Skip to main content
Top
Published in: Critical Care 1/2024

Open Access 01-12-2024 | Septic Shock | Brief Report

Thiamine administration in septic shock: a post hoc analysis of two randomized trials

Authors: Jacob Vine, John H. Lee, Max S. Kravitz, Anne V. Grossestreuer, Lakshman Balaji, Shannon B. Leland, Noa Berlin, Ari Moskowitz, Michael W. Donnino

Published in: Critical Care | Issue 1/2024

Login to get access

Abstract

Background

This is a post hoc analysis of combined cohorts from two previous Phase II clinical trials to assess the effect of thiamine administration on kidney protection and mortality in patients with septic shock.

Methods

Patient-level data from the Thiamine in Septic Shock Trial (NCT01070810) and the Thiamine for Renal Protection in Septic Shock Trial (NCT03550794) were combined in this analysis. The primary outcome for the current study was survival without the receipt of renal replacement therapy (RRT). Analyses were performed on the overall cohort and the thiamine-deficient cohort (thiamine < 8 nmol/L).

Results

Totally, 158 patients were included. Overall, thiamine administration was associated with higher odds of being alive and RRT-free (adjusted odds ratio [aOR]: 2.05 [95% confidence interval (CI) 1.08–3.90]) and not needing RRT (aOR: 2.59 [95% CI 1.01–6.62]). In the thiamine-deficient group, thiamine administration was associated with higher odds of being alive and RRT-free (aOR: 8.17 [95% CI 1.79–37.22]) and surviving to hospital discharge (aOR: 6.84 [95% CI 1.54–30.36]). There was a significant effect modification by baseline thiamine deficiency for alive and RRT-free (interaction, p = 0.016) and surviving to hospital discharge (p = 0.019).

