Sole causal therapy worsens outcome as compared to no therapy and combined causal and goal-directed supportive therapy in ovine septic shock

Background: There is dear evidence that early causal therapy improves outcome in sepsis and septic shock, whereas recent studies on supportive hemodynamic therapy have produced very conflictive results. The objective of the present study was to determine whether a supportive hemodvnamic therapy guided by clinically relevant invasive monitoring improves survival and organ function in a high-lethality model of septic shock in sheep as compared to sole causal therapy including surgical and antimicrobial treatment. Methods: Twenty healthy ewes were anaesthetized and instrumented for hemodynamic surveillance. After laparotomy and fecal withdrawal from the caecum, animals were randomly assigned to one of four groups: sham, control, causal and combined therapy. In all groups but the sham group, feces were injected into the peritoneal cavity. Septic shock was defined as mean arterial pressure (MAP) <= 60 mmHg and arterial lactate concentration >= 1.8 mmol(.)L(-1). Animals of the control group received no therapy, while the causal group received broad-spectrum antibiotic therapy and peritoneal lavage. The combined therapy group received causal therapy plus supportive hemodynamic therapy. Results: The sham animals showed no signs of systemic infection, while all other animals developed septic shock with arterial hypotension and lactic acidosis within 4.0 (4.0-6.8) hours. Induction of causal therapy did not impact on haemodynamics as compared to the control group. Notably, 50% of the control animals and none of the causal therapy animals survived the study. Combined therapy stabilized haemodynamics and improved organ function and survival as compared to control and causal therapy groups. Conclusions: The present data suggest that sole causal sepsis therapy without hemodynamic support worsens outcome even more than natural evolution of sepsis and combined causal and supportive therapy. This underlines the importance of early hemodynamic stabilization in parallel with antibiotic and surgical treatment of the sepsis focus.