Sepsis has become a commonplace condition in all hospitals and ICUs. Though familiar, sepsis can be unpredictable and rapidly progress into multi-organ failure or death. Most facilities have implemented sepsis “treatment bundles,” or standardized order protocols, that rely on titrations of drugs, oxygenation endpoints, and maintenance of blood perfusion to organs and extremities to steer patients toward recovery.
What if there were a better way? A cocktail of safe and inexpensive medications (vitamins!) that could improve patient outcomes? Stay tuned.
“C” You Later, Sepsis
There is a growing body of evidence suggesting that high-dose IV vitamin C infusion may have dramatically positive effects on patients with severe sepsis. Researchers are also evaluating a triple therapy, which combines IV vitamin C with IV thiamin and a corticosteroid, believing this combination may have a synergistic effect. In preliminary studies, the triple therapy has been associated with faster weaning from vasopressors, less incidence of organ failure, and reduced mortality.
Underlying Mechanism of Action
So, how is it that vitamin C and thiamin — two unlikely players — might eclipse sophisticated pharmacotherapies when it comes to improving patient outcomes? Let’s explore.
Vitamin C, of course, acts as an antioxidant. It takes care of those pesky free radicals and boosts immune function. Vitamin C is also a cofactor in the production of endogenous vasopressin (AKA anti-diuretic hormone), so it contributes to blood pressure management in hemodynamically unstable patients.
Just like vitamin C, thiamin also has anti-inflammatory properties. Low levels of serum thiamin can hinder basic metabolic processes and energy production. What’s more, a thiamin deficiency can escalate oxidative stress caused by a vitamin C deficiency, which is officially called a “double whammy.”
When vitamin C is administered with a corticosteroid, their anti-inflammatory properties are strengthened, which helps to reduce the oxidative stress, mitochondrial and endothelial damage, and organ failure associated with sepsis. Thiamin contributes by restoring mitrochondrial activity and energy production. Ultimately, the patient’s immune system is readjusted and repaired, putting the patient on the path to recovery.
Preliminary studies have administered vitamin C in doses that may make you a little nervous. Researchers are finding that mega-doses are required to achieve clinical benefit. What’s a mega-dose? Many studies are dosing 1,500 mg of vitamin C every six hours. That’s right — six grams of IV vitamin C per day.
Likewise, thiamin is often dosed 400 mg per day in divided doses. And the corticosteroid is generally 50 mg of hydrocortisone every six hours. The vitamins are administered for four days (16 doses), while the hydrocortisone is a seven-day course followed by a taper.
Why the extreme doses of vitamin C and thiamin? One study tested patients’ vitamin C levels prior to initiating the triple therapy, finding that all patients who received preliminary testing had below-normal levels of vitamin C.1 Other studies have made similar observations, not only with vitamin C, but with low levels of thiamin, too.2,3
A handful of randomized controlled trials are currently under way to provide more definitive conclusions regarding the use of high-dose vitamin C, thiamin, and hydrocortisone as a means to treat sepsis. Because of the lack of high-quality data, we cannot establish any cause-and-effect relationships yet. More information is coming, and it just may change the way we treat sepsis.
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Marik, PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock. 2017;151(6):1229-1238.
Nabzdyk CS, Bittner EA. Vitamin C in the critically ill—indications and controversies. World J Crit Care Med. 2018;7(5):52-61.
Marik, PE. Hydrocortisone, ascorbic acid and thiamine (HAT therapy) for the treatment of sepsis. Focus on ascorbic acid. 2018;10(11):1762.