Marik / HAT Trial (2017)

Sepsis remains a leading cause of mortality in critically ill patients, and conventional therapies often fall short. This study investigated whether a combination of hydrocortisone, vitamin C, and thiamine could improve outcomes in severe sepsis and septic shock, building on theoretical benefits of these agents in mitigating sepsis-induced organ dysfunction.

This was a retrospective before-after study conducted in a single medical intensive care unit. It compared outcomes of 47 patients with severe sepsis/septic shock treated with intravenous hydrocortisone, vitamin C, and thiamine (HAT protocol) to a historical control group of 47 patients who did not receive the HAT protocol. The primary endpoint was hospital mortality.

The HAT protocol group demonstrated significantly lower hospital mortality (8.5%) compared to the control group (40.4%, p < 0.001). Patients receiving the HAT protocol also had a more rapid resolution of shock, indicated by a shorter duration of vasopressor use (18.3 hours vs. 54.9 hours, p < 0.001). Additionally, there was an improvement in SOFA scores in the HAT group.

This observational study suggested a dramatic reduction in mortality and vasopressor dependence with the HAT protocol in severe sepsis and septic shock, prompting widespread interest and further investigation.

The study's major limitations include its retrospective, single-center, and non-randomized design, making it highly susceptible to bias and confounding. The small sample size also limits generalizability.