Improving Tissue Oxygenation in Breast Reconstruction Surgery

NCT04020172 | Completed Phase 1

• 1 other identifier: ANAE-341-19
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

Breast reconstruction is an integral part of breast cancer care. There are two main types of breast reconstruction: alloplastic (using implants), and autologous (using patient's tissue). The latter creates a more natural breast mound, and avoids long-term concerns requiring surgical re-intervention associated with implant-based surgery. The deep inferior epigastric perforator (DIEP) flap is the gold standard technique in autologous breast reconstruction. Complications, however, do occur with DIEP flap surgery and often stem from poor flap perfusion/oxygenation. Hence, the development of strategies to enhance flap perfusion (e.g., optimal perioperative fluid therapy) is essential. Current perioperative fluid therapy is usually guided by subjective criteria which leads to wide variations in fluids administered. We will randomly assign DIEP flap patients to receive optimal (cardiac output-guided) fluid therapy in combination with dobutamine (a medication which has potential to improve flap oxygenation) versus the current standard of care. Flap oxygenation will be monitored via near-infrared spectroscopy in all patients for up to 48 hours postoperatively. Optimal fluid therapy in combination with dobutamine may improve flap oxygenation and thereby, reduce complications.

Conditions

Perioperative Tissue Oxygenation

Keywords

tissue flap oxygenation; DIEP flap breast reconstruction surgery

Outcome Measures

Primary Outcomes (1)

• Tissue Flap Oxygenation

  Tissue oxygenation of the breast flap tissue (measured via near-infrared spectroscopy, NIRS), 45 minutes following vascular re-anastomosis of the DIEP flap within the perfusion zone that is furthest away from the perforator vessels.

  45 min following vascular re-anastomosis

Secondary Outcomes (7)

• Tissue Flap Oxygenation

  Immediately preoperatively until up to 48 hours postoperatively

• Complications Associated with Flap Mal-Perfusion

  Immediately postoperatively until 30 days postoperatively

• Other Complications

  Immediately postoperatively up until 30 days postoperatively

• Intravenous Fluids

  Immediately preoperatively until up to 48 hours postoperatively

• Hospital Length of Stay

  From date and time of end of surgery until the date and time of discharge from hospital or up to 30 days postoperatively (whichever comes first).

Study Arms (2)

Dobutamine + Goal-Directed Fluid Therapy

EXPERIMENTAL

All patients will receive a baseline infusion of Ringer's lactate at 2 ml/kg/h to satisfy maintenance fluid requirements. The intervention will commence at anesthesia induction and continue for up to 4 hours postoperatively. In addition to maintenance fluids, patients will receive 250 ml fluid challenges with crystalloid as required until they are no longer fluid responsive. The absence of fluid responsiveness will be defined as the absence of a sustained rise in stroke volume index of at least 10% for 20 minutes or more, at which point, the patient will be considered fluid optimized. At this point, a low-dose dobutamine infusion at a fixed rate (2.5 μg/kg/min) will be commenced and maintained until 4 hours postoperatively. The infusion rate will be halved and/or discontinued if the patient develops tachycardia (heart rate ≥ 100 bpm) for more than 30 minutes despite adequate anesthesia/analgesia and fluid status.

Drug: Dobutamine

Standard of care

NO INTERVENTION

Patients in the control group will also receive a baseline infusion of Ringer's lactate at 2 ml/kg/h to satisfy maintenance fluid requirements, which will be commenced upon admission to the operating room. The anesthetic management will otherwise be according to standard practice. No specific cardiac output monitoring device will be used to guide fluid therapy. Likewise, perioperative dobutamine will not be used unless clinically indicated to improve cardiac function.

Interventions

Dobutamine DRUG

intraoperative fluid administration will be guided by cardiac output monitoring

Also known as: intraoperative fluid administration

Dobutamine + Goal-Directed Fluid Therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Gender Eligibility Details: No it is not based upon gender identity. However this study is based upon sex because it examines an intervention used during DIEP flap breast reconstruction surgery which is most often performed on women.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• American Society of Anesthesiologists' (ASA) Physical Classification I-III;
• Undergoing elective unilateral or bilateral DIEP flap surgery;
• Competent to provide informed consent.

You may not qualify if:

• Dementia or neurological impairment;
• Scheduled for DIEP flap combined with any other secondary surgical procedure;
• Documented left ventricular dysfunction (ejection fraction \< 40%);
• Contraindication to low-dose dobutamine;
• Body mass index \< 18 or \> 40 kg/m2;
• Pregnant or lactating;
• Renal insufficiency (eGFR \< 30 ml/min/1.73m2);
• Known liver insufficiency (i.e., documented cirrhosis, coagulopathy and/or encephalopathy of hepatic origin).

Sponsors & Collaborators

• Dr. Glenio Mizubuti (MD, PhD): lead

Study Sites (2)

Kingston General Hospital

Kingston, Ontario, K7L2V7, Canada

Location

Hotel Dieu Hospital

Kingston, Ontario, Canada

Location

Related Publications (1)

• Mizubuti GB, Ho AM, Phelan R, DuMerton D, Shelley J, Vowotor E, Xiong J, Smethurst B, McMullen M, Hopman WM, Martou G, Edmunds RW, Tanzola R. Dobutamine and Goal-Directed Fluid Therapy for Improving Tissue Oxygenation in Deep Inferior Epigastric Perforator (DIEP) Flap Breast Reconstruction Surgery: Protocol for a Randomized Controlled Trial. JMIR Res Protoc. 2023 Nov 22;12:e48576. doi: 10.2196/48576.

  PMID: 37991835 DERIVED

MeSH Terms

Interventions

Dobutamine

Intervention Hierarchy (Ancestors)

Catecholamines; Amines; Organic Chemicals; Phenethylamines; Ethylamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Glenio B. Mizubuti, MD, MSc, FRCPC

  Queen's University - Anesthesiology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. Glenio Mizubuti (MD, MSc, FRCPC), Anesthesiologist

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: July 15, 2019
• Study Start: July 12, 2019
• Primary Completion: May 1, 2024
• Study Completion: May 1, 2024
• Last Updated: August 5, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)