Sepsis remains a major healthcare problem associated with significant morbidity and mortality. Roles for hydrocortisone, ascorbic acid (vitamin C), and thiamine (HAT therapy) as potential adjuvants remain controversial.
Two double-blinded, placebo-controlled, randomized trials involving 337 patients (ORANGES, n = 137; ACTS, n = 200) with sepsis and septic shock have shown that administration of ascorbic acid, thiamine, and hydrocortisone did not reduce organ dysfunction or improve overall mortality. However, both trials showed that this combination therapy was effective in reducing the time to achieve shock resolution or shock-free days.
Current management of septic shock includes early administration of intravenous fluids, antimicrobial agents, and vasopressor support. While norepinephrine is recommended as the first-line vasopressor for septic shock in the 2016 Surviving Sepsis Campaign guidelines, vasopressin is a second-line vasopressor option that may be added.
Adult patients experiencing sepsis with hypotension but who did not meet the definition of septic shock received a median of 800 mL of intravenous fluid prior to initiation of norepinephrine 0.05 mcg/kg/min as a non-titratable infusion. Patients in this early vasopressor group had much lower odds of failing to achieve their primary outcome of adequate mean arterial pressure and tissue perfusion when early norepinephrine was provided.
In this systematic review and meta-analysis of randomized, controlled trials comparing administration of corticosteroids with placebo or standard supportive care in sepsis, corticosteroids were associated with reduced 28-day mortality.