CORTICUSOVMC LANDMARK TRIALS SERIES

Sprung CL, et al. "Hydrocortisone therapy for patients with septic shock". New England Journal of Medicine.

2008. 358(2):111-24.

Corticosteroid Therapy of Septic Shock (CORTICUS)

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.

CLINICAL QUESTION

Does low dose hydrocortisone therapy improve survival in critically ill, septic shock patients?

DESIGN

Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial N=499

Hydrocortisone (n=251) Placebo (n=248)

Mean follow-up: 28 days

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

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)

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

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?

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)

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?

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

BOARD-LIKE QUESTION72yo 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 2.2ABG 7.31/51/87

ADAPTED FROM MKSAP 17

QUESTIONWhich is the most appropriate next step in treatment?A. Give 500cc mL of 12.5% albumin

q6hourB. Start hemodialysisC. Start hydrocortisoneD. Discontinue IVNS

BOARD-LIKE QUESTIONEducational Objective: Septic Shock and AKIKey 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.

ANSWERWhich is the most appropriate next step in treatment?A. Give 500cc mL of 12.5% albumin

q6hourB. Start hemodialysisC. Start hydrocortisoneD. Discontinue IVNS