“From this perspective the traditional understanding of the inflammatory response in sepsis and critical illness as an initial overwhelming, disproportional and exaggerated reaction followed by ‘immune paralysis’ may need to be reconsidered. The inflammatory response may be regarded as the organism’s utmost and adequate attempt to definitely cope with the danger.”

John C. Marshall’s article on Lipopolysaccharide is a great read that informed my viewpoint. Marshall wrote about sepsis:

“Randomized trials have an important impact in establishing optimal approaches to contemporary management of diseases. However, the questions evaluated through such trials are shaped and constrained by conceptual models of the disease being
studied, and it is appropriate, from time to time, to reevaluate the model in light of an accumulating body of scientific data. Such a reevaluation in sepsis promises to be both timely and rewarding.”

True in 2005. True when Marshall wrote this in 2014:

“The current challenge for sepsis research lies in a failure of concept and reluctance to abandon a demonstrably ineffectual research model.”

Even truer now.

Alverdy and Krezalek recently wrote about the misguided belief that: “pharmacologic interference will stop the insidious inflammatory disorder common to all sepsis. The many failures of clinical trials informed by this approach are testament to the failed thinking of this mechanistic framework…As one author declared “medicine needs evolution” and this is certainly the case with sepsis research.” (emphasis added)

Alverdy and Krezalek’s observation is a good reminder that abstract submissions are now open for the 4th annual meeting of ISEMPH – The International Society for Evolution, Medicine and Public Health in beautiful Park City, Utah. I am organizing a special symposium on Evolution, Emergency and Critical Illness.

Coffee and I also talked about the FEAST trial. More here. FEAST was also the subject of this podcast: Drowning in good intentions. The Hypress trial of corticosteroids in sepsis, was the topic of this previous podcast.

You can read more about my favorite failed sepsis drug Xigris here. Listen also to the Xigris podcast.

We mention the Bickell 1994 trial that studied IV fluids in trauma patients. In that study, fluids were associated with increased death; Coffee called this “pop the clot.” I wrote about that more here: Fluid resuscitation in trauma: Is less more?

Coffee and I mention John Ioannidis, a physician who has spent his career exposing bad science.  Read John Ioannidis’s now classic article Why most published research findings are false. An easily digestible write up of that paper appeared in the journal Atlantic. Lies, damned lies, and medical science.