Septic Shock

Perfusion-Centered Approach

Septic shock refers to the adverse circulatory reaction to a severe inflammatory process triggered by an infectious agent and is associated with a mortality rate between 30% to 50%, largely unchanged over the last decade or more. The circulatory reaction is characterized by a reduction in blood flow to organs deemed non-immediately vital for survival while initially maintaining blood flow to the heart and brain, i.e., redistribution of blood flow toward “vital organs”. Yet, if not promptly corrected, the circulatory reaction leads to rapid demise by being unable to sustain vital organ blood flow or demise after protracted deterioration of non-immediately vital organs leading to multiorgan system failure.

Septic shock typically presents with a reduction in mean arterial pressure (MAP). Current guidelines recommend maintaining a MAP of 65 mmHg by administering fluids and, if necessary, vasopressor agents. Fluids act by increasing the amount of blood filling the heart, with competent hearts able to pump it out and increase blood flow, i.e., cardiac output. Vasopressors are drugs infused intravenously to increase blood pressure predominantly by increasing the tone of small arteries, known as arterioles, hence promoting an increase in MAP without necessarily increasing organ blood flow. Accordingly, securing a MAP of 65 mmHg is not an indication that organ blood flow has been restored, and in fact, could be worse if large doses of vasopressors are used, causing intense vasoconstriction with decreased organ blood flow, leading to organ ischemia, dysfunction, and eventual death, explaining the high mortality of septic shock.

Moreover, the recommended MAP target has never been independently validated and many experts in the field advocate for personalized management to identify the optimal blood pressure, anticipating in many cases to be lower than 65 mmHg, minimizing detrimental effects of excessive fluid and excessive vasopressor administration, which is associated with increased morbidity and mortality.

Even adhering to current recommendations and precisely delivering fluids and vasopressors is a challenge, given the dynamic nature of septic shock requiring continuous adjustment of fluid and vasopressor delivery to maintain the recommended targets. This is a serious challenge to healthcare providers with multiple competing responsibilities, especially in resource-limited healthcare environments.

Accordingly, a new and patient-tailored approach to the management of septic shock is needed, enabling not only to continuously and precisely adjust fluid and vasopressor interventions but also to ensure that organ blood flow is adequately maintained, until the infectious process and the inflammatory reaction subside, a process that may take several hours, if not days, to its successful resolution.

Related Publications:

  1. 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.
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  2. 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.
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  3. 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.
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  4. 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.
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DEVELOPMENTS

We have developed an Autonomous Circulatory Management System (ACMS) research prototype designed to optimize the treatment of septic shock and other conditions of hemodynamic instability. The ACMS is expected to promote a paradigm shift in the management of septic shock, leading to improved survival with less organ dysfunction, shorter hospital stays, and more efficient critical care resource utilization.

Central to the ACMS is the continuous and dynamic optimization of the delicate balance between systemic blood flow and systemic vascular resistance while securing adequate organ blood flow expected to profoundly impact patients’ outcomes.

We have:

  1. Successfully tested our research prototype in a translationally relevant swine model of endotoxic shock that recapitulates the clinical manifestations of septic shock,
  2. Demonstrated the ability to autonomously provide precise and uninterrupted hemodynamic management for the entire duration of the episode, and
  3. Filed a U.S. Provisional Patent Application on August 7, 2025