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Physiology of Extracorporeal Gas Exchange

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Abstract

Circulating venous blood outside the body, through an artificial lung (membrane oxygenator), and returning oxygenated blood to the patient is extracorporeal gas exchange. Oxygen and carbon dioxide exchange in a membrane lung is controlled by regulating blood flow, blood composition, and device design. With this control, lung function can be replaced for weeks by artificial organs. © 2020 American Physiological Society. Compr Physiol 10:879‐891, 2020.

Figure 1. Figure 1. In a simple membrane lung, venous blood flows in laminar fashion past the gas exchange membrane. Oxygen passes through the membrane in response to the partial pressure gradient. Desaturated red cells at the membrane surface become fully oxygenated quickly, but the adjacent red cells are exposed to a lower gradient. The amount of oxygen transferred per membrane surface area is controlled by this “boundary layer” of oxygenated red cells. CO2 is cleared in response to the partial pressure gradient but is not limited by a boundary layer (B in the figure). PCO2 in the exhaust gas goes from 0 to 40 over the length of the membrane. Modified from Bartlett RH, 2005 1.
Figure 2. Figure 2. In a “hollow fiber” membrane lung, venous blood flows through a bundle of thousands of small tubes made of gas permeable membrane. A representative sample of the fiber bundle and blood is shown in the expanded figure. Blood mixes by the generation of secondary flows as it passes through the bundle, disrupting the boundary layer which exists in laminar flow.
Figure 3. Figure 3. The steps in fabricating a typical hollow fiber membrane lung. The 380‐μm fibers are woven into a mat 30 cm wide. The void space between the fibers determines the resistance to blood flow in the final device (A). The mat is wrapped around a central tube which can be the blood outlet in this device Spacers are added to divert blood flow through the device. The tightness of the wrap also determines resistance (B). The fiber bundle is encased in a housing. This housing has two blood inlets to minimize resistance (C). Fiber bundle is cut close to the housing (D) and the exposed fibers are potted in silicone rubber, making the blood side completely closed (E). The potted ends are cut across, exposing the ends of the fibers at both ends of the device (F). The potted ends are encased in a header at gas inlet and outlet ends of the final device, so the “sweep” gas (oxygen) passes through the fibers while blood passes around the fibers (G). This example is a prototype membrane lung fabricated in our lab 12.
Figure 4. Figure 4. The amount of oxygen supplied by a membrane lung is the increase in oxygen content per deciliter of blood times the number of deciliters per minute (the blood flow). In this figure, ECMO flow is expressed in dL/min to match the oxygen content described as cc/dL. O2 supply is cc/min. If the oxygen added is 5 cc/dL, and the flow is 40 dL/min, the amount of oxygen supplied is 200 cc/min (see text).
Figure 5. Figure 5. An example of “rated flow” for a specific device. Inlet blood has a hemoglobin of 12 g/dL which is 70% saturated. The PO2 is 40 mmHg and the oxygen content is 11 cc/dL. At low flow (long transit time), the outlet blood is 100% saturated. The outlet PO2 is 300 mmHg and the oxygen content is 16 cc/dL. The outlet minus inlet oxygen difference is 5 cc/dL of flow. As flow is increased, the amount of oxygen delivered increases proportionately. Eventually, the blood flows through the device so fast that some of the red cells are not fully oxygenated. The outlet saturation falls below 100%. The flow at which the outlet saturation is 95% is designated the rated flow (3 liter/min for this device). When blood flow increases above rated flow, the outlet saturation continues to fall. The result is that the amount of oxygen delivered plateaus when the rated flow is exceeded (150 cc/min for this device). Modified from Brogan T, 2018 7.
Figure 6. Figure 6. Oxygen supplied by fully saturated blood at variable flows and hemoglobin concentration. The amount of oxygen supplied per unit of flow depends on the amount of hemoglobin in the blood. N = the normal point for adults at rest. O2 supply is cc/min. Reused from Brogan T, 2018 7.
