Secondary Logo

Share this article on:

News: Vitamin C for Sepsis Remains Controversial

Sorelle, Ruth MPH

doi: 10.1097/01.EEM.0000521586.33960.61
News

To say the headline caused a stir would be putting it mildly. The response was quick and sure — and deflating for the treatment it promised.

The headline?

“A Cure for Sepsis? Dramatic Improvement Seen in Patient Survival in the ICU.” (Eastern Virginia Medical School and Sentara Healthcare press release, March 23, 2017; http://bit.ly/2rmH3dA.)

That was a claim that had the Twittersphere wishing it were true while simultaneously debunking the finding. After all, sepsis affects more than 26 million people worldwide each year, and is the leading cause of death in U.S. hospitals. (http://bit.ly/2rmK2mx.) But a cure seemed just too good to be true, especially when emergency physicians learned that the treatment was a combination of vitamin C, hydrocortisone, and thiamine.

The press release was based on a report by the well-known critical care specialist, Paul Marik, MBBCh, a professor of internal medicine and the chief of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk. His findings were published ahead of print in the journal Chest, and immediately sparked controversy. (2016 Dec 6; doi: 10.1016/j.chest.2016.11.036.) As an observational study controlled retrospectively, it would not claim to be more than a hypothesis-generating exercise, and Dr. Marik acknowledged that that was true.

He and his colleagues compared the outcomes and clinical course for 47 consecutive sepsis or septic shock patients treated normally with the addition of intravenous vitamin C, hydrocortisone, and thiamine over a seven-month period and 47 patients with similar characteristics who were treated in the intensive care unit in the seven months prior. The control group did not receive vitamin C- hydrocortisone-thiamine cocktail.

Patients in the treatment group received 1.5 g IV vitamin C every six hours, 50 mg hydrocortisone IV push every six hours for four days, and 200 mg intravenous thiamine every 12 hours for four days. This cocktail was given as an adjunct to usual care for sepsis in the intensive care unit, Dr. Marik said. Both groups received broad-spectrum antibiotics, which were reduced over time according to microbiological and clinical progress. They were also managed by a conservative, physiologic-based fluid and vasopressor strategy, and ventilated with a lung-protective strategy.

Back to Top | Article Outline

A Controversial Cure

The startling results showed that four (8.5%) patients in the treatment group died in the hospital compared with 19 (40.4%) of those in the control population. The sequential organ failure assessment (SOFA) decreased in all patients in the treatment group with none developing progressive organ failure.

“This is an adjunct treatment,” Dr. Marik said. “You have to do all the other stuff and do it well, or you are not serving the patient. I am not saying don't give antibiotics or the other stuff. We provide state-of-the-art care, and this goes on top of it.”

He began using the vitamin C cocktail when a young woman in his intensive care unit seemed to be dying from sepsis. He had read about vitamin C's value in studies of different diseases, and decided to try using it with thiamine and hydrocortisone. She left the intensive care unit soon after the treatment began and ultimately recovered. He tried it again in two other seriously ill patients with similar results.

Animals make vitamin C, but humans don't, said Dr. Marik. When animals are stressed, their vitamin C levels increase to fight off infection. When humans become infected, their levels of vitamin C become undetectable. The only way to raise them is to give the vitamin intravenously.

Dr. Marik said he was aware that his treatment had generated controversy. A randomized, controlled clinical trial would be a good way to overcome some of the objections, he said. He is already collaborating with researchers in Greece to do such a trial, and he is working to do one himself in the United States. The treatment, however, has become standard in his hospital, and he said it would be difficult to carry out a trial ethically there. “What if you have a 50-year-old man with three kids with pneumonia and sepsis who is not responding to usual treatment?” Dr. Marik asked. “It would be more acceptable to do a randomized trial in places where it is not standard of care.”

He has collected data on more than 250 sepsis patients, who have had similar responses to the vitamin C-hydrocortisone-thiamine cocktail. “It is reproducible time and time again,” he said.

Back to Top | Article Outline

The Clamor for More Proof

Ken Milne, MD, MSc, the editor of the blog The Skeptics' Guide to Emergency Medicine (SGEM) and the chief of staff at South Huron Hospital Association in Exeter, Ontario, Canada, said Dr. Marik's study is just observational. “It gets you to association, not causation. I'm hoping it works. We all want patients to survive this horrific illness. But the evidence in this study is not strong enough.”

Salim Rezaie, MD, the creator and founder of the blog R.E.B.E.L. EM and a clinical assistant professor of emergency medicine at the University of Texas Health Science Center at San Antonio, agreed with Dr. Milne's take on the existing evidence. “This is a hypothesis-generating study,” said Dr. Rezaie, who was among many asked to comment about the study on the SGEM website.

The original preliminary study has been hyped not only in the medical world but also in the popular media. “It's hard to come down on the side of doing something without better information to guide our care,” Dr. Milne said. His opinion is echoed across the internet and blogosphere.

Andrew Worster, MD, MSc, said in a comment on the SGEM site that the study suffers from too many biases for the results to be considered valid. “No one should be recommending this protocol,” said Dr. Worster, a professor of emergency medicine at McMaster University and a former chair of the knowledge translation project, Best Evidence in Emergency Medicine, at the university.

Dr. Milne said a randomized controlled trial would eliminate systemic biases. “We want to find out the truth,” he said. “If it doesn't work, that's not bad. Lots of things have been tried to treat sepsis that have not worked. Science is incremental. We learn, and it's self-correcting. We are all pulling for his hypothesis to be true. We all hope we have a treatment that is affordable and available to everyone.”

Back to Top | Article Outline

The Sepsis Protocol

Read a Q&A about this sepsis protocol by Dr. Paul Marik on the EMN website: http://bit.ly/EMNBreakingNews, and find videos of him discussing the treatment at http://bit.ly/MarikSepsis.

Back to Top | Article Outline

What Would You Do?

What do you think of the Marik sepsis protocol? Would you try it if your sepsis treatment failed and your patient was dying? Tell us by writing to emn@lww.com.

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.