Thiamine As An Adjuvant Therapy For Hyperlactatemia In Septic Shock Patients: A Prospective Randomized Study

Introduction

Thiamine (Vitamin B1) is an essential component for cellular metabolism. It circulates in our body as free thiamine as well as active phosphorylated form - thiamine pyrophosphate (TPP). TPP acts as a co-factor for mitochondrial oxidative decarboxylation process and glycolytic pathway. In the deficient/ absence of thiamine, anaerobic metabolism occurs and causing lactate production with severe biochemical derangement.

Thiamine deficiency has shown to be more prevalent in critically ill patients, with rates ranging from 20 % to 70 % . The deficient might due to the lack of intake or increased losses. Patients who had previous bariatric surgery or gastrointestinal disorders such as peptic ulcer disease, Crohn's disease and bowel obstruction will suffer from thiamine deficiency due to malabsorption. In addition, malnutrition related to oncology, prolonged parenteral nutrition without adequate vitamin supplementation, septic shock patients with renal replacement therapy In septic shock, there is often associated with macro and micro-circulatory dysfunctions causing tissue hypoperfusion with elevation of serum lactate. A study done by Puskarich et al (2013) showed that early lactate normalization (within 6 hours) was an independent predictor of survival in patients treated for sepsis and septic shock. Nguyen et al (2004) also showed that early lactate clearance within 12 hours of resuscitation had twofold reduction of the relative risk of death for severe sepsis patients. Therefore, Surviving Sepsis Guidelines in 2016 had included early lactate clearance within first 6 hours of resuscitation will be the goal of treatment resuscitation.

A study done by Donnino et al (2010) concluded that there was an association of low thiamine levels with lactic acidosis in septic shock patients. In general, the lactate level of 2.0-2.5 mmol/L is considered elevated, however when the lactate level raised > 4mmol/L it is considered 'high' with corresponding lactic acidosis (pH < 7.35). With lactic acidosis, severe cardiovascular adverse effects of hemodynamic instability, myocardial depression and reduced responsiveness to the inotropic supports and vasopressors will occured.

In view of the severity of lactic acidosis with thiamine deficiency, Donnino et al in 2016 studied intravenous thiamine as the resuscitation drug for septic shock patients and found that there was significantly reduced lactate at 24 hours for patients with thiamine deficiency. However, there were no significant differences in the lactate level in patients with normal baseline of thiamine level.