Ron Daniels | Chief Executive and Founder, UK Sepsis Trust; Consultant in Critical Care, University Hospitals Birmingham NHS Foundation Trust, UK
What does your role as Chief Executive of the UK Sepsis Trust entail, and what have been your greatest achievements to date in this position?
I first developed an interest in sepsis in 2004, when I watched a young man, a 37-year-old, die of sepsis in my intensive care unit. It became apparent that the system had let him down, at multiple opportunities, to recognise this illness. We had not taken proper observations and had failed to provide adequate safety netting to his family. His death was almost certainly avoidable. For several years after, I started to develop clinical tools for health professionals and engage with hospitals. This ultimately led to a groundswell of support among medical practitioners. In addition, we developed the Sepsis Six care bundle and managed to get this implemented in approximately 100 hospitals across England by 2010. However, it became apparent that this was only part of what was needed in terms of health professional education. It was also necessary to work with the public and empower them to access healthcare rapidly. Furthermore, we needed to work with policymakers to ensure that, at a national level, sepsis was recognised as a clinical priority. Over the 2 year period leading up to 2012, we founded and eventually registered the UK Sepsis Trust. Since that time, as the Founder and Chief Executive, I have led the charity. I now co-lead it with Sarah Hamilton-Fairley and dedicate 27 hours of my time each week to that leadership role. Within the charity, I am responsible for setting the strategic direction. I oversee both the clinical and campaign sides. In the clinical space, I lead the support team, which is a team of senior intensive care nurses who have received training and counselling. These nurses provide telephonic and email support and, outside of the COVID-19 pandemic, they offer face-to-face peer support groups to people affected by sepsis. The second area of clinical work involves continuing the process that I started in 2004. This relates to the iteration of the clinical tools for health professionals and the provision of education, lectures, and design of e-learning.
Politics is the third area of clinical work I am concerned with. This encompasses the development of relationships and collaborative working, often with multi-stakeholder groups, to refine national guidance and ensure that it is fit for purpose. One example would be the support we gave to the National Institute for Health and Care Excellence (NICE) when they released NICE guideline NG51. In the campaign space, we prioritise empowerment. Essentially, we empower the public to ask: “Could it be sepsis?” I co-design the tools with Hamilton-Fairley, we promote them to people who can activate them, and we form networks to disseminate at scale. We worked closely with the frozen food retailer Iceland, who put messages raising awareness of sepsis and its symptoms on 100 million milk bottles. There was no cost to the supermarket because milk labels need to be printed anyway. They simply chose to put potentially life-saving information on them. In terms of major achievements, it’s difficult to pick with precision the one we are most proud of, especially because the charity is now entering its 10th birthday year. However, I think we can safely say that we have put sepsis on the map for the National Health Service (NHS), meaning that it has become a clinical priority. We lobbied, through the Department of Health and Social Care (DHSC), to ensure that sepsis was a commissioning incentive, and NHS England actually applied a Commissioning for Quality and Innovation incentive. Hospitals were asked to screen patients for sepsis and, once they suspected sepsis, treat them rapidly with antibiotics. This resulted in significant process improvements, saving hundreds of lives without the adverse consequence of increasing total antibiotic usage and fuelling the development of antimicrobial resistance. A second success was the NICE clinical guideline NG51, produced in 2016. This was a ministerial mandate that paved the way for a unified pan-UK approach to sepsis. In the near future, the Academy of Medical Royal Colleges (AoMRC) is going to update that advice and release new guidelines. In summary, we can be very proud that we have increased awareness among health professionals. At a policy and statutory body level, we secured lasting changes that will help ensure healthcare organisations can continue prioritising sepsis. We also heightened public awareness of the condition. In our early polls, approximately one in three members of the public had heard of sepsis. Prior to the pandemic, we were in a position where 80% had heard of sepsis. Of that 80%, over two-thirds knew what to do about sepsis, recognised it as a medical emergency, and were aware of how to access medical help. I think this combination of factors has ensured that we are saving lives. Importantly, we are also improving outcomes for survivors. Our nurses are available during office hours, and they support hundreds of sepsis survivors every year, helping them understand the recovery journey, become engaged in the recovery process, and improve their quality of life.
The goal of the UK Sepsis Trust is: “To end preventable deaths from sepsis and improve outcomes for sepsis survivors.” In your opinion, what research priorities should be set to achieve this?