Figure 7. Figure 7. Oxygen supply and CO2 clearance with a membrane lung. In an adult, the out‐in content difference for oxygen is usually 5 cc/dL, and hemoglobin is around 10 g/dL so oxygenation for a 70 kg man requires 4.5 liters/min. At a sweep gas flow of 4.5 liter/min the amount of CO2 removed is the same as the amount of oxygen added. Higher sweep gas flow does not change oxygen added and can remove much more CO2 (like hyperventilation in the normal lung). So 200 cc of CO2, for example, can be removed at 1 to 2 liter/min of blood flow. Reused from Brogan T, 2018 7.
Figure 8. Figure 8. The relationships of PO2, saturation, and oxygen content. For any level of PO2 or saturation, the actual amount of oxygen in the blood depends on the amount of hemoglobin. There is half as much oxygen in anemic blood (Hb 7.5 g/dL) than in normal blood (Hb 15 g/dL), although the PO2 and saturation are the same in both. Reused from Bartlett RH, et al., 1972 3.
Figure 9. Figure 9. Metabolism is measured as oxygen consumption per minute (120 cc/m2/min in adults). Oxygen is delivered by arterial blood (600 cc/m2/min in adults). Twenty percent of the oxygen delivered is used in metabolism, so 80% of the oxygen is still there in venous blood. m = m2/min. Modified from Brogan T, 2018 7.
Figure 10. Figure 10. The relationships between oxygen delivery (D˙o2), oxygen consumption (V˙o2), and venous blood saturation (assuming arterial saturation is 100%). Normal values for adults are V˙o2 3 cc/kg and D˙o2 15 cc/kg. (A) normal resting metabolism for an adult. (B) Oxygen delivery is reduced to 8 mL/kg/min (by anemia, hypoxemia, or low cardiac output), but oxygen consumption is not affected. (C) D˙o2 is less than twice V˙o2. Anaerobic metabolism, lactate production, and shock occur. (D) Increased metabolism (V˙o2 is 4 mL/kg/min). Cardiac output increases to maintain the D˙o2/V˙o2 ratio 5:1. Reused from Cain SM, 1983 8; Cain SM, 2011 9; Hirschl RB, et al., 1992 14.
Figure 11. Figure 11. Venoarterial blood access. Blood is drained from the right atrium, oxygenated, and returned to the systemic circulation. VA access is shown in a newborn infant. In infants, VA access is used for cardiac or respiratory support. Reused from Brogan T, 2018 7.
Figure 12. Figure 12. Venovenous access. Venous blood is drained from the superior and inferior vena cavae, oxygenated, then returned to the right atrium where it mixes with the native venous return which did not go to the ECMO circuit. The mixed blood passes through the right ventricle, though the nonfunctional lungs and into systemic circulation. The variables which are monitored and calculated are shown in the boxes. Abbreviations: PPlat, inspiratory plateau pressure; PEEP, inspiratory end expiratory pressure; P, ventilator pressure; V, ventilator tidal volume, SVR, systemic vascular resistance; PVR, pulmonary vascular resistance; BP, systemic blood pressure; PAP, pulmonary artery pressure; CO, cardiac output; SvO2, systemic arterial saturation; SVO2, venous saturation; Monitor P, circuit pressure; ACT, activated clotting time. Reused from Brogan T, 2018 7.
Figure 13. Figure 13. Using the venous drainage saturation (or content) and the arterial saturation (or content), the ratio between the ECMO flow and the native venous flow can be determined. The ECMO flow is known, so the native venous flow can be determined from this diagram. For example, if the venous saturation is 60%, the ECMO flow saturation is 100%, and the arterial saturation is 80%, the ECMO and native venous flows are equal (the ratio is 1:1). The cardiac output (total venous return) is the sum of the ECMO and native venous flows. SO2, oxyhemoglobin saturation; Sat, oxyhemoglobin saturation. Reused from Brogan T, 2018 7.
Figure 14. Figure 14. The equation describing the arterial content or saturation which will result from mixing ECMO flow with the native venous blood which does not go to the ECMO circuit. These calculations assume no native lung function (which is often the case). If there is some native lung function (during recovery for example), the arterial saturation and content will be better than predicted by the formula. Reused from Brogan T, 2018 7.
Figure 15. Figure 15. Basal oxygen requirement for an 80 kg man is 240 cc/min (3 cc/kg/min). The blood flow required to supply 240 cc/min depends on the hemoglobin concentration (assuming the venous blood is 60% saturated and the ECMO outlet blood is 100%). The risks of transfusion (mismatch, hepatitis) are rare and minimal compared to the risk of high flow (blowout, hemolysis, high pressure), for example. Therefore, if the patient is anemic, transfusion is favored over high flow when optimizing oxygen delivery (see text).
Figure 16. Figure 16. The clinical course of a patient with severe respiratory failure managed with V‐V ECMO.


