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Could $100 Million Change the Future of Sepsis Management?
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Key Point |
At a recent professional meeting, prominent critical care experts discussed how they would spend research dollars to advance care for sepsis and acute lung injury. |
ORLANDO—One hundred million dollars is a lot of money, and just about any intensivist would be pleased to have the opportunity to use these funds as he or she saw fit. Experts in the field were presented with this scenario at the Society of Critical Care Medicine’s 36th Critical Care Congress. In a session titled “If I Had $100 Million: The Future of Research,” several lecturers described their ideas of how the money could be spent.
SEPARATE PATHS FOR SEPSIS AND ACUTE LUNG INJURY
“First, let’s put this $100 million into context,” said Edward Abraham, MD, Chair of the Department of Medicine at the University of Alabama in Birmingham. “We have already spent many hundreds of millions of dollars in research to date: How many therapies are there that significantly reduce mortality in patients with acute lung injury and sepsis?”
The answer is that the list of such therapies is small and disappointing, Dr. Abraham acknowledged. “So if we are really going to leverage $100 million, we need a paradigm shift to move forward,” he said.
The shift, he explained, would be to no longer view acute lung injury and sepsis as homogeneous conditions but rather to understand that there are important differences in the cellular pathways that lead to organ dysfunction. In a context that viewed the conditions independently, the money could be used to better define each condition’s etiology and to develop targeted therapies.
This strategy is already guiding the research of other diseases, Dr. Abraham noted. For example, investigators are studying the interrelationships of more than 70 nucleotide polymorphisms on chromosome 2 that are implicated in the various manifestations of asthma. Similar analyses involving other chromosomes are under way, with the ultimate goal of creating gene profiles for specific asthma types. “This example could serve as a model for how to approach differing sepsis presentations,” emphasized Dr. Abraham.
Of course, developing such models for acute lung injury and sepsis may be substantially more complex, as these conditions involve the up-regulation and down-regulation of proteins. In addition, the universe of proteins is vastly larger than the universe of genes. However, the goal would be similar: to identify individualized protein expression profiles that would serve as a basis for choice of currently available sepsis treatments and for clinical trials of new treatments.
Another potential benefit of this approach is that treatment would be initiated earlier in the disease process—before the development of organ dysfunction. This advance, in particular, would help to reduce mortality in acute lung injury and sepsis, Dr. Abraham said.
WISH: THE ABILITY TO PREDICT INDIVIDUAL OUTCOMES
One hundred million dollars could go a long way toward developing rapid tests that can predict the course of sepsis in individual patients, suggested Daniel G. Remick, MD, Chairman of Pathology and Laboratory Medicine at Boston University. “You want to have rapid tests available that permit delivery of appropriate care,” he stated.
Based on mouse models, it appears that during the early phase of sepsis, rapid tests involving frequent blood sampling would probably be most effective. Mice that died during the first five days of sepsis showed elevated plasma concentrations of interleukin-6, tumor necrosis factor a, and other proinflammatory cytokines, Dr. Remick pointed out.
Importantly, plasma interleukin-6 and tumor necrosis factor levels most accurately predicted death during the first 24 hours of sepsis. Macrophage inflammatory protein 2 concentration also predicted death during the first 24 hours with a good degree of accuracy, Dr. Remick said. All three cytokines were somewhat effective for predicting death within 48 hours, he added.
Other anti-inflammatory and proinflammatory cytokines that showed good accuracy for predicting sepsis mortality within 24 hours were interleukin-1b,
keratinocyte-derived chemokine, interleukin-1 receptor antagonist, and tumor necrosis factor–soluble receptors I and II. None of the cytokines measured were accurate predictors of six- to 28-day mortality or of survival. With further research, it may be possible to create a personal profile for each patient that facilitates individualized sepsis treatment that targets the appropriate cytokines, suggested Dr. Remick.
—Timothy Begany
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