Capillary Refill-Guided Resuscitation Improves Outcomes in Early Septic Shock: ANDROMEDA-SHOCK-2 Trial
USA: A large international randomized clinical trial suggests that a personalized hemodynamic resuscitation approach targeting capillary refill time (CRT) can improve patient-centered outcomes in early septic shock compared with usual care.
The findings are from the ANDROMEDA-SHOCK-2 trial, published in JAMA by Glenn Hernandez, MD, PhD, from the Department of Intensive Care Medicine, Pontificia Universidad Católica de Chile, Santiago, and colleagues.
Septic shock remains a major cause of mortality in intensive care units, and the best approach to early hemodynamic resuscitation is still uncertain. Conventional strategies rely on global measures such as blood pressure and lactate, which may not accurately reflect tissue perfusion. Capillary refill time, a simple bedside marker of peripheral perfusion, has therefore gained attention as a target for personalized resuscitation.
The ANDROMEDA-SHOCK-2 trial was conducted in 86 intensive care units across 19 countries and enrolled patients within four hours of septic shock between March 2022 and April 2025. Of the 1,501 patients randomized, 1,467 were included in the primary analysis. The mean age was 66 years, and 43% of participants were women.
Patients were randomized to a personalized resuscitation protocol aimed at normalizing capillary refill time or to usual care. The personalized approach used repeated CRT assessments along with pulse pressure, diastolic arterial pressure, fluid responsiveness testing, and bedside echocardiography to guide fluids, vasopressors, and inotropes. Usual care followed standard hemodynamic management based on local practice.
The following were the notable findings:
- The primary endpoint was a hierarchical composite at 28 days that included mortality, duration of vital organ support (vasopressors, mechanical ventilation, and kidney replacement therapy), and length of hospital stay.
- A personalized capillary refill time–guided resuscitation strategy showed a statistically significant advantage over usual care using a win ratio analysis.
- Nearly 49% of patient comparisons favored the intervention group compared with just over 42% in the usual care group, resulting in a win ratio of 1.16.
- The overall benefit of the personalized strategy was largely driven by a shorter duration of vital organ support.
- Mortality differences between groups were modest, but patients in the CRT-guided group required fewer days of vasoactive therapy, mechanical ventilation, and renal replacement therapy.
- A reduction in hospital length of stay also contributed to the favorable composite outcome observed with the personalized approach.
The investigators acknowledge several limitations, including the unblinded design and potential variability in clinical decision-making across centers. The protocol also required specific bedside assessments that may be subject to interobserver variation and could be perceived as labor-intensive. However, most patients achieved CRT normalization with early, lower-tier interventions, and the strategy proved feasible across diverse health care settings.
Overall, the findings support the use of a personalized hemodynamic resuscitation strategy targeting capillary refill time in the early management of septic shock. By focusing on tissue perfusion rather than solely on global hemodynamic variables, this approach may help clinicians reduce the burden of organ support and improve meaningful outcomes for patients during the critical early phase of septic shock.
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