Scoring a HAT trick in Sepsis

In soccer, a hat trick happens when one player scores three goals in a single game. Now, if we switch gears to the world of clinical sepsis therapy, HAT is like a dream team of intravenous treatments: hydrocortisone at 50 mg every 6 hours, ascorbic acid (vitamin C) at a whopping 1500 mg every 6 hours, and thiamine at 200 mg every 12 hours—the main focus of our discussion today. Together, these treatments pack a serious punch, working hard to combat the severe effects of sepsis and septic shock in the body.

Introduction

Thiamine (vitamin B1) is an essential nutrient important for cell functions, especially in seriously ill patients. Its active form, thiamine pyrophosphate (TPP), is required for key enzymes like pyruvate dehydrogenase and transketolase, which support energy production and metabolism. Without enough thiamine, enzyme activity can decrease, causing energy issues and potential cell death.

Sepsis and organ injury

Organ injury due to an unbalanced response to infection is key to sepsis. While poor oxygen delivery was previously thought to be the main cause of organ injury in septic shock, it’s now understood that other factors, like mitochondrial dysfunction, also play a significant role. Research shows that organ injury can happen even when blood flow is stable, and damaged tissues often exhibit cell death instead of ischemic. While managing septic shock typically focuses on maintaining stable blood pressure, there is increasing interest in other injury mechanisms, including the importance of thiamine for mitochondrial health.

Thiamine in Septic Shock Management

In humans, septic shock is linked to lower activity of pyruvate dehydrogenase (PDH), and thiamine might help improve this function. However, studies on its effects on patient outcomes have mixed results. Recent observational studies hint that thiamine might help clear lactate and lower death rates in patients with septic shock, but these studies have limitations due to their retrospective nature and possible biases. A major randomized trial did not find a significant difference in outcomes between thiamine and placebo, but it indicated that thiamine could be helpful for those with a deficiency.

Thiamine, known for being safe and potentially beneficial, is being studied as an additional treatment for patients in septic shock, a condition characterized by a life-threatening response to infection that can lead to organ failure. While a recent study did not show overall improvement in survival rates or clinical outcomes for all patients, it suggested possible benefits for those with thiamine deficiency, highlighting the importance of assessing individual nutritional status in critically ill patients. Ongoing research, including a phase II trial, is looking into thiamine’s effects, particularly its possible benefits for kidney health, as preliminary data indicate that thiamine supplementation may help improve renal function and reduce the risk of acute kidney injury in susceptible individuals. These promising avenues of inquiry could pave the way for personalized treatment strategies that better address the underlying nutritional deficiencies often present in severe illness, ultimately contributing to improved patient outcomes.

Conclusions

Thiamine supplementation in septic shock is considered safe and may benefit specific populations at risk for deficiency. Studies suggest that thiamine plays a crucial role in energy metabolism and may enhance cellular function during critical illness, making it potentially advantageous for patients with sepsis. However, further research is needed to determine the optimal timing, dosage, and effectiveness of thiamine supplementation across different sepsis groups to establish guidelines that could improve patient outcomes.

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