Septic shock is a life-threatening circulatory emergency characterized by impaired oxygen delivery to tissues and oxygen utilization by cells leading to organ dysfunction, consequent to an infectious process. A common hemodynamic feature is hypotension. Current guidelines recommend rapid fluid administration and use of vasopressors to maintain a mean arterial pressure (MAP) of 65 mmHg. Yet, ensuring the recommended MAP often leads to escalation of vasopressor therapy, which is associated with increased mortality. Organ blood flow depends on the microcirculatory pressure downstream from arterioles.
The main effect of vasopressors is arteriolar vasoconstriction, and therefore excessive use of vasopressors increases MAP without correspondingly increasing microcirculatory (and therefore organ) blood flow. In addition, organs have autoregulatory mechanisms and can tolerate lower MAP levels without compromising blood flow.
We propose a perfusion-centered strategy focused on reversing organ hypoperfusion without a predefined MAP target. With this approach, interventions are centered on increasing cardiac output primarily by fluid administration while dynamically assessing fluid responsiveness and using vasopressors to prevent life-threatening reductions in vital organ perfusion, using safe MAP target levels likely to be lower than 65 mmHg.1-4
- Gazmuri RJ, Añez de Gomez CI, Siddiqui M, Schechtman J, Nadeem AUR. Severe Sepsis and Septic Shock Early Management Bundle Risks Aiding Vasopressor Misuse. Crit Care Med. 2019 Aug;47(8):e717.
- Gazmuri RJ, de Gomez CA. From a pressure-guided to a perfusion-centered resuscitation strategy in septic shock: Critical literature review and illustrative case. J Crit Care. 2020 Apr;56:294-304.
- Gazmuri RJ, de Gomez CA. Septic shock patients with adequate tissue perfusion parameters still need the recommended minimal Mean Arterial Pressure: Not really. J Crit Care. 2020 Apr;56:308-310.
- Shahid A, Fanapour P, Gazmuri RJ. Restriction of Intravenous Fluid in ICU Patients with Septic Shock. N Engl J Med. 2022 Sep 1;387(9):856.
We are developing a swine model of septic shock to test our perfusion-centered approach, develop automated closed-loop systems for safe and effective clinical translation of these concepts, and test new pharmacological therapies for septic shock.