METHYLENE BLUE-ENHANCED BLOOD WASHING DURING ZERO-BALANCE ULTRAFILTRATION REDUCES FLUID OVERLOAD AND INFLAMMATORY RESPONSE FOLLOWING CARDIOPULMONARY BYPASS: A RANDOMIZED CLINICAL TRIAL
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Systemic Inflammation
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 20 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of cardiac disease requiring surgery with cardiopulmonary bypass (CPB)
- •Age ≥ 18 years
- •Ability to provide informed consent
排除标准
- •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
研究组 & 干预措施
Conventional ultrafiltration
Conventional ultrafiltration (G-CUF) patients in this group underwent conventional ultrafiltration widely used in cardiac surgery with extracorporeal circulation.
干预措施: Methylene Blue (Drug)
Conventional ultrafiltration
Conventional ultrafiltration (G-CUF) patients in this group underwent conventional ultrafiltration widely used in cardiac surgery with extracorporeal circulation.
干预措施: Conventional ultrafiltration (Procedure)
Conventional ultrafiltration
Conventional ultrafiltration (G-CUF) patients in this group underwent conventional ultrafiltration widely used in cardiac surgery with extracorporeal circulation.
干预措施: Zero-balance ultrafiltration (Procedure)
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.
干预措施: Methylene Blue (Drug)
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.
干预措施: Conventional ultrafiltration (Procedure)
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.
干预措施: Zero-balance ultrafiltration (Procedure)
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.
干预措施: Methylene Blue (Drug)
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.
干预措施: Conventional ultrafiltration (Procedure)
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.
干预措施: Zero-balance ultrafiltration (Procedure)
结局指标
主要结局
Systemic Inflammation
时间窗: Three years
To assess systemic inflammation, blood samples were collected via central venous access through the internal jugular vein at five time points: before surgery, during surgery, 10 minutes after cannulation, 10 minutes after blood lavage with methylene blue and ultrafiltration, and 4 hours after ICU admission. Samples were drawn into EDTA-containing syringes (50 mM, pH 8.0) at one-tenth of the total blood volume. Plasma was separated by centrifugation at 1,700 × g for 10 minutes at 4 °C, transferred to new tubes avoiding the buffy coat, and centrifuged again at 11,000 × g for 2 minutes at 4 °C. Plasma was aliquoted and stored at -80 °C. Cytokine concentrations were quantified using a Luminex xMAP multiplex immunoassay (8-27-plex) in triplicate, enabling simultaneous measurement of up to seven cytokines, chemokines, and interleukins from 50 μL plasma.
Water overload
时间窗: Three years
Fluid balance was meticulously monitored, including fluids removed by conventional ultrafiltration, surgical suction, sponges, and urine output. Discrepancies between infused and removed volumes were corrected using zero-balance ultrafiltration (ZBUF), removing excess fluid or compensating deficits to match preoperative volemic status. For example, if 100 mL more than planned had been removed, only 900 mL were withdrawn. Body fluid composition was assessed with the InBody S10 bioimpedance device. Extracellular water (ECW) was measured at 5 kHz, total body water (TBW) at 250 kHz, and intracellular water (ICW) calculated as TBW-ECW. The ECW/TBW ratio served as the primary parameter to monitor fluid status and detect overload.
Intravascular volume assessment using IVC indices
时间窗: Three years
Intravascular volume will be evaluated by analyzing mechanical and hemodynamic changes in the inferior vena cava (IVC) using subcostal ultrasound images. The collapsibility index (CI = (IVCmax - IVCmin)/IVCmax) will be used during spontaneous breathing, and the distensibility index (DI = (IVCmax - IVCmin)/IVCmin) during mechanical ventilation. Time Frame: Preoperatively, immediately postoperatively, and 24 hours after surgery. Unit of Measure: Percentage (%).
次要结局
- Length of stay in the intensive care unit (ICU)(Three years)
研究者
André Timóteo Sapalo
Principal Investigator
University of Sao Paulo