Revolutionizing Sepsis Understanding:
- The Sepsis Problem
- Costs of Untimely, Uncertain Diagnosis
- Understanding Host Response
- Sepsis Diagnosis: Today and in the Future
- Benefits of Early, Accurate Diagnoses
Sepsis is a medical emergency. Every few seconds, someone in the world dies of sepsis. It is a complication caused by a patient’s overwhelming and life-threatening immune response to infection and can lead to tissue damage, organ failure and death. It remains the primary cause of death from infection despite advances in modern medicine like vaccines, antibiotics and specialized critical care facilities. When recognized and treated early, lives are saved and costs are reduced. Between 30 and 50% of all sepsis patients die. In the developing world, sepsis accounts for 60 to 80% of all deaths. It kills more than 6 million infants and young children, and 100,000 new mothers every year.
Incidence is increasing dramatically
The number of sepsis cases continues to increase. Sepsis hospitalizations have more than doubled over the last 10 years, and in many countries, more people are hospitalized each year for sepsis than for heart attacks. 20-40% of sepsis patients requiring intensive care treatment, develop sepsis outside the hospital. In the United States, the incidence of post-surgical sepsis tripled between 1997 and 2006.
Sepsis is often diagnosed too late
Standardized, rapid and objective diagnostics are needed for better clinical agreement in these patients. Today, sepsis diagnosis is often delayed because:
- clinical symptoms (raised temperature, increased pulse or breathing rate, white blood cell count, etc.) are not specific, and
- confirmation of a clinical diagnosis of sepsis relies on pathogen detection, which can take up to several days.
In children, the signs and symptoms may be very subtle, and deterioration rapid. Early infection in suspected sepsis cases is under-recognized and patients without infection are over-treated.
Despite new definitions, the pathophysiology of sepsis remains poorly understood. Although improving, documentation of sepsis as a cause of death is poor, and there are significant limitations of current sepsis diagnostic tools, as well as inconsistent application of standardized clinical guidelines to treat sepsis.
Cost of sepsis is high – and rising
Sepsis is the most expensive in-patient cost in U.S. hospitals, totaling over $20 billion each year. The length of stay (LoS) for non-sepsis patients is 3.4 days compared with more than 7 days for sepsis patients. Between 1997 and 2008, total costs for treating patients hospitalized for sepsis increased by an average of 11.9% each year, adjusted for inflation. In Germany, the cost of a typical episode of sepsis has more than doubled over the last decade, from approximately €25,000 to 55,000. The costs related to long-term damage resulting from sepsis are unknown.
Over-treatment of patients without sepsis
In the majority of suspected sepsis patients, clinicians need to begin treatment without clinical test results. This leads to over-treatment of patients without infection, contributing to antibiotic resistance and hospital acquired infections. In the US, up to 50% of sepsis cases are hospital acquired.
The immune system responds specifically to an invading pathogen. Determining infection status in suspected sepsis patients has traditionally focused on finding and characterizing the invading pathogen. However, detecting the specific immune response can determine infection earlier and more accurately, and characterize the type of pathogen to which the host response is developing – viruses, bacteria, yeast and fungi. Small differences in the pathogen, host, or circumstances of the infection result in differences in the immune response.
Finding and characterizing the invading pathogen can take many hours, sometimes days. In many cases, the causative pathogen is never identified. To be found, the causative pathogen must be in the sample in the first place, and this occurs in only 10 to 30% of suspected sepsis cases. In contrast, the specific host response can be detected within minutes to a couple of hours, and provide actionable clinical information in 100% of suspected sepsis cases.
Managing sepsis by only focusing on trying to find the pathogen is therefore fraught with challenges. For example, a negative pathogen result does not mean that the patient is not septic; it simply means that the pathogen was not likely in the patient’s sample. This is termed a “false negative”. On the other hand, a positive pathogen result could result from contamination of the sample (the likelihood of which increases, the more sensitive the pathogen assay). This is termed a “false positive”. Moreover, a positive pathogen result does not prove that the pathogen grown (or detected) is the one causing the septic response.
It is because of these challenges that combining a result from a host response assay WITH pathogen information is essential if sepsis management is going to improve. Not only does the host response allow differentiation of infection positive and infection-negative systemic inflammation, but the host response allows the clinician to better interpret positive and negative pathogen results.
The consequences of making incorrect diagnostic and treatment decisions for patients suspected of sepsis are significant. In addition to direct costs to hospital systems and healthcare budgets, sepsis is a large contributor to indirect healthcare costs including morbidity (i.e. reduced quality of life, shortened life span, chronic pain and inability to work) and antibiotic resistance (which is estimated to cost the US over $75 billion each year).
Click here for a PDF version of this information about sepsis and the host response approach: Sepsis Infographic
Source information on epidemiology of sepsis: World Sepsis Day