Methylene Blue-Enhanced Ultrafiltration Improves Outcomes After Cardiopulmonary Bypass

NCT ID: NCT07212842

Last Updated: 2025-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-12
• Study Completion Date: 2024-03-16

Brief Summary

Introduction: Fluid overload and systemic inflammation are major contributors to postoperative complications in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Objective: To evaluate the effects of blood washing with methylene blue during zero-balance ultrafiltration (ZBUF) on fluid overload and systemic inflammatory response. Methodology: Fluid status was assessed using the InBody S10 precision bioimpedance device, measuring extracellular water (ECW), total body water (TBW), intracellular water (ICW), and the ECW/TBW ratio. Pulmonary congestion and intravascular volume were evaluated separately using a Philips Lumify S4-1 transducer with a Samsung tablet. Pulmonary congestion was confirmed by the presence of B-lines on lung ultrasound. Intravascular volume was assessed via the inferior vena cava (IVC) distensibility index (DI) during mechanical ventilation and collapsibility index (CI) during spontaneous breathing. Inflammatory cytokine levels were measured using a Luminex xMAP-based multiplex immunoassay.

Conditions

Cardiopulmonary Bypass Surgery; Aortic Valve Surgery; Mitral Valve Surgery; Myocardial Revascularization Surgery With Extracorporeal Circulation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Conventional ultrafiltration

Conventional ultrafiltration (G-CUF) patients in this group underwent conventional ultrafiltration widely used in cardiac surgery with extracorporeal circulation.

Group Type: ACTIVE_COMPARATOR

Methylene Blue

Intervention Type: DRUG

This protocol was designed to perform intraoperative blood lavage with methylene blue at the end of surgery, with a duration of 20 minutes. A low dose of 1 mg/kg of body weight was administered. The objective was not to elicit hemodynamic effects, which require higher doses, but rather to exploit the anti-inflammatory and antioxidant properties of methylene blue.

Methylene blue was diluted in 1000 mL of 0.9% saline. An equivalent volume of fluid was removed simultaneously by zero-balance ultrafiltration, maintaining a fluid-equilibrium state throughout the 20-minute procedure. For this purpose, a dedicated circuit was developed to enable concurrent blood lavage and ultrafiltration. Blood was withdrawn through a dedicated port integrated into the SORIN oxygenator and directed by a centrifugal pump to a small reservoir containing the methylene blue solution. From this reservoir, the blood passed through a hemoc

Conventional ultrafiltration

Intervention Type: PROCEDURE

Conventional ultrafiltration (CUF). CUF during cardiopulmonary bypass (CPB) is performed to remove excess fluid and solutes from the patient's blood during cardiac surgery, thereby limiting fluid accumulation and attenuating pro-inflammatory effects. This technique increases hematocrit, improves cardiopulmonary function, and reduces the need for blood transfusions. Unlike modified ultrafiltration (MUF), which is performed after weaning from CPB, CUF is carried out simultaneously with CPB while the heart-lung machine remains in operation.

Zero-balance ultrafiltration

Intervention Type: PROCEDURE

Zero-balance ultrafiltration (Z-BUF). Z-BUF is performed during cardiopulmonary bypass (CPB) to maintain fluid equilibrium by removing plasma water and solutes while simultaneously infusing an equal volume of replacement fluid, thereby achieving a net zero fluid balance. This technique has been shown to decrease urine output, reduce tissue edema and the inflammatory response, improve arterial oxygenation (PaO₂), and lower the need for postoperative blood transfusions.

Blood washing with physiological solution combined with zero-balance ultrafiltration

Blood washing with physiological solution combined with zero-balanced ultrafiltration (G-ZBUF) patients in this group underwent zero-balanced ultrafiltration, and for this purpose, the simulation was performed with physiological solution.

Group Type: PLACEBO_COMPARATOR

Methylene Blue

Intervention Type: DRUG

This protocol was designed to perform intraoperative blood lavage with methylene blue at the end of surgery, with a duration of 20 minutes. A low dose of 1 mg/kg of body weight was administered. The objective was not to elicit hemodynamic effects, which require higher doses, but rather to exploit the anti-inflammatory and antioxidant properties of methylene blue.

Methylene blue was diluted in 1000 mL of 0.9% saline. An equivalent volume of fluid was removed simultaneously by zero-balance ultrafiltration, maintaining a fluid-equilibrium state throughout the 20-minute procedure. For this purpose, a dedicated circuit was developed to enable concurrent blood lavage and ultrafiltration. Blood was withdrawn through a dedicated port integrated into the SORIN oxygenator and directed by a centrifugal pump to a small reservoir containing the methylene blue solution. From this reservoir, the blood passed through a hemoc

Conventional ultrafiltration

Intervention Type: PROCEDURE

Conventional ultrafiltration (CUF). CUF during cardiopulmonary bypass (CPB) is performed to remove excess fluid and solutes from the patient's blood during cardiac surgery, thereby limiting fluid accumulation and attenuating pro-inflammatory effects. This technique increases hematocrit, improves cardiopulmonary function, and reduces the need for blood transfusions. Unlike modified ultrafiltration (MUF), which is performed after weaning from CPB, CUF is carried out simultaneously with CPB while the heart-lung machine remains in operation.

Zero-balance ultrafiltration

Intervention Type: PROCEDURE

Zero-balance ultrafiltration (Z-BUF). Z-BUF is performed during cardiopulmonary bypass (CPB) to maintain fluid equilibrium by removing plasma water and solutes while simultaneously infusing an equal volume of replacement fluid, thereby achieving a net zero fluid balance. This technique has been shown to decrease urine output, reduce tissue edema and the inflammatory response, improve arterial oxygenation (PaO₂), and lower the need for postoperative blood transfusions.

