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Septic Shock: Current Controversies and Areas for Future Research and Development

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We review current recommendations by the Surviving Sepsis Campaign Guidelines and controversies regarding the hemodynamic management of septic shock with a special focus on vasopressors and fluid resuscitation in light of pertinent physiological concepts related to the macrocirculation and the ...

We review current recommendations by the Surviving Sepsis Campaign Guidelines and controversies regarding the hemodynamic management of septic shock with a special focus on vasopressors and fluid resuscitation in light of pertinent physiological concepts related to the macrocirculation and the microcirculation. We provide a robust discussion of the appropriateness of using a predefined mean arterial pressure to guide the use of vasopressors and entertain alternative approaches in which the focus pivots from a pressure-driven to a perfusion-driven management.

We include specific discussion on the brain during septic shock and the less well-known effects of vasopressor agents. We also examine evolving concepts on the optimal management of fluid resuscitation acknowledging that preload optimization requires a dynamic approach whereby incomplete or excessive fluid administration is increasingly recognized as compromising outcome. We also address mounting evidence suggesting that the endogenous sympathetic response to septic shock might be detrimental and discuss the effects of pharmacologically targeting this response.

To enable implementing new therapies, a more target-driven approach is required. Acknowledging that the core hemodynamic deficit of septic shock resides in the microcirculation and that paramount for survival is the restoration adequate microcirculatory and therefore organ blood flow, we discuss whether monitoring skin perfusion may be a good surrogate of organ perfusion and serve to effectively guide resuscitation interventions. We also address the concept of personalizing the choice of vasopressor therapy along with an automated closed-loop system for vasopressor delivery.

In summary, we expect to provide a succinct but inclusive overview of current challenges for the management of septic shock and discuss areas of ongoing research and further development that may have the potential for favorably impacting patient outcome.


Keywords: Fluid Resuscitation, Microcirculation, Septic Shock, Vasopressors, Surviving Sepsis Campaign Guidelines


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