Conference Coverage

Vitamin C for sepsis? Experts take sides in sharp debate



Powerful antibiotics come first to mind when hospitalized patients have sepsis, but a critical care pulmonology specialist urged colleagues to consider another treatment – heavy intravenous doses of vitamin C.

“There is evidence supporting benefit, and ample evidence supporting safety,” Michael H. Hooper, MD, who practices in Norfolk, Va., said in a pro-and-con debate over the use of vitamin C in sepsis at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Dr. Hooper’s debate opponent countered by noting the lack of quality research into vitamin C in sepsis and declared that its time has not yet come. “We need more data to know the safety of this drug,” said Andre Kalil, MD, professor of internal medicine and director of Transplant Infectious Diseases at the University of Nebraska Medical Center, Omaha.

Dr. Hooper was part of a member of a team led by Paul E. Marik, MD, FCCP, of Eastern Virginia Medical School, Norfolk, that made waves in 2017 with a study in Chest suggesting IV vitamin C has tremendous potential as a treatment for sepsis (Chest. 2017 Jun;151[6]:1229-38).

The retrospective study compared two groups of 47 patients with sepsis – a control group and a group that received treatment with intravenous vitamin C, hydrocortisone, and thiamine. Remarkably, the team found that 9% (4 of 47) of those in the treatment group died in the hospital, compared with 40% (19 of 47) in the control group (P less than .001).

The findings make sense, Dr. Hooper said, in light of the fact that “our patients are remarkably deficient” in vitamin C. He pointed to a 2017 study that found nearly 40% of 24 patients with septic shock were deficient in vitamin C – despite getting recommended enteral nutrition, parenteral nutrition or both – compared with 25% of patients who were not septic. The study authors believe the difference is probably due to “increased metabolism due to the enhanced inflammatory response observed in septic shock” (Crit Care. 2017 Dec 11;21[1]:300).

“We’re dealing with a population of patients who need some sort of repletion of this vitamin,” Dr. Hooper said.

Why not try oral administration of vitamin C? “Oral administration at regular doses doesn’t work,” he said. “If you have normal volunteers who are made deficient, then you administer the recommended allowance, it takes days or weeks to return levels to normal.”

Dr. Hooper added that the goal of vitamin C therapy isn’t simply to restore proper levels in plasma. In addition, he said, “we’re trying to restore levels in crucial organs.”

He said the cost of treatment with IV vitamin C is low, and no serious adverse events have been seen in studies of the vitamin’s use in critical care.

In his comments at the debate, Dr. Kalil pointed to several weaknesses in the 2017 study of vitamin C in sepsis. According to him, it had many problems, including a sample size that lacked statistical power and imbalances in the two groups. He raised concerns about the study in a 2017 letter published in Chest titled “Vitamin C Is Not Ready for Prime Time in Sepsis but a Solution Is Close,” noting that the control group was sicker and none of those patients had their vitamin C levels measured (Chest. 2017 Sep;152[3]:676).

Dr. Andre Kalil, University of Nebraska Medical Center, Omaha Randy Dotinga/MDedge News

Dr. Andre Kalil

He added that “acute renal failure is associated with high doses of vitamin C.”

As of July 2018, several clinical trials into vitamin C, hydrocortisone, and thiamine for the treatment of septic shock were underway or planned, according to a report that described the current randomized, placebo-controlled, multicenter Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial in the United States. The report notes that “robust evidence” for this approach is lacking, although “the potential effectiveness of this medication combination is rooted in biologic plausibility and supported by small clinical trials of the various individual components.” (Crit Care. 2018;22:283)

Dr. Hooper is an executive committee member and principal investigator with the Vitamin C, Thiamine And Steroids in Sepsis (VICTAS) study. Dr. Kalil reports no relevant disclosures.

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