We have to acknowledge and reinforce that not every death from sepsis is preventable. Sepsis can be a mode of death in people approaching the natural end of life. Of course, where mortality from sepsis is avoidable, it is important that we understand how to prevent deaths in that situation in the future. The main research priority is a top-level one, which will not be delivered by a single piece of research. It is around moving towards precision medicine. Currently, there is one definition of sepsis, which applies the same thresholds regardless of whether a patient is a healthy 18-year-old or a frail 85-year-old. This is illogical because the phenotype, vital signs, and laboratory parameters of the 18-year-old, who requires urgent antibiotics and source control, are likely to be very different to those of the 85-year-old, who needs similar. Depending on the set of comorbidities, age, and type of infection, certain individuals will need to be given immediate antimicrobials. However, in other individuals, it might be feasible to wait until more information is accrued before administering therapy. To differentiate between these groups, patient-level data on a large scale is required. Such data systems must be intraoperable and pattern recognition strategies should be applied to them. Only then will it be possible to understand what sepsis looks like at an individual patient level. This will ultimately allow clinicians to use antibiotics more judiciously and prioritise those who need them most urgently. It also paves the way for further research into immunomodulatory therapies, which can help health professionals deliver precision medicine to the patient.
Please could you provide an overview of the Sepsis Six treatment pathway? What are the potential facilitators and barriers towards implementing this care bundle?
The Sepsis Six is a set of interventions developed and curated by the UK Sepsis Trust. It takes evidence-based guidelines that are, by necessity, very thorough and it operationalises them into a simplified bundle. The pathway consists of the six steps of care that, at present, academic experts and key opinion leaders suggest are the most important. We seek to work with stakeholders such as NICE to ensure that there is a degree of endorsement for the bundle and that it is delivered responsibly and rapidly. Step one is to ensure that a senior clinician attends the patient. This is important because senior clinicians can expedite and facilitate care. They can also look for non-sepsis conditions that mimic sepsis, and move patients onto alternative pathways if necessary. Step two is to correct hypoxia (e.g., administering O2 if a patient’s O2 saturation is low). Step three is to secure intravenous access and send a full set of blood tests. In this instance, we are looking for organ dysfunction, we are looking to risk stratify, and we are looking for pathogens. This enables us to tailor antimicrobial therapy. Step four is to control the infection. This is achieved by giving antibiotics and, if appropriate, source control (e.g., removal of an infected intravascular device or surgery for an abscess that might be precipitating sepsis). Step five is to consider fluids. Intravenous fluids may be given, particularly if the patient shows evidence of shock. Finally, step six is ongoing monitoring (e.g., continue monitoring the National Early Warning Score [NEWS] 2, urine output, and lactate). Collectively, this package of care is now in use in at least two dozen countries around the world. In part, this is because it is empowering; simple; and directed towards junior health professionals, providing them with a tool they can readily utilise at the bedside. As mentioned above, I think the biggest enabler of Sepsis Six is its empowerment value. It is memorable, logical, and allows junior staff to act rapidly when faced with deteriorating patients. There are two main barriers. In low- and middle-income countries as well as resource-constrained high-income countries, there are issues with access to the equipment that is needed to deliver the interventions. This could range from the availability of blood culture bottles through to how antibiotics are stored, how they are accessed by health professionals, and whether there is a prescriber available. Issues with availability also include access to point-of-care testing, for example, to measure lactate. In my opinion, the biggest barrier remains the perception that delivering reliable and rapid sepsis care negatively impacts antimicrobial resistance. Over the last decade, there has been a profound change within the NHS from a culture of wanting to rapidly treat sepsis to an appreciation that if we overtreat it, then we are likely to exacerbate the spread of antimicrobial resistance. We are now encouraging organisations to look at their sepsis protocols, make sure that they are compliant with the NICE clinical guideline NG51, and, in the near future, to make sure they are compliant with the AoMRC guidance. We also advise that organisations empower their junior staff to act but do not mandate their actions. If a member of staff exercises clinical judgment and has doubt that sepsis is the diagnosis, then they should equally be empowered to withhold antibiotics, seek senior help, or wait for investigations to come back in a timely fashion.
How important is the clinical concept of Red Flag Sepsis in the identification of patients at high-risk of sepsis-related mortality?
