Physiological limits of capillary refill time: a human endotoxemia study.

BACKGROUND: The capillary refill test is a widely used bedside marker of tissue perfusion, but its reliability during acute inflammation is not well characterised. The guiding 3-s threshold rests on limited physiological validation and on visual assessment with high observer variability. How finger capillary refill time (CRT) behaves during acute inflammation remains unclear. Using quantitative capillary refill time (qCRT), which removes observer variability, we determined how finger qCRT behaves over an acute inflammatory episode in a controlled human endotoxemia model. METHODS: In a double-blind, randomized, crossover study, 25 healthy volunteers received an intravenous bolus of Escherichia coli lipopolysaccharide (0.8 ng/kg) or saline placebo. Finger qCRT was measured by polarized reflectance imaging at baseline and 1.5, 3.5, and 5 h, and analysed with censored (Tobit) mixed-effects models adjusting for physiological covariates. RESULTS: Finger qCRT followed a biphasic course that crossed the 3-s clinical threshold in both directions within a single inflammatory episode. From a baseline near 3.5 s, it was prolonged to 8.31 s at 1.5 h, with 14 of 25 reaching the 10-s ceiling, then shortened to 1.27 s at 5 h during persisting systemic inflammation. Estimated marginal contrasts against placebo were 4.13 s and - 3.10 s at these time points (both p < 0.0001). The early prolongation persisted after adjustment for physiological covariates, whereas the late shortening was attenuated after adjustment for concurrent thermoregulatory and haemodynamic covariates. Skin temperature was the strongest qCRT covariate, with each standard-deviation increase associated with a 1.62 s decreased qCRT. No formal mediation analysis was performed. Resting values were highly variable, with between-subject differences explaining a minority of total variance (intraclass correlation 0.30). CONCLUSIONS: Finger qCRT tracks the course of acute systemic inflammation but crosses the 3-s clinical threshold in both directions within a single episode. Because between-subject differences account for a minority of total variance and resting values depend strongly on skin temperature, a single value against a fixed threshold is unreliable, whereas change over time within a participant is informative. These findings in healthy participants are not directly generalizable to septic shock and require confirmation in prospective patient studies before informing clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT06618716. Registered September 27, 2024.