Adrenal Trial : Steroids are down but not out

B. Venkatesh, S. Finfer, J. Cohen, D. Rajbhandari et el published results of eagerly awaited “Adrenal” trial (Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock).

WHAT THEY DID

Randomized adult patients with septic shock undergoing mechanical ventilation(documented or strong
clinical suspicion of infection, had two or more criteria of the SIRS, on vasopressors or inotropic agents for a minimum of 4 hours ) to receive 200mg hydrocortisone daily by infusion versus placebo.  Patients receiving steroids for other indications as well as patients who received Etomidate were excluded.

3800  patients were enrolled in the trial at 69 medical–surgical ICUs in Australia (45 sites), the United Kingdom (12), New Zealand (8), Saudi Arabia (3), and Denmark (1).

RESULTS

Primary outcome which was mortality rate at 90 days, Was similar in both groups[27.9% (Hydrocortisone)vs 28.8%(Placebo) p=0.50].  There was no difference in the predefined subgroups analysis as well.

In terms of secondary outcomes, Resolution of shock was shorter in hydrocortisone group, Time to discharge from ICU was shorter in hydrocortisone group, shorter initial episode of mechanical ventilation in hydrocortisone group.

Patients in hydrocortisone group received fewer blood transfusions.

DISCUSSION

Current surviving sepsis guidelines recommend not using hydrocortisone routinely  if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability. If this is not achievable, Then they recommend using hydrocortisone intravenously.

Role of steroids in sepsis was first studied by Bennett in 1960s which showed no difference between the 2 groups. Further studies in 70s and 80s, confirmed the findings of Bennett. 

Role of steroids in sepsis  was reignited when Annane published a multicenter French study involving 19 ICUs from 1995-1999, owing that Hydrocortisone administration was associated with decreased 28-day mortality (53% vs. 63 %), ICU mortality (58% vs. 70%), hospital mortality (61% vs. 72%) and shorter duration of vasopressor use in those patients with inadequate adrenal reserve (the ‘non responders’).

In 2008, Corticus Trial was published, which showed no difference in 28-day mortality  in patients with septic shock, either overall or in patients who did not have a response to corticotropin, although hydrocortisone hastened reversal of shock in patients in whom shock was reversed.

In 2017, Gibbison published meta analysis of 22 studies and concluded that  Hydrocortisone delivered as a bolus or as an infusion was more likely than placebo and methylprednisolone to result in shock reversal.

In this study, hydrocortisone in septic shock patients who are undergoing mechanical ventilation, has shown to not affect the mortality at 90 days.  However, resolution of shock was quicker as well as time of discharge from ICU along with fewer blood transfusions in patients treated with hydrocortisone.  Also noted to have shorter duration of mechanical ventilation.

Furthermore, there was no harm associated with hydrocortisone use in septic shock.

With all this evidence, I think we should continue using current surviving sepsis guidelines, which recommend using hydrocortisone if adequate fluid resuscitation and vasopressor therapy is not able to restore hemodynamic stability.

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