Conclusion

In the combined analysis of two previous randomized trials, thiamine administration was associated with higher odds of being alive and RRT-free at hospital discharge in patients with septic shock. This signal was stronger in patients with thiamine deficiency.
Appendix
Available only for authorised users
Literature
1.
go back to reference Moskowitz A, Andersen LW, Cocchi MN, Karlsson M, Patel PV, Donnino MW. Thiamine as a renal protective agent in septic shock. A secondary analysis of a randomized, double-blind, placebo-controlled trail. Ann Am Thorac Soc.2017;14:737–41.CrossRefPubMedPubMedCentral Moskowitz A, Andersen LW, Cocchi MN, Karlsson M, Patel PV, Donnino MW. Thiamine as a renal protective agent in septic shock. A secondary analysis of a randomized, double-blind, placebo-controlled trail. Ann Am Thorac Soc.2017;14:737–41.CrossRefPubMedPubMedCentral
2.
go back to reference Moskowitz A, Berg KM, Grossestreuer AV, Balaji L, Liu X, Cocchi MN. Thiamine for renal protection in septic shock (TRPSS): a randomized, placebo-controlled, clinical trial. Am J Respir Crit Care Med. 2023;208:570–8.CrossRefPubMed Moskowitz A, Berg KM, Grossestreuer AV, Balaji L, Liu X, Cocchi MN. Thiamine for renal protection in septic shock (TRPSS): a randomized, placebo-controlled, clinical trial. Am J Respir Crit Care Med. 2023;208:570–8.CrossRefPubMed
4.
5.
go back to reference Honore PM, Jacobs R, Waele De E, Diltoer M, Spapen HD. Renal blood flow and acute kidney injury in septic shock: an arduous conflict that smolders intrarenally? Kidney Int. 2016;90:22–4.CrossRefPubMed Honore PM, Jacobs R, Waele De E, Diltoer M, Spapen HD. Renal blood flow and acute kidney injury in septic shock: an arduous conflict that smolders intrarenally? Kidney Int. 2016;90:22–4.CrossRefPubMed
6.
go back to reference Fink MP. Cytopathic hypoxia. Mitochondrial dysfunction as mechanism contributing to organ dysfunction in sepsis. Crit Care Clin. 2001;17:219–37.CrossRefPubMed Fink MP. Cytopathic hypoxia. Mitochondrial dysfunction as mechanism contributing to organ dysfunction in sepsis. Crit Care Clin. 2001;17:219–37.CrossRefPubMed
7.
go back to reference Donnino MW, Carney E, Cocchi MN, Barbash I, Chase M, Joyce N. Thiamine deficiency in critically ill patients with sepsis. J Crit Care. 2010;25:576–81.CrossRefPubMed Donnino MW, Carney E, Cocchi MN, Barbash I, Chase M, Joyce N. Thiamine deficiency in critically ill patients with sepsis. J Crit Care. 2010;25:576–81.CrossRefPubMed
8.
go back to reference Manzanares W, Hardy G. Thiamine supplementation in the critically ill. Curr Opin Clin Nutr Metab Care. 2011;14:610 617.CrossRefPubMed Manzanares W, Hardy G. Thiamine supplementation in the critically ill. Curr Opin Clin Nutr Metab Care. 2011;14:610 617.CrossRefPubMed
9.
go back to reference Frank RAW, Leeper FJ, Luisi BF. Structure, mechanism and catalytic duality of thiamine-dependent enzymes. Cell Mol Life Sci. 2007;64:892–905.CrossRefPubMed Frank RAW, Leeper FJ, Luisi BF. Structure, mechanism and catalytic duality of thiamine-dependent enzymes. Cell Mol Life Sci. 2007;64:892–905.CrossRefPubMed
10.
go back to reference Donnino MW, Andersen LW, Chase M, Berg KM, Tidswell M, Giberson T. Randomized, double-blind, placebo-controlled trial of thiamine as a metabolic resuscitator in septic shock: a pilot study. Crit Care Med. 2016;44:360–7.CrossRefPubMedPubMedCentral Donnino MW, Andersen LW, Chase M, Berg KM, Tidswell M, Giberson T. Randomized, double-blind, placebo-controlled trial of thiamine as a metabolic resuscitator in septic shock: a pilot study. Crit Care Med. 2016;44:360–7.CrossRefPubMedPubMedCentral
11.
go back to reference Costa NA, Azevedo PS, Polegato BF, Zornoff LAM, Paiva SAR, Minicucci MF. Thiamine as a metabolic resuscitator in septic shock: one size does not fit all. J Thorac Dis. 2016;8:E471–2.CrossRefPubMedPubMedCentral Costa NA, Azevedo PS, Polegato BF, Zornoff LAM, Paiva SAR, Minicucci MF. Thiamine as a metabolic resuscitator in septic shock: one size does not fit all. J Thorac Dis. 2016;8:E471–2.CrossRefPubMedPubMedCentral
12.
go back to reference Woolum JA, Abner EL, Kelly A, Thompson Bastin ML, Morris PE, Flannery AH. Effect of thiamine administration on lactate clearance and mortality in patients with septic shock*. Crit Care Med. 2018;46:1747–52.CrossRefPubMed Woolum JA, Abner EL, Kelly A, Thompson Bastin ML, Morris PE, Flannery AH. Effect of thiamine administration on lactate clearance and mortality in patients with septic shock*. Crit Care Med. 2018;46:1747–52.CrossRefPubMed
13.
go back to reference Miyamoto Y, Aso S, Iwagami M, Yasunaga H, Matsui H, Fushimi K. Association between IV thiamine and mortality in patients with septic shock: a nationwide observational study. Crit Care Med. 2020;48:1135–9.CrossRefPubMed Miyamoto Y, Aso S, Iwagami M, Yasunaga H, Matsui H, Fushimi K. Association between IV thiamine and mortality in patients with septic shock: a nationwide observational study. Crit Care Med. 2020;48:1135–9.CrossRefPubMed
14.
go back to reference Harun NF, Cheah SK, Yusof AM, Lau CL, Masdar A, Mahdi SNM. Intravenous thiamine as an adjuvant therapy for hyperlactatemia in septic shock patients. Crit Care Shock. 2019;22:288–98. Harun NF, Cheah SK, Yusof AM, Lau CL, Masdar A, Mahdi SNM. Intravenous thiamine as an adjuvant therapy for hyperlactatemia in septic shock patients. Crit Care Shock. 2019;22:288–98.
15.
go back to reference Petsakul S, Morakul S, Tangsujaritvijit V, Kunawut P, Singhatas P, Sanguanwit P. Effects of thiamine on vasopressor requirements in patients with septic shock: a prospective randomized controlled trial. BMC Anesthesiol. 2020;20:280.CrossRefPubMedPubMedCentral Petsakul S, Morakul S, Tangsujaritvijit V, Kunawut P, Singhatas P, Sanguanwit P. Effects of thiamine on vasopressor requirements in patients with septic shock: a prospective randomized controlled trial. BMC Anesthesiol. 2020;20:280.CrossRefPubMedPubMedCentral
16.
go back to reference Pereira AG, Costa NA, Amancio SCP, Okoshi MP, Zornoff LAM, Azevedo PS. Effect of thiamine on clinical outcomes in septic shock patients: a randomized, double-blinded pilot study. Am J Respir Crit Care Med. 2023;208:616 618.CrossRefPubMed Pereira AG, Costa NA, Amancio SCP, Okoshi MP, Zornoff LAM, Azevedo PS. Effect of thiamine on clinical outcomes in septic shock patients: a randomized, double-blinded pilot study. Am J Respir Crit Care Med. 2023;208:616 618.CrossRefPubMed
17.
go back to reference Fujii T, Salanti G, Belletti A, Bellomo R, Carr A, Furukawa TA, et al. Effect of adjunctive vitamin C, glucocorticoids, and vitamin B1 on longer-term mortality in adults with sepsis or septic shock: a systematic review and a component network meta-analysis. Intensive Care Med. 2022;48:16–24. Fujii T, Salanti G, Belletti A, Bellomo R, Carr A, Furukawa TA, et al. Effect of adjunctive vitamin C, glucocorticoids, and vitamin B1 on longer-term mortality in adults with sepsis or septic shock: a systematic review and a component network meta-analysis. Intensive Care Med. 2022;48:16–24.
Metadata
Title
Thiamine administration in septic shock: a post hoc analysis of two randomized trials
Authors
Jacob Vine
John H. Lee
Max S. Kravitz
Anne V. Grossestreuer
Lakshman Balaji
Shannon B. Leland
Noa Berlin
Ari Moskowitz
Michael W. Donnino
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2024
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-024-04818-1

Other articles of this Issue 1/2024

Critical Care 1/2024 Go to the issue