J Trauma
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Reactive species of oxygen have been implicated as being important mediators in a variety of pathologic conditions, including burns, various forms of ischemia/reperfusion injury, and hemorrhagic shock. Pyruvate, an intermediate in the metabolism of glucose, is a potent reactive species of oxygen scavenger. Pyruvate, however, is unstable in aqueous solutions, and has not been developed as a therapeutic agent. ⋯ Ringer's ethyl pyruvate solution (REPS) has been evaluated in a number of preclinical studies using animal models of mesenteric ischemia/reperfusion injury, hemorrhagic shock, and acute endotoxemia. Treatment with REPS, when compared with treatment with Ringer's lactate solution, has been shown to be able to improve survival and decrease expression of proinflammatory mediators. REPS warrants further evaluation for the resuscitation of patients with hemorrhagic shock.
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The systemic inflammation that occurs in shock states is believed to promote overexuberant microcirculatory activation, the release of toxic proteases and oxygen radicals causing microvascular damage, and subsequent tissue and organ injury. Although shock-associated microvascular failure is often unresolved after standard resuscitation, hypertonic saline (HTS) appears to reduce microvascular collapse, restoring vital nutritional blood flow. ⋯ Furthermore, fewer cellular interactions have been correlated with attenuation in microvascular wall permeability after resuscitation with HTS. Better characterization of microcirculatory effects by hypertonic saline may provide mechanisms for improved morbidity and mortality associated with hypertonic resuscitation.
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A number of oxygen therapeutics have completed safety trials and are now undergoing efficacy evaluation in multicenter phase III trials in North America and Europe. There are numerous potential advantages of these solutions when compared with packed red blood cells. ⋯ A few problems remain, including short biologic half-life, which may limit the application to times when the patient is most acutely anemic (i.e., in the intraoperative or immediate perioperative phase) or for emergent use. Nevertheless, a safe, effective alternative therapy providing oxygen delivery characteristics comparable to red blood cells may soon be available that could have significant impact on the way that we resuscitate trauma patients.
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Much can be learned from studying the deaths that occur in trauma systems as they have developed. Understanding these deaths and the potential effect of trauma systems on reducing death has major implications for designing clinical trials in fluid resuscitation. The availability of new, exciting information regarding fluid composition and physiologic effects argues for new, better-designed clinical trials. By agreeing on the form of resuscitation trials in the future, we will increase our ability to see clinically significant differences in outcome as we move from animal data to clinical efficacy.
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Controversy regarding crystalloids or colloids for resuscitation has existed for over five decades, and large numbers of clinical trials have failed to resolve the controversy. In fact, the limitations of these studies have intensified the debate. This overview aims to revisit the debate of fluid resuscitation in trauma patients by critically appraising the meta-analyses on the subject. ⋯ There is an urgent need for well-designed clinical trials. Because of many limitations, meta-analysis should be interpreted with caution, possibly as hypothesis generating. However, even considering all weaknesses and nuances of interpretation, the meta-analyses reviewed suggest that trauma patients should continue to be resuscitated with crystalloids.