Chest
Critical Care: Original ResearchOutcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis: The ORANGES Trial
Section snippets
Study Design
This was a randomized, double-blinded, placebo-controlled trial assessing the utilization of an ascorbic acid, thiamine, and hydrocortisone treatment bundle for the management of septic and septic shock patients admitted to an ICU. This study was performed from February 2018 to June 2019 in two community nonteaching hospitals in the United States. The study was approved by the Community Medical Center Institutional Review Board (IRB # 17-004). All participants were provided with written
Study Population
Between February 14th, 2018 and April 29th, 2019, 140 patients consented to participate in the study. Three patients were withdrawn from analysis after randomization because of a new diagnosis of terminal cancer. One hundred thirty-seven patients were randomized. Sixty-eight patients and 69 patients were randomized to the treatment arm (HAT) and comparator arms, respectively (Fig 1). Most of the patients received their first dose of study treatment between 3 and 14 hours (mean, 9.9 ± 4.5 hours)
Discussion
This randomized double-blinded controlled study of HAT therapy demonstrated a marked acceleration in the reversal of shock. This effect remained significant after adjusting for corticosteroid administration in the comparator group, accounting for approximately 15% of the variability observed. This suggests both an independent and synergistic effect of AA in the reversal of shock and in augmenting the hemodynamic effects of corticosteroids.5,21,22 This was in contrast to the recently published
Conclusions
HAT therapy is safe and decreases the duration of shock in patients with sepsis. This effect appears to be due to the ascorbic acid component of HAT therapy rather than the mineralocorticoid effect of steroids alone. Further randomized trials are needed, with larger cohorts to determine whether HAT therapy translates to improved mortality or a decrease in ICU length of stay.
Acknowledgements
Author contributions: All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis, including any adverse effects. All authors approved the final version to be published. A. V., J. I., V. P., J. S., Y. E., and J. C. drafted and revised the manuscript. All authors are guarantors of the paper.
Financial/nonfinancial disclosures: None declared.
Other contributions: The authors would like to thank all participants and
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FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.