Resus C4: What is the role of steroids in severe sepsis & septic shock?

Author:   Dr. Alex Sackeim
Reviewer & Edits:   Dr. John Greenwood

Clinical Case

23 y/o M with a PMHx of Crohn’s disease and a PICC line presents to the ED after two days of abdominal pain and fever.

Vital signs are: Temp: 101.4, HR: 122, BP: 88/42, RR: 23, Sp02 100% on RA.
On exam, the patient is drowsy but arousable, tachycardic, with cool extremities. PICC site looks good.

You suspect an infection and give a 30cc/kg fluid bolus and appropriate broad-spectrum antibiotics with improvement in the patient’s MAP & perfusion. However, 1 hour later the blood pressure begins to drop again! You ask the nurse to hang norepinephrine, and are now up to 0.1 mcg/kg/min.  Should we consider giving this patient corticosteroids?

Why do we give steroids in septic shock?
Pearl: Hydrocortisone is given to treat a relative adrenal insufficiency in patients with septic shock. 

Historically, the use of corticosteroids in sepsis is based on two different proposed pathophysiological mechanisms.

  • The leading theory is that septic patients have “relative adrenal insufficiency,” in which their cortisol levels do not rise sufficiently to address their low blood pressure and they could potentially benefit from corticosteroids. Cortisol has been shown to increase blood pressure during periods of stress to our bodies through a variety of mechanisms including sodium retention/volume expansion and direct vasopressor effects.
  • An alternative hypothesis is that corticosteroids blunt the inflammatory response to septic source and may be able to reduce the need for fluid/vasopressors.  Septic patients are in a hyper-inflammatory state and are releasing large amounts of cytokines that cause peripheral vasodilation leading to distributive shock.
When is the appropriate time to initiate hydrocortisone therapy?
Pearl: Corticosteroid administration should occur EARLY on in the patient’s resuscitation

Just as patients can develop acute kidney injury, encephalopathy, or heart failure as a result of poor perfusion, patients may also experience neuroendocrine dysfunction (hence the need for vasopressin, hydrocortisone, insulin replacement)

Over the last 50 years many studies and meta-analyses have been conducted to try to answer the question of when to give steroids and who may benefit from them including Schumer, Bone, Cronin, Jurney, Annane, CORTICUS, and COIITSS. The largest RCT to date on the subject, called ADRENAL, is currently underway. Below is a summary of what we know so far.Corticosteroids should only be considered in patients with severe septic shock (systolic < 90 mmHg) who have failed adequate fluid resuscitation and initial vasopressor therapy.*

  • Aim to start steroids within the first three hours of a patient’s treatment, especially if they are not responding to your initial resuscitation. This can and should be a treatment initiated in the emergency department.
  • Consider starting corticosteroids if you are increasing the dose of norepinephrine and starting to think about adding a second vasopressor (i.e. vasopressin).
  • Low/physiologic doses of steroids should be given (hydrocortisone 200 mg IV daily)
  • To avoid excess hyperglycemia and hypernatremia consider doing a continuous steroid infusion of hydrocortisone at a rate of 8-10mg/hr.  If this isn’t feasible you can bolus hydrocortisone 50mg q6 hours
  • Stop using the ACTH stimulation test for relative adrenal insufficiency as there appears to be no difference between responders vs non-responders in CORTICUS.

* For patients with known HPA axis insufficiency such as Addison’s disease, previous steroid dependence, concomitant COPD, or recent high dose steroid use, give steroids earlier.

Are there any adverse effects of hydrocortisone therapy?
Pearl: It’s unclear…

While steroids may hasten the reversal of septic shock, according to CORTICUS there appears to be a 27% higher risk of superinfections (new infections on top of the presenting infections), an 18% higher risk of hyperglycemia and a 58% higher risk of hypernatremia. Interestingly, patients had a nearly three-fold increase in their risk of recurrent septic shock (6% vs 2%). Other potential complications include impaired wound healing and neuromuscular weakness.

Are there any other immunomodulatory agents we should be giving?
To date there are only relatively small studies that have been conducted to determine whether there is a beneficial role for IVIG, plasmapheresis, high volume hemofiltration or nonsteroidal immunosuppressive drugs in the treatment of patients with septic shock. The results have been negative or conflicting at best. The largest RCT of IVIG showed no difference between control and intervention. At this time, there isn’t a clear role outside of clinical trials for these treatments.

Suggested Reading

  1. Annane D. Corticosteroids for severe sepsis: an evidence-based guide for physicians. Ann Intensive Care. 2011;1(1):7. [PubMed Link]
  2. Patel GP, Balk RA. Systemic steroids in severe sepsis and septic shock. Am J Respir Crit Care Med. 2012;185(2):133-9.  [PubMed Link]
  3. Sprung CL, et al; CORTICUS Study Group. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008 Jan 10;358(2):111-24. [PubMed Link]

Share this Post

Leave a Comment