Goal-directed Fluid Therapy During Deep Inferior Epigastric Perforator (DIEP) Free Flap Breast Reconstruction

NCT ID: NCT06080178

Last Updated: 2025-01-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-23
• Study Completion Date: 2026-10-01

Brief Summary

Adequate free flap perfusion during Deep Inferior Epigastric Perforator (DIEP) flap breast reconstruction surgery requires maintaining blood pressure above 100 mmHg and avoiding excessive fluid administration. This study aims to determine whether the use of a measurement of preload dependency (Pulse Pressure Variation = PPV), can guide fluid therapy and if it decreases the risk of flap oedema. For this purpose, two fluid management strategies will be compared:

• Static intraoperative fluid management: Administration of crystalloid fluids is limited to 5ml/kg/h
• Dynamic intraoperative fluid management: Crystalloid fluids are only administered if PPV exceeds 12% The purpose of this study is to compare the static and dynamic (= targeted) fluid strategy and to evaluate the effect on flap oedema and flap perfusion.

Detailed Description

For adequate free flap perfusion during Deep Inferior Epigastric Perforator (DIEP) flap breast reconstruction surgery, blood pressure must remain sufficiently high. General anaesthesia often induces systemic hypotension. To counteract this hypotension, the anaesthetist administers intravenous fluids (crystalloid fluids). However, fluid overload can lead to an increased risk of flap oedema and decreased flap perfusion and in exceptional cases to flap failure. To maintain blood pressure above 100 mmHg and to avoid excessive fluid administration, a vasopressor (norepinephrine) can be administered. This reduces the amount of fluids administered, thereby reducing the risk of flap oedema.

This study aims to determine whether the use of a measurement of preload dependency (Pulse Pressure Variation = PPV), can guide fluid therapy and if it decreases the risk of flap oedema. To this end, two fluid management strategies will be compared:

• Static intraoperative fluid management: Administration of crystalloid fluids is limited to 5ml/kg/h
• Dynamic intraoperative fluid management: Crystalloid fluids are only administered if PPV exceeds 12% The purpose of this study is to compare the static and dynamic (= targeted) fluid strategy and to evaluate the effect on flap oedema and flap perfusion.

All included patients are randomized in a 1:1 ratio to the static (n = 41) or dynamic group (n = 41).

To treat hypotension in patients randomized to the 'static' group, fluid administration is limited to 5 ml/kg/h. When the maximum fluid volume is administered but blood pressure remains below 100 mmHg, norepinephrine is administered.

Treatment of hypotension in patients randomized to the 'dynamic' (= targeted fluid therapy) group, is guided by PPV. PPV is measured continuously during the surgery and if the blood pressure is below 100 mmHg, fluids are only administered if PPV is > 12%. If blood pressure is below 100 mmHg but PPV is < 12% (indicating no fluid is needed), norepinephrine is administered.

At the end of the procedure, 2 sensors are applied, these sensors provide information about the perfusion of the free flap during patient's stay in Intensive Care or the recovery room.

Conditions

Hypotension During Surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Static group

When during surgery systolic blood pressure (SBP) is below 100mmHg:

• give a fluid bolus (Plasmalyte A) until 5ml/kg/h crystalloid (without maintenance infusion) is reached or until SBP is above 100mmHg
• if the 5ml/kg/h crystalloid limit is already reached: start or increase norepinephrine infusion until SBP is above 100mmHg (with a maximum dose of 0.2mcg/kg/min).

When SBP is above 120mmHg: decrease the norepinephrine infusion rate until SBP is below 120mmHg.

When SBP remains below 100mmHg after reaching a vasopressor dose of 0.2mcg/kg/min: the anaesthetist can decide to give a bolus of 6mg ephedrine intravenous (IV) (with a maximum dose of 12mg ephedrine iv per hour).

Group Type: ACTIVE_COMPARATOR

Plasma-lyte (static group)

Intervention Type: DRUG

Plasmalyte will be administered intravenously: (1) as a maintenance infusion 1ml/kg/h (from anaesthesia induction until ICU/PACU discharge); (2) as a fluid bolus until 5ml/kg/h crystalloid (without maintenance infusion) is reached or until SBP is above 100mmHg

Norepinephrine (static group)

Intervention Type: DRUG

When during surgery SBP is below 100mmHg, if the 5ml/kg/h crystalloid limit is already reached, start or increase norepinephrine infusion until SBP is above 100mmHg (with a maximum dose of 0.2mcg/kg/min).

