Infection, sepsis and clinical negligence

There are plenty of blogs and articles written about sepsis, because it is such an important topic, both medically and medicolegally.

Why is sepsis so important?

Sepsis is important for a number of reasons: it is common, with an estimated nearly a million cases per year in the UK; it has high mortality rates, with an estimate of about 50,000 deaths per year in the UK; it also has high morbidity rates; not only is it costly in human terms, but it is costly in financial terms, costing an estimated 1% of the NHS budget and costing more than asthma; it is frequently treatable; and, accordingly, early detection is paramount.

What are the definitions?

The definition of sepsis has changed over time and has passed through a number of iterations, in an attempt to improve the precision with which sepsis is to be suspected, diagnosed and ultimately treated. A helpful lay definition of sepsis is known as the Merinoff definition:

A life-threatening condition that arises when the body’s response to an infection injures its own tissues and organs.

The most recent definition for healthcare professionals is that found in Sepsis-3, introduced in 2016:

Sepsis is characterised by a life-threatening organ dysfunction due to a dysregulated host response to infection.

This definition removed some of the older SIRS (systemic inflammatory response syndrome) criteria because they were too non-specific and Sepsis-3 introduced the concept of life-threatening organ dysfunction.

‘Septic shock’ is a subset of sepsis which can be defined as:

A subset of sepsis where particularly profound circulatory, cellular and metabolic abnormalities substantially increase mortality

 This definition involves persisting hypotension requiring vasopressor therapy to maintain a mean arterial pressure (MAP) of 65 mmHg or more and a serum lactate level greater than 2 mmol/L despite adequate volume resuscitation.

Sepsis is thought to be a multifactorial response to an infecting pathogen but the precise pathophysiology behind the development of sepsis is unknown.

Despite the specific definitions, sepsis can perhaps broadly be thought of as a syndrome of physiological, pathological and biochemical abnormalities induced by infection.

As can be seen, most importantly, sepsis begins with an infection.

What is the issue with sepsis?

In short, the primary issue is the need to identify patients who are at risk of developing sepsis so that appropriate treatment can be implemented early. This in particular includes patients who have a local infection which may go on to develop into life-threatening sepsis.

As The Sepsis Manual notes (at page 15): “Risk factors for sepsis should always prompt a high index of suspicion for sepsis – health professionals should always ‘think sepsis’… Of course, though patients with risk factors are more prone to developing sepsis, it is important not to rely upon risk factors alone. NICE, in NG51, also recommended the application of clinical acumen – to ‘think sepsis’ if a patient looks unwell, if they are deteriorating unexpectedly or failing to improve as expected”.

As further noted in the BMJ Best Practice article on Sepsis in adults (updated 12 June 2024): “The key to improving outcomes is early recognition and prompt treatment, as appropriate, of patients with suspected or confirmed infection who are deteriorating and at risk of organ dysfunction. By the time the diagnosis becomes obvious, with multiple abnormal physiological parameters, risk of mortality is very high”.

The key is, therefore, the index of suspicion.

One of the major problems is recognising those patients who are at risk of developing sepsis but in whom the clinical features are subtle and indolent. This can be a major challenge and it is this, along with ensuring rapid treatment, which has led to the evolution of various forms of guidance over the last decade or so.

What is the guidance?

The Sepsis-3 Taskforce in 2016 recommended the use of the rather complex and not especially pragmatic SOFA (Sequential Organ Failure Assessment) as a screening tool for sepsis. SOFA assesses organ dysfunction. It can, however, hardly be described as user-friendly.

Also in 2016, NICE in NG51 provided a list of helpful ‘traffic light’ criteria for stratification of risk from sepsis for various age ranges, based on specific clinical categories including behaviour, respiration, circulation and hydration, skin and temperature.

In 2017, the Royal College of Physicians launched NEWS2, the second iteration of the National Early Warning Score, which was endorsed by NHS England. This is a standardised scoring system to assess patient deterioration, relying on certain clinical parameters, including respiratory rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness/confusion and temperature. It has been widely adopted.

In 2024, in an attempt to continue to raise awareness of sepsis, NICE updated NG51 to include recommendations on recognition and early assessment, initial treatment, care escalation, identifying the infection source and early monitoring. In particular, the guidance emphasises the need for a high index of suspicion for sepsis, with revised definitions of sepsis and septic shock (as set out above) and use of early recognition and risk stratification tools, including the use of NEWS2.

Also in 2024, in response to the updated NG51, The Sepsis Trust updated its Red Flag Sepsis Screening Tool, which had been originally launched in 2015. This provides a very helpful algorithm approach to aid healthcare practitioners to think about screening for an infection and sepsis, to ascertain whether there are any red or amber flags, and then to consider whether they should be initiating (broadly) the Sepsis Six (for red flags) or further review (for amber flags). The Sepsis Six is: (1) inform senior clinician, (2) give oxygen if required (3) send bloods including cultures (4) give iv antibiotics, think source control (5) give iv fluids and (6) monitor, with consultant escalation if no improvement and reassess NEWS2 every ½ hour. This ‘Sepsis Screening Tool’ approach can be modified slightly for different practice areas and/or ages. There is no doubt it is a very helpful tool.

What is the clinical negligence angle?

