Use of hydrocortisone, ascorbic acid, and thiamine in adults with septic shock

Emily A. Vail, Hannah Wunsch, Ruxandra Pinto, Nicholas A. Bosch, Allan J. Walkey, Peter K. Lindenauer, Hayley B. Gershengorn

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Rationale: In December 2016, a single-center study describing significant improvements in mortality among a small group of patients with severe sepsis and septic shock treated with hydrocortisone, high-dose ascorbic acid, and thiamine (HAT therapy) was published online. Objectives: This study aims to describe the administration of HAT therapy among U.S. adults with septic shock before and after study publication and to compare outcomes between patients who received and did not receive HAT therapy. Methods: We performed a retrospective cohort study of 379 acute care hospitals in the Premier Healthcare Database including patients discharged from October 1, 2015, to September 30, 2018. Exposure was quarter year of hospital discharge; postpublication was defined as January 2017 onward (July 2017 for effectiveness analyses). The primary outcome was receipt of HAT at least once during hospitalization. We conducted unadjusted segmented regression analyses to examine temporal trends in HAT administration. In patients with early septic shock, we compared the association of early HAT therapy (within 2 d of hospitalization) with hospital mortality using multivariable modeling and propensity score matching. Measurements and Main Results: Among 338,597 patients, 3,574 (1.1%) received HAT therapy, 98.7% in the postpublication period. HAT administration increased from 0.03% of patients (95% confidence interval [CI], 0.02-0.04) before publication to 2.65% (95% CI, 2.46-2.83) in the last quarter, with a significant step up in use after December 2016 (P, 0.001). Receipt of early HAT was associated with higher hospital mortality (28.2% vs. 19.7%; P, 0.001; adjusted odds ratio, 1.17 [95% CI, 1.02-1.33]; primary propensity-matched model adjusted odds ratio, 1.19 [95% CI, 1.02-1.40]). Conclusions: Publication of a single-center retrospective study was associated with significantly increased administration of HAT. Among patients with early septic shock, receipt of HAT was not associated with mortality benefit.

Original languageEnglish (US)
Pages (from-to)1531-1539
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number11
StatePublished - Dec 1 2020


  • Ascorbic acid
  • Critical care
  • Physicians' practice patterns
  • Septic shock

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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