Increased serum levels of procollagen type III peptide in severely injured patients

Objectives: To determine the serum concentrations of procollagen type in peptide in severely injured patients with different outcomes and to evaluate the relationship between serum procollagen type III peptide concentrations, sources of increased posttraumatic fibrotic activity (wounds, lung, liver, kidney), and decreased elimination of procollagen type III peptide (liver). Design: Prospective study. Setting: Surgical ICU, university hospital. Patients: Fifty-seven patients (mean injury severity score: 38.5 points, range 13 to 75 points), between 16 and 70 yrs of age, treated in our institution within 6 hrs after the accident. Measurements: Serial measurements were started on admission and continued on a 6-hr basis. After 48 hrs, the monitoring interval was extended to 24 hrs until recovery (but at least until day 14) or death. At each point of evaluation, pulmonary and circulatory function parameters and chest radiographs (once a day) were evaluated, the results were recorded, and blood samples were drawn to determine procollagen type III peptide, total bilirubin, creatinine, [gamma]-glutamyl transferase, polymorphonuclear elastase, and other parameters. Statistic evaluation was done with the Wilcoxon test, Spearman rank correlation, and a multiple regression model. Results: Mean procollagen type m peptide serum concentrations (+/- sd) were significantly different in patients who died (8.0 +/- 3.8 U/mL) compared with those patients who survived with organ failure (2.7 +/- 1.3 U/mL) or without complications (1.4 +/- 0.5 U/mL), respectively. Significant correlations of procollagen type HI peptide concentrations with the serum bilirubin concentrations (r = .7), days with need of mechanical ventilation (r = .64), Pao2/Fio2 ratio (r = -.6), polymorphonuclear elastase (r = .6), serum creatinine concentrations (r = .55), and injury severity score (r = .33) were observed. There was a tendency toward higher serum procollagen type III peptide concentrations in patients with severe skeletal injuries. Conclusions: Serum procollagen type III peptide concentrations in severely injured patients may be considerably increased in correlation with injury severity and outcome. Procollagen type III peptide serum concentrations seem to reflect the sum of increased collagen formation from wound healing and fibrogenesis of mediator-related organ damage (especially lung) and decreased procollagen type HI peptide excretion due to impaired liver function. Further data are necessary to evaluate the role of hepatic elimination in these patients

Inflammatory mediators, infection, sepsis, and multiorgan failure after severe trauma

The relation of (multiple) organ failure (OF) to the release of inflammatory mediators and the incidence of infection and sepsis was studied prospectively in 100 patients with multiple trauma (injury severity score=37). Sixteen patients died of OF, 47 patients survived OF, and 37 patients had no OF. Fifteen (24%) of the patients with OF showed no signs of infection. In patients with early onset of OF (n=45), infection followed with a lag of 2 or more days. In 16 (44%) of these patients, infection led to a deterioration in organ function. With late onset of OF (n=18), infection preceded OF in nine patients. Polymorphonuclear leukocyte—elastase, neopterin, C-reactive protein, lactate, antithrombin III, and phospholipase A discriminated significantly among the three outcome groups. Of all factors, only polymorphonuclear leukocyte—elastase showed a difference between patients with and without infection or sepsis, respectively. These data indicate that infection might not play a crucial role in the pathogenesis of posttraumatic OF in a substantial portion of patients with trauma. Early OF, especially, seems to be mainly influenced by the direct sequelae of tissue damage and shock (eg, the release of inflammatory mediators). Since infection and sepsis did not lead to an augmented release of mediators in patients with trauma, the role of both entities remains unclear

Inhibition of Plasma Kallikrein with Aprotinin in porcine endotoxin Shock

Activation of the contact phase of coagulation has been implicated in the pathogenesis of septic shock. We wanted to determine if inhibition of plasma kallikrein can prevent arterial hypotension and liberation of kinins from kininogen, induced by an infusion of bacterial lipopolysaccharide (LPS) in anesthetized, ventilated 20-kg pigs. The LPS was given IV in a dose of 5 [mu]g/kg/h for 8 hours. The plasma kallikrein inhibitor aprotinin, 537 [mu]mol, was given IV during 8 hours, resulting in plasma levels above 10 [mu]mol/L. Ten animals (SA) received LPS and aprotinin and ten randomized controls (SC) received LPS and saline. Kinin-containing kininogen was determined on the basis of the amount of kinin releasable in plasma samples by incubation with trypsin. Kininogen decreased to 58% +/- 4% of the baseline value without any difference between groups. This may indicate participation of other processes than degradation by plasma kallikrein in the decrease of kininogen. Arterial blood pressure was higher at 7 hours in the SA animals than in the SC group (101% +/- 11% vs. 68% +/- 8%; mean +/- SEM; p = 0.026). Fibrin monomer and C3adesArg plasma levels were attenuated by aprotinin treatment. These findings underscore the important role of the contact system in LPS shock