In recent years, many advances in the sepsis literature have occurred, including new definitions, changes to the Surviving Sepsis Campaign (SSC) bundles, new pharmacologic agents, and adjunct treatments. There are also several areas of ongoing research that have the potential to change sepsis care in the future.
During a session on Monday, Sepsis Advances: What Is Coming Down the Pike?, panelists provided overviews of some important recent advances and ones they expect to be on the horizon in the near future.
Meghan Pennini, PhD, a scientist with the Biomedical Advanced Research and Development Authority (BARDA), US Department of Health and Human Services, opened the session with a discussion on work from the BARDA Solving Sepsis program looking at technologies to aid in the presymptomatic diagnosis of sepsis.
“We started this program because all roads lead to sepsis—any infection can lead to sepsis, but there is a critical gap in our ability to identify and triage infected patients who are at higher risk for poor outcomes,” Dr. Pennini said. “So we are working with various partners to develop technologies—in vitro diagnostics or algorithm-based diagnostics—that can specifically predict whether someone will progress into that severe infection state and get sepsis.”
Among the solutions they are exploring, she said, is the use of host-based tools enhanced by machine-learning algorithms to provide risk-based assessments that can aid clinical decisions.
“The benefit to these types of diagnostics is that they are pathogen-agnostic, so you don’t necessarily need to know the underlying cause or underlying pathogen to guide clinical management and target precision interventions,” Dr. Pennini said. “These are not traditional diagnostics, so there’s not a binary input—it’s not yes or no—so people will need to become familiar with how to interpret the output, and we still need convincing data to really show that these can have clinical impact.”
Andre Holder, MD, MSc, Assistant Professor of Medicine in the Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine at Emory University, followed with further discussion on studies looking at the potential of “Big Data” technologies to predict sepsis.
“We know that early recognition of sepsis leads to early treatment, which leads to saved lives,” Dr. Holder said. “The use of machine learning and artificial intelligence (AI) is really the new frontier and is at the heart of research today with respect to sepsis recognition.”
While most of the studies to date in this area have been retrospective, Dr. Holder cited a recent small pilot study using a prediction algorithm in patients with sepsis that showed an improvement in mortality.
“Not only was there an improvement in mortality, but there was also a reduction in length of stay—about 3 days—and nearly 3-hour earlier antibiotic administration just based on use of this particular algorithm,” he said. “There are challenges associated with the adaptation of these tools into current clinical practice, but it’s clear that we should redefine sepsis recognition to include earlier detection and better characterization, specifically endotyping, which have the potential to improve outcomes.”
Looking at sepsis treatment, Jonathan Sevransky, MD, MHS, FCCP, Professor of Medicine at Emory University School of Medicine, discussed current research looking at the use of vitamin C in sepsis treatment.
A principal investigator on the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) trial, Dr. Sevransky said that randomized controlled trials in patients with sepsis and septic shock have not confirmed the treatment effect of vitamin C that was seen in nonrandomized trials.
“The differences between outcomes in trials may be due to the differences in the dose of vitamin C, the timing of infusion of vitamin C, differences in whether the control group or comparator group received steroids,” he said. “Many of the studies had different primary outcome measures as well. There are few additional trials being done now that will likely inform future discussion.”
Pauline Park, MD, Professor of Surgery in the Division of Acute Care Surgery and Co-Director of the Surgical Intensive Care Unit at the University of Michigan Hospitals, concluded the session with a look at the ongoing question of early fluids and early vasopressors in patients with sepsis. Current literature, she said, still leaves many questions unanswered.
“Overall, there’s clearly a sense that we’re moving to drier resuscitation earlier, but whether that’s right or wrong, we still don’t know what the overall dose response should be,” she said. “There are randomized trials pending that will hopefully answer questions on the best strategies to improve outcomes in septic shock.”
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