In patients who are admitted to the intensive care unit (ICU) for the management of sepsis, the coadministration of hydrocortisone, ascorbic acid, and thiamine (HAT therapy) was safe and reduced the time to resolution of shock, according to the results of a clinical trial published in CHEST.

A randomized, double-blind, placebo-controlled trial ( Identifier: NCT03422159) was conducted between February 2018 and June 2019 at 2 community, nonteaching hospitals in the United States.

Investigators sought to evaluate the use of an HAT treatment bundle for the management of sepsis and septic shock in patients admitted to an ICU. The primary study outcomes were resolution of shock and change in the Sequential Organ Failure Assessment (SOFA) score. Secondary study outcomes included 28-day mortality, hospital mortality, ICU mortality, hospital length of stay (LOS), ICU LOS, number of ventilator-free days, and procalcitonin clearance levels.

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A total of 137 patients were randomly assigned to either the treatment group (n=68) or the comparator group (n=69). A statistically significant difference was reported in the time that patients required the use of vasopressors, demonstrating a more rapid reversal of shock in the HAT arm compared with the comparator arm (27±22 hours vs 53±38 hours, respectively; P <.001). No statistically significant change in SOFA scores was reported between the 2 groups (P =.17).

Furthermore, no significant differences in secondary end points and laboratory markers obtained in the first 4 days of treatment were observed between the 2 study groups. ICU mortality was 9% in the HAT group vs 14% in the comparator group (odds ratio [OR], 1.75; 95% CI, 0.59-5.1; P =.37). Hospital mortality was also similar between the 2 groups (16.4% in the HAT arm vs 19% in the comparator arm; OR, 1.25; 95% CI, 0.5-2.97; P =.65). Additionally, no significant differences were reported between the groups with respect to ICU and hospital LOS, ventilator-free days, and procalcitonin clearance levels.

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The investigators concluded that additional randomized studies with larger numbers of patients are warranted to confirm these findings and evaluate any potential mortality benefits or decreases in ICU LOS derived from the use of HAT therapy.


Iglesias J, Vassallo AV, Patel VV, Sullivan JB, Cavanaugh J, Elbaga Y. Outcomes of metabolic resuscitation using ascorbic acid, thiamine, and glucocorticoids in the early treatment of sepsis [published online March 16, 2020]. CHEST.  doi:10.1016/j.chest.2020.02.049