Effect of Dexmedetomidine on Microsurgery Reconstruction in Cancer Patient

NCT06993740 | Recruiting

• 1 other identifier: DP.04.03/D.XII/5182/2025
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

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.

Conditions

Flap Monitoring; Inflammation; Thrombosis; Oxidative Stress; Glycocalyx; Anesthesia; Surgery; Flap Ischemia; Flap Necrosis; Flap Failure Risk Factors; Microsurgery

Keywords

SOD-1; IL-6; IL-10; VEGF; Syndecan-1; Dexmedetomidine; SDF; PAI-1; Flap Failure; Flap Salvage

Outcome Measures

Primary Outcomes (1)

• Flap Viability Score

  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.

  48 hours postoperatively

Secondary Outcomes (7)

• 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

• Vascular Endothelial Growth Factor (VEGF) Level

  Baseline (preoperative) and 12 hours postoperatively

Study Arms (2)

Placebo Group

PLACEBO COMPARATOR

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.

Drug: NaCl 0,9%

Dexmedetomidine Group

ACTIVE COMPARATOR

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.

Drug: Dexmedetomidine

Interventions

NaCl 0,9% DRUG

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.

Also known as: Normal Saline

Placebo Group

Dexmedetomidine DRUG

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.

Also known as: Dexmedetomidine Hydrochloride

Dexmedetomidine Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dharmais National Cancer Center Hospital: lead

Study Sites (2)

Dharmais National Cancer Center Hospital

Jakarta, DKI Jakarta, 11420, Indonesia

NOT YET RECRUITING

Dharmais National Cancer Center Hospital

Jakarta, DKI Jakarta, 11420, Indonesia

RECRUITING

Related Publications (19)

• Petersen SM, Greisen G, Hyttel-Sorensen S, Hahn GH. Sidestream dark field images of the microcirculation: intra-observer reliability and correlation between two semi-quantitative methods for determining flow. BMC Med Imaging. 2014 May 6;14:14. doi: 10.1186/1471-2342-14-14.

  PMID: 24885423 BACKGROUND

• Atmodiwirjo P, Priambodo PS, Dilogo IH. Pengaruh Titrasi Indocyanine Green terhadap Intensitas Fluoresensi pada Perfusi Flap Bebas dalam Menunjang Tindakan Bedah Mikro Rekonstruksi: Tinjauan terhadap Suhu, TcPCO2, TcPO2, Ekspresi HIF-1α, dan Histopatologi Flap. Universitas Indonesia; 2024.

  BACKGROUND

• Preidl RHM, Reuss S, Neukam FW, Kesting M, Wehrhan F. Endothelial inflammatory and thrombogenic expression changes in microvascular anastomoses - An immunohistochemical analysis. J Craniomaxillofac Surg. 2021 May;49(5):422-429. doi: 10.1016/j.jcms.2021.02.006. Epub 2021 Feb 12.

  PMID: 33608202 BACKGROUND

• Chen Z, Shao DH, Mao ZM, Shi LL, Ma XD, Zhang DP. Effect of dexmedetomidine on blood coagulation in patients undergoing radical gastrectomy under general anesthesia: A prospective, randomized controlled clinical trial. Medicine (Baltimore). 2018 Jul;97(27):e11444. doi: 10.1097/MD.0000000000011444.

  PMID: 29979445 BACKGROUND

• Fang M, He J, Ma X, Li W, Lin D. Protective effects of dexmedetomidine on the survival of random flaps. Biomed Pharmacother. 2020 Aug;128:110261. doi: 10.1016/j.biopha.2020.110261. Epub 2020 May 20.

  PMID: 32446114 BACKGROUND

• Wijanarko B, Airlangga PS, Fitriati M, Sumartono C, Kriswidyatomo P, Lestari P. Effect of dexmedetomidine administration on malondialdehyde levels in lower extremity surgery using tourniquets. Bali Medical Journal. 2023 May 6;12(2):1459-65.

