The Future of Sepsis Treatment

Just as alarming is the fact that one out of every three patients who die in a hospital had sepsis.¹ Physicians and researchers have learned more about sepsis from clinical trials and studying its complexity at the cellular level, but perhaps the most important concept to date is the need for early detection.
 
 “The biggest obstacles to surviving sepsis include early diagnosis and treatment—getting to a medical facility that can manage sepsis quickly,” said Christa A. Schorr, DNP, MSN, RN, FCCM, a clinical nurse scientist at Cooper University Hospital in Camden, New Jersey, USA. “Physicians have recognized that sepsis is an emergency where early diagnosis and appropriate treatment truly can make the difference in survival.”
 
Dr. Schorr moderated a conversation about the future of sepsis as part of the Society of Critical Care Medicine’s 50th Critical Care Congress. “Surviving Sepsis 2071” featured presentations by Dr. Schorr; Hector R. Wong, MD, FCCM; Michael J. Morowitz, MD; Judith Hellman, MD; and Shamim Nemati, PhD. Topics ranged from biomarkers and predictive analytics to microbiomes and immunomodulation.
 
One challenge with treating sepsis is the variety of reactions that come with it. As Dr. Schorr explained, some organs may require support from a ventilator, dialysis, or medication to maintain blood pressure. “Some patients recover in a few days, where others may be hospitalized for weeks to months,” she said. “Many survivors of sepsis experience challenges after hospital discharge including physical, cognitive, and mental health issues. In some cases, the organ failure is too overwhelming for the body and results in death.”

For guidelines and tools on sepsis management, visit the Surviving Sepsis Campaign.
 
To understand who has sepsis and, more importantly, how it may impact them, physicians can turn to biomarkers. Dr. Wong, a member of the Division of Critical Care Medicine at Cincinnati Children’s Hospital Medical Center, explained that, traditionally, people consider biomarkers in a diagnostic situation—essentially to understand who has or does not have sepsis. Biomarkers have the potential to do far more than that, he explained. They can be used for prognostic enrichment, such as evaluating whether patients who have sepsis are at low or high risk for a bad outcome. They also can be used toward predictive enrichment and allow clinicians to estimate who among the high-risk patients are likely to positively respond to a particular therapy.
 
Immunomodulation is another type of intervention that has been considered to help treat sepsis. Dr. Hellman, vice chair for research in the Department of Anesthesia and Perioperative Care at the University of California, San Francisco, explained that researchers have conducted clinical trials over the course of several decades to try to target acute inflammation to treat sepsis. These trials focused on agents that block or reduce proinflammatory responses, agents that block proinflammatory mediators or their receptors, and corticosteroids that have a broad effect on immune function. These trials were unsuccessful, Dr. Hellman explained, although retrospective analysis suggests that some of the antimediator therapies might protect certain patient subgroups.
 
In contrast, endogenous immunomodulation appears to be a potential option for treating patients with sepsis. This process, in which endogenous factors and pathways fine-tune innate immune responses and inflammation, appears to lead to beneficial responses, including wound repair and the restoration of immune homeostasis, Dr. Hellman said.
 
Dr. Hellman also shared her laboratory’s research into the role cannabis plays in affecting acute inflammation. This research is focused on the endocannabinoid system, a system still with significant unknowns, she said. “Despite the use of cannabis products to manage symptoms associated with inflammation, the immune effects of cannabis and the intrinsic role of the cannabinoid system in regulating immune functions are not well understood,” Dr. Hellman said.
 
Her laboratory is currently studying the endocannabinoid system in infection models of sepsis and trying to figure out how to study the system in humans. “Cannabis-derived cannabinoids are widely being used for medicinal and recreational purposes,” Dr. Hellman said. “We need to better understand their effects and their mechanisms of action in order to use them wisely. The endocannabinoid system may represent a novel target for immunomodulatory therapies.”
 
In her presentation, Dr. Schorr examined the challenges and failures faced in sepsis research over the past 30 years. She believes that the panelists’ presentations represent promise and hope for the future of sepsis treatment. “Recovery from sepsis, both short term and long term, is a fertile area for research and quality improvement,” Dr. Schorr said. “As demonstrated in this session, researchers are studying methods to stratify patients using biomarkers and other tools including artificial intelligence, which we may add to the sepsis toolbox. Over the next five years, sepsis treatment will become more streamlined with consideration and emphasis for the individual, type of infection, chronic conditions, and patient-related goals of care.”
 
 
References
 

1. Centers for Disease Control and Prevention. Sepsis. Clinical Information. Page last reviewed. December 7, 2020. Accessed January 28, 2021. https://www.cdc.gov/sepsis/clinicaltools/index.html