Clinical Question: Does personalized resuscitation improve outcomes in early septic shock when targeting capillary refill compared to usual care?
Background: Resuscitation in early septic shock is focused on improving tissue perfusion and the correction or prevention of severe metabolic derangements. Individualized management to optimize treatment of septic shock remains unclear.
Study Design: Multicenter, randomized, clinical trial
Setting: 86 intensive care units across 19 countries in North and South America, Europe, and Asia
Synopsis: 1,501 adult patients with septic shock (defined as suspected or confirmed infection, lactate greater than 2 mmol/L, and requiring vasoactive medication to maintain mean arterial pressure greater than 65 after at least 1 liter of intravenous fluid) were randomized to the trial protocol versus usual care over six hours. The capillary refill timing (CRT) algorithm was two-tiered and based on utilization of CRT as a target of hemodynamic resuscitation, identification of the patient’s baseline hemodynamics, assessment of fluid responsiveness, and two one-hour hemodynamic tests with a prescribed method for CRT assessment.
The primary outcome was a hierarchical composite of mortality, duration of vital support, and length of hospital stay measured 28 days following randomization. There was statistical significance in the composite primary outcome (P=0.04) but not in the individual components (measured as secondary outcomes).
There were multiple limitations to the trial, including that it was unblinded to both physicians and patients, there was interrater variability in the specific measurements used, and the protocol was labor-intensive, which likely resulted in more frequent hemodynamic reassessment in the CRT group, which may have affected outcomes and also may be clinically impractical.
Bottom Line: There is data to support an individualized approach using CRT for hemodynamic resuscitation in early septic shock, but further research is likely needed to establish a practical clinical approach to its utilization.
Citation: ANDROMEDA-SHOCK-2 Investigators for the ANDROMEDA Research Network et al. Personalized hemodynamic resuscitation targeting capillary refill time in early septic shock: the ANDROMEDA-SHOCK-2 randomized clinical trial. JAMA. 2025;334(22):1988-1999. doi:10.1001/jama.2025.20402.
Dr. Gallagher
Dr. Gallagher is a hospitalist at UC San Diego Health in San Diego.