Skip to main content

Procalcitonin is an essential biomarker for hydrocortisone, ascorbic acid, and thiamine (HAT) therapy in patients with sepsis

There is increasing interest in the use of hydrocortisone, ascorbic acid, and thiamine (HAT Rx) as adjunctive treatment in the management of patients with sepsis and septic shock [1, 2]. We believe that the serial (daily) measurement of procalcitonin (PCT) is an essential component of this strategy. In our pivotal pilot study, we noted that in patients treated with HAT, PCT decreased exponentially [1]. The rate of decline of PCT over 72 h (calculated as the initial PCT minus PCT at 72 h, divided by the initial PCT × 100) was 86% in treated patients compared to 34% in controls (see Fig. 1). The half-life of PCT is reported to be about 24 h [3]; this suggests that with HAT Rx, gene transcription of PCT is switched off, with the decline reflecting the elimination of PCT. Such a rapid decline in PCT has not been reported with any other therapeutic intervention for sepsis [4, 5]. This observation provides biological proof that supports our hypothesis that HAT Rx markedly attenuates the pro-inflammatory response in patients with sepsis, thereby limiting organ failure and improving patient survival [1]. Furthermore, the exponential decline in PCT is not observed with vitamin C alone, when administering vitamin C as a continuous infusion (as a component of HAT Rx) or with alternative dosing strategies (e.g., q 12 hourly dosing of vitamin C). Remarkably, the rapid decline of PCT is even noted in patients with chronic renal failure; this finding being consistent with previous studies [3]. We have now treated over 1200 patients with HAT Rx, and the exponential decline in PCT has been a reproducible finding with few notable exceptions. We have noted that at 24 h after the initiation of therapy, the baseline PCT has failed to fall by 50% in two specific circumstances, namely (i) resistant organism (wrong antibiotic) or (ii) inadequate source control. This is a critical finding as it allows for the early change in antibiotics (broaden spectrum) and/or more aggressive source control. Once these issues are adequately addressed, the PCT then falls in its usual exponential trajectory. Serially monitoring PCT for at least 4 days therefore provides definitive biological proof that HAT therapy is working; failure of the typical PCT trajectory allows early recognition of ongoing inflammation (sepsis) and the need for additional interventions.

Fig. 1
figure 1

Time course of the serum procalcitonin (PCT) over the 4-day treatment period in the group that received hydrocortisone, ascorbic acid, and thiamine (HAT Rx) as compared to the control group, as reported in our pivotal pilot study [1]. PCT plotted on a semilog scale. *p < 0.001 for comparison of treatment group vs control group. Reproduced with permission from CHEST


  1. Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, vitamin C and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. Chest 2017; 151:1229–1238.

    Article  PubMed  Google Scholar 

  2. Moskowitz A, Andersen LW, Huang D, Berg KM, Grossesteuer A, Marik PE, Sherwin R, Hou P, Donnino MW. Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation. Crit Care. 2018;22:283.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Meisner M, Schmidt J, Huttner H, Tschaikowsky K. The natural elimination rate of procalcitonin in patients with normal and impaired renal function. Intensive Care Med. 2000;26(Suppl 2):S212–6.

    Article  PubMed  Google Scholar 

  4. Schuetz P, Bretscher C, Bernasconi L, Mueller B. Overview of procalcitonin assays and procalcitonin-guided protocols for the management of patients with infections and sepsis. Expert Rev Mol Diagn. 2017;17:593–601.

    Article  CAS  PubMed  Google Scholar 

  5. Schuetz P, Birkhahn R, Sherwin R, Jones AE, Singer A, Kline JA, Shapiro NI. Serial procalcitonin predicts mortality in severe sepsis patients: results from Multicenter Procalcitonin MOnitoring SEpsis (MOSES) study. Crit Care Med. 2017;45:781–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references





Availability of data and materials

Available on request.

Author information

Authors and Affiliations



The author has reviewed the final version of the manuscript and approves the manuscript for publication.

Corresponding author

Correspondence to Paul E. Marik.

Ethics declarations

Author’s information

Not applicable.

Ethics approval and consent to participate

Not applicable.

Competing interests

The author declares no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Marik, P.E. Procalcitonin is an essential biomarker for hydrocortisone, ascorbic acid, and thiamine (HAT) therapy in patients with sepsis. Crit Care 23, 151 (2019).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI:


  • Vitamin C
  • Sepsis
  • Septic shock
  • Procalcitonin
  • Thiamine
  • Hydrocortisone