Unsurprisingly, it is the suspicion and recognition issues that I see most in the infection and sepsis-related cases in my clinical negligence caseload. In my experience, from a medicolegal perspective, and in keeping with the concerns identified by the guidelines mentioned above, it is not so much sepsis per se that is the problem but the identification of those patients with an infection who are at risk of developing sepsis. From my own personal medicolegal experience, The Sepsis Trust’s concern is entirely on point. As mentioned above, a fundamental aspect of managing sepsis is having a suitable or appropriate index of suspicion in relation to the originating infection before it evolves into sepsis, be that in an at risk individual or one not at risk. Most infections are initially only local, confined to a particular organ or anatomical location, but if not treated they then can become systemic and ultimately cause organ failure and sepsis; and this process can occur surprisingly rapidly.

What causes the negligence?

It is this ‘pre-sepsis’ period which causes so many problems. Patients will often appear well, even with an early systemic infection. It is perhaps sometimes surprising how much physiological reserve some patients have and how well they can be (or appear to be) despite having a burgeoning systemic infection, and how they will continue to appear well until they fall off the proverbial cliff. I have had many clinical negligence cases of this over the years, in various guises, ranging from the comparatively common intra-abdominal infections, for example arising from an anastomotic leak or surgical bowel perforation, and chest infections, through the less common meningitis and spinal infections, to the much rarer infections such as infective endocarditis, macrophage activation syndrome or necrotising fasciitis.

One of the things that I have learned from these cases is that there are four primary problem areas which recur and, at least in my experience, almost always one, some or all of these factors have ultimately ended up playing a crucial part in the case. I shall frame these factors as assessment, recognition, diagnosis and trends, and will briefly discuss each in turn.

Assessment

The first aspect is the assessment of the patient and, in short, the failure to carry out a sufficiently detailed assessment. This is by virtue of taking a proper history and performing a proper examination and thereby eliciting abnormalities. I have had lots of cases in which either the history or the examination, or sometimes both, were unacceptably lacking. A detailed and thorough assessment is critical to identifying the subtle presentation of evolving infection and a lack of such an assessment may miss such a presentation. A proper assessment involves the old-fashioned but time-honoured arts and techniques of proper history-taking and proper examination. Unfortunately, nowadays these are all too frequently found wanting. I have seen inadequate assessments so often that it drives home how vitally important good history-taking and examination remains, even in modern medicine with all its technological sophistication. This often, but not always, arises in the context of junior doctors, also a recurring theme. Why this issue is so common is outside the scope of this article but what I can also say is that an inadequate history and examination is by no means limited to infection or sepsis cases, sadly, so it is clearly a wider problem.

Recognition

The second factor sounds obvious, but I have also seen plenty of cases in which certain relevant abnormal clinical findings or parameters are not identified or recognised as being relevant. Unlike with the assessment above, the clinical features or parameters may be correctly elicited but, unfortunately, their relevance is simply not appreciated by the healthcare practitioner, so they are not acted upon. This tends to arise with inexperienced clinicians who may have reasonable clinical acumen but who have a lack of appropriate knowledge and experience to be able to appreciate the relevance of an abnormal finding. It can also be a symptom of a lack of sufficiently senior and experienced clinicians being involved in a patient’s care.

Diagnosis

The third factor is a curious one: it concerns the clinician who has detected all the relevant clinical features, identified the parameters, who has an appropriate index of suspicion but who then, for whatever reason, inexplicably fails to make the diagnosis of infection or sepsis and instead makes some other diagnosis, resulting in inappropriate treatment. In some respects, this is the most frustrating factor, as more than enough will have been done to make the correct diagnosis, but nevertheless it simply does not happen. It sometimes feels as if the clinician does not want or cannot believe infection or sepsis to be the diagnosis. Perhaps there is an element of bias, be it over-confidence, confirmation, anchoring or visceral bias. Fortunately, this factor tends to be a less common occurrence than the others.

Trends

Finally, the fourth – and vitally important – factor is trends. This concerns cases in which a clinical assessment has been carried out, a set of bloods taken or some other investigation has been performed, appropriately, but which catches only a snapshot of time: the findings are interpreted either as being normal or as having only very minor (and inconsequential) abnormalities. However, if there is then no, or insufficient, follow-up, with no attempt to ascertain the series of subsequent findings or results, then a developing trend can easily be missed; and it is the trend that often is so very important. In my experience of infection cases, trends are often crucial to suspecting and detecting the subtly deteriorating patient. I have seen in so many cases a detailed serial analysis of the symptoms, signs, observations, investigation results, etc. show slow but clear deterioration, which was missed. Trends for vital signs and/or blood results in particular are important: they can often be seen most clearly when charted out, either in a cumulative results chart or as a graph, which can neatly demonstrate the trend visually. However, identifying the relevant results over a period of time can be a laborious and time-consuming process and I suspect it is this time factor, at least in part, which is why trends are often missed. It is worth noting that it is not just the previous single result that is pertinent but the series of results over a relevant period of time. Further, the findings or results then need to be contextualised with all the patient’s other parameters to be able to ascertain the significance of the trend. However, I cannot emphasise enough the importance of trends.

Conclusion

There are, of course, many other relevant factors, but the above are the four that I have seen repeatedly occur in my infection-related clinical negligence cases. What is perhaps most frustrating is that these are – or certainly should be – easily soluble issues. Taking a proper history, performing a proper examination, identifying relevant symptoms and signs, recognising trends, having a sufficient index of suspicion, and making and acting upon the correct diagnosis so that the appropriate treatment can be initiated: all of these arise from the most basic tenets of medicine. There is no doubt in my mind from my own experience that proper attention to the basics of medicine can make a huge difference in infection and sepsis cases, importantly preventing significant harm but also reducing the clinical negligence claims which arise out of such cases.