Chronic porcine two-hit model with hemorrhagic shock and Pseudomonas aeruginosa sepsis.

BACKGROUND: Sepsis is still a major cause of death despite well-developed therapeutical strategies such as antibiotics and supportive medication. The aim of this study was to characterize the long-term effects of a two-hit porcine sepsis model with a hemorrhagic shock as 'first hit' followed by a Pseudomonas aeruginosa infusion as 'second hit'. MATERIALS AND METHODS: Twelve juvenile healthy pigs were anesthetized and hemodynamically monitored. The two-hit group (n = 6) underwent a hemorrhagic shock with a 50% reduction of the mean arterial pressure and/or cardiac index for 45 min, followed by resuscitation, while the control group (n = 6) received no pretreatment. All chronically catheterized conscious pigs were challenged with a P. aeruginosa infusion (1.6 x 10(7) CFU/kg/h for the first 24 h followed by 1.6 x 10(6) CFU/kg/h for the next 24 h) and observed for another 48 h. RESULTS: The two-hit group showed the following significant differences to the control group: higher APACHE II scores prior to sepsis induction, increased persisting mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) during bacterial challenge. In contrast, systemic vascular resistance (SVRI) was reduced at the end of the study. Throughout the observation period, the mean arterial pressure (MAP) was significantly reduced. CONCLUSIONS: The present study shows that the clinical course and hemodynamic effects of a P. aeruginosa sepsis will be aggravated by a preceding hemorrhagic shock during an observation period of 96 h. This two-hit model represents a valid, clinically relevant experimental protocol in sepsis research.

The influence of ischemic bowel wall damage on translocation, inflammatory response, and clinical course.

BACKGROUND: While vascular patency and overall viability of the gut can be evaluated perioperatively, damage to the mucosal barrier can hardly be judged in the perioperative setting and, moreover, will probably determine the clinical course. METHODS: In 19 consecutive cases with intestinal ischemia, the clinical course was correlated to the severity of the disease (APACHE II; Septic Severity Score, SSS), the intraabdominal and systemic inflammatory response, and the translocation of bacteria and endotoxin. RESULTS: The comparison of the 10 survivors with the nonsurviving group revealed no differences as to the length of history, serum lactate levels, white blood cell counts, body temperature, markers of the inflammatory response, or quantity and macroscopic quality of the exudate. Differences were found in intraperitoneal bacteriology (prevalence 0.37, negative predictive value for lethal outcome 0.8), endotoxin concentrations in the exudate (P = 0.02) and in the plasma (P = 0.015), fibrinopeptide A levels (exudate P = 0.036; plasma P = 0.015), PGE2 plasma concentration (P = 0.0357), and APACHE II (P = 0.0034) and SSS (P = 0.0027) values. CONCLUSION: The clinical course of ischemic bowel wall necrosis seems to depend on the severity of the disease at admission and on the integrity of the mucosal barrier rather than on inflammatory response, therapeutic measures, or supportive treatment.