Personalized Management of Septic Shock Guided by Multimodal Circulatory and Perfusion Monitoring: The PRISM Trial

BackgroundSepsis-related organ dysfunction results from complex interactions between systemic hemodynamics, microcirculatory alterations, and cellular metabolic failure. Conventional resuscitation strategies guided by global parameters may miss persistent tissue hypoperfusion, a phenomenon termed "hemodynamic incoherence." The PRISM trial was designed to determine whether individualized management guided by advanced multimodal circulatory and perfusion monitoring improves outcomes in septic shock. MethodsThe PRISM trial is a multicenter, randomized, controlled, open-label study with blinded outcome assessment. Adults with septic shock (Sepsis-3 criteria) are randomized (1:1) to structured multimodal monitoring versus standard care. The intervention integrates advanced systemic hemodynamic indices --including mean circulatory filling pressure analogue and other determinants of venous return, heart efficiency, cardiac power output, power efficiency, and volume efficiency-- with a comprehensive perfusion panel (capillary refill time, mottling score, temperature gradients, lactate kinetics, central venous oxygen saturation, venous-arterial carbon dioxide difference, near-infrared spectroscopy-derived skeletal muscle tissue oxygen saturation, and arterial-interstitial glucose gradients). A predefined treatment algorithm links abnormal thresholds to therapeutic interventions. The primary endpoint is change in SOFA and SAPS II scores from baseline to 72 hours. Secondary endpoints include 28-day mortality, ICU and hospital length of stay, ventilator- and vasopressor-free days, lactate clearance, and safety outcomes. DiscussionBy combining advanced hemodynamic physiology with structured multimodal perfusion monitoring, the PRISM trial tests whether individualized, pathophysiology-guided resuscitation can overcome hemodynamic incoherence and improve patient-centered outcomes in septic shock.