Diagnosing Sepsis in The Emergency Department Setting
Sepsis is a potentially life-threatening dysregulated (exaggerated and abnormal) response to infection, causing body organ damage. Sepsis can damage organs such as the heart, brain, kidneys, lungs, and liver. Consequently, sepsis is a potentially life-threatening complication of an infection. Sepsis is a global public health challenge and a leading cause of preventable death, with about 20% of all deaths worldwide associated with sepsis. Meanwhile, most hospital deaths in Ireland, like many other developed countries, are associated with an infection or sepsis.
Sepsis occurs when, for unclear reasons, the body’s response to an infection injures its tissues, causing significant damage to vital organs such as the heart, brain, kidneys, lungs, and liver. In sepsis, substances (mediators) into the bloodstream to fight an infection trigger inflammation in the whole body. This inflammation can trigger a cascade of changes that can damage many organ systems in the body, causing them to fail. If sepsis progresses to septic shock, blood pressure dramatically drops, which may lead to death.
Prompt identification and treatment are vital to improve a patient’s chances of survival and reduce their likelihood of death and longterm or permanent disability. It is in that context that the emergency department (ED) has a critical role in preventing death and long-term disability in patients presenting to a hospital with sepsis because the ED is the entry point of many patients with sepsis admitted to the hospital. However, unlike other common time-sensitive medical emergencies treated in an ED that require relatively expensive drugs and infrastructure, such as acute myocardial infarction (AMI [heart attacks]) and acute strokes, the treatment of sepsis, if diagnosed early, before shock sets in, is cheaper because it usually requires relatively inexpensive drugs and equipment. Early sepsis treatment involves quickly administering an appropriate antibiotic(s), ensuring oxygenated blood flow supports intravenous fluids and, if feasible, controlling the source of the sepsis (surgically or non-surgically.
If early sepsis treatment is simple and cheap, why is sepsis still a deadly global public health challenge? From an ED perspective, the main reasons that sepsis still kills so many people are the non-specific (and subtle) way sepsis can present in the ED and the lack of a reliable gold standard test for promptly diagnosing sepsis. Sepsis can be especially hard to spot in babies, young children, pregnancy, people with a compromised immune system, dementia, a learning disability or difficulty communicating (e.g. due to a speech or language impairment). Even when sepsis progresses to septic shock, more than 30% of patients still present with vague and non-specific symptoms such as fatigue and weakness. The Sepsis Alliance, a leading United States (US) sepsis organisation, has a helpful acronym called TIME for patients, patient carers, the general public and healthcare professionals when it comes to identifying the symptoms of sepsis; the T stands for Temperature (higher or lower than normal); the I stands for Infection (may have symptoms of an infection); M stands for Mental decline (confused, sleepy, difficult to rouse) and E stands for Extremely ill (severe pain, discomfort, shortness of breath).
In the ED setting, the lack of a reliable test for diagnosing sepsis leads to variability in sepsis treatment, patient outcomes and healthcare costs. Other timesensitive medical emergencies treated in EDs, such as AMI and acute strokes, have objective (gold standard) and reliable tests to diagnose them immediately. For AMI, all that is frequently required is the patient’s symptoms and a relatively simple test, an electrocardiogram (ECG), for objective diagnosis and initiation of treatment. In the case of acute stroke, all that is frequently required is the patient’s symptoms, physical signs, and an appropriate neuroimaging study (e.g., computed tomography [CT] or magnetic resonance imaging [MRI] scan of the brain) for objective diagnosis and initiation of treatment. The ECG, in the case of AMI, and the appropriate neuroimaging study, in the case of acute stroke, provide visual evidence of the diagnosis that avoids subjective interpretation of the patient’s symptoms. Similar objective and reliable tests to diagnose AMI and strokes are not available for ED patients with sepsis; there is no objective and reliable single test result to tell an ED nurse or doctor a patient has sepsis. Instead, we currently base the diagnosis of sepsis on searching for evidence of damage to body tissues and organs (heart, brain, kidneys, lungs, and liver) in a patient with an infection. In a patient with a suspected or presumed infection, ED nurses and doctors can find evidence of damage to body tissues and organs at the bedside (such as an acutely altered mental state and high respiratory rate) and from the results of blood tests (such as abnormal white cell count, renal and liver function tests).
