FRIDAY, Aug. 9, 2019 — Sepsis is a life-threatening infection that lands its victims in the hospital, but the dangers don’t end for survivors who have high levels of inflammation long after being discharged, a new study finds.
“Sepsis is the leading cause of death among hospitalized patients. Patients discharged from the hospital aren’t out of the woods yet. Approximately one out of every three sepsis survivors will die in the following year,” said study lead author Dr. Sachin Yende. He is a professor of critical care medicine and clinical and translational science at the University of Pittsburgh’s School of Medicine.
“Our new findings about chronic inflammation post-discharge suggest that addressing this condition may be important to improve patients’ long-term outcomes,” added Yende, vice president of critical care and deputy chief of staff at Veterans Affairs Pittsburgh Healthcare System.
Nearly all sepsis patients have increased inflammation in their bloodstream during the first few days of hospitalization, but how long the inflammation can persist and what effects it might have were unclear.
To find out, the researchers followed 483 people who survived hospitalization with sepsis at 12 U.S. hospitals between 2012 and 2017. They were assessed at three, six and 12 months after hospital discharge.
Up to a year after hospitalization, about one-fourth of the patients had elevated levels of inflammation and half had elevated levels of immunosuppression biomarkers, the findings showed.
These patients had higher rates of hospital readmission (particularly due to heart disease and stroke) and death than patients whose inflammation levels returned to normal after hospitalization.
According to senior study author Dr. Derek Angus, “The participants with increased inflammation had levels that were twice as high as levels in healthy individuals, and that elevated inflammation persisted long after hospital discharge.” Angus is chair of the department of critical care medicine at the University of Pittsburgh.
“Sepsis increases risk of heart disease and stroke, and, for the first time, we’ve linked these adverse outcomes to persistent inflammation,” he said in a university news release. “This opens the door to future studies into why high levels of inflammation persist for at least a year after hospital discharge, and the development of treatments aimed at modifying the inflammation with the hope that will improve health.”
The study was published online Aug. 7 in JAMA Network Open.
Sepsis affects more than 30 million people worldwide every year, according to the World Health Organization.
The U.S. Centers for Disease Control and Prevention has more on sepsis.
MONDAY, Sept. 10, 2018 — Survivors of serious bloodstream infections called sepsis are at increased risk for stroke and heart attack for four weeks after leaving the hospital, a new study finds.
The study included roughly 42,300 sepsis patients in Taiwan. Of those, 22 percent died within 30 days of hospital admission.
Among the survivors, 1,012 had a cardiovascular event, 831 had a stroke and 184 had a heart attack within 180 days after leaving the hospital, the study found.
The risk was highest shortly after leaving the hospital, with more than one-quarter (26 percent) of heart attacks or strokes occurring during the first seven days, and 51 percent occurring within 35 days, the researchers reported.
Sepsis patients aged 20 to 45 had a higher risk of heart attack or stroke than those older than 75, according to the study published Sept. 10 in the CMAJ (Canadian Medical Association Journal).
Similar findings were made in a Danish study, the researchers said in a journal news release.
“Based on our study (Han Chinese) and the study in Denmark (European) that reported similar findings for two different ethnic groups, it is likely that these results are generalizable to different populations,” Dr. Chien-Chang Lee, who’s with the department of emergency medicine at National Taiwan University Hospital in Taipei, and colleagues wrote.
The investigators called for further research in different patient populations.
Sepsis causes about 8 million deaths worldwide each year, the study authors said.
May 21, 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 an emergency room doctor in Virginia in beating back sepsis, one of the leading causes of hospital deaths.
Paul Marik, MD, 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.
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.”
An ancient danger
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.
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
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.
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.
Similar studies are underway in New Jersey, Slovenia, China, Australia, and Qatar.
Limited risk of side effects
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.
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.”
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.
“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.
FRIDAY, Aug. 11, 2017 — Adults who’ve been hospitalized with pneumonia or sepsis have a higher risk of heart disease, a new European study reports.
Researchers examined data from nearly 237,000 Swedish men. They were followed from age 18 into middle age. The study found that those admitted to the hospital with pneumonia or sepsis (a bacterial infection of the blood) had a six times higher risk of heart disease in the following year.
The rate dropped significantly during the second and third years, but was still more than double. And, by the fourth and fifth years, the risk remained almost two times higher in those who’d been hospitalized for sepsis or pneumonia compared to those who hadn’t.
The study was published recently in the European Journal of Preventive Cardiology.
While most patients with sepsis or pneumonia recover from these conditions, many still have inflammation after the infections. Inflammation is a risk factor for cardiovascular disease, including coronary heart disease and stroke, the researchers said.
