A recent study published in the New England Journal of Medicine found that the administration of glucocorticoids among patients with septic shock did not result in lower 90-day mortality rates. The trial found that those patients that received hydrocortisone experienced a quicker resolution of sepsis and a shorter time period of initial necessary mechanical ventilation when compared to the patients that received placebo. However, there were no differences between the two groups in the time spent outside of the intensive care unit or hospital in general, the recurrence of mechanical ventilation, the need for kidney replacement therapy or new onset of bacteremia of fungemia.
This is a significant finding due to the fact that hydrocortisone has been one of the mainstays of adjuvant therapy for septic shock for the past 40 years. Sepsis has no proven pharmacological treatment besides attempting to treat the underlying causative agent, which is often pneumonia, kidney infection or bacteremia. However, current clinical guidelines recommend administering glucocorticoids – specifically hydrocortisone – if adequate fluid resuscitation and treatment with vasopressors have not restored hemodynamic stability.
The trial was managed by the George Institute for Global Health in Australia and examined 3800 randomly-selected patients who were treated for septic shock from March 2013 to April 2017 in Australia, the United Kingdom, New Zealand, Saudi Arabia and Denmark. Out of the initial group enrolled, 3658 met the criteria for the study 1832 of whom were administered hydrocortisone and 1826 of whom received placebo. 90 days after the study had begun, 511 (27.9%) of the hydrocortisone patients and 526 (28.8%) of the placebo patients had passed away.
The study did note several beneficial results achieved among the group of patients that received hydrocortisone. Patients in that group had a shorter time to ICU discharge and earlier cessation of the initial episode of mechanical ventilation. Notably however, the hydrocortisone patients also had a higher mean arterial pressure and a higher plasma lactate level between days 1 and 7 of the trial.
In sum, this important study seems to show that there may be some evidence that administration of hydrocortisone leads to an earlier resolution of the initial severe clinical symptoms of septic shock but one should not expect hydrocortisone to have any impact on short to medium-term patient mortality.
Venkatesh B, Finfer S, Cohen J, et al. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med 2018; 378:797-808.