Tim-Gerald Kampmeier1, Michael Hessler1, Philip Helge Arnemann1, Martin Westphal1,2, Laura Mareen Seidel1, Andrea Morelli3, Hugo Van Aken1, Sebastian Rehberg4, Christian Ertmer1. 1. Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital of Muenster, Muenster, Germany. 2. Fresenius Kabi Deutschland, Else-Kröner-Straße 1, Bad Homburg, Germany. 3. Department of Anesthesiology and Intensive Care, University of Rome "La Sapienza", Rome, Italy. 4. Department of Anesthesiology, Intensive Care, Emergency Medicine, Transfusion Medicine and Pain Therapy, Protestant Hospital of the Bethel Foundation, Bielefeld, Germany.
Abstract
BACKGROUND: There is clear 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 hemodynamic 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.
BACKGROUND: There is clear 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 hemodynamic 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.
Authors: Christopher W Seymour; Foster Gesten; Hallie C Prescott; Marcus E Friedrich; Theodore J Iwashyna; Gary S Phillips; Stanley Lemeshow; Tiffany Osborn; Kathleen M Terry; Mitchell M Levy Journal: N Engl J Med Date: 2017-05-21 Impact factor: 91.245
Authors: R P Dellinger; Mitchell M Levy; Andrew Rhodes; Djillali Annane; Herwig Gerlach; Steven M Opal; Jonathan E Sevransky; Charles L Sprung; Ivor S Douglas; Roman Jaeschke; Tiffany M Osborn; Mark E Nunnally; Sean R Townsend; Konrad Reinhart; Ruth M Kleinpell; Derek C Angus; Clifford S Deutschman; Flavia R Machado; Gordon D Rubenfeld; Steven Webb; Richard J Beale; Jean-Louis Vincent; Rui Moreno Journal: Intensive Care Med Date: 2013-01-30 Impact factor: 17.440