“Conventional cardiovascular risk factors (such as obesity, high blood pressure and inactivity) are still important but infection may be the primary source of risk for a limited time,” study co-author Scott Montgomery, said in a journal news release.
“Our findings provide another reason to protect against infection and suggest that there is a post-infection window of increased cardiovascular disease risk. We did not study any interventions that could be initiated during this period, but preventative therapies such as statins could be investigated,” he said.
Montgomery directs the clinical epidemiology group at Orebro University in Sweden.
April 4, 2017 — The possibility of curing sepsis with a common vitamin has put one of history’s greatest killers back in the spotlight.
Sepsis has been in the medical books since Hippocrates. It occurs when the body’s immune system responds to an infection with overwhelming force. That can trigger complications that can cause blood clots 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. But today, there are hundreds of thousands of U.S. cases each year — and 25% to 50% of them are fatal. It’s one of the leading causes of death for people in hospitals, particularly those in intensive care. Survival often depends on an early dose of the right antibiotic and intravenous fluids, along with tests to look for signs of an infection or organ failure.
“We have simple treatments that work, but so far, none of the fancier treatments have worked,” says Jonathan Sevransky, MD, who works with critically ill patients at Emory University Hospital in Atlanta.
To treat sepsis, doctors have to tackle not only the underlying infection, but the complications that come from the body’s immune response, Sevransky says. In addition, there’s no simple test to identify sepsis early — something that’s particularly dangerous for patients in intensive care, Sevransky says.
“When you look at people who die in the hospital, between one in three or even one in two will die from sepsis,” he says. “Sometimes it’s because they have so many other problems that we can’t solve all the problems and the infection, but sometimes it’s because we don’t think of it early enough.”
The problem got a new look in recent months after Virginia doctors who used a cocktail of vitamin C, corticosteroids, and vitamin B1 said it helped fight off organ failure and death in patients with sepsis. Among 47 patients who received that mix, all but four survived, the doctors reported in a recent study.
But that study involved a small number of patients in one hospital, and the authors noted that more research is needed to confirm those findings.
“For the type of study that it was, it was nicely done,” Sevransky says. But he says a follow-up study will need to involve more patients, some of whom would get the treatment and others who wouldn’t.
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. Other studies have tried to focus on restraining the immune overreaction that causes sepsis.
That overreaction makes it harder for blood to flow. And it’s possible that non-steroidal anti-inflammatory drugs (NSAIDs) — a group that includes popular over-the-counter painkillers like ibuprofen — may be able to offset that response, said Hang Hubert Yin, a biochemist at the University of Colorado.
Yin has been studying a family of naturally occurring enzymes called caspases, which fuel the kind of aggressive immune response that can lead to sepsis. When he and his colleagues sorted through a list of more than 1,200 drugs that can restrain caspases, he found about a dozen NSAIDs on that list.
Those findings, published in February, could help doctors find new drugs to help treat sepsis and other problems. But it’s not without risk: Yin notes that NSAIDs can cause heart and stomach problems, and those complications kill as many as 16,000 people a year. It will take several years before NSAIDS are tested to treat sepsis in humans.
But other potential anti-sepsis drugs failed to live up to their initial promise. A drug that targeted a protein involved in the body’s immune response failed a phase III clinical trial in 2011, while another aimed at improving blood flow in sepsis patients was pulled from the market the same year after disappointing results.
“The basic biology here, the pathology of sepsis, is extremely challenging to fight with pharmaceuticals,” Yin says. Once sepsis sets in, death can occur in 24 to 48 hours. The underlying infection may be resistant to antibiotics, and organ damage that happens can be “extremely difficult” to halt with drugs.
For now, Sevransky says the most important thing doctors can do is detect signs of sepsis early — something that is often difficult. Patients with certain types of infections, infants, people over 65, and those with weakened immune systems are more likely to get sepsis. Symptoms include fever, chills, and sweating; extreme pain or discomfort; difficulty breathing; and an elevated heart rate. And in some patients, confusion is the first outward sign of the problem, he says.
“They often have symptoms that don’t often jump and say, ‘I have an infection.’ Somebody gets confused, somebody gets sore, somebody has trouble breathing — that suggests that they’re sick, but may not necessarily have a flag sticking up that says, ‘I have a bad infection, and I need treatment rapidly,’ “ Sevransky says.
The CDC has started urging doctors to “Think Sepsis.” A similar push is under way by the Society for Critical Care Medicine and its European counterpart, the European Society of Intensive Care Medicine.
“It’s tremendously important, because a lot of people have it,” Sevransky says. “But it’s not complicated, which is maybe why people haven’t paid a lot of attention to this. It’s really bread-and-butter medicine, but we don’t do as good as a job as we’d like to do.”