Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial.

Summary

In 1467 patients within 4 hours of septic shock, a CRT-targeted personalized resuscitation protocol achieved a win ratio of 1.16 versus usual care (95% CI 1.02-1.33; P=0.04) for a hierarchical composite of death, duration of vital support, and hospital stay. Benefits were driven mainly by shorter duration of vital support, with similar mortality proportions between groups.

Key Findings

• Win ratio 1.16 (95% CI 1.02-1.33; P=0.04) favoring CRT-PHR for the hierarchical composite outcome at 28 days.
• Individual pairwise wins: death 19.1% vs 17.8%; duration of vital support 26.4% vs 21.1%; length of hospital stay 3.4% vs 3.2% (CRT-PHR vs usual care).
• Trial enrolled 1501 patients; 1467 analyzed across 86 centers in 19 countries; effect mainly driven by shorter duration of vital support.

Clinical Implications

Implementing CRT-guided personalized resuscitation, including structured assessment of pulse pressure, diastolic pressure, fluid responsiveness, and bedside echocardiography, may reduce time on vasopressors and organ support in early septic shock. Protocolized training and workflow integration are required.

Limitations

• Open-label pragmatic design with potential performance bias.
• Primary benefit driven by duration of vital support; mortality difference was small.

Future Directions

Evaluate mortality effects and implementation strategies, including automation of CRT assessment, and test CRT-PHR within sepsis subphenotypes and resource-limited settings.