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Vitamin Cocktail for Sepsis Getting Wider Test

Matt Smith

May 29, 2018

A simple vitamin cocktail to treat sepsis has shaken up the medical world, raising hopes of a more effective treatment for one of history's great killers. But will it stand up to tougher tests?


Researchers at several hospitals around the world are trying to reproduce the success reported by a critical-care doctor in Virginia in beating back sepsis, one of the leading causes of hospital deaths.


Paul Marik, MD, chief of pulomonary and criitical care medicine at Eastern Virginia Medical School, reported in 2017 that he gave a mix of vitamin C, vitamin B1, and a steroid to nearly four dozen patients who had sepsis in his Norfolk intensive care unit. In the 7 months before he started using the treatment, 19 of 47 sepsis patients died. Of the 47 who got the treatment, all but four survived.

2017年,东弗吉尼亚医学院呼吸和重症医学科主任Paul Marik对47名全身性感染的ICU患者同时给予维生素C、维生素B1和皮质激素。在开始上述治疗前的7个月内,47名全身性感染患者中的19名死亡。在接受上述治疗的47名患者中,仅有4名死亡。

The results got a lot of attention. But it was a small study, comparing before-and-after patient outcomes. Now, researchers are gearing up to test the therapy with large-scale trials using patients selected at random, with some given the cocktail and others given a placebo.


"Dr. Marik feels very strongly that it's worked in his patients, and he's changed his practice because of his own experience," says Jonathan Sevransky, MD, a critical care doctor at Emory University in Atlanta who is leading one of the studies. "If you think something works, it makes sense for a doctor to try something and to change their own practice. But if you want to change other people's practices, the way to do that is do a randomized, controlled trial -- and ideally, you'd have more than one randomized, controlled trial."

“Marik医生坚信这种治疗对他的患者有效,而且,基于上述经验,他改变了临床治疗。”Jonathan Sevransky如此说到。Jonathan Sevransky是位于亚特兰大的Emory大学的一名ICU医生,他正在领导进行众多验证试验中的一项。“如果你认为某些治疗有效,那么医生当然会进行尝试并改变自己的临床实践。但是,如果你希望改变其他人的行为,你只能依靠随机对照临床试验—理想的情况下,应当有超过一项随机对照试验。”

An Ancient Danger 对于人类健康的古老威胁

Sepsis has been in the medical books since the time of Hippocrates. It happens when the body's immune system responds to an infection with overwhelming force, triggering complications that can cause blood clots, inflammation, and other problems, leading to organ failure and death.


In the days before sterile instruments and antibiotics, sepsis was a frequent and deadly complication of wounds. It still hits than 1 million people in the United States every year, and between a quarter and half of them die.


Survival often depends on an immediate dose of antibiotics and intravenous fluids, along with tests to look for signs of an infection or organ failure. Estimates of how much it costs to treat sepsis approach $24 billion a year.


Jarone Lee, MD, medical director of the intensive care unit at Massachusetts General Hospital, says finding a good treatment for sepsis would solve a lot of health care problems.

麻省总医院ICU主任Jarone Lee医生认为,找到全身性感染的有效治疗措施将解决很多健康问题。

But it's too early to declare victory without better data, says Lee, who is not involved in the ongoing trials.


"What I think we're looking for is essentially hard science and great science about how this will work," he says. "It doesn't even have to show the amazing results like Paul did, just that we're moving the needle forward and decreasing mortality or some other process measure that improves outcomes."


Ambitious Studies Planned 雄心勃勃的研究计划

Sevransky's study plans to involve at least 500 and up to 2,000 patients at multiple hospitals for about a year and a half. The plan is to wrap up work in December 2019.


The researchers will be looking at what the vitamin mixture does to speed recovery in sepsis patients who need life support, either by mechanical means or through drugs that help keep blood pressure at normal levels. They will also be watching the results for any improvements in death rates and may extend the study if it shows promise, Sevransky says.


"The thing that's most likely to change people's care is if the treatment does show a difference in mortality," he says.


A second study, led by Michael Donnino, MD, at Harvard's Beth Israel Deaconess Medical Center, involves about 200 patients and  a wider number of hospitals. It is expected to end in a year, says Ari Moskowitz, MD, a pulmonary care and critical care specialist at Beth Israel Deaconess.

