A model of porcine polymicrobial septic shock
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Published:2023-06-02
Issue:1
Volume:11
Page:
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ISSN:2197-425X
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Container-title:Intensive Care Medicine Experimental
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language:en
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Short-container-title:ICMx
Author:
Zurek-Leffers Finnja Marie, Lehmann Florian, Brabenec Laura, Kintrup Sebastian, Hellenthal Katharina E. M., Mersjann Kira, Kneifel Felicia, Hessler Michael, Arnemann Philip-Helge, Kampmeier Tim-Gerald, Ertmer Christian, Kellner Patrick, Wagner Nana-MariaORCID
Abstract
Abstract
Background
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Mortality of patients with sepsis is high and largely unchanged throughout the past decades. Animal models have been widely used for the study of sepsis and septic shock, but translation into effective treatment regimes in the clinic have mostly failed. Pigs are considered as suitable research models for human diseases due to their high comparability and similarity to human anatomy, genetics, and the immune system. We here evaluated the previously reported models of septic shock in pigs and established a novel model of polymicrobial sepsis that meets the clinical criteria of septic shock in pigs.
Materials and methods
The literature search was performed using the keywords “pig”, “sepsis” and “septic shock”. For the establishment of septic shock in n = 10 German landrace pigs, mechanical ventilation was initiated, central venous and arterial lines and invasive hemodynamic monitoring via pulse contour cardiac output measurement (PiCCO) established. Peritoneal polymicrobial faecal sepsis was induced by application of 3 g/kg body weight faeces into the abdominal cavity. Septic shock was defined according to the third international consensus definitions (Sepsis-3). Upon shock, pigs underwent the 1-h bundle for the treatment of human sepsis. Cytokine levels were measured by ELISA.
Results
Published porcine sepsis models exhibited high methodological variability and did not meet the clinical criteria of septic shock. In our model, septic shock developed after an average of 4.8 ± 0.29 h and was associated with a reproducible drop in blood pressure (mean arterial pressure 54 ± 1 mmHg) and significant hyperlactatemia (3.76 ± 0.65 mmol/L). Septic shock was associated with elevated levels of interleukin-6 (IL6) and initial cardiac depression followed by a hyperdynamic phase with significant loss of systemic vascular resistance index after initial resuscitation. In addition, organ dysfunction (acute kidney injury) occurred.
Conclusions
We here established a model of septic shock in pigs that meets the clinical criteria of septic shock utilized in human patients. Our model may thus serve as a reference for clinically relevant sepsis research in pigs.
Funder
Deutsche Forschungsgemeinschaft Westfälische Wilhelms-Universität Münster
Publisher
Springer Science and Business Media LLC
Subject
Critical Care and Intensive Care Medicine
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