An estimated 15 to 19 million cases of sepsis occur annually worldwide. While the 28-day mortality rate from sepsis in high-income countries has declined to 25%—compared with 60% in low-income countries—in recent years thanks to more timely diagnosis and improved supportive care, the mortality rate from septic shock remains as high as 50%. Despite more than 100 phase II and III trials over the last 30 years of numerous novel pharmacologic agents and therapeutic interventions that were hoped to improve sepsis and septic shock outcomes, none resulted in the development of effective therapeutic approaches to sepsis.

 

Testing a Metabolic Resuscitation Protocol

Based on experimental and emerging clinical data, as well as personal experience, Paul E. Marik MD, FCCP, FCCM, and colleagues conducted a study—published in Chest—to confirm the effectiveness of combination IV vitamin C, hydrocortisone, and thiamine in treating septic patients. “This was a retrospective before-after study,” says Dr. Marik. “We compared mortality among patients with severe sepsis and septic shock who had a procalcitonin greater than 2 ng/Ml and were treated with our ‘metabolic resuscitation protocol’ over 7 months with that of a matched group of patients in the previous 7 months who had received standard care (control group).” A propensity score was generated to adjust the primary outcome of hospital survival.

Dr. Marik and colleagues found a hospital mortality rate of 8.5% in the treatment group, compared with a rate of 40.4% in the control group. Among patients treated with the vitamin C protocol, the propensity adjusted odds of mortality was 0.13. Sepsis-Related Organ Failure Assessment scores decreased for all patients in the treatment group, and none developed progressive organ failure. While patients treated with the vitamin C protocol were weaned off vasopressors an average of 18.3 hours after starting treatment, those in the control group had an average length of vasopressor use of 54.9 hours.

“Our results suggest that the early use of intravenous vitamin C together with corticosteroids and thiamine is effective in preventing progressive organ dysfunction, as well as in reducing the mortality of patients with severe sepsis and septic shock,” says Dr. Marik. “The data we collected also suggest that our protocol impacts the pathophysiology of sepsis, thereby limiting organ failure, reducing vasopressor requirements, and reducing the mortality from sepsis.”

 

Important Implications

Dr. Marik notes that the vitamin C protocol used in the study combines three readily available agents with no known side effects. “It is exceedingly cheap and has the potential to save thousands of lives,” he says. Because the study was a single center, non-randomized, retrospective study, randomized controlled trials are needed to confirm the benefits of the treatment protocol. Such trials are currently being planned in the United States and worldwide.

In the meantime, Dr. Marik recommends that emergency clinicians consider using this therapeutic approach in patients presenting to the ED with severe sepsis or septic shock. “This protocol is exceedingly safe,” he adds.

References

Marik P, Khangoora V, Rivera R, Hooper M, Catravas J. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. 2017;6:1229-1238. Available at http://journal.chestnet.org/article/S0012-3692(16)62564-3/fulltext.

Tanaka H, Matsuda T, Miyagantani Y, et al. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. Arch Surg. 2000;135:326-331.

Zabet M, Mohammadi M, Ramezani M, et al. Effect of high-dose ascorbic acid on vasopressor requirement in septic shock. J Res Pharm Pract. 2016;5:94-100.

Marik P. “Vitamin S” (steroids) and vitamin C for the treatment of severe sepsis and septic shock! Crit Care Med. 2016;44:1228-1229.