Guidelines for the Use of Steroids in Septic Shock
In which sepsis patients should I use steroids? The large clinical trials that found a benefit to low-dose steroids included patients with a systolic blood pressure <90 mm/Hg for more than one hour, despite aggressive fluid and vasopressor therapy. Based on these and other smaller trials, the Surviving Sepsis Campaign recommends the addition of IV steroids to those patients with septic shock who don’t respond to adequate fluid and vasopressor resuscitation.19
Should I obtain ACTH stimulation test in these patients? Although the Annane study showed that “nonresponders”—those who did not achieve ≥9 mcg/dL increase in cortisol level after 30 to 60 minutes of ACTH administration—were more likely to benefit from steroids, the overall trial population appeared to benefit regardless of the ACTH response.16
Furthermore, the CORTICUS study showed no difference between the corticotropin responder and nonresponder group. Also, most cortisol immunoassays measure total cortisol (free and protein-bound), whereas the free cortisol level is the more clinically relevant measurement. Hence, current guidelines from the American College of Critical Care Medicine and Surviving Sepsis Campaign do not recommend performing an ACTH stimulation test prior to administration of steroids.20
What type of steroids should I use, and at what dose? Current guidelines recommend IV hydrocortisone in a dose of 200 mg/day to 300 mg/day given as 50 mg every six hours or 100 mg every eight hours for at least seven days before tapering. Alternatively, IV hydrocortisone can be given as a bolus of 100 mg followed by a continuous infusion at 10 mg/hr (240 mg/day). Hydrocortisone at this dose has intrinsic mineralocorticoid activity, obviating the need for adding fludrocortisone. Fludrocortisone may otherwise be added as 50 mcg daily, if using a corticosteroid without significant mineralocorticoid activity. Patients with septic shock should not be treated with dexamethasone, which causes immediate and prolonged suppression of the hypothalamic-pituitary-adrenal axis.21
Do I need to taper off the steroids? It is recommended to wean the steroids after seven or more days of use, when vasopressors are no longer required. Keh and colleagues noted a 30% recurrence of shock in patients when the steroids were not tapered.22 There was also evidence of immunologic rebound after abrupt cessation of steroids, with an increase in inflammatory markers.23 The taper should decrease the dose every two or three days in small steps.
What potential side effects should I be concerned about? Overall, the use of higher dose corticosteroids is associated with significant potential side effects, including a worsening of the underlying infection, new infection, hyperglycemia, hypernatremia, and gastrointestinal bleeding. In a meta-analysis of nine clinical trials with high-dose corticosteroids (a starting dose of ~30mg/kg/day of methylprednisolone), Cronin and colleagues found a trend toward increased mortality due to secondary infections (relative risk 1.70; 95% confidence interval, 0.70 to 4.12).24 A recent meta-analysis of 15 trials found low-dose corticosteroids reduced ICU mortality and increased the proportion of shock reversal by Day 7 and by Day 28 without increasing the rate of gastroduodenal bleeding, super-infection, or hyperglycemia.25
Back to the Case
Our patient was admitted to the medical ICU. After obtaining urine and blood cultures, she was started on IV levofloxacin. She remained hypotensive despite IV fluids and IV norepinephrine. She was started on IV hydrocortisone 50 mg every six hours. Over the next 48 hours, her hemodynamic parameters improved. Urine and blood cultures came back positive for E. coli. Her BUN and creatinine decreased to 24 mg/dL and 1.4 mg/dL, respectively.