Figure 1. In a simple membrane lung, venous blood flows in laminar fashion past the gas exchange membrane. Oxygen passes through the membrane in response to the partial pressure gradient. Desaturated red cells at the membrane surface become fully oxygenated quickly, but the adjacent red cells are exposed to a lower gradient. The amount of oxygen transferred per membrane surface area is controlled by this “boundary layer” of oxygenated red cells. CO2 is cleared in response to the partial pressure gradient but is not limited by a boundary layer (B in the figure). PCO2 in the exhaust gas goes from 0 to 40 over the length of the membrane. Modified from Bartlett RH, 2005 1.


Figure 2. In a “hollow fiber” membrane lung, venous blood flows through a bundle of thousands of small tubes made of gas permeable membrane. A representative sample of the fiber bundle and blood is shown in the expanded figure. Blood mixes by the generation of secondary flows as it passes through the bundle, disrupting the boundary layer which exists in laminar flow.


Figure 3. The steps in fabricating a typical hollow fiber membrane lung. The 380‐μm fibers are woven into a mat 30 cm wide. The void space between the fibers determines the resistance to blood flow in the final device (A). The mat is wrapped around a central tube which can be the blood outlet in this device Spacers are added to divert blood flow through the device. The tightness of the wrap also determines resistance (B). The fiber bundle is encased in a housing. This housing has two blood inlets to minimize resistance (C). Fiber bundle is cut close to the housing (D) and the exposed fibers are potted in silicone rubber, making the blood side completely closed (E). The potted ends are cut across, exposing the ends of the fibers at both ends of the device (F). The potted ends are encased in a header at gas inlet and outlet ends of the final device, so the “sweep” gas (oxygen) passes through the fibers while blood passes around the fibers (G). This example is a prototype membrane lung fabricated in our lab 12.


Figure 4. The amount of oxygen supplied by a membrane lung is the increase in oxygen content per deciliter of blood times the number of deciliters per minute (the blood flow). In this figure, ECMO flow is expressed in dL/min to match the oxygen content described as cc/dL. O2 supply is cc/min. If the oxygen added is 5 cc/dL, and the flow is 40 dL/min, the amount of oxygen supplied is 200 cc/min (see text).


Figure 5. An example of “rated flow” for a specific device. Inlet blood has a hemoglobin of 12 g/dL which is 70% saturated. The PO2 is 40 mmHg and the oxygen content is 11 cc/dL. At low flow (long transit time), the outlet blood is 100% saturated. The outlet PO2 is 300 mmHg and the oxygen content is 16 cc/dL. The outlet minus inlet oxygen difference is 5 cc/dL of flow. As flow is increased, the amount of oxygen delivered increases proportionately. Eventually, the blood flows through the device so fast that some of the red cells are not fully oxygenated. The outlet saturation falls below 100%. The flow at which the outlet saturation is 95% is designated the rated flow (3 liter/min for this device). When blood flow increases above rated flow, the outlet saturation continues to fall. The result is that the amount of oxygen delivered plateaus when the rated flow is exceeded (150 cc/min for this device). Modified from Brogan T, 2018 7.


Figure 6. Oxygen supplied by fully saturated blood at variable flows and hemoglobin concentration. The amount of oxygen supplied per unit of flow depends on the amount of hemoglobin in the blood. N = the normal point for adults at rest. O2 supply is cc/min. Reused from Brogan T, 2018 7.


Figure 7. Oxygen supply and CO2 clearance with a membrane lung. In an adult, the out‐in content difference for oxygen is usually 5 cc/dL, and hemoglobin is around 10 g/dL so oxygenation for a 70 kg man requires 4.5 liters/min. At a sweep gas flow of 4.5 liter/min the amount of CO2 removed is the same as the amount of oxygen added. Higher sweep gas flow does not change oxygen added and can remove much more CO2 (like hyperventilation in the normal lung). So 200 cc of CO2, for example, can be removed at 1 to 2 liter/min of blood flow. Reused from Brogan T, 2018 7.


