Persistently high morbidity and significant mortality characterise sepsis syndrome, Fundamental limitations in both animal and patient models have contributed to a lack of therapeutic progress in human sepsis. Surgery provides a biologically and clinically relevant model that avoids many such limitations. This article sets out the case for major surgery, and highlights recent data demonstrating the superior suitability of this model being adopted.
Translational research in critically ill human patients presents many methodological challenges. Diagnostic uncertainty, coupled with poorly defined co-morbidities, make the identification of a suitable control population for case-control investigations an arguably insurmountable challenge. Healthy volunteer experiments using endotoxin infusion as an inflammatory model are methodologically robust, but fail to replicate the onset of, and diverse therapeutic interventions associated with, sepsis/trauma. Animal models are also limited by many of these issues. Major elective surgery addresses many of these shortfalls and offers a key model for exploring the human biology underlying the sepsis syndrome. Surgery triggers highly conserved features of the human inflammatory response that are common to both tissue damage and infection. Surgical patients sustain a predictable and relatively high incidence of sepsis, particularly within the ‘higher risk’ group. The collection of preoperative samples enables each patient to act as their own control. Thus, the surgical model offers unique and elegant experimental design features that provide an important translational bridge between the basic biological understanding afforded by animal laboratory models and the d fore novo presentation of human sepsis.
Bench to bedside:
David J Cain, Ana Gutierrez del Arroyo, and Gareth L Ackland
Man is the new mouse: Elective surgery as a key translational model for multi-organ dysfunction and sepsis
Journal of the Intensive Care Society 1751143714564826, first published on January 7, 2015 doi:10.1177/1751143714564826