The Effect of Dexmedetomidine Administration on the Success of Reconstructive Microsurgery in Cancer Patients: A Study of Glycocalyx Integrity, Inflammatory Response, Thrombosis, Angiogenesis, Oxidative Stress, and Tissue Microcirculation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Flap Viability Score
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This trial employs a double-blind masking design in which both participants and clinical staff, including surgeons and outcome assessors, are blinded to the treatment allocation. The dexmedetomidine and placebo infusions will be prepared and administered by an independent pharmacist or designated unblinded personnel not involved in patient care or data collection, ensuring unbiased assessment of outcomes.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (aged 18-65 years) diagnosed with cancer who are scheduled to undergo microsurgical flap reconstruction.
- •Patients within the age range of 18 to 65 years at the time of enrollment.
- •Patients who provide written informed consent to participate in the study.
排除标准
- •Patients with a history of uncontrolled diabetes mellitus.
- •Patients diagnosed with chronic kidney disease.
- •Patients with known liver failure.
- •Patients receiving corticosteroid therapy prior to surgery.
- •Patients with uncontrolled hypertension.
- •Patients with a history of chemotherapy or radiotherapy prior to surgery.
- •Patients diagnosed with preoperative sepsis.
- •Patients requiring perioperative vasopressor support.
- •Patients with a history of prior surgery in the same operative field.
- •Patients who decline to participate in the study.
研究组 & 干预措施
Placebo Group
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.
干预措施: NaCl 0,9% (Drug)
Dexmedetomidine Group
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.
干预措施: Dexmedetomidine (Drug)
结局指标
主要结局
Flap Viability Score
时间窗: 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.
次要结局
- Vascular Endothelial Growth Factor (VEGF) Level(Baseline (preoperative) and 12 hours postoperatively)
- Tissue Syndecan-1 Expression(Intraoperative tissue sampling)
- Tissue Superoxide Dismutase 1 (SOD1) Expression(Intraoperative tissue sampling)
- Interleukin-6 (IL-6) Level(Baseline (preoperative) and 12 hours postoperatively)
- Interleukin-10 (IL-10) Level(Baseline (preoperative) and 12 hours postoperatively)
- Plasminogen Activator Inhibitor-1 (PAI-1) Level(Baseline (preoperative) and 12 hours postoperatively)
- Microcirculation Assessment Using Sidestream Dark Field (SDF) Imaging(Immediate postoperative (sublingual site), 12 hours postoperative (flap tissue), and 48 hours postoperative (flap tissue))
研究者
Gardian Lukman Hakim
Anestesiologist
Dharmais National Cancer Center Hospital