Red Flag Sepsis is a tool of empowerment; however, it is not intended to replace clinical judgment. Red flags are there for patients about whom we are not sure what to do. They are parameters that can quickly and easily be identified at the bedside, and are intended to empower the often junior health professional to act decisively and rapidly. Contextually, there is an international consensus definition of sepsis, but it is a definition that requires a full set of laboratory tests available at the point of decision, together with an understanding of intensive care terminology. Operationally, the reality is that the Sequential Organ Failure Assessment (SOFA) score, which is this official definition of sepsis, is impracticable at the bedside. This is where red flags come into their own.
Could you summarise the principal findings and wide relevance of the 2019 article that you co-authored, entitled ‘Life After Sepsis: An International Survey of Survivors to Understand the Post-sepsis Syndrome’?
The first thing to say about this study is that it was a survey, and it therefore comes with all the associated caveats. We almost certainly had selection bias in the patients who reported in to us. It is highly unlikely that somebody who survived sepsis, has remained well, and returned to normal life is going to respond to such a study. However, with those caveats in place, the findings were unsurprising, and they mirrored other evidence. Forty percent of people who survived sepsis have a deficiency in one of three domains persisting at 1 year after their original illness. The three domains are psychological, physical, and cognitive. The psychological domain ranges from relatively mild (e.g., difficulty sleeping, the occasional panic attack, or heightened anxiety) through to severe (e.g., post-traumatic stress disorder, which occurs in approximately one in five survivors of sepsis). The physical domain ranges from the very visible (e.g., the loss of digits or limbs) through to the equally disabling invisible physical sequelae (e.g., the severe pain that people can experience in their limbs and joints, and the more common but equally disabling fatigue). Similarly, the cognitive domain ranges from the relatively minor (e.g., poor short-term memory or concentration) to the disabling (e.g., where an individual’s judgment and ability to conduct basic tasks is impaired). Collectively, these symptoms cause a reduction in the patient’s attitude, can be detrimental to their mental health, and can compromise their ability to return to work at their previous level of function. Their ability to manage and sustain relationships, including in the home, can also be impaired. Overall, these findings were not surprising. However, certain elements health professionals might traditionally have perceived as trivial were shown to cause significant problems to patients. These elements included brittle hair and nails as well as the sensation of loose teeth. Also of interest are the results of a previous Scandinavian study. At 1 year after infection with sepsis, 57% of previously employed adults had returned to work. However, 43% had not. I would like anyone accessing this resource to consider how the inability to return to work because of the after-effects of sepsis would impact on their own lives.
Have there been any recent innovations in the development of rapid diagnostic tests for sepsis that you believe are particularly noteworthy?
The challenge with sepsis is that it is so heterogeneous. We could have a young person with a urinary tract infection who presents to healthcare within 12 hours of their first symptoms. Alternatively, we could have an older person, with more comorbidities and significant risk factors for infection, who develops pneumonia and delays accessing healthcare for 48 hours. For this reason, it is unlikely that a single biomarker or pathogen identification test will provide a transformational answer. I have previously referred to the need for big data and precision medicine. However, I think the biggest transformation we are going to see over the coming years is a move towards diagnostics being closer to the patients. This will include risk stratification diagnostics, which might involve lactate being more available, alongside other risk stratification tools, such as point-of-care assessment of kidney and liver function. It will also include pathogen identification strategies and molecular techniques for the rapid identification of pathogens, which are coming increasingly to the fore. It is anticipated that these will no longer be subsumed within a laboratory, which delays their impact on the decisions of the prescribing clinician. Increasingly, these are going to be integrated more closely into the healthcare system and accessible at the point of care.
Why is it important to standardise national track and trigger systems across primary and secondary care?
