Effect of Dexmedetomidine on Microsurgery Reconstruction in Cancer Patient

NCT ID: NCT06993740

Last Updated: 2025-06-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-10

Study Completion Date

2026-08-22

Brief Summary

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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

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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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.

Group Type PLACEBO_COMPARATOR

NaCl 0,9%

Intervention Type 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.

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.

Group Type ACTIVE_COMPARATOR

Dexmedetomidine

Intervention Type 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.

Interventions

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NaCl 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.

Intervention Type DRUG

Dexmedetomidine

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.

Intervention Type DRUG

Other Intervention Names

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Normal Saline Dexmedetomidine Hydrochloride

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dharmais National Cancer Center Hospital

OTHER_GOV

Sponsor Role lead

Responsible Party

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Gardian Lukman Hakim

Anestesiologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Dharmais National Cancer Center Hospital

Jakarta, DKI Jakarta, Indonesia

Site Status NOT_YET_RECRUITING

Dharmais National Cancer Center Hospital

Jakarta, DKI Jakarta, Indonesia

Site Status RECRUITING

Countries

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Indonesia

Central Contacts

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Gardian Lukman Hakim, Anestesiologist

Role: CONTACT

81218088113 ext. +62

Facility Contacts

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Gardian Lukman Hakim, Anesthesiologist-Intensivist

Role: primary

81218088113 ext. +62

Gardian Lukman Hakim, Anesthesiologist-Intensivist

Role: primary

81218088113

References

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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.

Reference Type BACKGROUND
PMID: 24885423 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 33608202 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29979445 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32446114 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 26196332 (View on PubMed)

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.

Reference Type 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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 32076394 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 33933842 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32035883 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 28486888 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 28391079 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33438765 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36752558 (View on PubMed)

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.

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PMID: 33538338 (View on PubMed)

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

Reference Type BACKGROUND

Other Identifiers

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DP.04.03/D.XII/5182/2025

Identifier Type: -

Identifier Source: org_study_id

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