Why Capillary Refill Time Slows in Sepsis: Six Mechanisms Mapped

Capillary refill time, once a quick bedside observation, has become an actual resuscitation target in septic shock. A new narrative review in Critical Care sets out a framework for understanding why the sign can become prolonged in sepsis and septic shock, proposing six mechanisms that are not mutually exclusive and are broadly ordered according to the strength and directness of the supporting evidence.

The review, authored by Ricardo Castro, Eduardo Kattan, Tomas Urbina, Paulo Melo, Matthias Jacquet-Lagrèze, Stefan Andrei, Pierre-Gregoire Guinot, Hafid Ait-Oufella, Gustavo Ospina-Tascón, Christopher Lai, Jan Bakker and Glenn Hernández, together with the COPERNICUS Study Group, was published on 26 October 2026 as an open access article. The authors emphasize that although capillary refill time is simple to measure, it reflects the restoration of cutaneous microvascular blood flow after transient external compression, and therefore integrates multiple physiological processes rather than signaling a single failure.

The first and best-supported mechanism is reduced effective tissue perfusion, which may trigger sympathetically mediated redistribution of blood flow away from the skin.

Second, the review considers inadequate upstream flow generation. Hypovolemia, ventricular dysfunction, adverse ventriculo-arterial coupling, arrhythmias, or excessive afterload can each limit the flow delivered to the microcirculation, slowing the return of color to compressed skin. Third, inflammatory endothelial and microvascular injury may impair reactive hyperemia through glycocalyx degradation, edema, capillary derecruitment, microvascular obstruction, altered hemorheology, and flow heterogeneity.

Fourth, the authors describe the loss of coordinated myogenic, neurogenic, and endothelial vasomotor regulation, which may uncouple systemic pressure from effective capillary recruitment. In other words, a blood pressure reading that appears adequate at the arterial level may not translate into properly perfused capillaries when the local control mechanisms that normally match flow to demand are disrupted.

Fifth, severe vasoplegia may alter the arterial closing-pressure boundary and vascular-waterfall behavior, potentially increasing the pressure dependence of microvascular flow. The review is careful to note that CRT-specific observational associations support this proposal, but that its causal contribution to capillary refill time prolongation remains unproven. Sixth, elevated venous and interstitial pressures could impair microvascular perfusion; the authors describe this proposed contribution as hypothesis-generating because direct CRT-specific evidence is lacking.

A central message of the framework is that these mechanisms may coexist, with their relative contributions varying according to hemodynamic phenotype, disease severity, treatment, and the timing of assessment. A prolonged capillary refill time early in resuscitation may therefore reflect a very different physiological situation than the same finding hours later, even in the same patient.

Because no single mechanism can be assumed, the authors argue that capillary refill time should be interpreted dynamically and integrated with other measurements, including preload responsiveness, cardiac output, arterial pressure, vasopressor exposure, skin temperature, mottling, venous congestion, and complementary perfusion markers. Responses to controlled hemodynamic interventions may help characterize what the authors call peripheral perfusion responsiveness, although they caution that such responses cannot, by themselves, establish the underlying mechanism.

The review is explicitly framed as a way to generate testable hypotheses about why capillary refill time becomes prolonged, while distinguishing established physiology and observational associations from unproven causal mechanisms. For clinicians, the practical implication is that a slow refill in septic shock is not a single-answer finding: it is a composite signal whose meaning depends on the surrounding hemodynamic context, and whose interpretation should evolve as resuscitation proceeds.

Subject of Research: Pathophysiological mechanisms that may prolong capillary refill time in sepsis and septic shock

Article Title: Capillary refill time prolongation in sepsis and septic shock: supported and potential mechanisms from a pathophysiological perspective

Article References: Castro, R., Kattan, E., Urbina, T., Melo, P., Jacquet-Lagrèze, M., Andrei, S., Guinot, P.-G., Ait-Oufella, H., Ospina-Tascón, G., Lai, C., Bakker, J., Hernández, G., & COPERNICUS Study Group (2026). Capillary refill time prolongation in sepsis and septic shock: supported and potential mechanisms from a pathophysiological perspective. Critical Care. https://doi.org/10.1186/s13054-026-06409-8

Image Credits: AI Generated

DOI: 10.1186/s13054-026-06409-8

Keywords: capillary refill time, sepsis, septic shock, microcirculation, resuscitation, endothelial injury, vasoplegia, perfusion, hemodynamics, narrative review, Capillary, refill