Published on October 18, 2016
1. CORTICUS OVMC LANDMARK TRIALS SERIES Sprung CL, et al. "Hydrocortisone therapy for patients with septic shock". New England Journal of Medicine. 2008. 358(2):111-24.
2. Corticosteroid Therapy of Septic Shock (CORTICUS)
3. BACKGROUND Prior to CORTICUS, trials (eg Annane Trial, 2002) showed benefit from hydrocortisone and fludrocortisone in septic shock and patients with relative adrenal insufficiency Subsequent studies were not able to replicate Annane Trial and even showed harm (related to infection) when hydrocortisone was given Hydrocortisone has both glucocorticoid and mineralocorticoid activity.
4. CLINICAL QUESTION Does low dose hydrocortisone therapy improve survival in critically ill, septic shock patients?
5. DESIGN Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial N=499 Hydrocortisone (n=251) Placebo (n=248) Mean follow-up: 28 days
6. POPULATION Inclusion Criteria Patients 18 years and older All patients hospitalized in ICU Septic shock within the past 72h (as defined by sBP <90 despite IV fluid resuscitation OR need for vasopressors >1h) and hypoperfusion or organ dysfunction attributable to sepsis Exclusion Criteria Underlying disease with poor prognosis Life expectancy <24h Immunosuppression Treatment with long-term corticosteroids within past 6 months or short-term corticosteroids within past 4 weeks
7. INTERVENTIONS Participants randomly assigned to: Hydrocortisone 50mg IV q6hour, tapered over 6 days Placebo IV q 6 h, tapered over 6 days High dose of (250mcg) ACTH-stimulation test was performed 60 minutes prior to admin of meds Patients were classified as responsive (cortisol increase >9 mcg/dL) or non-responsive to ACTH (cortisol increase ≤9 mcg/dL)
8. CRITICISMS The trial was underpowered (needed enrollment of 800) Patient population was less ill than patients enrolled in prior trials of corticosteroids in shock Inclusion criteria of 72 hours may have missed the optimal window of opportunity. No studies on myopathy induced in patients by hydrocortisone Post-hoc analysis showed appropriate antibiotics in 72% vs. 78%, outcomes reported as NSS; this means that one-quarter of patients did not receive appropriate antibiotics
9. BOTTOM LINE Hydrocortisone hastens the reversal of shock BUT does not confer a survival benefit among patients with septic shock. Based on CORTICUS and selected other studies, corticosteroids should not be routinely used in adult patients with septic shock. NEVERTHELESS, there may be a benefit among selected patients. Blood pressure is dropping, patient already on 3 pressors… Should we start Steroids?
10. SURVIVING SEPSIS CAMPAIGN Guidelines for Severe Sepsis and Septic Shock If unable to reverse hemodynamic instability with fluid resuscitation and pressors, then Hydrocortisone 200mg IV daily can be used Recommend against ACTH stimulation test in adults with septic shock (Grade 2B) Recommend against using hydrocortisone when vasopressors aren’t required (Grade 2D) Recommend against using corticosteroids in sepsis without shock (Grade 1D)
11. DISCUSSION QUESTIONS Based on the CORTICUS trial, should hydrocortisone be given in patients with septic shock? What is a criticism for why the CORTICUS trial cannot be extrapolated to all patients with septic shock? When should Hydrocortisone be given in critically ill patients with septic shock?
12. DISCUSSION QUESTIONS Based on the CORTICUS trial, should hydrocortisone be given in patients with septic shock? ANSWER: Yes, with the understanding that Hydrocortisone can reverse shock, but not improve survival. What is a criticism for why the CORTICUS trial cannot be extrapolated to all patients with septic shock? ANSWER: The patients in the CORTICUS trial were not as sick as prior trials. Also, 72 hour window may have missed optimal window for medication. When should Hydrocortisone be given in critically ill patients with septic shock? ANSWER: When fluids and pressors cannot achieve hemodynamic stability and patient is in persistent shock
13. BOARD-LIKE QUESTION 72yo F, admitted to ICU for CAP complicated by septic shock. Within past 24 hours, patient no longer requires Levophed to maintain blood pressure. He is currently receive 100cc/hr of IVNS. Net fluid balance since admission is 10L. Currently, he is receiving CTX, Azithromycin, and Dexmedetomidine. On PE, T 36.8, HR 78, BP 94/55. Labs: K 4, Creatinine 2.2 ABG 7.31/51/87 ADAPTED FROM MKSAP 17 QUESTION Which is the most appropriate next step in treatment? A. Give 500cc mL of 12.5% albumin q6hour B. Start hemodialysis C. Start hydrocortisone D. Discontinue IVNS
14. BOARD-LIKE QUESTION Educational Objective: Septic Shock and AKI Key Point: In patients with septic shock, aggressive fluid resuscitation is known to be beneficial only during early period (within first several hours). After initial period, fluids unlikely to make kidneys better (and may worsen it). Can trial d/c IV fluids and start diuretics. Albumin can cause harm during recovery phase, hemodialysis currently not indicated. Hydrocortisone has not consistently shown benefit. Additionally, this patient is able to maintain BP without pressors so hydrocortisone should not be used. ANSWER Which is the most appropriate next step in treatment? A. Give 500cc mL of 12.5% albumin q6hour B. Start hemodialysis C. Start hydrocortisone D. Discontinue IVNS