Harvard医学院Beth Israel Deaconess医学中心的Michael Donnino医生主导进行了第二项研究。他计划从更多的医院纳入200名患者。Beth Israel Deaconess医学中心呼吸与重症医学科的Ari Moskowitz医生表示,研究预计在1年内结束。

Moskowitz says they hope the vitamin cocktail will  help limit injury to organs, such as the kidneys or heart. The study will evaluate how well it prevents organ injury along with survival rates. "Saving lives is the ultimate goal of the intervention," he says.

Ari Moskowitz医生谈到,他们希望维生素鸡尾酒疗法有助于限制器官(如肾脏或心脏)损伤。研究将评估治疗对器官损伤及生存率的影响。“”他说到。“挽救患者生命是治疗的最终目的。”

Similar studies are underway in New Jersey, Slovenia, China, Australia, and Qatar.


Limited Risk of Side Effects 副作用有限

Marik says he's pleased with the interest and has spoken with some of the researchers involved in the planned trials, but he's not waiting on the results. He's now treated more than 700 sepsis patients with the vitamin-steroid mixture, which supplements -- but doesn't replace -- other drugs like antibiotics. He says his patients have not had any serious side effects.


People who take a lot of vitamin C can be more likely to get kidney stones, Sevransky says. And vitamin C can throw off measurements of blood sugar, which may be a concern for people who are getting extra glucose in the hospital. So people who are being given the therapy should use meters that aren't likely to be thrown off by that effect, he says.


The dose being studied is about 1.5 grams intravenously, every 6 hours for 4 days -- several times higher than people get from ordinary vitamin supplements or eating fruit, but less than some patients get while having chemotherapy, he said.

他谈到,研究中采用的剂量约为1.5 g iv,每6小时一次,疗程4天 — 与日常补充维生素或食用水果的人群相比,剂量增加数倍,但剂量小于接受化疗的部分患者。

Lee says Massachusetts General has used Marik's cocktail sometimes in patients that aren't responding to conventional treatment -- "But it's not routine in any way, and I don't think it should be routine in any way until the data is better."

Lee医生说到,对于传统治疗无效的患者,麻省总医院有时会采用Marik的鸡尾酒疗法 — “但无论如何这并非常规治疗,除非有更好的数据支持,否则我不认为这能够成为常规治疗。”

In a follow-up paper in April, Marik wrote that vitamin C lowers oxidative stress and inflammation, and it helps stop blood vessels from dilating, which helps maintain blood pressure. People who have sepsis often don't have enough vitamins C and B1, and those vitamins appear to combine with the steroid hydrocortisone to boost the effects.


"There is in fact an enormous amount of basic science to support this," he says. An Australian study found that if Marik's mixture works, it could shave more than 40% off the long-term cost of treating the disease.


"The bottom line is it saves billions of dollars and millions of life-years, and at worst, if it doesn't work, all it does is waste a little bit of money and nothing is lost," he says.


Sevransky says previous research has suggested vitamin C can improve blood flow to tissues in the body of a sepsis patient, keeping the cells supplied with nutrients and oxygen and preventing organ failure.


And an earlier study by Donnino's team at Harvard found that vitamin B1, or thiamine, could help prevent kidney failure in sepsis patients. Thiamine is essential to the mitochondria, your cells' powerhouses, and patients with vitamin B and C deficiencies show some of the same symptoms as people with sepsis -- including low blood pressure and an increase in blood acid levels.

Harvard医学院Donnino医生团队较早的一项研究发现,维生素B1有助于预防全身性感染患者的肾功能衰竭。维生素B1对于线粒体功能非常关键,维生素B1和C缺乏患者的临床表现与全身性感染相似 — 包括低血压及酸中毒。

"When we targeted select populations of critically ill patients, we have found that upwards of 30% may be thiamine deficient," Harvard's Moskowitz says.


But Sevransky says research is full of promising cures that never panned out.


"Even though the theory behind it was solid, the treatment didn't work," he says.



National Institute of General Medical Sciences: "Sepsis."


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