The effectiveness of synthetic glucocorticoids on the disease course, treatment, and outcome of severe sepsis and septic shock

1 , Miriam Cupic 1 , Ines Potocnjak 2 , Matias Trbusic Abstract Due to the high morbidity and mortality rates, severe sepsis and septic shock, present a major global public health problem. The treatment and management of severe sepsis and septic shock is based on a set of international guidelines called the Surviving sepsis campaign (SSC). SSC guidelines suggest the use of hydrocortisone at a dose of 200 mg IV in adult patients with septic shock refractory to fluid resuscitation and vasopressors. During the last century, the importance of cortisol as an essential hormone at times of stress, such as septic shock, has been recognized. Therefore, the therapeutic use of synthetic glucocorticoids has been the subject of many studies during the last few decades but their results are not consistent. Two of the largest studies (CORTICUS and French study) showed different effects of synthetic glucocorticoids on mortality rates, but they both showed a significantly shorter duration of septic shock. There is an ongoing large, multicenter, double-blind, randomized study (ADRENAL study) and its primary goal is to assess the impact of hydrocortisone therapy on 90-day survival rate. It is expected that the results of this study might provide answers to the questions raised by previously conducted studies. This review will summarize the pathophysiology of sepsis and septic shock and the role of cortisol in its development, and will highlight the most important clinical studies pertaining to synthetic glucocorticoid administration in sepsis and septic shock.