Capillary Refill Time—A Physiologic Anchor for Sepsis Resuscitation (ANDROMEDA-SHOCK-2 trial)
- Mazen Kherallah
- Nov 7
- 3 min read
The ANDROMEDA-SHOCK-2 trial, published in JAMA (2025), represents a major evolution in early septic shock management. Across 86 intensive care units in 19 countries, researchers compared a personalized hemodynamic resuscitation strategy targeting capillary refill time (CRT-PHR) with usual care. Among 1467 analyzed patients, CRT-guided therapy demonstrated superiority on a hierarchical composite outcome of 28-day mortality, duration of vital support, and length of hospital stay (win ratio 1.16; 95% CI, 1.02–1.33; P = .04). The benefit was driven primarily by fewer days requiring vasopressors, mechanical ventilation, or kidney replacement therapy.
A Shift Toward Personalized, Physiology-Driven Resuscitation
Traditional sepsis targets—such as lactate clearance and central venous oxygen saturation—have meaningful limitations. They require laboratory or invasive monitoring and may lag behind real-time physiology. ANDROMEDA-SHOCK-2 instead operationalizes a multilayered, bedside physiologic assessment, with CRT at the center of decision-making.
CRT was paired with two simple hemodynamic cues:
Pulse pressure <40 mm Hg, indicating possible low stroke volume and prompting fluid-responsiveness testing.
Diastolic arterial pressure <50 mm Hg or pulse pressure >40 mm Hg, signaling vasoplegia, guiding norepinephrine titration to restore vascular tone.
Patients with abnormal CRT moved through a structured sequence: fluids if fluid responsive, vasopressor adjustments for vasoplegia, bedside echocardiography to detect ventricular dysfunction, and, when indicated, a MAP trial (transiently increasing norepinephrine to attain a MAP of 80 to 85 mm Hg for 1 hour) or low-dose dobutamine test. Each step targeted the predominant physiologic abnormality rather than applying uniform therapy.
This approach directly linked physiology to intervention, allowing clinicians to respond to hypovolemia, vasodilation, or cardiac dysfunction in a tailored manner.
Performance and Clinical Impact
By six hours, 85.9% of patients in the CRT-PHR group achieved a refill time ≤3 seconds, compared with 61.7% in usual care. CRT-targeted patients received less fluid overall (595 mL vs 847 mL) and showed lower lactate concentrations and central venous pressures—reflecting optimized perfusion without excessive fluid administration. Safety signals were comparable between groups, and no increase in adverse events or mortality was observed.
The accompanying JAMA editorial emphasized that CRT brings clinicians back to the bedside, enabling immediate assessment of microcirculatory recovery. CRT responds quickly to changes in perfusion, making it a practical marker for dynamic resuscitation.
Applicability Across Clinical Environments
Although CRT is especially helpful in environments where invasive monitoring or lactate testing may be delayed or unavailable, its value is not limited to resource-constrained settings. The trial was performed across diverse ICUs—including high-income centers—and demonstrated that CRT-guided care can complement existing monitoring, refine fluid and vasopressor use, and accelerate perfusion recovery.
Its appeal lies in its universality: CRT, pulse pressure, and diastolic pressure can be assessed in any ICU, emergency department, or rapid response setting. They provide immediate, actionable information and integrate seamlessly with echocardiography, dynamic fluid assessments, and multimodal perfusion evaluation.
Future Directions
While ANDROMEDA-SHOCK-2 did not reduce mortality, it meaningfully decreased the duration of organ support—an outcome relevant to patients, clinicians, and health systems. Faster liberation from mechanical ventilation or vasopressors may reduce complications, improve throughput, and enhance patient recovery trajectories.
Further research will help refine CRT use across skin tones, temperature states, and patient populations. Understanding how CRT interacts with other markers—such as ScvO₂, CO₂ gap, or advanced cardiac ultrasound—will strengthen its integration into multimodal resuscitation frameworks.
Final Reflection
Capillary refill time has reemerged as a powerful, evidence-supported component of sepsis resuscitation. When combined with pulse pressure and diastolic pressure, CRT enables clinicians to customize therapy in real time, matching treatment to the patient’s immediate physiology. The ANDROMEDA-SHOCK-2 results encourage a modern sepsis strategy grounded in bedside assessment, responsiveness to change, and efficient resource use.
References
Hernández G, et al. JAMA. 2025; doi:10.1001/jama.2025.20402
Machado F R, Semler M W. JAMA. 2025; doi:10.1001/jama.2025.20518