Methylene Blue-Enhanced Ultrafiltration Improves Outcomes After Cardiopulmonary Bypass

University of Sao Paulo

Status and phase: Completed; Phase 2

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

Treatments: Drug: Methylene Blue; Procedure: Conventional ultrafiltration; Procedure: Zero-balance ultrafiltration

Study type: Interventional

Funder types: Other

Identifiers

NCT07212842

2.462.520

Details and patient eligibility

About

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.

Enrollment: 124 patients

Sex: All

Ages: 20 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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124 participants in 3 patient groups, including a placebo group

Conventional ultrafiltration

Active Comparator group

Description:

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

Treatment:

Procedure: Zero-balance ultrafiltration

Procedure: Conventional ultrafiltration

Drug: Methylene Blue

Blood washing with physiological solution combined with zero-balance ultrafiltration

Placebo Comparator group

Description:

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.

Treatment:

Procedure: Zero-balance ultrafiltration

Procedure: Conventional ultrafiltration

Drug: Methylene Blue

Methylene blue wash combined with zero-balanced ultrafiltration

Experimental group

Description:

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.

Treatment:

Procedure: Zero-balance ultrafiltration

Procedure: Conventional ultrafiltration

Drug: Methylene Blue