It is intuitively logical that the absence of a gold standard diagnostic test for sepsis is a significant contributory factor for delayed diagnosis, misdiagnosis and death currently associated with sepsis. However, since the first National Clinical Effectiveness Committee National Clinical Guideline for Sepsis in Ireland was published in 2014 after the Health Service Executive (HSE) established the National Clinical Programme (NCP) for Sepsis, the early recognition and evidencebased management of sepsis has demonstrably improved. For example, the 2021 National Sepsis Report published in March 2023 revealed a 22.3%% reduction in age-adjusted mortality from sepsis/ septic shock since 2011 in Ireland. This reduction in age-adjusted mortality from sepsis/septic shock since 2011 in Ireland is attributable to the development and implementation of the Sepsis Management for Adults (including maternity) National Clinical Guideline and the National Implementation Plan for implementing the International Guidelines for the Management of Septic Shock & Sepsis-Associated Organ Dysfunction in Children which provide a standardised approach to the recognition and management of sepsis. The increased awareness and action of healthcare professionals were the key drivers behind these improvements in the care of patients with sepsis and the associated reduction in age-adjusted mortality.
Regarding the current challenges in diagnosing sepsis in the ED setting posed by the absence of a gold standard diagnostic test for sepsis, omics provide hope for overcoming this problem. Omics is a new term that describes the exciting and innovative field of large-scale, data-rich biology. Omics research aims to collectively characterise and quantify the pools of biological molecules that translate into the structure, function, and dynamics of an organism or organisms. Current advances in omics research provide hope that, in future, we may have a simple finger-stick blood test based on sepsis blood biomarkers (short for biological markers), like current finger-stick glucose monitoring for people with diabetes. The availability of such a simple finger-stick blood test may make ED sepsis screening and diagnosis as accessible and accurate as current diabetes screening and diagnosis. Machine learning and artificial intelligence (AI) provide another source of hope in overcoming the diagnostic challenge of sepsis. Proof-of-concept research shows AI algorithms have the potential to predict sepsis hours before its onset. While several AI-powered sepsis diagnosis algorithms are under development, this technology may still have some time away from routine clinical use. However, the United States Food and Drug Administration (FDA) approved the first AI-powered sepsis diagnostic tool earlier this year. The tool uses 22 different parameters like temperature, heart rate and laboratory test results to help clinicians assess a patient’s sepsis risk; the tool then generates an overall risk score and four categories that correlate to a patient’s risk of deterioration. Despite FDA approval of the AI-powered sepsis diagnostic tool, scientifically valid clinical validation is pending. Combining machine learning, AI, and omics research can potentially improve the timeliness and accuracy of ED sepsis diagnosis in future. Until then, we must rely on ED healthcare professionals’ knowledge of sepsis and their actions in the fight against it. ED healthcare nurses and doctors should promptly approach each ED patient with an infection with the mindset that they have sepsis until proven otherwise, using the national sepsis guideline’s sepsis screening form to metaphorically sniff out those with sepsis among the over one million patients who attend EDs in Ireland annually.
Ultimately, to meaningfully tackle sepsis as a global public health challenge, the truism that prevention is better than cure is highly relevant. The HSE’s National Sepsis Outcome Report 2021 states that prevention is the most effective way to reduce sepsis mortality. These preventative measures include sanitation, personal hygiene, healthy eating, moderate exercise, breastfeeding, avoiding unnecessary antibiotics, and vaccination for vaccine-preventable infections. The report also highlights that during the COVID-19 pandemic, we have learned of the benefit of good infection prevention and control measures, including social distancing, mask-wearing and handwashing. We should not forget the lessons learned from the COVID-19 pandemic if we are to reduce the societal burden of sepsis significantly.
References Available on request