The cellular, immune, and metabolic response to trauma

The major challenge in treatment of the multiple trauma victim has shifted from early and effective resuscitation to treatment of the host response to injury. Patients surviving for the first 24 h after major injury as a result of effective resuscitation remain at risk of progressive organ failure and death from what appears to be an uncontrolled inflammatory process. A septic cause is frequently not identifiable, yet the response is as if the patient were infected. While organ-supportive measures such as mechanical ventilation, extracorporeal membrane oxygenation, renal replacement therapies, and total parenteral nutrition help to maintain tissue substrate delivery and metabolite removal, these therapies eventually fail if the microvaculature ceases to function. As the soluble and cell-mediated pathways of the inflammatory response are now being unraveled, possible interventions designed to attenuate selected elements of the inflammatory pathways are being developed. These measures include antioxidants, enzyme inhibitors, pharmacological agents, antibodies both to soluble mediators and cell surface receptor antagonists. Most of these interventions are at the experimental stage and so far have only met with limited clinical success. A major problem with attenuation of the inflammatory response is the overlap of inflammatory pathways, such that modulation of one or two is unlikely to be of benefit in a patient with major injuries. In addition, the speed of these responses, once initiated, requires that therapies have to be administered very soon after injury to be effective. However, the tremendous increase in knowledge of the inflammatory response, and the increasing sophistication of laboratory science that can provide both assessment of mediators of inflammation and the patients' response to the inflammatory process allows early identification of patients at risk of post-trauma organ failure. Armed with this knowledge, treatment can be tailored to each patients' individual response to injury, and when definitive antiinflammatory regimes are available, patients who can benefit from this treatment can be identified rapidly.