Dexmedetomidine enhances recovery after gastrointestinal cancer surgery by protecting the endothelial glycocalyx: A randomized, double-blind, placebo-controlled study

Abstract

BACKGROUND

The vascular endothelial glycocalyx (VEG) plays a critical role in maintaining vascular barrier integrity, regulating inflammation, and ensuring microcirculatory homeostasis. Surgical stress and systemic inflammation can disrupt the glycocalyx, leading to endothelial dysfunction, impaired microcirculation, and adverse postoperative outcomes. dexmedetomidine (DEX), an α2-adrenergic agonist with anti-inflammatory and organ-protective properties, has been suggested in preclinical and clinical studies to mitigate glycocalyx degradation, yet evidence in gastrointestinal cancer surgery remains limited.

AIM

To determine whether perioperative DEX attenuates surgical inflammation-induced VEG degradation and preserves endothelial barrier function in patients undergoing gastrointestinal cancer resection.

METHODS

This was a prospective, single-center, randomized, double-blind, placebo-controlled trial conducted at the First Affiliated Hospital of University of Science and Technology of China. A total of 110 patients undergoing elective gastric or colorectal tumor resection were randomly assigned (1:1) to receive intraoperative DEX or saline placebo. Anesthesia and analgesia were standardized across groups. The primary outcome was plasma syndecan-1 concentration, a marker of endothelial glycocalyx injury, measured at four perioperative timepoints (T0-T3). Secondary outcomes included inflammatory biomarkers [interleukin-6 (IL-6), tumor necrosis factor-alpha, C-reactive protein, heparan sulfate], microcirculatory parameters [perfused vessel density (PVD), flow index, P(v-a)CO₂, lactate], and clinical endpoints [extubation time, opioid use, Visual Analog Scale (VAS) scores, Quality of Recovery-15 Questionnaire (QoR-15), length of stay, and 30-day complications]. Postoperative complications were defined by Clavien-Dindo criteria and adjudicated by blinded investigators. The trial was registered prospectively (ChiCTR2500109633) and powered to detect a clinically meaningful difference in syndecan-1 levels.

RESULTS

A total of 110 patients were randomized equally to the DEX or control group, with well-balanced baseline characteristics. Compared with controls, DEX significantly reduced postoperative infections (7% vs 16%) and intensive care unit admissions (7% vs 13%), shortened extubation time (13.1 ± 3.0 minutes vs 18.4 ± 4.0 minutes; P < 0.001), and decreased opioid use (23.1 ± 5.0 mg vs 27.3 ± 6.0 mg; P = 0.004) and VAS pain scores (P = 0.002). At abdominal closure, DEX attenuated endothelial glycocalyx injury, as evidenced by lower plasma syndecan-1 (44.72 ± 7.10 ng/mL vs 48.73 ± 6.26 ng/mL; P = 0.002) and heparan sulfate levels (P = 0.001). IL-6 was significantly reduced at 24 hours (110.77 ± 29.72 pg/mL vs 138.86 ± 35.95 pg/mL; P < 0.0001) and positively correlated with syndecan-1 (r = 0.71). Microcirculatory function improved with DEX, including higher PVD (21.40 ± 3.50 mm/mm² vs 19.94 ± 2.93 mm/mm²; P = 0.019), increased flow index, lower P(v-a)CO₂ (P < 0.001), and reduced lactate (P = 0.003). DEX also improved recovery outcomes, with higher QoR-15 scores (P = 0.001), shorter hospital stays (6.49 ± 1.29 days vs 7.29 ± 1.59 days; P = 0.005), and fewer overall 30-day complications (12.7% vs 30.9%; P = 0.036). Receiver operating characteristic analysis identified syndecan-1 > 45 ng/mL at abdominal closure as a potential predictor of postoperative complications (area under the curve = 0.68, 95%CI: 0.59-0.76), and multivariable analysis showed a near-significant association (OR = 2.88, P = 0.057). Subgroup analyses demonstrated consistent anti-inflammatory and endothelial-protective effects of DEX across age and surgical approach strata.

CONCLUSION

Perioperative administration of DEX confers significant endothelial-protective effects by mitigating glycocalyx degradation, suppressing systemic inflammation, and promoting enhanced postoperative recovery. These findings support its clinical utility as a valuable adjunctive therapy in the perioperative management of patients undergoing oncologic gastrointestinal surgery.

Keywords: Dexmedetomidine; Vascular endothelial glycocalyx; Syndecan-1; Surgical inflammation; Gastrointestinal neoplasms

Core Tip: This randomized controlled trial demonstrates that perioperative dexmedetomidine (DEX) infusion attenuates vascular endothelial glycocalyx degradation (as evidenced by reduced syndecan-1 and heparan sulfate levels) and suppresses systemic inflammation in patients undergoing gastrointestinal tumor resection. These mechanistic benefits were associated with improved microcirculatory perfusion, reduced postoperative complications, and enhanced recovery, including shorter hospital stay. The study identifies syndecan-1 as a potential biomarker for perioperative risk stratification and supports the integration of DEX as an endothelial-protective adjunct within Enhanced Recovery after Surgery protocols for oncologic surgery.