  BACKGROUND

• Li B, Li Y, Tian S, Wang H, Wu H, Zhang A, Gao C. Anti-inflammatory Effects of Perioperative Dexmedetomidine Administered as an Adjunct to General Anesthesia: A Meta-analysis. Sci Rep. 2015 Jul 21;5:12342. doi: 10.1038/srep12342.

  PMID: 26196332 BACKGROUND

• Hsu TC, Lin CH, Sun FJ, Chen MJ. Postoperative Serum Levels of Interleukin-6 are Affected by Age in Patients with Colorectal Cancer. Int J Gerontol. 2017 Jun;11(2):75-9.

  BACKGROUND

• Finke JC, Yang J, Bredell M, Fritschen U von, Glocker MO. Plasma Cytokine and Growth Factor Profiling during Free Flap Transplantation. In: Issues in Flap Surgery. InTech; 2018.

  BACKGROUND

• Lei D, Sha Y, Wen S, Xie S, Liu L, Han C. Dexmedetomidine May Reduce IL-6 Level and the Risk of Postoperative Cognitive Dysfunction in Patients After Surgery: A Meta-Analysis. Dose Response. 2020 Feb 5;18(1):1559325820902345. doi: 10.1177/1559325820902345. eCollection 2020 Jan-Mar.

  PMID: 32076394 BACKGROUND

• Yuki K. The immunomodulatory mechanism of dexmedetomidine. Int Immunopharmacol. 2021 Aug;97:107709. doi: 10.1016/j.intimp.2021.107709. Epub 2021 Apr 29.

  PMID: 33933842 BACKGROUND

• Abassi Z, Armaly Z, Heyman SN. Glycocalyx Degradation in Ischemia-Reperfusion Injury. Am J Pathol. 2020 Apr;190(4):752-767. doi: 10.1016/j.ajpath.2019.08.019. Epub 2020 Feb 6.

  PMID: 32035883 BACKGROUND

• Pillinger NL, Kam P. Endothelial glycocalyx: basic science and clinical implications. Anaesth Intensive Care. 2017 May;45(3):295-307. doi: 10.1177/0310057X1704500305.

  PMID: 28486888 BACKGROUND

• Pang CY, Neligan PC. Flap Pathophysiology and Pharmacology. In: Gurtner GC, Neligan PC, editors. Plastic Surgery, Volume 1: Principles. Fourth Ed. Canada: Elsevier Inc.; 2018. p. 433-443.e7.

  BACKGROUND

• Sigaux N, Philouze P, Boucher F, Jacquemart M, Frobert P, Breton P. Efficacy of the postoperative management after microsurgical free tissue transfer. J Stomatol Oral Maxillofac Surg. 2017 Jun;118(3):173-177. doi: 10.1016/j.jormas.2017.03.007. Epub 2017 Apr 5.

  PMID: 28391079 BACKGROUND

• Han M, Ochoa E, Zhu B, Park AM, Heaton CM, Seth R, Knott PD. Risk Factors for and Cost Implications of Free Flap Take-backs: A Single Institution Review. Laryngoscope. 2021 Jun;131(6):E1821-E1829. doi: 10.1002/lary.29382. Epub 2021 Jan 13.

  PMID: 33438765 BACKGROUND

• Pu LLQ, Song P. Reoperative Microsurgical Free Flap Surgery: Lessons Learned. Ann Plast Surg. 2023 May 1;90(5S Suppl 2):S187-S194. doi: 10.1097/SAP.0000000000003370. Epub 2023 Jan 18.

  PMID: 36752558 BACKGROUND

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

• Riskesdas. Hasil Utama Riskesdas 2018. Kementrian Kesehatan Republik Indonesia. 2018.

  BACKGROUND

MeSH Terms

Conditions

Inflammation; Thrombosis

Interventions

Saline Solution; Dexmedetomidine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Gardian Lukman Hakim, Anestesiologist

CONTACT

81218088113; gardian.hakim@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Anestesiologist

Model Details: 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.

Study Record Dates

• First Submitted: May 19, 2025
• First Posted: May 29, 2025
• Study Start: June 10, 2025
• Primary Completion (Estimated): May 26, 2026
• Study Completion (Estimated): August 22, 2026
• Last Updated: June 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

ID (2)