The pathogenesis of postinjury multiple organ failure (MOF) is not clear. Traditionally, MOF has been viewed as a sequential cascade of organ failure. Consequently, basic and clinical research efforts have focused on late events (e.g. sepsis and bacterial translocation). Recent basic work, however, indicates that various insults (e.g. burns, gut ischemia, zymozan IP) can provoke multiple organ injuries as a primary systemic event and serve to emphasize that the initial insult can cause or prime the host of MOF. Clinically, it is well recognized that a massive insult can precipitate early MOF. On the other hand, less severely injured patients enter a similar hyperinflammatory state. This is presumably beneficial, but patients appear vulnerable (i.e., primed) during this phase to a second insult (e.g., aspiration or pneumonia) which triggers the full blown MOF syndrome. Clinical research is hampered by the inability to identify, study and potentially protect these """"""""primed"""""""" patients. Recently, oxygen supply/demand imbalance has been implicated to be a critical risk factor for MOF. We, therefore, prospectively subjected high risk trauma patients to a resuscitation protocol aimed at maximizing oxygen delivery (DO2) and found that inadequate early VO2 accurately predicted late MOF. Patients with inadequate VO2 can be divided into two groups: those whose DO2 (i.e., cardiac performance) cannot be augmented (all died or developed MOF) versus those whose DO2 can be pushed to supranormal levels (three-fourths developed MOF). Based on this latter groups data, we hypothesize that moderate tissue injury followed by the early inability to consume oxygen despite supra- normal DO2 does not itself produce MOF, but identifies the patient at risk (i.e., primed) for developing MOF.
Our specific aims are: 1. To determine if tissue injury (quantitated by Injury Severity Score) is sufficient to produce MOF. 2. To determine if moderate tissue injury followed by flow dependent oxygen consumption (VO2) is sufficient to produce MOF. 3. To determine if moderate tissue injury followed by flow independent impaired VO2 is sufficient to produce MOF. 4. To determine if moderate tissue injury followed by flow independent impaired VO2 identifies the patient at risk (i.e., primed) for MOF.
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