Figure 8. The relationships of PO2, saturation, and oxygen content. For any level of PO2 or saturation, the actual amount of oxygen in the blood depends on the amount of hemoglobin. There is half as much oxygen in anemic blood (Hb 7.5 g/dL) than in normal blood (Hb 15 g/dL), although the PO2 and saturation are the same in both. Reused from Bartlett RH, et al., 1972 3.


Figure 9. Metabolism is measured as oxygen consumption per minute (120 cc/m2/min in adults). Oxygen is delivered by arterial blood (600 cc/m2/min in adults). Twenty percent of the oxygen delivered is used in metabolism, so 80% of the oxygen is still there in venous blood. m = m2/min. Modified from Brogan T, 2018 7.


Figure 10. The relationships between oxygen delivery (D˙o2), oxygen consumption (V˙o2), and venous blood saturation (assuming arterial saturation is 100%). Normal values for adults are V˙o2 3 cc/kg and D˙o2 15 cc/kg. (A) normal resting metabolism for an adult. (B) Oxygen delivery is reduced to 8 mL/kg/min (by anemia, hypoxemia, or low cardiac output), but oxygen consumption is not affected. (C) D˙o2 is less than twice V˙o2. Anaerobic metabolism, lactate production, and shock occur. (D) Increased metabolism (V˙o2 is 4 mL/kg/min). Cardiac output increases to maintain the D˙o2/V˙o2 ratio 5:1. Reused from Cain SM, 1983 8; Cain SM, 2011 9; Hirschl RB, et al., 1992 14.


Figure 11. Venoarterial blood access. Blood is drained from the right atrium, oxygenated, and returned to the systemic circulation. VA access is shown in a newborn infant. In infants, VA access is used for cardiac or respiratory support. Reused from Brogan T, 2018 7.


Figure 12. Venovenous access. Venous blood is drained from the superior and inferior vena cavae, oxygenated, then returned to the right atrium where it mixes with the native venous return which did not go to the ECMO circuit. The mixed blood passes through the right ventricle, though the nonfunctional lungs and into systemic circulation. The variables which are monitored and calculated are shown in the boxes. Abbreviations: PPlat, inspiratory plateau pressure; PEEP, inspiratory end expiratory pressure; P, ventilator pressure; V, ventilator tidal volume, SVR, systemic vascular resistance; PVR, pulmonary vascular resistance; BP, systemic blood pressure; PAP, pulmonary artery pressure; CO, cardiac output; SvO2, systemic arterial saturation; SVO2, venous saturation; Monitor P, circuit pressure; ACT, activated clotting time. Reused from Brogan T, 2018 7.


Figure 13. Using the venous drainage saturation (or content) and the arterial saturation (or content), the ratio between the ECMO flow and the native venous flow can be determined. The ECMO flow is known, so the native venous flow can be determined from this diagram. For example, if the venous saturation is 60%, the ECMO flow saturation is 100%, and the arterial saturation is 80%, the ECMO and native venous flows are equal (the ratio is 1:1). The cardiac output (total venous return) is the sum of the ECMO and native venous flows. SO2, oxyhemoglobin saturation; Sat, oxyhemoglobin saturation. Reused from Brogan T, 2018 7.


Figure 14. The equation describing the arterial content or saturation which will result from mixing ECMO flow with the native venous blood which does not go to the ECMO circuit. These calculations assume no native lung function (which is often the case). If there is some native lung function (during recovery for example), the arterial saturation and content will be better than predicted by the formula. Reused from Brogan T, 2018 7.


Figure 15. Basal oxygen requirement for an 80 kg man is 240 cc/min (3 cc/kg/min). The blood flow required to supply 240 cc/min depends on the hemoglobin concentration (assuming the venous blood is 60% saturated and the ECMO outlet blood is 100%). The risks of transfusion (mismatch, hepatitis) are rare and minimal compared to the risk of high flow (blowout, hemolysis, high pressure), for example. Therefore, if the patient is anemic, transfusion is favored over high flow when optimizing oxygen delivery (see text).


Figure 16. The clinical course of a patient with severe respiratory failure managed with V‐V ECMO.
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How to Cite

Robert H. Bartlett. Physiology of Extracorporeal Gas Exchange. Compr Physiol null, 10: 879-891. doi: 10.1002/cphy.c190006