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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
124
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 Blood was withdrawn through a dedicated port integrated into the SORIN oxygenator and directed by a centrifugal pump to a small reservoir containing the methylene blue solution.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 (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 (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.
University of São Paulo Medical School in Ribeirão Preto
Ribeirão Preto, São Paulo, Brazil
Systemic Inflammation
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.
Time frame: Three years
Water overload
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.
Time frame: Three years
Intravascular volume assessment using IVC indices
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 (%).
Time frame: Three years
Length of stay in the intensive care unit (ICU)
Secondary outcomes included the length of stay in the intensive care unit (ICU), measured in hours, to evaluate the clinical impact of zero-balance ultrafiltration with methylene blue. This parameter was recorded for all patients and analyzed in relation to fluid balance, pulmonary congestion, intravascular volume, and systemic inflammatory markers, providing a comprehensive assessment of the intervention's effects on postoperative recovery.
Time frame: Three years
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