Similarly to cancer, sepsis consists of many conditions with varying clinical characteristics that could benefit from different treatments. A new study involving more than 100,000 patients revealed these previously unknown subtypes and could explain why several recent clinical trials of treatments for the condition have been unsuccessful. Findings were published in JAMA.
“For over a decade, there have been no major breakthroughs in the treatment of sepsis; the largest improvements we've seen involve the enforcing of 'one-size fits all' protocols for prompt treatment,” said Clead author Christopher Seymour. “But these protocols ignore that sepsis patients are not all the same. For a condition that kills more than 6 million people annually, that's unacceptable. Hopefully, by seeing sepsis as several distinct conditions with varying clinical characteristics, we can discover and test therapies precisely tailored to the type of sepsis each patient has.”
The research, funded by the National Institutes of Health (NIH), used computer algorithms to analyse clinical variables found in the electronic health records of more than 20,000 patients diagnosed with sepsis within six hours of hospital arrival from 2010 to 2012.
The algorithm categorised the patients into four distinct sepsis types:
- Alpha: most common type (33%), patients with the fewest abnormal laboratory test results, least organ dysfunction and lowest in-hospital death rate at 2%
- Beta: older patients, comprising 27%, with the most chronic illnesses and kidney dysfunction
- Gamma: similar frequency as beta, but with elevated measures of inflammation and primarily pulmonary dysfunction
- Delta: least common (13%), but most deadly type, often with liver dysfunction and shock, and the highest in-hospital death rate at 32%.
The team then studied the electronic health records of another 43,000 sepsis patients from 2013 to 2014, which confirmed the findings. Further evidence was provided when the team studied rich clinical data and immune response biomarkers from nearly 500 pneumonia patients enrolled at 28 hospitals in the US.
Following this work, researchers applied their findings to several recently completed international clinical trials that tested different promising therapies for sepsis, all of which had ended with disappointing results. When trial participants were classified by the four sepsis types, it highlighted that some trials might not have been failures but merely of varying effectiveness depending on the subtype.