Methylene blue wash combined with zero-balanced ultrafiltration

Methylene blue lavage combined with zero-balance ultrafiltration (MB+G-ZBUF). Patients assigned to this group underwent zero-balance ultrafiltration with concomitant blood lavage using methylene blue at a low dose of 1 mg/kg of body weight. Methylene blue was diluted in 1000 mL of 0.9% saline. An equivalent volume of fluid was simultaneously removed by zero-balance ultrafiltration, ensuring a balanced fluid state throughout the 20-minute procedure. For this purpose, a dedicated circuit was developed to allow simultaneous blood lavage and ultrafiltration. Blood was withdrawn through a dedicated port integrated into the SORIN oxygenator and directed by a centrifugal pump to a small reservoir containing the methylene blue solution. From this reservoir, the blood passed through a hemoconcentrator for filtration before being returned to the central reservoir of the cardiopulmonary bypass (CPB) circuit.

Group Type: EXPERIMENTAL

Methylene Blue

Intervention Type: DRUG

This protocol was designed to perform intraoperative blood lavage with methylene blue at the end of surgery, with a duration of 20 minutes. A low dose of 1 mg/kg of body weight was administered. The objective was not to elicit hemodynamic effects, which require higher doses, but rather to exploit the anti-inflammatory and antioxidant properties of methylene blue.

Methylene blue was diluted in 1000 mL of 0.9% saline. An equivalent volume of fluid was removed simultaneously by zero-balance ultrafiltration, maintaining a fluid-equilibrium state throughout the 20-minute procedure. For this purpose, a dedicated circuit was developed to enable concurrent blood lavage and ultrafiltration. Blood was withdrawn through a dedicated port integrated into the SORIN oxygenator and directed by a centrifugal pump to a small reservoir containing the methylene blue solution. From this reservoir, the blood passed through a hemoc

Conventional ultrafiltration

Intervention Type: PROCEDURE

Conventional ultrafiltration (CUF). CUF during cardiopulmonary bypass (CPB) is performed to remove excess fluid and solutes from the patient's blood during cardiac surgery, thereby limiting fluid accumulation and attenuating pro-inflammatory effects. This technique increases hematocrit, improves cardiopulmonary function, and reduces the need for blood transfusions. Unlike modified ultrafiltration (MUF), which is performed after weaning from CPB, CUF is carried out simultaneously with CPB while the heart-lung machine remains in operation.

Zero-balance ultrafiltration

Intervention Type: PROCEDURE

Zero-balance ultrafiltration (Z-BUF). Z-BUF is performed during cardiopulmonary bypass (CPB) to maintain fluid equilibrium by removing plasma water and solutes while simultaneously infusing an equal volume of replacement fluid, thereby achieving a net zero fluid balance. This technique has been shown to decrease urine output, reduce tissue edema and the inflammatory response, improve arterial oxygenation (PaO₂), and lower the need for postoperative blood transfusions.

Interventions

Methylene Blue

This protocol was designed to perform intraoperative blood lavage with methylene blue at the end of surgery, with a duration of 20 minutes. A low dose of 1 mg/kg of body weight was administered. The objective was not to elicit hemodynamic effects, which require higher doses, but rather to exploit the anti-inflammatory and antioxidant properties of methylene blue.

Methylene blue was diluted in 1000 mL of 0.9% saline. An equivalent volume of fluid was removed simultaneously by zero-balance ultrafiltration, maintaining a fluid-equilibrium state throughout the 20-minute procedure. For this purpose, a dedicated circuit was developed to enable concurrent blood lavage and ultrafiltration. Blood was withdrawn through a dedicated port integrated into the SORIN oxygenator and directed by a centrifugal pump to a small reservoir containing the methylene blue solution. From this reservoir, the blood passed through a hemoc

Intervention Type: DRUG

Conventional ultrafiltration

Conventional ultrafiltration (CUF). CUF during cardiopulmonary bypass (CPB) is performed to remove excess fluid and solutes from the patient's blood during cardiac surgery, thereby limiting fluid accumulation and attenuating pro-inflammatory effects. This technique increases hematocrit, improves cardiopulmonary function, and reduces the need for blood transfusions. Unlike modified ultrafiltration (MUF), which is performed after weaning from CPB, CUF is carried out simultaneously with CPB while the heart-lung machine remains in operation.

Intervention Type: PROCEDURE

Zero-balance ultrafiltration

Zero-balance ultrafiltration (Z-BUF). Z-BUF is performed during cardiopulmonary bypass (CPB) to maintain fluid equilibrium by removing plasma water and solutes while simultaneously infusing an equal volume of replacement fluid, thereby achieving a net zero fluid balance. This technique has been shown to decrease urine output, reduce tissue edema and the inflammatory response, improve arterial oxygenation (PaO₂), and lower the need for postoperative blood transfusions.

Intervention Type: PROCEDURE

Other Intervention Names

zero-balance ultrafiltration

Eligibility Criteria

Inclusion Criteria

Clinical diagnosis of cardiac disease requiring surgery with cardiopulmonary bypass (CPB)

Age ≥ 18 years

Ability to provide informed consent

Exclusion Criteria

Chronic renal failure

Recent cardiac catheterization within the past month

Planned cardiac surgeries with an estimated CPB time of less than 60 minutes

Aortic surgery

Significantly impaired hepatic function

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Sao Paulo

OTHER

Sponsor Role: lead

Responsible Party

André Timóteo Sapalo

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of São Paulo Medical School in Ribeirão Preto

Ribeirão Preto, São Paulo, Brazil

Countries

Brazil

Other Identifiers

2.462.520

Identifier Type: -

Identifier Source: org_study_id