Dynamic group

After insertion of an arterial line, a pulse contour analysis system will be installed (Acumen IQ sensor, Edwards) for measuring PPV and cardiac index (CI).

When during surgery SBP is below 100mmHg and PPV is above 12%:

• give a fluid bolus (Plasmalyte A) until PPV is below or equal to 12% or SBP is above 100mmHg

When during surgery SBP is below 100mmHg and PPV is below or equal to 12%:

• start or increase norepinephrine infusion until SBP is above 100mmHg (with a maximum dose of 0.2mcg/kg/min) When SBP is above 120mmHg: decrease the norepinephrine infusion rate until SBP is below 120mmHg.

When SBP remains below 100mmHg after reaching a vasopressor dose of 0.2mcg/kg/min, and CI is < 2.2 L/min/m², a bolus of 6mg ephedrine iv will be given (with a maximum dose of 12mg ephedrine iv per hour).

Group Type: EXPERIMENTAL

Plasma-lyte (dynamic group)

Intervention Type: DRUG

Plasmalyte will be administered intravenously:

(1) as a maintenance infusion 1 ml/kg/h (from anaesthesia induction until ICU/PACU discharge); (2) as a fluid bolus until PPV is below or equal to 12% or SBP is above 100mmHg.

Norepinephrine (dynamic group)

Intervention Type: DRUG

When during surgery SBP is below 100mmHg and PPV is below or equal to 12%: start or increase norepinephrine infusion until SBP is above 100mmHg (with a maximum dose of 0.2mcg/kg/min).

When SBP is above 120mmHg: decrease the norepinephrine infusion rate until SBP is below 120mmHg.

Interventions

Plasma-lyte (static group)

Plasmalyte will be administered intravenously: (1) as a maintenance infusion 1ml/kg/h (from anaesthesia induction until ICU/PACU discharge); (2) as a fluid bolus until 5ml/kg/h crystalloid (without maintenance infusion) is reached or until SBP is above 100mmHg

Intervention Type: DRUG

Norepinephrine (static group)

When during surgery SBP is below 100mmHg, if the 5ml/kg/h crystalloid limit is already reached, start or increase norepinephrine infusion until SBP is above 100mmHg (with a maximum dose of 0.2mcg/kg/min).

Intervention Type: DRUG

Plasma-lyte (dynamic group)

Plasmalyte will be administered intravenously:

(1) as a maintenance infusion 1 ml/kg/h (from anaesthesia induction until ICU/PACU discharge); (2) as a fluid bolus until PPV is below or equal to 12% or SBP is above 100mmHg.

Intervention Type: DRUG

Norepinephrine (dynamic group)

When during surgery SBP is below 100mmHg and PPV is below or equal to 12%: start or increase norepinephrine infusion until SBP is above 100mmHg (with a maximum dose of 0.2mcg/kg/min).

When SBP is above 120mmHg: decrease the norepinephrine infusion rate until SBP is below 120mmHg.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Female adult patients, between 18 and 70 years of age
• Patients scheduled for DIEP free flap breast reconstruction
• Signed written informed consent form (ICF)

Exclusion Criteria

• present atrial fibrillation (AF)
• heart failure New York Heart Association (NYHA) classification 2 or higher
• chronic kidney disease (CKD) stage 3B or higher
• American Society of Anesthesiologists (ASA) classification III or higher
• known allergy to study specific medication
• participation in another clinical trial
• Inability of the patient to understand Dutch sufficiently
• Patients who are pregnant or breastfeeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Algemeen Ziekenhuis Maria Middelares

OTHER

Sponsor Role: lead

Responsible Party

Silvie Allaert

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Silvie Allaert, MD

Role: PRINCIPAL_INVESTIGATOR

AZ Maria Middelares Gent

Locations

AZ Maria Middelares

Ghent, East Flanders, Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Silvie Allaert, MD

Role: CONTACT

silvie.allaert@mijnziekenhuis.be

+32 9 246 17 00

Ella Hermie, MSc

Role: CONTACT

ella.hermie@mijnziekenhuis.be

+32 9 246 17 03

Facility Contacts

Steffi Ryckaert, MSc

Role: primary

klinische.studies@mijnziekenhuis.be

00322461708

Other Identifiers

MMS.2023.036

Identifier Type: -

Identifier Source: org_study_id