Multiple Therapeutic Agents - Will Individual Therapies, Each of Which Improves Patients, When Given Together, Change Mortality?

  • A. E. Baue
Conference paper


Recent discouragement over the failure of many exciting potential therapeutic agents (magic bullets) to reduce 28-day mortality in patients has led to many diverse recommendations. One such recommendation is to use alternative or surrogate endpoints such as a reduction in severity of illness score, decreased ICU time, decreased time on a ventilator, and other evidence of clinical improvement. This is all well and good but if such an improved patient dies as frequently as do control patients, what have we accomplished? Another proposal is to use multi-agent therapy. There are many reasons why the older and more recent clinical trials have been negative. One important reason is that injury, infection and inflammation bring about complex changes and responses in the host. There are multiple pro-proinflammatory mediators with overlap, redundancy, and cross stimulation. This is followed by an anti-inflammatory response to try to control the process before it gets out of hand. The timing and variability of these processes are inconsistent. Even with similar diseases there is great variability [1]. This has led to consideration of multiple therapeutic agents for patients with diseases or injuries which stimulate an inflammatory response. I have recently reviewed the reasons why many of the clinical trials in the distant and recent past have failed [1].


Acute Pancreatitis Short Bowel Syndrome Isonicotinic Acid Magic Bullet Isonicotinic Acid Hydrazide 
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© Springer-Verlag Italia, Milano 1999

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  • A. E. Baue

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