By Tonya Jagneaux, MD, Chadd K. Kraus, DO, DRPH, And Hollis O’Neal, MD

Today, most emergency departments (EDs) face overcrowding, high patient volumes and a strain on our increasingly limited staff and resources. As a result, the average patient experiences ED wait times of about two-and-a-half hours, with some reaching nearly four hours.

The possibility of sepsis makes these delays even trickier. More than one-third of all in-hospital deaths are attributed to sepsis, making it the leading cause of death in U.S. hospitals. But addressing sepsis isn’t so straightforward. A confluence of variables results in patients either being underdiagnosed – which means they can quickly deteriorate, face organ damage, and have to be readmitted – or misdiagnosed, which leads to overtreating patients with broad-spectrum antibiotics and overlooking the patient’s true condition.

About 80 percent of sepsis patients present in the ED, but they can have highly variable, heterogeneous symptoms, including generalized weakness, low blood pressure, and fever – all of which could point to a number of different emergent conditions. In fact, one in eight sepsis cases present to the ED without meeting the threshold of two systemic inflammatory response syndrome (SIRS) criteria often used to screen for sepsis. This scenario of occult sepsis, where sepsis occurs without clear initial symptoms, is particularly concerning since those patients are typically released back into the waiting room, where their condition could deteriorate quickly.

Current diagnostics fall short.

The traditional diagnostic toolkit for sepsis relies on the careful interpretation of biomarkers, culture data, and molecular testing, along with a clinical assessment. Each of these tools has limitations and drawbacks. Procalcitonin (PCT) levels are sometimes used as a biomarker for sepsis, but they have only demonstrated moderate accuracy in diagnosing sepsis and often deliver false positives when sepsis does not involve bacteria. Culture data is not helpful in the ED since it can take days to return results. Even rapid pathogen identification takes hours and is of limited use in the ED.

In the ED, where every minute counts, ED clinicians are inherently comfortable with risk stratification but often report that they follow their clinical gestalt to identify sepsis in lieu of a definitive tool to diagnose. When symptoms are not definitive – especially in those who appear clinically stable – high-risk patients risk being placed back in the waiting room rather than getting the immediate treatment they need. Ultimately, this is not the ideal approach since the risk of death from sepsis increases by up to 8 percent for each hour that it goes untreated.

A new approach: host response technology

These challenges highlight the need for new technologies that allow for the early, accurate, and reliable recognition of immune dysregulation, which is the hallmark of sepsis. Host response technologies offer the promise of recognizing and treating sepsis based on a patient’s immune response rather than variable, often subtle symptoms.

Focusing on the analysis and interpretation of the body’s immune response to pathogens or other stimuli, host response technology aims to detect signs of immune activation that indicate the presence of sepsis. It also can provide visibility into the level of immune activation and the probability of sepsis even before other symptoms become evident. By using a simple blood test in the ED with results returned in as little as 8 minutes, host response technology will enable quick identification of patients who do not look sick but are actually at high risk for sepsis.

A recent peer-reviewed study published in Academic Emergency Medicine demonstrated strong diagnostic performance using a host response test for sepsis detection. The study analyzed 1,002 patients, with the host response technology correctly identifying patients without sepsis 98 percent of the time. This diagnostic performance is similar to other screening tests, such as high-sensitivity troponin for acute coronary syndrome and d-dimer for venous thromboembolism.

Host response technology that enables clinicians to see the biology of sepsis has been successfully integrated into ED triage as part of a nurse-driven protocol at Our Lady of the Lake Regional Medical Center in Baton Rouge, Louisiana. In use for the past year, this technology has resulted in substantial improvements in the speed of identification and treatment of patients with sepsis. In one example, a patient was clinically stable and would have been deemed low-risk by traditional early sepsis markers, including vital signs. However, the patient was tested using the novel host response technology and was quickly identified as high-risk sepsis. The patient recalls being “plucked from the waiting room” and diagnosed with a ruptured appendix as the source of sepsis. Using host response technology, Our Lady of the Lake has reduced ED length of stay by 1.4 days and spared 2,000 patients from getting blood cultures compared to what the hospital ran in the same time span a year prior without IntelliSep, with an average cost savings of $1,429 per patient tested with the technology.

Successful integration of host response technology at Our Lady of the Lake offers a strong model for how EDs can transform their approach to sepsis, more quickly and more accurately identifying patients with sepsis. By taking this new approach, EDs can better ensure all patients, particularly those at risk of occult sepsis, are given the care they require without delay.

Sepsis has always been a priority for hospitals given its prevalence and costliness and, more importantly, the high morbidity and mortality for patients. Given increased government and payor pressures over the past year, sepsis remains a top priority for hospital and health system leaders. Those increased pressures include the Centers for Medicare & Medicaid Services (CMS) addition of SEP-1 to the Hospital Value-Based Purchasing Program (a pay-for-performance measure), with measurement beginning in 2024 and payment beginning in fiscal year 2026. SEP-1 is a quality measure that consists of diagnostic and therapeutic interventions that clinicians are expected to perform within the first hours of identifying patients with sepsis. Additionally, the Centers for Disease Control and Prevention (CDC) released the Hospital Sepsis Program Core Elements last August with the hopes of strengthening survival and recovery rates for septic patients. As a result, there is an increased incentive to optimize existing sepsis processes and augment existing detection tool sets with the right technologies, like a host response test, to diagnose sepsis faster and with greater accuracy.

Tonya Jagneaux is a pulmonary and critical care physician. Chadd K. Kraus is an emergency medicine physician. Hollis O’Neal is a pulmonary and critical care physician.