“We need to intensify research into sepsis and coordinate it better”

Luregn Schlapbach, World Sepsis Day was last week, when the medical community and those who’ve been affected drew attention to a disease that rarely hits the headlines. Why is the topic of sepsis important? And how many people fall ill from it?

Luregn Schlapbach: Around 50 million people are affected worldwide, half of which are children. Although the impact is more severe in developing countries, sepsis is also a grave problem in highly developed industrialized countries such as the US and the Western European nations. In Switzerland alone, around 20,000 people suffer sepsis each year, and we record around 3,500 deaths annually. In principle, all age groups are affected, although the risk is greatest in the first years of life.

What is sepsis?

Luregn Schlapbach: Sepsis occurs when the body reacts so strongly to an infection that individual organs can no longer fulfill their function, resulting in life-threatening organ failure due to a dysregulation of the immune system. In the majority of cases, sepsis is triggered by a bacterial infection, but viruses or a combination of viruses and bacteria can also lead to sepsis. Many patients died from sepsis during the Covid-19 pandemic. And it was a similar situation during the influenza pandemic of 1918 – many victims of the Spanish flu were actually sepsis cases.

Sepsis is also referred to as blood poisoning. Why?

Luregn Schlapbach: In colloquial speech, this term is frequently heard. The name sepsis stems from the Ancient Greek term for decay. Sepsis cases can develop when a local injury turns into a local infection and bacteria enter the bloodstream and “poison” the body. But most sepsis cases have other causes.

Are young children over-proportionally affected because their immune system isn’t fully developed yet?

Luregn Schlapbach: Yes, children in the early years of life are at greater risk of sepsis than healthy adults, because their immune system is comparatively weak. This means their immune cells and proteins have greater difficulty in recognizing certain germs and fighting them efficiently. Organ failure in people with sepsis results from a complex interaction between the germ and the immune system, coagulation and the blood vessels. The first organs to be affected are often those of the circulatory system. That can compromise heart function and jeopardize the blood flow. In children with septic shock this shows as paleness, the skin appears marbled and is often cool to the touch, in advanced stages the blood pressure drops. Often the lungs and respiration are also affected. Parents report that their child’s breathing has become increasingly heavy and gasping. A further organ that can be affected is the brain, causing impaired cognition and changes in behavior. Such patients will then be very sleepy, for instance, or may become confused.

What treatment options are there?

Luregn Schlapbach: If a bacterial sepsis is suspected, antibiotics should be administered at the earliest possible stage of the disease. It’s important to refer the patient to an intensive care unit so that any organ failure can be treated swiftly. In intensive care units, patients will be supported with circulatory drugs, ventilation and renal replacement therapy, and in the most severe cases may be connected to a heart-lung machine. What we currently still lack are targeted agents for re-balancing the immune system. We only have broadly acting drugs such as steroids, which simply dampen the immune system. This approach works well with some patients, but less so with others. We urgently need more research on this, so that in future we can offer those affected more personalized treatments. This would mean that we have drugs available which are tailored to the individual risk profile of the patient. That’s the direction current clinical research is heading in.

Is sepsis difficult to diagnose?

Luregn Schlapbach: Recognizing sepsis in the early stages is very challenging. Initially, sepsis barely differs from a normal, febrile infection. This presents great difficulties for general practitioners and emergency departments, who have to decide whether someone needs to be treated with antibiotics or not. The key is to recognize the switch from a simple infection to an infection with signs of deteriorating organ function. At that point, swift action is required. The disease is also challenging to diagnose because we don’t yet have a blood test that is sufficiently precise. And even here in this country there’s room for improvement when it comes to the clinical recognition of sepsis.

Does that mean there are misdiagnoses?

Luregn Schlapbach: I wouldn’t say misdiagnoses as such, but we repeatedly see cases where the correct diagnosis of sepsis could have been arrived at more quickly. But as I said, diagnosing sepsis can be very difficult and also requires a lot of experience. In hospitals abroad, so-called early warning scores are increasingly being used, so that patients whose condition is worsening can be identified more easily. In Switzerland this approach hasn’t been adopted yet, neither with children nor with adults.

In collaboration with colleagues, you publicized standardized guidelines on diagnosing sepsis earlier this year. Why did you take this step, and what’s the advantage of these criteria?

Luregn Schlapbach: Previously, sepsis in children was variably defined, which meant that clinicians weren’t always talking about the same disease pattern. We needed to establish a conclusive set of criteria for diagnosing sepsis. So over the course of the past few years, we have analyzed data relating to more than 3.5 million children from all over the world. These evidence-based criteria allow researchers to develop new drugs in a targeted manner. At the same time, the standardized criteria also improve early diagnosis and thus the chances of recovery.

So there’s an urgent need for higher education institutions and industry to carry out more research in the field of sepsis?

Luregn Schlapbach: When we look at the large number of cases and the long-term effects of this illness, then yes, it’s really important to intensify research in this field and coordinate it better. Over the course of the Covid-19 pandemic, we witnessed how beneficial it is when research is pooled and well-coordinated – only thanks to this focusing of knowledge could progress be made so rapidly. I would like to see the same happen in the field of sepsis, both in terms of diagnosis and treatment. We need to consider the fact that most children with sepsis are under five years old, this means they still have another 80 years of life ahead of them if they survive the illness. A third of these children go on to suffer from long-term effects – if better treatment was possible, it would have a huge impact on the children, their families and our society.

You’ve been able to publish a four-part series on the topic of sepsis in the renowned journal The Lancet. In what way do the Children’s Hospital and UZH excel in this area?

Luregn Schlapbach: The Lancet wanted a comprehensive and up-to-date account of all significant aspects and challenges of the disease. As a result of the work carried out by our research group at the University Children’s Hospital Zurich, I was commissioned to lead an international working group which authored this series of articles. As well as providing an overview of the current level of knowledge in terms of epidemiology, causes, diagnosis and treatment, we also tried to illustrate what obstacles exist in medical and research settings that hamper progress in the field of sepsis. Based on this, we drafted a set of recommendations for quality improvement, research and better use of digitalization, which will hopefully contribute to advances in the field and help save lives.