Characterization of an experimental model of septic shock induced by fecal peritonitis in pigs

Introduction

Pathophysiological human studies in sepsis are difficult to perform due to ethical and methodological concerns. In this context, animal models of severe sepsis can be useful to better understand this condition and to test new therapeutic interventions.

Objective

The purpose of this study was to describe and characterize a clinically relevant experimental model of septic shock in pigs that could be useful to test different therapeutic interventions.

Methods

Five White Large pigs (35–45 kg) were anesthetized and instrumented with arterial and Swan-Ganz catheters. A splenectomy was performed and sepsis was induced by peritoneal instillation of 1.5 g/kg fecal content. Several biochemical indicators of organ dysfunction as well as infectious parameters were measured. The animals were followed until death, when fragments of the heart, small bowel, liver and kidney were removed for pathology. Three nonseptic animals served as controls.

Results

The animals survived 17 hours on average (range 16–18 hours). Septic shock was characterized as a significant increase in heart rate (102 ± 27 baseline vs 139 ± 16 bpm before death, P < 0.001) and a decrease in mean arterial pressure (111 ± 9 vs 62 ± 9 mmHg, P = 0.009). Septic pigs developed a nonsignificant decrease in cardiac output (109.4 ± 54.5 vs 71.2 ± 20.1 ml/min/kg, P = 0.221) and mixed venous oxygen saturation (74 ± 2 vs 34 ± 13%, P = 0.110) during the study period. These animals were fully resuscitated (mean 12.2 ± 2.4 l Ringer lactate) as evidenced by stable values of central venous pressure (12.8 ± 2.4 vs 20.4 ± 7.4 mmHg, P = 0.905) and wedge pressure (11.4 ± 6 vs 19.0 ± 3.6 mmHg, P = 0.903). E. coli was recovered from blood cultures of all the septic animals. Although biochemical data did not demonstrate important organ dysfunction, some pigs developed clinical signs of organ injury, such as oliguria. Histology depicted only focal or minor abnormalities. Control animals were sacrificed 24 hours after surgery without developing significant changes in hemodynamic, respiratory or metabolic variables.

Conclusion

Fecal peritonitis in pigs is a reliable and clinically relevant model of sepsis that can be useful to test several different therapeutic interventions.