Steroids in Sepsis and Septic Shock

May 2018

Steroids in Sepsis and Septic Shock

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You’re working the weekend shift in TCC when you get a page:  triage patient to 3L for low BP.  You meet the patient in the room and find a critically ill-appearing 55 year-old female with one week of cough and increased shortness of breath.  Her vital signs are:

HR 125          BP 65/30          Sp02 89% on room air          RR 28

She is struggling to breathe, getting out 2 to 3 word sentences, and is oriented only to self.  You immediately ask the nurses to get two large-bore IVs and hang two liters or normal saline on pressure bags while you prepare to intubate.  Following intubation (during which you administer two boluses of phenylephrine, 100 mcg each, for dropping blood pressure), you get a stat portable chest x-ray showing multifocal pneumonia.  After your initial two liters of fluid have been administered, followed by a third (and broad-spectrum antibiotics), the patient’s blood pressure still only 80/45.

You place a right-sided internal jugular central line under ultrasound guidance and start a norepinephrine drip.  Your deftly placed arterial line begins to demonstrate an improved BP and MAP and you find the patient a bed in the medical ICU.  As the patient is being transferred, you begin to wonder whether steroids would be beneficial in this patient with clear septic shock.  After all, you know that much of the problem in sepsis is the inflammatory response, which would theoretically be mitigated by steroid administration.  You begin to search the literature and realize this has been a controversial topic dating back over 10 years…

PICO Question

Population: Adults patients with either severe sepsis without septic shock of with septic shock

Intervention: IV steroids, administered as an intermittent bolus or a continuous infusion.

Comparison: Placebo and standard of care

Outcome: Mortality, resolution of septic shock, development of septic shock, ICU and hospital length of stay, duration fo mechanical ventilation, need for renal replacement therapy.

Search Strategy

PubMed was searched using the terms “steroids AND sepsis” and limiting the results to clinical trials (https://tinyurl.com/y9wswub5).  This strategy yielded 363 studies, from which the four most relevant articles were chosen.  The Cochrane Database of Systematic Reviews was also searched in an attempt to find a meta-analysis of results, but no such articles was identified.

Articles

Article 1: Sprung CL, Annane D, Keh D, et al; CORTICUS Study Group. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008 Jan 10;358(2):111-24.
ANSWER KEY

Article 2:  Keh D, Trips E, Marx G, et al; SepNet–Critical Care Trials Group. Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial. JAMA. 2016 Nov 1;316(17):1775-1785.
ANSWER KEY

Article 3:  Venkatesh B, Finfer S, Cohen J, et al; ADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med. 2018 Mar 1;378(9):797-808.
ANSWER KEY

Article 4: Annane D, Renault A, Brun-Buisson C, et al; CRICS-TRIGGERSEP Network. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med. 2018 Mar 1;378(9):809-818.
ANSWER KEY

Bottom Line

In 2002, a landmark study published in JAMA (Annane 2002) demonstrated a significant reduction in 28-day mortality with the use of low-dose steroids among patients with septic shock who did not respond appropriately to a corticotropin stimualation test (adjusted odds ratio (OR) 0.54, 95% CI 0.31-0.97).  Despite adjusting outcomes for baseline characteristics in this randomized controlled trial (with no difference in outcomes looking at raw data), the authors condluded that steroids were beneficial in non-responders.  Since this study was published, several studies have been conducted to reevaluate the effects of steroids on the course of septic shock.  We looked at four such articles, including two high-impact articles published earlier this year.

In 2008, the CORTICUS trial was published as a follow-up to the initial 2002 study.  This international, mlticenter trial again evaluated the efficacy of steroids in both corticotropin non-responders and responders with septic shock, and found no differences in 28-day mortality among either group (relative risk (RR) 1.09, 95% CI 0.77 to 1.52 and RR 1.09, 95% CI 0.84-1.41, respectively).  The authors therefore concluded that “hydrocortisone cannot be recommended as general adjuvant therapy for septic shock (vasopressor responsive), nor can corticotropin testing be recommended to determine which patients should receive hydrocortisone therapy”.

Amiodarone, which was first approved by the FDA in 1985, became a mainstay of arrhythmia management after being added to the ACLS guidelines in 2000.  At that time, amiodarone was recommended ahead of lidocain for management of hemodynamically stable wide-complex tachycardia but was only included as a consideration for refractory VF and pulseless VT.  In the 2010 update, amiodarone was recommended as a “first line anti arrhythmic agent” in refractory VF/pulseless VT, based on limited evidence for improved rates of ROSC and hospital admission.  In addition, amiodarone been recommended for use in recent-onset AF for over twenty years (Hou 1995).  Given the rise in prominence of procainamide use in AF (see Ottawa Agressive Protocol by Stiell et al), and an increased focus on longer term outcomes in cardiac arrest, we decided to review evidence for a variety of amiodarone indications frequently seen in the ED.