The Effect of a Single Dose of Thiamine on Oxygen Consumption in Patients Requiring Mechanical Ventilation for Acute Illness: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

IMPORTANCE:Lower oxygen consumption is associated with worse survival in septic shock and in other forms of critical illness. No treatment that increases oxygen extraction, a key determinant of oxygen consumption, has been found. Thiamine is required for aerobic metabolism, and deficiency is common in the critically ill. OBJECTIVES:We evaluated the effect of thiamine on oxygen consumption in patients requiring mechanical ventilation for an acute illness. DESIGN:Phase II, randomized, double-blind, and placebo-controlled trial. SETTING AND PARTICIPANTS:ICUs in a tertiary care hospital in the United States. Patients admitted to the ICU and requiring mechanical ventilation were screened for enrollment. INTERVENTIONS:After enrollment, baseline measurement of oxygen consumption and baseline laboratories including lactate, central venous oxygen saturation, and pyruvate dehydrogenase, a single dose of 200 mg IV thiamine or placebo was administered. Oxygen consumption was then monitored for 6 additional hours and repeat laboratories were drawn at the end of the protocol. MAIN OUTCOMES AND MEASURES:The primary outcome was the change in oxygen consumption. Analysis was done using linear regression with a first-order autoregressive variance-covariance structure to account for repeated measures within subjects. Secondary outcomes included change in lactate, central venous oxygen saturation, and pyruvate dehydrogenase quantity and activity. RESULTS:Sixty-seven patients were enrolled. After excluding 11 patients due to inadequate quantity or quality of oxygen consumption data, 56 patients were included. There was no difference in change in oxygen consumption in the 6 hours after study drug. Results for secondary outcomes were similarly negative. In the prespecified subgroup of 18 thiamine deficient patients, there was a difference in the two oxygen consumption curves (p = 0.006), although no difference in median oxygen consumption or area under the curve. CONCLUSIONS AND RELEVANCE:A single dose of IV thiamine did not alter oxygen consumption in patients requiring mechanical ventilation for acute illness.