Imperial researcher to investigate blood poisoning with new professorship

Credit: Helle Asbjorn Sorensen / Intensive Care Foundation

An Imperial scientist has received a £1.5 million professorship to investigate how treatment for sepsis can be tailored better for patients.

Sepsis is the body’s response to severe infection, often known as blood poisoning in the past. It is very common worldwide and has a high death rate. In the UK alone, more than 120,000 patients are admitted to intensive care units with sepsis each year and the NHS spends more than £2 billion caring for them.

Professor Anthony Gordon, Chair in Anaesthesia and Critical Care at Imperial College London, has been awarded a five-year National Institute for Health Research (NIHR) Professorship, which aims to fund translational research that will directly affect patients.

Professor Gordon’s project will provide insight into targeting sepsis treatments to improve outcomes, reduce side-effects and lessen the use of antibiotics. He and his team will be working closely with clinicians, research nurses and patients at Imperial College Healthcare NHS Trust.

Professor Gordon spoke to Franca Davenport about his research and how it will help those working with patients with sepsis.

Why is personalised medicine so important for sepsis?

Sepsis can be difficult to diagnose initially and can progress to a critical state very quickly. When patients reach the Intensive Care Unit, current practice is to treat all patients with a similar regimen of antibiotics, intravenous fluids and powerful adrenaline-like drugs to support the heart. However, there are problems with these treatments. If antibiotics are delayed, or the wrong antibiotics are prescribed whilst waiting for laboratory test results, this can increase the likelihood of death. Whilst the adrenaline-like drugs are very effective we know they also have serious side-effects in some patients.

As such it is very important to try and make sure the treatment fits the patient as closely as possible. We always tailor our treatment, but now we have the technologies to make this process much more precise and quicker.

The research I am planning to do with the NIHR research professorship will investigate how to use and optimise these technologies.  If we can find quick and efficient ways of targeting the treatment to the individual patient then the outcomes will be better and ultimately we could save more lives.

Can you explain in more detail what you are proposing to do in your research?

There will be a number of strands to the research.  We will be investigating whether genetic make-up affects how patients respond to different treatments for septic shock. Septic shock occurs when the sepsis is so severe that blood pressure drops, which then results in poor blood flow to the kidney and other vital organs.

We will also be looking at whether we can classify patients into different sub-groups of high and low risk based on their gene expression, which is the type of message that comes from the gene to determine which proteins are produced. Identifying patients as high or low risk in this way could be very helpful in informing what types of treatment they receive.

Lastly we will be evaluating the use of a chip to analyse the DNA of the actual bacteria that cause the infection so we can target the use of antibiotics. Currently we tend to treat sepsis with multiple antibiotics while we wait for an analysis of the bacteria. With this chip we could potentially make a much faster analysis at the bedside and target the use of antibiotics more effectively and efficiently.  

How will you conduct the genetic analysis that is needed for the research?

In terms of the research with patients with septic shock and the sub-grouping of patients, we have already collected genetic samples and data on their response to treatment. For this we are collaborating with the Wellcome Trust Centre for Human Genetics in Oxford, who will be analysing the samples.

For the analysis of bacterial DNA we will be comparing the performance of the gene sequencing chip with that of current tests in 500 patients. The chip was developed by the Imperial spin-out company DNA Electronics and has been used in research into other areas, but this is the first time it will be used in an Intensive Care Unit, where speed is of the essence in order to turnaround the analysis to inform antibiotic treatment.

Can you tell me a bit about the research team?

We currently have about eight people on the research team itself, but this will expand. We also have a central team of research nurses involved in recruitment that provide cover  seven days a week as patients come in at all times of day and night. Most of them have previously been clinical nurses working in intensive care and decided to get involved in research. This means they know the subject inside out so they are excellent at talking to the patients and their families.

What are the challenges of researching this area?

I think the very nature of sepsis makes it a difficult area to research. Patients arrive at the intensive care unit in distress and needing immediate treatment, so asking them or their family to take part in research has to be done with both sensitivity and clarity. That is why our research nurses are so important.  So far nobody has ever been upset by being asked to take part in research and the majority of patients like the idea of being involved.

We try to be as patient-centred as possible in everything we do. That is why the fourth strand of our project is so important. This is looking at how best to combine new diagnostic tests with treatments so that we actually translate the findings of our research in the most effective way. This will involve talking to both patients and staff and asking them questions such as ‘What do you want to from a diagnostic test?’ and ‘What level of information is most useful and meaningful?’ It will also investigate possible trade-offs such as whether patients and clinicians prefer results to be quicker or more accurate.

Although it is a challenge, our hope is that by researching these different elements of diagnosis, treatment and working with patients we will be able to develop an improved system to treat sepsis so that our care is more patient-centred and more effective.