The Flag of Permanent Defeat

Epistemic Crisis and Failure in Sepsis Research

"He was an old man who fished alone in a skiff in the Gulf Stream and he had gone eighty-four days now without taking a fish. In the first forty days a boy had been with him. But after forty days without a fish the boy's parents had told him that the old man was now definitely and finally salao, which is the worst form of unlucky, and the boy had gone at their orders in another boat which caught three good fish the first week. It made the boy sad to see the old man come in each day with his skiff empty and he always went down to help him carry either the coiled lines or the gaff and harpoon and the sail that was furled around the mast. The sail was patched with flour sacks and, furled, it looked like the flag of permanent defeat."

In "The Old Man and the Sea" Hemingway presents the story of an old fisherman who struggles to catch a colossal fish in the waters of the Gulf Stream, only to discover he would fail. His experience led him to underestimate the task. In other words, his usual premises were useless.

Trial after trial, failure warns us that the current understanding of sepsis and the way it translates into clinical trials is fundamentally flawed. In this post, the aim is to discuss the weaknesses of the assumptions that support sepsis research in acknowledgment that our big fish swims beneath the boat, and we are still figuring out a way to pull him.

The epistemic crisis

How can one develop a treatment for a disease that has no pathophysiologic hallmark? Many spent the last decades contemplating what resembles a contemporary version of a Zen paradox.

However, the more profound, unheard-of questions are: What is the fundamental biological attribute of sepsis that is absent in infection? And the corollary: Does sepsis exist as an entity distinct from infection?

In this post

• Is Sepsis more than Infection?

• The banality of the Surviving Sepsis Campaign

• No disease model - no hint to marginal utility

• Time for a paradigm shift?

• The much-needed Kuhnian revolution

• Where will innovation come from?

• The current sepsis definition is the flag of permanent defeat