ANIMAL-MODELS OF SEPSIS AND SHOCK - A REVIEW AND LESSONS LEARNED

Over the past decade, the biotechnology/pharmaceutical industry has be en diligently working on the development of immunomodulatory agents fo r the treatment of shock and sepsis, and the literature is rife with d escriptions of novel and innovative molecules that promise to become t he panacea for these conditions. Unfortunately, despite promising prec linical evidence, dozens of these new agents have failed to demonstrat e clinical efficacy in controlled, randomized clinical trials, abandon ing the bedside physician to the traditional armamentarium of drugs an d therapeutics for the treatment of patients with these complex, progr essive, and life-threatening conditions. The reasons for this quandary are controversial, complex, and multifactoral. This review focuses on the concept that the preclinical trials of many of these agents were conducted using models of sepsis and shock that do not adequately refl ect the clinical realities of these conditions, As a result, it is not surprising that clinical trials of agents based on clinically flawed models failed to demonstrate clinical efficacy. The lack of clinical i nsight during preclinical development of these agents has contributed to the current impasse of the development of safe, efficacious, and po tentially lifesaving agents for the treatment of shock and sepsis. Thu s, the goal of this review article is to review the advantages and dis advantages of commonly used sepsis and shock models in light of lesson s learned from these clinical trials.