+ Adrenal Insufficiency (AI) in the Septic Patient Fady Youssef, MD PGY-2 2014 + 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. + 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 + 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 + 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 + HPA Axis 2ry AI Where is the dysfunction occurring in secondary AI? + 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. + 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 + 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 + 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 + 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