What Is Sepsis?
Sepsis is defined as an extreme reaction of the body to an infection. It is a severe and life-threatening medical emergency. Sepsis occurs when the infection triggers a series of reactions throughout the body. The infections cause sepsis to start mostly in the lungs, urinary tract, skin, or gastrointestinal tract. Sepsis can be fatal in case of treatment delay leading to tissue damage, organ failure, and death. In addition, sepsis can lead to a life-threatening condition known as septic shock. In this condition, the blood pressure drops drastically to a low level after an infection. Recent studies have found that in 2017, around 11 million sepsis-related deaths accounted for 19.7 percent of the total deaths. The mortality rate is much higher in septic shock, a severe form of sepsis.
How Is Sepsis Treated?
To date, the standard treatment modality of sepsis is infection control with the help of antibiotics and organ support. With the lack of effective sepsis-specific treatments, the therapies mainly focus on reducing the dysregulated immune response to improve the prognosis of people with sepsis and septic shock. Present management for sepsis patients includes:
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Early copious fluid resuscitation.
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Antibiotic therapies.
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Hemodynamic support with vasopressors.
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The control of the infected sites.
These treatment modalities have been shown to improve the condition of the patients, yet the mortality rate remains high. Therefore, cost-effective and low-risk procedures are needed to reduce the rate of fatality in patients with sepsis. For this reason, a combination of vitamin C, thiamine, and steroids, to treat sepsis effectively has gained predominance due to various research and studies conducted.
What Is the Role of Vitamin C, Thiamine, and, Steroids in the Treatment of Sepsis?
Recently there has been some development in the use of metabolic resuscitation as an adjunctive therapy for treating sepsis and septic shock. Such metabolic resuscitation involves a combination of vitamin C, glucocorticoids, and vitamin B1 (thiamine).
1. Vitamin C - Vitamin C or ascorbic acid has a bacteriostatic (stops bacterial growth) activity through the oxidative-stress mediated cellular damage. It acts as an antioxidant by removing the free radicals immunity stimulator to restore the deficiencies, regulating the function of specific white blood cells, and reducing the mediators causing inflammation. In patients with sepsis, vitamin C is entirely exhausted due to poor intake and increased metabolic requirements. Thus its administration has caused an improvement in the contractile activity in the muscles of the blood vessels and reduced organ dysfunction, making it an essential agent in treating the pathophysiological changes of septic shock with anti-inflammatory and antioxidant properties.
2. Thiamine - Vitamin B1 (thiamine), an essential factor in cellular metabolism, gets depleted in people with sepsis, leading to impairments within the cells. The administration of thiamine has been found to reduce the levels of lactate (a substance produced in the body when the food is turned into energy) in patients with sepsis thus increasing oxygen consumption.
3. Corticosteroids - Corticosteroids are thought to cause several immunological effects in septic shock. It has been found that adding extra low-dose of corticosteroids in cases of septic shock increased ventilator-free days, a decrease in the use of vasopressors (a group of medications responsible for contracting the blood vessels increasing the blood pressure), a shorter stay in the ICU (intensive care unit), to and a lower rate of mortality. Hydrocortisone has been found to improve the survival and rate of reversal of septic shock in patients with adrenal insufficiency (a disorder in which the body does not produce enough of the adrenal hormone that regulates blood pressure, immune system and metabolism). A recent study has shown that low-dose glucocorticoids can lead to a shorter duration of artificial organ support but do not significantly reduce mortality.
The combination of Hydrocortisone, vitamin C (ascorbic acid), and thiamine (HAT) is a promising therapy for sepsis resuscitation, leading to improved patient outcomes. The anti-inflammatory properties of glucocorticoids and ascorbic acid decrease the production of proinflammatory mediators and reactive oxygen species (ROS) associated with the injury of the blood vessels and organ failure, which are the characteristics of sepsis. Thiamine acts with corticosteroids, and vitamin C helps in reducing oxidative injury and restoring the production of energy within the cells. Several studies have evaluated the combined effect of HAT therapy in sepsis and its effectiveness in reducing mortality.
What Were the Outcomes of the Studies Conducted?
Several studies have been conducted on the combination of vitamin C, Hydrocortisone, and thiamine for effectively treating sepsis patients. Subsequent randomized control trials were conducted on the triple therapy. These studies have found that 'HAT' therapy quickens the shock reversal process.
1. Primary Outcome
- The mortality rate was found to be significantly lower in the individuals.
- Patients on Ascorbic acid alone, or glucocorticoid plus Ascorbic acid, had lower short-term mortality.
2. Secondary Outcomes
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Longer-Term Mortality: Several studies showed longer-term mortality of more than 90 days.
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Resolution Time of Shock: The combined effect of glucocorticoid, thiamine, and vitamin C, has been shown to reduce the time to resolution of septic shock.
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Duration of Mechanical Ventilation: The time of mechanical ventilation has been found to reduce with the combined therapy of the drugs.
3. Tertiary Outcomes
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Hospital and ICU Stay: The period of stay in the ICU or hospital has been found to decrease negligibly while the patient was on the combined use of the drugs.
Adverse Effects - The use of glucocorticoid alone or combined with other drugs, ascorbic acid, and thiamine, has been found to be associated with hyperglycemia or high blood sugar. The adverse events related to thiamine or ascorbic acid were not significant and very rare.
Conclusion
Sepsis and septic shock are life-threatening conditions due to the compromised response of the immune system to the infection. Till now, the standard management of the condition was infection control by antibiotic therapy in combination with support to the organs. However, due to the lack of effective treatment for sepsis, new therapeutics are being researched to focus on reducing the dysregulated immune response in order to improve the prognosis of individuals with sepsis and septic shock. In people with sepsis or septic shock, combined glucocorticoid, vitamin C, and thiamine therapy is inexpensive, readily available, and decreases the mortality rate.
