Effect of Dexmedetomidine on Microsurgery Reconstruction in Cancer Patient

Not Applicable

Recruiting

• Conditions: Flap Monitoring; Inflammation; Thrombosis; Oxidative Stress; Glycocalyx; Anesthesia; Surgery; Flap Ischemia; Flap Necrosis; Flap Failure Risk Factors
• Interventions: Drug: NaCl 0,9%; Drug: Dexmedetomidine

• Registration Number: NCT06993740
• Lead Sponsor: Dharmais National Cancer Center Hospital

Brief Summary

This double-blinded randomized controlled trial aims to investigate the effect of intraoperative dexmedetomidine administration on early flap viability and microvascular integrity in cancer patients undergoing elective microvascular reconstructive surgery. The primary outcome is clinical flap viability within 48 hours postoperatively, assessed using a standardized scoring system based on flap color, temperature, capillary refill time, and tissue turgor. Secondary outcomes include the evaluation of biomarkers related to endothelial glycocalyx degradation (syndecan-1), oxidative stress (SOD-1), inflammation (IL-6, IL-10), thrombosis (PAI-1), and angiogenesis (VEGF), as well as microcirculatory assessment using Sidestream Dark Field (SDF) imaging. The study is designed to determine whether dexmedetomidine improves early surgical outcomes by modulating pathophysiological processes involved in microvascular flap success.

Detailed Description

Microvascular reconstructive surgery is commonly performed in cancer patients following tumor excision to restore both form and function. However, flap failure remains a major postoperative complication, particularly in oncologic patients who are more susceptible to inflammation, endothelial injury, thrombosis, and impaired tissue perfusion. Recent evidence suggests that anesthetic agents may play a role in modulating microvascular and endothelial responses during surgery, providing opportunities to enhance surgical outcomes.

Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist known for its sedative, analgesic, sympatholytic, and anti-inflammatory properties. In addition to its hemodynamic stability profile, dexmedetomidine has demonstrated protective effects on the endothelium and glycocalyx, along with potential benefits in preserving tissue perfusion and reducing inflammatory and thrombotic responses. However, its clinical impact on microvascular flap outcomes in cancer patients undergoing reconstructive surgery has not been well established.

This study is a double-blinded randomized controlled trial involving 60 adult cancer patients (aged 18 to 65 years) undergoing elective microvascular reconstructive surgery. Participants will be randomized into two groups: an intervention group receiving intravenous dexmedetomidine, and a control group receiving normal saline. Both infusions will be prepared in identical syringes to maintain allocation concealment.

The primary outcome of this study is flap viability within the first 48 hours postoperatively, assessed using a standardized clinical scoring system. This scoring incorporates four key parameters: flap color, surface temperature, capillary refill time, and tissue turgor. Each parameter is evaluated to provide an integrated assessment of early microvascular flap function.

The secondary outcomes include exploratory analysis of biological processes related to microvascular integrity and function. These outcomes include the evaluation of biomarkers indicative of endothelial glycocalyx degradation (syndecan-1), oxidative stress (SOD-1), inflammatory activity (IL-6 and IL-10), prothrombotic state (PAI-1), and angiogenesis (VEGF). These markers will be analyzed from plasma and/or flap tissue at defined perioperative time points to better understand the physiological impact of dexmedetomidine.

Furthermore, real-time assessment of tissue microcirculation will be performed using Sidestream Dark Field (SDF) imaging, a non-invasive technique that enables visualization of capillary density and flow quality in the reconstructed flap area. This provides an objective and dynamic measure of tissue-level perfusion and complements the clinical viability scoring.

All patients will undergo general anesthesia induced with fentanyl 2 µg/kg and propofol 1-2 mg/kg. In the intervention group, dexmedetomidine will be administered with a loading dose of 1 µg/kg over 10 minutes, followed by a continuous infusion at 0.4 µg/kg/hour until 48 hours after surgery. The control group will receive a matched volume of normal saline according to the same timeline.

This study is expected to provide new insights into the role of dexmedetomidine in enhancing microvascular outcomes in cancer patients undergoing reconstructive surgery, potentially offering a simple yet impactful strategy to improve flap success and postoperative recovery.

