Authors' reply, re: A response to Zhou et al. regarding thiamine supplementation in altered mental status.

We thank Drs. Trebach and Hoffman for their thoughtful remarks and use this opportunity to discuss their concerns. We acknowledge the limitations of a single institution-based, retrospective, cohort study and have addressed these in our manuscript extensively [1]. In this practice-based, real-world study, we examined hospital outcomes and thiamine prescription patterns among a diverse group of hospital-based providers who were licensed and credentialed to manage patients with altered mental status from all-causes, including those with hypoglycemia. While we found wide variations in the thiamine prescription patterns (timing, dosage, and route of administration), we are not unique in reporting such variations in clinical practice [2– 6]. It is possible that differences in prescription patterns such as glucose-first vs. thiamine-first or parenteral vs. enteral vs. no thiamine could be the result of disease severity. While we controlled for disease severity using Medicare Severity Diagnosis-Related Group (MS-DRG) weight in our models, it is possible that this measure may not have captured the breadth of clinical severity. Additional analyses of the effects of different dosages on outcomes were not feasible due to wide variations in clinical practice resulting in small patient numbers in groups. We acknowledge the growing evidence for the lack of benefit of supplemental thiamine in critically ill patients [7,8]. It has also been reported that glucose administration before or without thiamine would not acutely worsen the effects of thiamine deficiency unless the glucose administration is prolonged [9]. However, in our study, we found that patients who received glucose before or without thiamine had increased inhospital mortality rate after controlling for disease severity. Based on the results of our study, we cannot in good conscience, argue against the current medical practice (dogma) of administering parenteral thiamine before glucose for critically ill patients with altered mental status from all causes.