Original Investigation
Caring for the Critically Ill Patient
Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial
The ANDROMEDA-SHOCK-2 Investigators for the ANDROMEDA Research Network, Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), and Latin American Intensive Care Network (LIVEN)
JAMA Published Online: October 29, 2025
doi: 10.1001/jama.2025.20402
Key Points
Question Does a personalized hemodynamic resuscitation strategy targeting capillary refill time normalization improve outcomes in early septic shock compared with usual care?
Findings In this randomized clinical trial including 1467 patients with septic shock treated in 86 intensive care units, a personalized hemodynamic resuscitation strategy had a significant beneficial effect on the composite hierarchical outcome comprising mortality, duration of vital support, and length of stay through 28 days after randomization, compared with usual care (win ratio, 1.16).
Meaning A personalized hemodynamic resuscitation strategy targeting capillary refill time normalization improves patient-centered outcomes in early septic shock.
Abstract
Trial of Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock
Visual Abstract.
Importance The optimal strategy for hemodynamic resuscitation in early septic shock remains uncertain.
Objective To determine the effect of a personalized hemodynamic resuscitation protocol targeting capillary refill time (CRT-PHR) on a hierarchical composite outcome of mortality, duration of vital support, and length of hospital stay.
Design, Setting, and Participants This randomized clinical trial was conducted in 86 centers in 19 countries. Patients within the first 4 hours of septic shock were included between March 2022 and April 2025, with last follow-up in July 2025.
Interventions Patients were randomized to undergo CRT-PHR (n = 720), including assessment of pulse pressure, diastolic arterial pressure, fluid responsiveness, and bedside echocardiography, to tailor fluids, vasopressors, and inotropes, vs usual care (n = 747).
Main Outcomes and Measures The primary outcome was a hierarchical composite of mortality, duration of vital support (vasoactives, mechanical ventilation, and kidney replacement therapy), and length of hospital stay assessed at 28 days. A win ratio was calculated for the primary outcome by comparing all possible patient pairs, starting with the first event in the hierarchy and stratified by median APACHE (Acute Physiology and Chronic Health Evaluation) II score at admission. Secondary outcomes were mortality, vital support–free days, and length of hospital stay at 28 days.
Results From 1501 randomized patients, 1467 were included in the primary analysis (mean age, 66 [17] years; 43.3% female). There were 131 131 wins (48.9%) in the CRT-PHR group vs 112 787 (42.1%) in the usual care group for the hierarchical composite primary outcome, with a win ratio of 1.16 (95% CI, 1.02-1.33; P = .04). Individual wins for death were 19.1% vs 17.8%; duration of vital support, 26.4% vs 21.1%; and length of hospital stay, 3.4% vs 3.2% in the intervention vs usual care groups, respectively.
Conclusions and Relevance Among patients with early septic shock, a personalized hemodynamic resuscitation protocol targeting capillary refill time was superior to usual care for the primary composite outcome, primarily due to a lower duration of vital support.
Trial Registration ClinicalTrials.gov Identifier: NCT05057611
