Sepsis: the truth about this hidden killer
At the end of May, the World Health Organization adopted a new resolution mandating all of its member states to have national action plans in place to tackle sepsis, a disease being called the “deadliest killer you’ve never heard of”. Even conservative estimates place the annual death toll at 6 million worldwide, a health burden equivalent to that of tobacco. In the UK alone, sepsis is responsible for 44,000 deaths every year, more than bowel, breast and prostate cancer combined. Despite this, a recent survey found that 44% of people in the UK have never heard of sepsis and have little idea that it is a life-threatening emergency.
So, what exactly is sepsis and why does it continue to slip through the net of our collective consciousness? The new international definition of sepsis describes it as a condition that arises when the body’s response to infection causes organ dysfunction. “There’s a range of ways in which this can happen,” says Prof Anthony Gordon, chair in anaesthesia and critical care at Imperial College London, and an National Institute for Health Research professor investigating sepsis. “The body’s immune response can be simply overwhelmed by the infection, or there’s a dysfunctional response producing too much inflammation. The body may already be immunosuppressed due to a trauma or fighting an initial infection, so the immune response is too weak.”
Depending on the infection, sepsis can affect any organ, resulting in a diverse variety of symptoms. If the brain is affected, this may cause confusion; if the lungs are affected, this may result in breathing difficulties. Very young children and the elderly are particularly at risk, along with individuals with pre-existing medical conditions. Studies in the 1980s, examining registries and death certificates, identified evidence of an inherited risk of sepsis after finding a link between early death from infection in adopted children whose biological parents had died early from infection, while there was no such link with their adopted parents.
Sepsis is typically treated through the rapid administration of antibiotics; in the pre-antibiotic era, typical patient prognosis was grim. With 30m cases of sepsis globally every year, doctors are fearful of the rising threat of antibiotic resistance. “At the moment we’re still OK,” Gordon says. “Although bacteria are resistant to many antibiotics, there’s usually something still available that will work. But we’re worried about that for the future.”
Despite the statistics, sepsis has flown beneath the radar. This is partly because the majority of fatalities resulting from sepsis have not been accurately reported. One study found that sepsis was only written on the death certificate in 40% of cases where patients had died from the condition.
“Often patients are discharged from hospital completely unaware that they’ve had sepsis,” says Dr Ron Daniels, founder of the UK Sepsis Trust. “They could be admitted with a chest infection and end up in intensive care with multi-organ failure, but they think they’ve just had pneumonia, not realising that’s sepsis.”
Part of the problem has been one of terminology. While the word “sepsis” is of Greek origin and has existed for thousands of years, the medical community didn’t come to a conclusive definition until 1991. As a result, a range of terms, from “blood poisoning” to “septicaemia”, have been bandied around to describe the same thing. “This is why so few people have been aware of it,” Daniels says. “Despite being this hidden killer and the most common cause of deterioration and death in secondary-care settings, funding resources haven’t followed it and for a long time there’s been no specific commissioning for better sepsis care.”
Belatedly, progress is being made. The NHS has provided GPs with automated prompts alerting them to potential sepsis cases, while all staff are being encouraged to think of sepsis in response to a high national early-warning score. Procedural changes mean that ambulance teams now alert hospital emergency services of incoming sepsis patients, as is commonplace with heart-attack or stroke patients. Extra commissioning incentives have been put in place for hospitals to reward good practice in sepsis care. “We know that they’re more reliably screening for sepsis, and more reliably delivering antibiotics than they were prior to this,” Daniels says.
As a result, mortality rates from sepsis patients admitted into intensive care are falling, down from 35% a decade ago to 27%. For further improvements, the main challenge is to improve early diagnosis, while continuing to educate medical staff to remember to watch out for the often extremely subtle initial signs. “All the changes being made still rely on someone actually thinking sepsis and considering that as a possibility,” Daniels says. “They’re useless otherwise.”
One of the biggest diagnosis challenges is to speed up the identification of the pathogen responsible for the underlying infection, allowing the use of antibiotics in a more targeted fashion. The gold-standard diagnostics right now typically take between 48 and 72 hours to give an answer. However, while these rely on culturing the bacteria in the lab, new techniques are being developed that could cut diagnostic times down to a few hours, a difference which could be lifesaving.
Studies are also investigating gene-expression levels. “We’re trying to look at whether we can predict the body’s likely response to the infection and treat accordingly,” Gordon says. “So if they’re vulnerable due to excessive inflammation, maybe we can dampen that down. Or if they are immunosuppressed, perhaps we can give their immune system a boost. I don’t think we will ever be able to say we can cure every single case of sepsis. It is, by its nature, a life-threatening condition, and can be overwhelming even with antibiotics. But what we’re saying is, what can we do to reduce the death rate as much as we possibly can?”