Steroids for Septic Shock

In early septic shock, IV steroid boluses possibly reduce mortality, but likely improve secondary patient-centred outcomes of ventilator-free days, LOS in the ICU, vasopressor dependence.

Reasonable to initiate IV hydrocortisone for patients in septic shock that is refractory to initial vasopressor therapy.

Accelerates resolution of shock by 1.5 days
Increases vasopressor-free days by 1.5 days
Increases neuromuscular weakness
No clear effect on short or long-term mortality

Dosing

Typical regimen: IV hydrocortisone 50 mg q.6h or 200 mg/d continuous infusion
Unclear optimal regimen, most studies used the above dosing regimen.
Duration was 7 days in APROCCHSS, 5 days with 6 day taper in VANISH.
Unclear whether there's a dose response benefit

Literature

Annane 2002 (French study)

Annane D, Sébille V, Charpentier C, et al. Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock. JAMA. 2002;288(7):862-871. doi:10.1001/jama.288.7.862

This trial examined ~300 patients with septic shock and mechanical ventilation within 3-8 hours of meeting critieria. Patients were given a 250-mcg cosyntropin stimulation test and classified as "responders" or "non-responders". - Patients: septic shock, hypotensive despite >5 mcg/kg dopamine or current treatment with NE/E, intubated, lactate >2, oliguric. - Intervention: Hydrocortistone 50 mg IV q6H + Florinef 50 mcg PO daily x 7 days - Control: Placebo - Results: 28-day mortality - Overall: Reduced 28-day mortality (55% vs 61%). Driven by non-responders - Non-Responders: Reduced 28-day mortality (53% vs 63%), and extended the median time to death from 12 to 24 days. HR 0.67. NNT is 7. - Responders: No effect seen (61% vs 53%), but underpowered (P=0.81) - Results: vasopressor requirements - Overall: Reduced time on vasopressors (7 vs 9 days) - Non-Responders: Reduced time on vasopressors (7 vs 10 days) - Responders: No significant difference (9 vs 7 days), underpowered. - Adverse events: no significant differences.

Annane 2002

IV hydrocortisone + PO Florinef in severe septic shock improves and delays mortality, and reduces dependence on vasopressors. Most pronounced in those with critical illness associated adrenal insufficiency.

ADRENAL (2018)

Venkatesh B, Finfer S, Cohen J, et al. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. New England Journal of Medicine. 2018;378(9):797-808. doi:10.1056/NEJMoa1705835

This study examined mechanically ventilated patients with septic shock. - Patients: 3800 patients with early septic shock and on the ventilator - Intervention: IV hydrocortisone 200 mg/24 h continuous infusion for 7 days - Control: placebo for 7 days - Results: 90-day mortality - No difference in 90-day mortality (28% vs 29%) - Secondary outcomes: - No difference in 28-day mortality - Shorter duration of shock (3 vs 4 days) - Shorter ICU LOS (10 vs 12 days) - Shorter duration of initial mechanical ventilation (6 vs 7 days) but no difference in total ventilated days - No differences in recurrent shock, hospital LOS, RRT outcomes, and new-onset bacteremia or fungemia - Higher MAP (5.4 mmHg higher) and a lower mean HR (6.6 BPM less).

ADRENAL 2018

IV hydrocortisone has a vasopressor sparing effect in septic shock but by itself, had no convincing effect on mortality (when given as a continuous infusion).

APROCCHSS (2018)

Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. New England Journal of Medicine. 2018;378(9):809-818. doi:10.1056/NEJMoa1705716

VANISH (2016)

Gordon AC, Mason AJ, Thirunavukkarasu N, et al. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA. 2016;316(5):509-518. doi:10.1001/jama.2016.10485