A bland title—“Sepsis: a roadmap for future research”—gives little indication of the passion with which a Commission of doctors is calling for action against a common but exceptionally lethal condition. This condition, properly known as sepsis but sometimes misleadingly called “blood poisoning,” is thought to contribute to between a third and a half of all hospital deaths. Despite its high death toll, sepsis is poorly understood. And, to the frustration of doctors of The Lancet Infectious Diseases Commission, sepsis research seems to have stalled.
The Commission seeks to kick-start sepsis research. In an article that appears in the May issue of The Lancet Infectious Diseases, the Commission offers a slew of recommendations, including the following:
- Prioritize research into biomarkers for sepsis, which could allow quicker diagnosis.
- Better educate medical staff and improve public awareness, ensuring earlier recognition.
- Adopt a more nuanced approach to clinical trial design—avoid the limitations of “all comer” patient selection.
- Recognize that sepsis affects different patients differently.
This last point brings up the possibility of using the power of modern genetics to develop targeted treatments. Such treatments would be a welcome realization of the personalized medicine approach.
“Sepsis is a complex disorder that can occur in many clinical contexts, be caused by a wide range of different microorganisms, and is almost certainly driven by the interplay of a diverse range of pathological processes,” the Commission’s report indicated. “Each of these processes probably operates in different ways, at differing rates, and to differing extents, depending on the patient, and is driven—at least partly—by varying genetic susceptibility. This complexity is fertile ground for the development and assessment of personalized medicine, an approach that has so far had little or no effect on the usual clinical approach to patients with sepsis.”
Beyond these specifics, the Commission made a general case against complacency or, worse, any tendency toward defeatism: “After dozens of failed trials in recent decades, [it is important to ensure] that universities and drug companies do not abandon research into new drug treatments,” insisted a press release issued by The Lancet.
Although mortality rates from sepsis in high-income countries appear to be falling in recent decades, the Commission authors pointed out that the paucity of accurate estimates of the incidence of sepsis means that the true extent of the condition is poorly understood, and apparently reduced mortality rates may be an artefact of improvements in hospital reporting of milder cases.
“The number of people dying from sepsis every year—perhaps as many as six million worldwide—is shocking, yet research into new treatments for the condition seems to have stalled,” said Professor Jonathan Cohen, lead author of the Commission and Emeritus Professor of Infectious Diseases at the Brighton & Sussex Medical School. “Researchers, clinicians, and policymakers need to radically rethink the way we are researching and diagnosing this devastating condition.”
In sepsis, an infection triggers an extreme immune response, resulting in widespread inflammation, blood clotting, and swelling. Among the early (but not universal) symptoms of sepsis are high temperature and fast breathing; if left untreated, it frequently leads to organ failure and death. Although no specific cure for the condition exists, it can often be treated effectively with intensive medical care including antibiotics and intravenous fluid, if identified early enough.
In low-income and middle-income countries, where most sepsis cases occur outside hospital, there are virtually no data on the condition's incidence, and the number of people killed by sepsis is likely to far exceed the already high rates in more wealthy countries. Moreover, rising rates of antibiotic resistance globally mean that even if mortality rates from sepsis are improving in some high-income countries, there is no room for complacency.
In addition to the high fatality rate from sepsis, survivors are at an increased risk of long-term chronic illness and mental or physical impairment, although research into the long-term consequences of surviving sepsis is relatively scarce, so doctors have little evidence available on which to base long-term care plans for these patients.