Over the past few years I have regularly come across newspaper articles about people who have been sent home from hospital emergency departments, only to die soon after from unrecognised sepsis. Most recently, I have been reading about the Coroner’s Inquest into the death of five-year-old Ava Macfarlane. She tragically died of toxic shock caused by sepsis on December 15 2017, two days after being discharged home from Queen’s Medical Centre in Nottingham. Every such incident provides us a reminder both of the difficulties in diagnosing sepsis and of the catastrophic effects of delayed diagnosis. These tragedies have continued to occur despite an increasing awareness of sepsis, both among doctors and members of the general public.
Sepsis is an important cause of death, accounting for around 52,000 deaths a year in the UK, and around six million deaths worldwide, most of which can be prevented by early diagnosis and treatment. Most deaths from sepsis continue to occur in developing countries, often due to a shortage of resources.
So, what exactly is sepsis? The medical definition of sepsis has changed over the last two decades. The consensus definition of Sepsis-1 (1991) has since evolved into Sepsis-3 (2016). Sepsis is defined by an abnormal response of the body to overwhelming bacterial infections of the bloodstream. It can be the end-result of a variety of infections, ranging from infected skin wounds to infections of the lungs, urine, bowels, nervous system, bones and joints.
The key feature of sepsis is a sequential and potentially life-threatening failure of the body’s organs that follows overwhelming infection. The processes of inflammation and blood clotting (coagulation) are activated by a variety of chemical mediators. These products of bacterial multiplication act on the smallest of the blood vessels, which form the microcirculation of the various organs. A reduced supply of oxygen, the accumulation of the toxic by-products of metabolism, and impaired function of the mitochondria within the cells trigger a cascade of changes that cause progressive damage to these organs. The kidneys, lungs, liver, brain and heart are all affected by sepsis. Multiple organ failure eventually leads to death when untreated. Even with prompt and appropriate treatment, the likelihood of death from severe sepsis remains high, with as much as 25 per cent to 30 per cent of all patients dying as a result of sepsis.
The term sepsis includes a range of illnesses of varying severity. Some septic patients may appear quite well to start with, especially if previously in good health. To confuse matters, many people who appear to be septic may actually be suffering from another non-septic illness that mimics sepsis. The presence of a fever does not necessarily mean that an infection is the cause. All of these observations add to difficulties with the diagnosis of sepsis. Less serious viral flu-like illnesses can resemble early sepsis, leading to the diagnosis of “flu” when the actual diagnosis is far more serious. All of this means that doctors’ working diagnoses of sepsis or the absence of sepsis are frequently incorrect.
The diagnosis of sepsis should be considered in the presence of appropriate physiological responses of the body to systemic infection, as measured by changes in the heart rate, respiratory rate, blood pressure, temperature, and white blood cell count. Measurements of these so-called vital signs form the basis of many clinical scoring systems. In the UK, the National Early Warning Score 2 (most recently updated in 2017) is used to help identify patients with suspected sepsis. A NEWS of 3 or more indicates immediate screening for sepsis. Serial measurements of such scores may also help identify those people who are continuing to deteriorate with ongoing sepsis. None of the changes in such scores are, however, specific to sepsis.
Of all the abnormal findings on examination that suggest sepsis, changes in the skin, such as skin rashes that do not blanch on the application of pressure (as shown by the so-called glass tumbler test) or a generalised redness of the skin are often the easiest to identify and act upon.
There is no blood test that can be relied upon to confirm or rule out the diagnosis of sepsis. Serum (blood) levels of lactate rise in response to the reduced perfusion of organs with blood, but these elevations are not specific to sepsis. Early diagnosis depends on the detection in the blood of so-called biomarkers (biochemical markers) of sepsis and on tests to amplify nucleic acids and thereby detect genes associated with bacterial infection using the polymerase chain reaction. No single available biomarker can, however, be relied upon to consistently diagnose sepsis. Sepsis is usually confirmed by the demonstration of multiplying bacteria on blood cultures, but these results may take two to three days to be available and a single negative blood culture does not necessarily rule out sepsis.
Better public awareness of the ways in which sepsis presents is a necessary first step. The UK Sepsis Trust has developed useful checklists of signs of sepsis in adults and in children. The acronym SEPSIS, for suspected sepsis in adults, stands for Slurred speech or confusion, Extreme shivering or muscle pain, Passing no urine (in a day), Severe breathlessness, It feels like you’re going to die, and Skin mottled or discoloured.
Better treatment of sepsis requires early diagnosis, along with a set of interventions (referred to as a sepsis bundle) within the hospital, including early antibiotic treatment and fluid replacement, even before the diagnosis has been confirmed. In the emergency department, these actions should be initiated by the first health care professional to see the patient, who often happens to be a nurse. Guidelines should be readily available and the treatment of patients with sepsis should be regularly audited so that any deviations from recommended protocols can be identified and remedied. Continued education and training of doctors and nurses is essential if the results of sepsis treatment are to improve.
Ashis Banerjee (have treated countless patients with sepsis).