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In a series of 71 patients with trauma, we measured weekly the blood levels of a number of complement proteins and activation products. We also measured the following: leukocytes, platelets, granulocyte enzyme elastase, alpha 1-antitrypsin, total protein, albumin, haptoglobin, and fibronectin. The intensity of complement activation and the blood levels of elastase correlated with the following factors: injury severity (especially the severity of limb injury), development of adult respiratory distress syndrome, development and severity of multiple organ failure, and probability of a fatal outcome. The plasma elastase level seemed to be the best predictor of adult respiratory distress syndrome and the best correlate of injury severity and multiple organ failure severity. Our findings support the hypothesis that posttraumatic activation of the complement system leads to activation of granulocytes, followed by microvascular injury and finally by organ failure.

Multiple-organ failure is generally attributed to bacterial infection, although a correlation with positive blood cultures is not consistently found. Consequently, we studied the effects of a local nonbacterial inflammatory stimulus on distant organ functions and metabolism. Wistar rats were inoculated intraperitoneally with zymosan. Heart and ventilatory rates, oxygen consumption, and body temperature were measured. Survivors were killed at day 12 for blood analysis, weighing of organs, and microscopy. Intraperitoneal zymosan resulted in an early hyperdynamic "septic" response with a 35% mortality. After a few days, oxygen consumption decreased, serum lactate levels increased, and the function of multiple organs deteriorated, while blood cultures remained sterile. The experiment was repeated in germ-free rats with similar results but a lower mortality. We concluded that a severe inflammatory response in itself is capable of inducing multiple-organ failure with "sepsis."

As multiple-organ failure (MOF) has been generally associated with sepsis, the importance of bacterial sepsis was evaluated retrospectively in 55 trauma and 37 intra-abdominal-sepsis patients with MOF. The severity of MOF was graded, and an analysis was made of day of onset, incidence, severity, sequence, and mortality of organ failures. No difference was found between groups in sequence, severity, or mortality of organ failures. In contrast, bacterial sepsis was found in 65% of intra-abdominal-sepsis patients but only in 33% of trauma patients. It is concluded that sepsis is probably not the essential cause of MOF. Instead, an alternative hypothesis is presented involving massive activation of inflammatory mediators by severe tissue trauma or intra-abdominal sepsis, resulting in systemic damage to vascular endothelia, permeability edema, and impaired oxygen availability to the mitochondria despite adequate arterial oxygen transport.