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HomeInternationalDrug-vitamin C combo may be breakthrough treatment for sepsis

Drug-vitamin C combo may be breakthrough treatment for sepsis

A simple infusion of vitamin C combined with low-dose corticosteroids and thiamine may be the next breakthrough treatment for sepsis, according to a US study. The global burden of sepsis is estimated as 15 to 19 million cases annually, with a mortality rate approaching 60% in low income countries.

Lead investigator Dr Paul Marik, chief of the division of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk, initially tried this combination in January 2015 on a woman with severe sepsis who had progressed to lung and kidney failure.

He based his choice on previous work by Dr Alpha 'Berry' Fowler, who had received an NIH grant to study whether high doses of vitamin C could effectively treat septic lung injury resulting from infection.

Deciding he had nothing to lose given the patient’s dire condition, Marik started the IV, still expecting his patient not to survive. But when he returned to the hospital the next day, she had made a dramatic recovery.

After similarly treating several more patients successfully, the vitamin C-based protocol became the hospital’s standard of care for patients with severe sepsis.

Marik then conducted the retrospective before-and-after clinical study. He compared the outcomes of two groups of consecutive septic patients: one group of 47 treated with IV vitamin C, hydrocortisone and thiamine during a seven-month period, and the other a control group of 47 treated in the same ICU during the preceding seven months.

The primary outcome was in-hospital mortality. Only four patients in the treatment group died (8.5%), compared with 19 controls (40.4%; P<0.001). The propensity-adjusted odds for death in the patients treated with the vitamin C protocol was 0.13 (95% CI, 0.04-0.48; P=002).

Since completing the study, Marik has treated 150 patients with sepsis, and only one has died. “This has enormous potential. The ingredients are all affordable and readily available, which means it would not only save lives, but reduce costs,” he said. “But we need more studies to assess dose-response and the proper duration of therapy. I’m talking with other centers about using this approach and collecting data, and ultimately doing a randomised controlled trial, but that takes money and time.”

One critical care specialist who is interested in trying the combination therapy is Dr Jeffrey P Gonzales, an associate professor of critical care in the department of pharmacy practice and science at the University of Maryland School of Pharmacy in Baltimore.

“We see a fair amount of sepsis in our ICU, and I would be interested in this further,” he said. “Their numbers in terms of reduction of mortality are very positive, especially considering the severity of the population.”

But Gonzales noted that the relatively small size of the study, along with its “before and after” design, require caution. “Before we get too excited and start implementing it everywhere, it should be validated in a prospective randomized study in a larger population,” he said. Although the three components of the IV therapy are all generally safe, Gonzales warned that high doses of vitamin C may accumulate in the kidneys and cause acute kidney injury.

“They didn’t see an increase in acute kidney injury in the patients in this study,” he said. “But in patients with renal impairment, you could see an increase in drug concentration along with decreased elimination, and potential crystallisation in the kidneys. I would be more careful with that population until we get more data on the safety of high-dose intravenous vitamin C.”

Gonzales said he is excited about the findings, especially given that about 1,000 people die from sepsis in the US every day. “This group of patients had a high severity of illness, and even with that they saw a reduction in mortality in the treatment group. With the exception of timely and proper antibiotics, we don’t know of much that can improve outcomes in these patients. We need more studies of this nature in the sepsis literature.”

Background: The global burden of sepsis is estimated as 15 to 19 million cases annually with a mortality rate approaching 60% in low income countries.
Methods: In this retrospective before-after clinical study, we compared the outcome and clinical course of consecutive septic patients treated with intravenous vitamin C, hydrocortisone and thiamine during a 7-month period (treatment group) compared to a control group treated in our ICU during the preceding 7 months. The primary outcome was hospital survival. A propensity score was generated to adjust the primary outcome.
Findings: There were 47 patients in both treatment and control groups with no significant differences in baseline characteristics between the two groups. The hospital mortality was 8.5% (4 of 47) in the treatment group compared to 40.4% (19 of 47) in the control group (p < 0.001). The propensity adjusted odds of mortality in the patients treated with the vitamin C protocol was 0.13 (95% CI 0.04-0.48, p=002). The SOFA score decreased in all patients in the treatment group with none developing progressive organ failure. Vasopressors were weaned off all patients in the treatment group, a mean of 18.3 ± 9.8 hours after starting treatment with vitamin C protocol. The mean duration of vasopressor use was 54.9 ± 28.4 hours in the control group (p<0.001).
Conclusion: Our results suggest that the early use of intravenous vitamin C, together with corticosteroids and thiamine may prove to be effective in preventing progressive organ dysfunction including acute kidney injury and reducing the mortality of patients with severe sepsis and septic shock. Additional studies are required to confirm these preliminary findings.

Paul E Marik; Vikramjit Khangoora; Racquel Rivera; Michael H Hooper; John Catravas

[link url=""]Infectious Disease Special Edition material[/link]
[link url=""]Chest abstract[/link]

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