Randomized, Double-Blind, Placebo-Controlled Trial of... : Critical Care Medicine

Late Breaker Articles

A Pilot Study

Donnino, Michael W. M.D.1,2; Andersen, Lars W. M.D.1,3; Chase, Maureen M.D. M.P.H.1; Berg, Katherine M. M.D.2; Tidswell, Mark M.D.4; Giberson, Tyler B.S.1; Wolfe, Richard M.D.1; Moskowitz, Ari M.D.5; Smithline, Howard M.D.6; Ngo, Long Ph.D.5; Cocchi, Michael N. M.D.1,7 for the Center of Resuscitation Science Research Group

1Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA.

2Department of Medicine, Division of Pulmonary and Critical Care, Beth Israel Deaconess Medical Center, Boston, MA.

3Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark.

4Department of Medicine, Division of Pulmonary and Critical Care, Baystate Medical Center, MA.

5Department of Medicine, Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA.

6Department of Emergency Medicine, Baystate Medical Center, MA.

7Department of Anesthesia Critical Care, Division of Critical Care, Beth Israel Deaconess Medical Center, Boston, MA.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

This study was funded by a grant from the National Institute of Alternative and Complementary Medicine (5R21AT005119).

Dr. Donnino received support for article research from the National Institutes of Health (NIH), received funding from the National Institute of Alternative and Complementary Medicine (5R21AT005119), and disclosed off-label product use (Thiamine). Dr. Andersen disclosed off-label product use (Thiamine). Dr. Tidswell received support for article research from the NIH and disclosed off-label product use (Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock). His institution received funding from the National Institute for Alternative and Complementary Medicine (distributed to Baystate Medical Center through the primary site which was Beth Israel Hospital). Dr. Ngo received support for article research from the NIH. Dr. Cocchi received support for article research from the NIH. His institution received funding from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, Email: [email protected]

Abstract

Objective:

To determine if intravenous thiamine would reduce lactate in patients with septic shock.

Design:

Randomized, double-blind, placebo-controlled trial.

Setting:

Two US hospitals.

Patients:

Adult patients with septic shock and elevated (> 3 mmol/L) lactate between 2010 and 2014.

Interventions:

Thiamine 200 mg or matching placebo twice daily for 7 days or until hospital discharge.

Measurements and Main Results:

The primary outcome was lactate levels 24 hours after the first study dose. Of 715 patients meeting the inclusion criteria, 88 patients were enrolled and received study drug. There was no difference in the primary outcome of lactate levels at 24 hours after study start between the thiamine and placebo groups (median: 2.5 mmol/L [1.5, 3.4] vs. 2.6 mmol/L [1.6, 5.1], p = 0.40). There was no difference in secondary outcomes including time to shock reversal, severity of illness and mortality. 35% of the patients were thiamine deficient at baseline. In this predefined subgroup, those in the thiamine treatment group had statistically significantly lower lactate levels at 24 hours (median 2.1 mmol/L [1.4, 2.5] vs. 3.1 [1.9, 8.3], p = 0.03). There was a statistically significant decrease in mortality over time in those receiving thiamine in this subgroup (p = 0.047).

Conclusion:

Administration of thiamine did not improve lactate levels or other outcomes in the overall group of patients with septic shock and elevated lactate. In those with baseline thiamine deficiency, patients in the thiamine group had significantly lower lactate levels at 24 hours and a possible decrease in mortality over time.

Randomized, Double-Blind, Placebo-Controlled Trial of... : Critical Care Medicine (original) (raw)

Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock