NCT07212842

Methylene Blue-Enhanced Ultrafiltration Improves Outcomes After Cardiopulmonary Bypass

METHYLENE BLUE-ENHANCED BLOOD WASHING DURING ZERO-BALANCE ULTRAFILTRATION REDUCES FLUID OVERLOAD AND INFLAMMATORY RESPONSE FOLLOWING CARDIOPULMONARY BYPASS: A RANDOMIZED CLINICAL TRIAL

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 124 (actual)
• Sponsor: University of Sao Paulo · Academic / Other
• Sex: All
• Age: 20 Years – 60 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	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 Blood was withdrawn through a dedicated port integrated into the SORIN oxygenator and directed by a centrifugal pump to a small reservoir containing the methylene blue solution.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
PROCEDURE	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.
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.

Timeline

• Start date: 2021-04-12
• Primary completion: 2023-08-25
• Completion: 2024-03-16
• First posted: 2025-10-08
• Last updated: 2025-10-08

Locations

1 site across 1 country: Brazil