after an injury has occurred. The classic examples might involve reducing metabolic demand through induced hypothermia or induction of a hibernation state. Although study of the former might provide insights that lead to therapeutic strategies, it is unlikely that induction of hypothermia per se will be practical in any battlefield setting. The possibility of a pharmacologically induced state of "hibernation" in which the organism might be less susceptible to the effects of hypoxia and cell injury is an appealing concept. It is unclear whether naturally occurring animal models of hibernation do afford this protection and, if so, whether it is induced by some circulating factor or by a complex of events.

Recommendations

The committee found that much of the research on hemorrhagic shock has remained focused on hemodynamics or has been directed toward correcting a single biochemical abnormality that accompanies hemorrhage. Such strategies are unlikely to be successful. Rather, novel therapies should be aimed at the metabolic and cellular derangements that accompany traumatic shock. These approaches should take advantage of advances in other related fields (such as ischemia-reperfusion research in specific organs) and should be approached in a systematic manner that involves prophylaxis, immediate intervention, or the development of tolerance to global ischemia. Combinations of novel therapies should be explored, because multiple pathways lead to cell death. Prevention of any component of the shock syndrome's cascading pathologic processes is preferable to treating or attempting to reverse the effects of the syndrome. Correcting the imbalance between O2 supply and tissue demand is highly desirable. Providing a resuscitation fluid with increased O2-carrying capacity represents a potential target to achieve this goal. Numerous oxygen therapeutic agents have been developed, and several are in different stages of clinical trials. Whether a resuscitation fluid that enhances O2-carrying capacity or facilitates O2 delivery would reduce the rate of morbidity or mortality from hemorrhagic shock remains to be demonstrated. Because organ toxicity following hemorrhagic shock results from a complex of interrelated mechanisms that lead to death, it is unlikely that a single drug, vitamin, electrolyte, or other agent would be able to alter organ toxicity significantly. Some markedly altered physiologic states offer protection to cells and organs. Strategies that induce tolerance to hypoxia might improve the survival of patients with shock syndrome.

Recommendation 4.1 Evaluate the applicability of small-volume, stable oxygen (O2)-carrying and O2-facilitating agents that improve and sustain O2 delivery in the wounded subject for 24 to 48 hours.

Recommendation 4.2 Therapeutic agents that target the toxic effects of hypoxic injury (e.g., antioxidants, chelating agents, hormones, and nitric oxide inhibitors) should be studied with animal



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