Battling Sepsis: New findings may help doctors predict who is more likely to survive infection
New research published today found a predictive molecular signature that may allow doctors to determine the likelihood of survival for patients with sepsis. The research was led by investigators Raymond Langley, Ph. D., of the Lovelace Respiratory Research Institute (LRRI) in New Mexico, and Dr. Stephen Kingsmore, MB, ChB, BAO, DSc, FRCPath, of the Center for Pediatric Genomic Medicine at Children’s Mercy Hospital in Kansas City.
The findings are published in the paper "An integrated clinico-metabolomic model improves prediction of death in sepsis" today in the Science Translational Medicine journal, which is published by the American Academy for the Advancement of Science.
The paper can be found here: http://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.3005893
According to the National Institutes of Health, severe sepsis strikes about 750,000 Americans each year.
Sepsis refers to infection-causing symptoms, such as elevated temperature or heart rate. Today, physicians struggle with the decision whether to admit patients with sepsis to hospital for intensive treatment, or to provide treatment at home with rest and oral antibiotics. Delayed or wrong decisions can result in the patient’s death. It’s estimated that between 28 and 50 percent of sepsis patients do not survive, making sepsis one of the top ten causes of death in the U.S.
The study reports a molecular signature, which is a set of biochemical changes in the blood, present in patients’ blood at time of arrival at hospital emergency departments that could predict those who would survive the next 28 days. Non-survivors had a different molecular signature.
Sepsis is a huge stress on our bodies. In order to survive, patients must respond appropriately. One of the biggest responses is the body’s need for more energy. The patients who have been shown to survive, promptly “switch on” energy production by metabolizing fatty acids. The patients who die fail to make this change. That ability to switch on energy production is the bio-chemical signature the researchers observed.
The signature was independently validated with the Brigham and Women's Hospital Registry of Clinical Illness (RoCI) cohort in Boston, with Dr. Augustine Choi, MD, as the principal investigator. LRRI has a long-term collaborative research relationship with Brigham and Women’s Hospital.
The research for this study originated at National Center for Genome Resources based in New Mexico.
“Understanding this signature will be critical for medical caregivers as they confront septic infections,” Langley said. “In addition, this study will help in the effort to develop therapies to treat sepsis patients and hopefully give them a better chance at survival.”
The study looked at the blood chemistry of 300 patients as they arrived in emergency rooms with sepsis infections. Researchers compared the proteome and metabolome in survivors and non-survivors from their initial tests at arrival to those done 28 days later. The researchers were able to differentiate survivors and non-survivors when first seen. The patients who would survive promptly “switched on” fat-burning energy production. The patients who would die failed to make this change.
“The bottom line result of this study is that caregivers will now have a simple test to predict the sepsis patients who need aggressive treatment the most – and this will save lives,” Kingsmore said.
In addition to the principal authors, many researchers across the country contributed to this study including researchers at The National Center for Genome Resources, Duke University, the Henry Ford Hospital in Detroit, Durham VA Medical Center and University of North Carolina at Chapel Hill.
This study was funded by grants from the National Institutes of Health as well as funds provided by Pfizer and support from the National Center for Genome Resources, Children’s Mercy Hospital and LRRI.
About Lovelace Respiratory Research Institute
The Lovelace Respiratory Research Institute (LRRI) is a private, biomedical research organization dedicated to improving public health through research on the prevention, treatment and cure of respiratory disease. LRRI is committed to curing respiratory diseases through research aimed at understanding their causes and biological mechanisms; assessing and eliminating exposures to respiratory health hazards; and developing improved therapeutics, vaccines, and diagnostics. LRRI is based in Albuquerque, New Mexico, employs 1,200 people, and is a $125 million company. Learn more at www.lrri.org.