Capillary Refill Time Targets Trim Early Fluids in Septic Shock Trial

Patients with septic shock who were resuscitated according to capillary refill time received roughly a quarter liter less intravenous fluid in their first six hours than patients guided by lactate targets, according to a single-center randomized controlled trial published in Scientific Reports. In the lactate-targeted group, 41 patients were managed toward an arterial lactate concentration of 2 mmol/L or lower, or a decrease of more than 10 percent per hour. Both strategies were applied for six hours during the optimization phase that follows the initial rescue of the patient.

The prespecified secondary endpoint of six-hour total intravenous fluid input, which the authors subsequently prioritized as the main early resuscitation outcome after the trial fell short of its mortality-based recruitment target, came to a median of 1,135 mL (interquartile range 824 to 1,480 mL) in the capillary refill time group versus 1,350 mL (990 to 1,850 mL) in the lactate group. The Hodges-Lehmann location-shift estimate for the difference was minus 250 mL, with a 95 percent confidence interval of minus 500 to minus 20 mL and a P value of 0.035. Positive fluid balance at both six and 24 hours was also lower in the capillary refill time group, with nominal P values below 0.05.

Despite the reduced fluid exposure, there were no significant between-group differences in capillary refill time itself, arterial lactate concentrations, or norepinephrine dose measured between six and 24 hours, suggesting that the more conservative fluid strategy did not come at the cost of worse perfusion markers or higher vasopressor requirements during the observation window. Downstream clinical outcomes painted a more tentative picture. Twenty-eight-day mortality was 22.7 percent, or 10 of 44 patients, in the capillary refill time group compared with 29.3 percent, or 12 of 41 patients, in the lactate group, corresponding to a risk ratio of 0.78 with a 95 percent confidence interval of 0.38 to 1.60.

The trial was not powered to detect mortality differences, and the authors emphasize that this and all other downstream outcomes must be considered exploratory. Ventilator-free days within 28 days favored the capillary refill time strategy, at a median of 14 days (interquartile range 6.75 to 21.25) versus 12 days (0 to 12), with a Hodges-Lehmann estimate of plus 4.0 days (95 percent confidence interval 1.0 to 8.5; P = 0.005). However, renal replacement therapy-free days and vasopressor-free days did not differ significantly between the two groups, and the authors caution that the clinical importance of the ventilator finding remains uncertain given the trial's size and design.

The study carries several important limitations that the investigators disclose in detail. Because recruitment fell short of the mortality-based sample-size target, the fluid-volume analysis is interpreted as exploratory. A post hoc sensitivity analysis excluding patients whose baseline capillary refill time was already three seconds or less yielded a location-shift estimate of minus 240 mL (95 percent confidence interval minus 500 to 0 mL; P = 0.052; n = 77), leaving the primary fluid finding just outside conventional statistical significance.

The trial was also open-label, and it compares overall target-driven treatment strategies rather than isolating the specific effect of capillary refill time versus lactate as monitoring variables. Registration timing presents a further caveat. Although ethics and scientific review and a written protocol were completed before recruitment began, public registration in the Chinese Clinical Trial Registry (ChiCTR2500107145) was delayed by synchronization and review problems on the registry platform and was ultimately completed retrospectively on August 5, 2025, after enrollment had ended.

The retrospective entry covers the broader combined research program and does not establish prospective primacy of the six-hour fluid-volume endpoint, a limitation the authors explicitly acknowledge. The present trial adds randomized evidence that targeting this measure during the optimization phase is associated with modestly lower early fluid administration in septic shock. The authors conclude that the clinical importance and the fluid-component contribution of the observed difference remain uncertain, and that the findings do not establish improved clinical outcomes.

Subject of Research: Capillary refill time-guided versus lactate-guided fluid resuscitation in septic shock

Article Title: Effect of capillary refill time-guided resuscitation on early fluid administration and fluid balance in septic shock: a single-center randomized controlled trial

Article References: Gao, F., Xu, Y., Li, Z., Xu, H., Hui, J., Liang, C., Chen, Y., Wang, Q., & Liang, F. (2026). Effect of capillary refill time-guided resuscitation on early fluid administration and fluid balance in septic shock: a single-center randomized controlled trial. Scientific Reports. https://doi.org/10.1038/s41598-026-77226-w

Image Credits: AI Generated

DOI: 10.1038/s41598-026-77226-w

Keywords: septic shock, capillary refill time, lactate, fluid resuscitation, randomized controlled trial, hemodynamic optimization, fluid balance, ventilator-free days, intensive care, perfusion, Effect, capillary