CHEST Guidelines-Additional-Trials-of-Vitamin-C-in-Septic-Shock

Additional-Trials-of-Vitamin-C-in-Septic-Shock_che

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Sepsis is a critical global health issue, contributing to 11 million deaths in 2017, particularly in developing regions. A 2017 study published in CHEST gained attention by suggesting a combination of vitamin C, thiamine, and hydrocortisone could significantly decrease mortality rates for sepsis patients. This led to numerous randomized clinical trials (RCTs) to verify the findings.<br /><br />Recent trials, HYVCTTSSS and ORANGES, focused on this combination therapy. The HYVCTTSSS trial in China, involving 140 sepsis patients, was halted due to a higher incidence of severe hypernatremia in the treatment arm. Data from the trial showed no significant benefit in terms of mortality rates, ICU stay duration, or other outcomes, even though there was a greater improvement in the SOFA score in the intervention group. However, the lack of hydrocortisone in the control group cast doubt on the results.<br /><br />The ORANGES trial conducted in the U.S. with 137 adults highlighted a shorter duration of vasopressor dependency in the treatment group, but no significant difference in SOFA scores or secondary outcomes like mortality and hospital stay. Modifying the primary outcome after follow-up suggests potential issues in interpreting the findings as definitive.<br /><br />Subsequent trials, such as one comparing combination therapy with hydrocortisone alone, found no reduction in septic shock duration but did observe a greater SOFA score decrease with the combination. However, these trials suffer from design limitations, particularly around hydrocortisone usage in control groups, leading to inconclusive findings.<br /><br />Ongoing trials aim to address these issues and provide more definitive answers. Nevertheless, the inconsistent results highlight the necessity of fundamental sepsis treatment strategies such as focused resuscitation, timely antibiotics, and source control, while also indicating that combination therapies require careful and transparent research design.

Keywords

sepsis

global health

vitamin C

thiamine

hydrocortisone

randomized clinical trials

HYVCTTSSS trial

ORANGES trial

SOFA score

combination therapy