoid arthritis, and gastroesophageal reflux disease is admitted to the ICU after undergoing a bowel resection for perforated diverticulitis. Her home medications include lisinopril 10 mg, prednisone 15 mg, and omeprazole 40 mg. She is treated with piperacillin-tazobactam and receives adequate fluid resuscitation over the next 24 hours but continues to require vasopressors for hypotension.
Given a concern for adrenal insufficiency, which of the following steroids is most appropriate to administer to this patient?
Correct Answer: D
This patient has vasopressor-resistant septic shock despite adequate IV fluid resuscitation which may be due to adrenal insufficiency. Current guidelines on critical illness–related corticosteroid insufficiency recommend IV hydrocortisone <400 mg/d for ≥3 days in patients with septic shock that is not responsive to fluid resuscitation and requires moderate- to high-dose vasopressor therapy. Hydrocortisone is the synthetic equivalent to the physiologic final active compound, cortisol, so treatment with hydrocortisone directly replaces cortisol independently from metabolic transformation. In these large doses it provides both glucocorticoid and mineralocorticoid coverage. A potential disadvantage of hydrocortisone administration is that diagnostic testing of adrenal function cannot be performed while receiving the medication.
Dexamethasone does not have any intrinsic mineralocorticoid activity and therefore would not provide full repletion. Fludrocortisone would not be an adequate choice as it is pure mineralocorticoid and does not have any glucocorticoid activity. Additional mineralocorticoid replacement is not needed as long as the dose of cortisol exceeds 50 mg daily. If a patient is completely adrenally insufficient, then fludrocortisone should also be administered. Prednisone and cortisone are typically avoided in critically ill patients because they require hydroxylation to create the active compound (prednisone to prednisolone and cortisone to cortisol). In addition, these are only available for oral administration, and their use is limited in critical care where enteral absorption may be compromised.
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