Study Timeline

• Study First Submitted: 2025-05-19
• Study First Submitted QC: 2025-05-19
• Study First Posted: 2025-05-29
• Status Verified: 2025-06
• Study Start: 2025-06-10
• Last Update Submitted: 2025-06-11
• Last Update Posted: 2025-06-15
• Primary Completion: 2026-05-26
• Study Completion: 2026-08-22

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Adult patients (aged 18-65 years) diagnosed with cancer who are scheduled to undergo microsurgical flap reconstruction.
2. Patients within the age range of 18 to 65 years at the time of enrollment.
3. Patients who provide written informed consent to participate in the study.

Exclusion Criteria

1. Patients with a history of uncontrolled diabetes mellitus.
2. Patients diagnosed with chronic kidney disease.
3. Patients with known liver failure.
4. Patients receiving corticosteroid therapy prior to surgery.
5. Patients with uncontrolled hypertension.
6. Patients with a history of chemotherapy or radiotherapy prior to surgery.
7. Patients diagnosed with preoperative sepsis.
8. Patients requiring perioperative vasopressor support.
9. Patients with a history of prior surgery in the same operative field.
10. Patients who decline to participate in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Group	NaCl 0,9%	Participants in this arm will receive a continuous intravenous infusion of placebo (normal saline) administered in the same manner and duration as the dexmedetomidine group-starting after anesthesia induction and continuing for up to 48 hours postoperatively. This control infusion allows comparison of clinical and biochemical outcomes without the influence of dexmedetomidine.
Dexmedetomidine Group	Dexmedetomidine	Participants assigned to this arm will receive a continuous intravenous infusion of dexmedetomidine starting after anesthesia induction and maintained throughout the surgical procedure as well as for up to 48 hours postoperatively. The infusion dose will be titrated to achieve target sedation levels while maintaining stable hemodynamics. This extended administration aims to investigate the effects of dexmedetomidine on endothelial glycocalyx preservation, inflammation modulation, thrombosis prevention, angiogenesis promotion, oxidative stress reduction, and improvement of tissue microcirculation during both intraoperative and early postoperative periods.

Primary Outcome Measures

Name	Time	Method
Flap Viability Score	48 hours postoperatively	Clinical evaluation of flap viability using a standardized scoring system based on four parameters: flap color, surface temperature, capillary refill time, and tissue turgor. Each parameter is scored individually and combined into a composite viability score. The total score reflects the degree of perfusion and tissue viability at 48 hours after microsurgical reconstruction.

Secondary Outcome Measures

Name	Time	Method
Vascular Endothelial Growth Factor (VEGF) Level	Baseline (preoperative) and 12 hours postoperatively	Assessment of systemic angiogenic activity by measuring VEGF levels in serum using ELISA.
Tissue Syndecan-1 Expression	Intraoperative tissue sampling	Quantitative evaluation of syndecan-1 expression in flap tissue using immunohistochemistry (IHC) to assess endothelial glycocalyx integrity. Image analysis software will be used for objective quantification.
Tissue Superoxide Dismutase 1 (SOD1) Expression	Intraoperative tissue sampling	Quantitative analysis of SOD1 expression in flap tissue using IHC, serving as a marker of oxidative stress response. Expression will be measured using image-based digital quantification.
Interleukin-6 (IL-6) Level	Baseline (preoperative) and 12 hours postoperatively	Measurement of systemic IL-6 concentrations using Electrochemiluminescence Immunoassay (ECLIA) as an indicator of systemic inflammatory response.
Interleukin-10 (IL-10) Level	Baseline (preoperative) and 12 hours postoperatively	Quantification of serum IL-10 levels using Enzyme-Linked Immunosorbent Assay (ELISA), to evaluate anti-inflammatory cytokine response.
Plasminogen Activator Inhibitor-1 (PAI-1) Level	Baseline (preoperative) and 12 hours postoperatively	Measurement of PAI-1 levels in serum using ELISA to evaluate the fibrinolytic balance and thrombotic tendency.
Microcirculation Assessment Using Sidestream Dark Field (SDF) Imaging	Immediate postoperative (sublingual site), 12 hours postoperative (flap tissue), and 48 hours postoperative (flap tissue)	Evaluation of microcirculatory parameters using SDF imaging, including vessel density, perfused vessel density, and flow pattern. Measurements will be conducted at the sublingual site and in the flap tissue at specified time points to assess systemic and local microcirculatory dynamics.

Trial Locations

Locations (1)

Dharmais National Cancer Center Hospital; 🇮🇩 Jakarta, DKI Jakarta, Indonesia