How Ultrafiltration And MUF During Cardiopulmonary Bypass Really Work!
The mechanical separation of capillaries by edema decreases perfused capillary density which disrupts the oxygen pressure field. This can impact most of the soft tissues and organ systems in several ways and is frequently associated with organ failure. For example, the post CPB heart may lack strength and endurance, even though it is well perfused, due to a reduction in tissue oxygen concentration caused by edema. Simultaneously, in the pulmonary system, edema pushes the capillaries away from lung alveoli, causing a reduction in gas exchange. Pulmonary vascular resistance increases as well, impairing blood flow which reduces RV output. This is followed by a reduced LV preload and a further fall in cardiac output. Fluid administration to increase RV preload may provide only temporary improvement in cardiac output while simultaneously worsening the tissue edema. The airway may also be compromised from reduced pulmonary compliance, increased airway resistance and increased oxygen requirements to achieve adequate arterial oxygen saturation. A compensating increase in ventilation positive pressures can further reduce cardiac output. As a potential remedy for all this, removing fluid acquired before and during CPB with conventional ultrafiltration (CUF) and modified ultrafiltration (MUF) may reduce the systemic and pulmonary edema by targeting the corresponding capillary beds. A perfusionist using this strategy can wean most pediatric patients from CPB with negative fluid balances and less mortality than patients who have a positive fluid balance and require additional fluid resuscitation to wean from CPB (1). An observational study by Lowell and published again by Chappell (see below) demonstrates how excess fluid edema acquired during an assortment of major cardiac and non-cardiac surgeries correlates to mortality in the post-operative period (2,3).
Capillary targets (see below) are important in understanding CUF and MUF. During CPB, CUF sends hemoconcentrated blood into the systemic circulation via the aorta. This tends to remove fluid from the systemic circulatory tissues and reduces overall edema. After CPB, MUF sends hemoconcentrated blood directly into the lungs via the right atrium. This tends to remove fluid from the pulmonary system.
Many critical cardiopulmonary patients require extensive fluid resuscitation at some point during their treatment and will often develop massive edema (anasarca). Severe edema or anasarca pushes the capillaries apart and reduces perfused capillary density (PCD). The result is reduced tissue oxygen concentration and the potential development of an anoxic lethal corner. This mechanical separation decreases PCD which disrupts the oxygen pressure field (the radius of the Krogh cylinders increases). Systemic edema can impact most of the soft tissues and organ systems and is frequently associated with progressive organ failure. This organ failure might be caused by a lethal corner that forms as a result of the disrupted oxygen pressure field even though the capillaries are open. An edematous heart, even though it is well perfused, may lack strength and endurance caused by the decreased tissue oxygen concentration. Aggressive diuresis or ultrafiltration can reduce edema and bring capillaries closer together, restoring the oxygen pressure field to a more survivable configuration (see below).
Edema in the pulmonary system can also result in a decreased PCD that moves the capillaries away from gas exchange near the lung alveoli and increases the vascular resistance to blood flow. This commonly occurs during cardiopulmonary bypass when the lungs do not receive adequate perfusion.
Interstitial edema increases pulmonary vascular resistance and right ventricular filling pressures. This is followed by a reduced left ventricular preload and subsequent fall in cardiac output. Commonly, the treatment is to administer additional fluid to boost right heart output. This may provide temporary improvement in the cardiac output, but the additional fluid can worsen the edema as well.
The airway is also compromised by reduced pulmonary compliance, increased airway resistance and increased oxygen requirements to achieve an adequate arterial oxygen saturation. Combating the edema with ultrafiltration and diuresis can reduce the pulmonary edema and restore pulmonary circulation and function to normal (see below).
Oncotic pressure (colloid osmotic pressure, COP) is exerted across a permeable membrane by the larger molecules in plasma, mostly proteins. The higher COP in blood pulls water from the extravascular space across the capillary membranes and into the circulatory system. These larger molecules remain in the circulatory system and do not cross the capillary membrane.
Osmotic pressure is exerted by smaller molecules like glucose and salt ions in plasma. These also pull water from the extravascular space and into the circulatory system, but eventually the molecules cross the membrane and equilibrate with fluid on both sides of the membrane.
In infants and small children, blood passing through the hemoconcentrator during MUF develops a high COP as excess fluid is removed from it. The ratio of the blood passing through the hemoconcentrator to the total venous return to the right atrium is approximately 1:5 (MUF blood flow: venous return to the lungs = 100 ml/min MUF flow : 500 ml/min VR to the lungs). The high oncotic MUF blood combines with right heart venous return blood raising the oncotic pressure of the blood going directly to the lungs. This higher oncotic blood drags water from lung tissue, improving pulmonary and hemodynamic function. Typically there is a 5-10% hematocrit increase and the clotting factors are concentrated and more effective at reducing bleeding. The average fluid balance after CUF and MUF during CPB is a negative 32 mls/kg. The drop in the CVP from 16 to 8 mmHg illustrated in the diagram above does not only respresent this fluid loss, but more importantly, an improvement in right heart function. With improved right heart function, there is better preload to the left heart. This results in improved cardiac output and an increase in blood pressure from 40 to 80 mmHg. This is an unusual circumstance wherein removal of a subsantial amount of fluid (-32 mls/kg) will improve the patient’s hemodynamics. Patients with a positive fluid balance have twice the mortality rate as negative balance patients (1).
In adults, the ratio of the blood passing through the hemoconcentrator to the total venous return to the right atrium is approximately 1:20 (MUF blood flow: venous return to the lungs = 200 ml/min MUF flow : 4000 ml/min VR to the lungs). The high oncotic MUF blood is diluted by the high volume of right heart blood. The result is that blood with a relatively low COP goes to the lungs. So there is no significant oncotic pressure differential to drag water from lung tissue. The pulmonary benefits are negligible. The typical hematocrit increase is only 1- 4%. And the clotting factors may be minimally concentrated which may or may not reduce bleeding.
Fortunately the pulmonary effect of MUF can be improved in adults. For example, assume that after CPB the patient’s osmolarity is 300 mosmoles/L. Further assume that the residual circuit volume of 1 liter is the same osmolarity (300 mosmoles/L). By mixing 50 mEq/L NaHCO3 or 2 gm/L mannitol into the circuit volume, the osmolarity of residual circuit volume increases to 400 mosmoles/L. Upon commencing MUF, the MUF blood flow of 200 mls/min (400 mosmoles/L) combined with the venous return of 4000 mls/min patient blood (300 mosmoles/L) will increase the osmolarity of the blood passing through the right heart to the lungs from 300 to 305 mosmoles/L. The osmotic drag will remove 67 mls/min of fluid from lung tissue. A total of 335 mls can be removed from the lung tissue in 5 minutes of MUF, thus improving pulmonary and hemodynamic function.
Below is a diagram of the MUF circuit I used.