Flap Monitoring, Inflammation, Thrombosis, Oxidative Stress, Glycocalyx, Anesthesia, Surgery, Flap Ischemia, Flap Necrosis, Flap Failure Risk Factors, Microsurgery
Conditions
Keywords
SOD-1, IL-6, IL-10, VEGF, Syndecan-1, Dexmedetomidine, SDF, PAI-1, Flap Failure, Flap Salvage
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.
Interventions
DRUGNaCl 0,9%
NaCl 0.9% continuous intravenous infusion during microsurgical reconstruction surgery in cancer patients, started after anesthesia induction and maintained intraoperatively and up to 48 hours postoperatively.
DRUGDexmedetomidine
Dexmedetomidine continuous intravenous infusion during microsurgical reconstruction surgery in cancer patients, started after anesthesia induction and maintained intraoperatively and up to 48 hours postoperatively, titrated to maintain target sedation and hemodynamic stability.
Sponsors
Dharmais National Cancer Center Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
This study is a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the impact of perioperative dexmedetomidine administration on the success of microsurgical reconstruction in cancer patients. The intervention group will receive dexmedetomidine infusion during surgery, while the control group will receive a placebo. The study focuses on assessing surgical outcomes, particularly flap survival, alongside biochemical and histological markers related to endothelial glycocalyx integrity, inflammatory response, thrombosis, angiogenesis, oxidative stress, and microcirculatory function.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Indonesia
Contacts
Primary ContactGardian Lukman Hakim, Anestesiologist
Outcome results
None listed