When we talk about track and trigger systems within the UK for adults, particularly non-pregnant adults, we are primarily talking about the NEWS, which is now in its second incarnation. This has a significant evidence base in terms of the detection of deterioration in acute care in the secondary sector, and has an increasing evidence base in terms of its utility in the pre-hospital and community-based phases, including in general practice. I think it is important that we have a standardised tool. When referring a patient about whom they are concerned, a standardised language could support a general practitioner in dialogue with the receiving medical officer at the hospital. They can convey, quickly and easily, the level of deviation of that patient’s deterioration from normal in a language that the receiving medical officer can retain and understand. In obstetrics, we ought to move towards a standardised Obstetric Early Warning Score (OEWS). There is already work under way in standardising the Paediatric Early Warning Score (PEWS). Although it is important to have a common language, there are two aspects that we need to caveat this with. One is that the tools do not replace clinical judgment. The tools are not yet perfect and if clinical judgment suggests that the patient is unwell, despite the patient not triggering on a particular tool, then clinical judgment should be trusted and action should still be taken. I think the second caveat is that, just like the definitions for sepsis, it is important to understand that applying physiological thresholds at the same level to people of widely different ages, widely different baseline functions, and with widely different collections of comorbidities is likely to be imprecise. As we understand in a more granular and cohort-specific way what deterioration looks like for a particular group of patients, we can anticipate that early warning scores might become customised according to the baseline risk factors of the patient.
You were on the Scientific Committee of the World Sepsis Congress (WSC) 2021. Please could you provide a brief summary of the key take-home messages from this event?
One of the biggest attractions of online congresses, providing that people can access mobile data, is that they are accessible to individuals in low- and middle-income countries in a similar way to being accessible to people in high-income countries. One of the greatest learnings we had from this was that the engagement of people in resource-poor nations was both relatively straightforward and also hugely appreciated by the clinicians working in those settings, who would normally find it difficult to access key opinion leaders, particularly from high-income countries around the world. Another learning from the WSC was that sepsis is a whole systems issue. It is not around an individual biomarker, it is not just around pathogen identification, and it is not around secondary care only or community-based care only. It is about the healthcare system as a whole. This includes the public health aspects of the healthcare system (e.g., making the public aware of sepsis and emphasising the need to access healthcare urgently) and also integration between community-based care and secondary care in order to speed up access to hospitals, facilitate rapid recognition of sepsis, and promote the timely delivery of life-saving antimicrobials. On the subject of antimicrobials, it is key to understand that sepsis is intrinsically interlinked with antimicrobial resistance. There is an increasing drive towards a more holistic approach by governments and policy makers with respect to infections management, which is based on four pillars: antimicrobial resistance, rapid treatment of sepsis, infection prevention, and pandemic preparedness. It is imperative that these four pillars are all addressed with equal vigour. Another learning from the recent congress was around the direct relationship between severe acute respiratory syndrome coronavirus 2 infection, COVID-19, and sepsis. The majority of individuals who became critically ill with COVID-19, particularly in high-income countries, had sepsis precipitated by a viral cause, and this is really important to understand. Finally, there was a consideration of exciting future developments. I have already mentioned several of these in my answers above. They include the development of more intelligent and customised biomarkers to guide care; the development of pathogen identification strategies; and the development of regional research networks, such as the proposed Pan-European Sepsis Network, to drive the research agenda, elucidate the burden of sepsis on society, and understand how we can move toward precision-based medicine.
Please could you outline the primary duties and key projects you undertake as Vice President of the Global Sepsis Alliance (GSA)?
The GSA is based on multistakeholder engagement. We have regional offices that broadly geographically mirror the World Health Organization (WHO) regional offices. It is about facilitating collaborative work in often challenging regions, such as the African Sepsis Alliance (ASA). It is also around public engagement. For instance, World Sepsis Day messaging is used to nurture events related to sepsis in countries across the globe. At least 80 countries now have World Sepsis Day events every year, which engage clinicians, members of the public, and policymakers. Of course, there is the strategic policy engagement. We cannot talk about the GSA without mentioning the WHO. In 2017, we presented a resolution to the WHO, proposing that countries heighten their public awareness of sepsis; ensure robust infection prevention strategies are implemented through vaccination, clean water, sanitation, and hygiene; and that they strengthen the resilience of their healthcare systems against sepsis. It is also important for countries to measure their performance against sepsis metrics. Although the resolution was adopted, progress has been hindered by the pandemic. However, as we move into 2022, we are looking forward to an implementation task force, developed jointly with the WHO, in order to consider the recommendations within the resolution and start to work across the regions to activate them. The final thing is around the WHO being made aware of the infection management strategy, considering the holistic approach to infections management, and being made aware of the Infection Management Coalition (IMC) White Paper. This report was produced as a collaborative stakeholder strategy in the UK and has now gone to the top of the WHO. Hopefully, it will establish a template for governments to plan and deliver a more cohesive approach to infection management at a policy level.