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

TL;DR

Capillary refill time (the classic bedside test where you press a fingertip until it turns white, then time how fast color returns) doesn't behave as expected during acute inflammation. A controlled human endotoxemia study found that this marker swings wildly in both directions within a single inflammatory episode, crossing the standard 3-second clinical threshold twice and reaching as high as 8+ seconds, suggesting the fixed threshold is unreliable .

What the Study Found

Capillary refill time (CRT) has long been a staple of bedside clinical assessment. Press on a fingernail or fingertip until the blood drains out and the skin blanches. Release, and count how many seconds it takes for color to return. The bedside rule: if it takes longer than 3 seconds, something is wrong with tissue perfusion. Yet this threshold rests on thin physiological ice. Observers disagree on what they're seeing. The test has never been properly characterized during acute inflammation.

Researchers at Copenhagen University Hospital set out to fix this. They used quantitative capillary refill time (qCRT), measured by polarized reflectance imaging, to eliminate the subjectivity problem. In a double-blind, randomized crossover study, 25 healthy volunteers received either intravenous E. coli lipopolysaccharide (LPS, 0.8 ng/kg) or saline placebo. This induces a controlled, temporary systemic inflammatory response: fever, activation of immune cascades, changes in blood flow. Researchers measured qCRT at baseline and at 1.5, 3.5, and 5 hours afterward.

The results shattered the simple model. Baseline qCRT averaged around 3.5 seconds, already at or near the clinical threshold. After LPS, qCRT followed a biphasic course. At 1.5 hours, it prolonged dramatically to 8.31 seconds on average. Fourteen of the 25 participants hit the measurement ceiling of 10 seconds. This is the direction you'd expect during inflammatory shock: impaired perfusion, delayed capillary refill. But by 5 hours, as inflammation persisted, qCRT reversed course entirely, shortening to just 1.27 seconds. The finger was now refilling faster than baseline, despite active systemic inflammation. The contrast against placebo at both time points was statistically robust (p < 0.0001).

This biphasic pattern raises a physiological question. The early prolongation held even after adjusting for heart rate, blood pressure, and other hemodynamic variables. The late shortening, however, was attenuated when researchers accounted for skin temperature and thermoregulatory changes. Skin temperature emerged as the dominant predictor: for every standard-deviation increase in skin temperature (roughly 2.8 degrees Celsius), qCRT decreased by 1.62 seconds. That's a massive effect. The authors note that resting CRT values were highly variable between people and showed low reproducibility (intraclass correlation 0.30), meaning individual baseline values predicted only 30% of the variance. The other 70% remains unexplained, or driven by unmeasured factors.

What This Means for You

This study does not directly translate to clinical practice yet. All participants were healthy, and the endotoxemic response is not the same as septic shock in hospitalized patients. The authors explicitly state their findings require confirmation in prospective patient studies before informing clinical decisions.

That said, the findings carry important caution flags for bedside medicine:

The 3-second threshold is unreliable without context. A single measurement against a fixed cutoff can be misleading. During the early phase of inflammation in this study, most participants would have been flagged as having poor perfusion by that rule, even though the underlying physiology was transient and compensating. By hour 5, the opposite error would occur: normal or fast refill time despite persisting systemic illness.

Change over time within an individual is more informative than a single value. The study shows that trend matters more than threshold crossing. If you're a clinician using this test, serial measurements on the same patient, compared against their own baseline (when well), capture more signal than a population-based cutoff.

Skin temperature is a major confounder. A cold finger will naturally have slower capillary refill, independent of perfusion state. A warm finger will refill quickly. If this test is used clinically, environmental temperature control and skin temperature measurement become relevant confounders to acknowledge.

Observer-dependent visual assessment adds noise on top of biological variability. The shift to quantitative measurement (using imaging) reduced variance, but biological variability remains high. This implies that any clinical rollout of CRT assessment should either use objective measurement devices or acknowledge that visual assessment alone carries substantial uncertainty.

Study Details

Sources

Poulsen MK, et al. Physiological limits of capillary refill time: a human endotoxemia study. *Critical Care*. 2024. PubMed: 42706575