New horizons (Baltimore, Md.)
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The continuing study of multiple organ failure (MOF) has led to the development of inflammatory models of tissue injury in contrast to earlier infectious models. This change of focus is in response to more recent clinical observations suggesting that postinjury MOF frequently occurs in the absence of infection. In the alternative "two-hit" inflammatory model that has been proposed, the initial traumatic insult "primes" the inflammatory response such that a delayed, otherwise innocuous, inflammatory insult triggers an exaggerated response. ⋯ PMN priming and activation are also operable in an in vivo model of gut ischemia/reperfusion, a surrogate of shock and trauma resuscitation, leading to distant organ damage. Finally, in clinical studies of severely injured trauma patients, PMN priming and activation sequences identify patients at risk for developing MOF with its associated high mortality. Further characterization of the mechanisms that regulate PMN priming and activation in the trauma patient is necessary for the development of new therapeutic interventions designed to block deleterious PMN responses which lead to MOF while not compromising beneficial PMN functions of host defense and tissue repair.
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In the past, most investigators failed to consider time relationships in their studies of circulatory problems. Because of this, data obtained in middle- or late-stage shock during organ failure are often presented as being characteristic of specific shock syndromes. Even "early" studies are not physiologically early, but instead have often come to mean early after ICU admission or early after life-threatening hypotensive events. ⋯ Data of survivors revealed increased cardiac function (CI and oxygen delivery) shortly after surgery, trauma, and sepsis; this response is needed to meet the increased metabolic demands defined by the increased oxygen consumption. Nonsurvivors have limited responses to the added metabolic demands of external stressors. Therapy should augment naturally occurring compensations, but it must be given promptly within appropriate time limits.