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Extracorporeal gas exchange
Chapter 2 2
Extracorporeal gas exchange
The stimulus for the development of extracorporeal gas exchangers was cardiac surgery. Certain procedures were possible with stopped circulation, often prolonged by the induction of hypothermia. However, more intricate operations required an open heart for periods in excess of 20 minutes and this could not be achieved safely with simple cardiac arrest and hypothermia. The design of extracorporeal gas exchangers has been based on the principles of the real lung. A large interface is required between blood and gas and this has been achieved both with and without a membrane at the interface which would correspond to the alveolar/capillary membrane.
Factors in design The lungs of an adult have an interface between blood and gas of the order of 126 2 m (page 16). It is not possible to achieve this in an artificial substitute and artificial lungs can be considered to have a very low 'diffusing capacity'. Nevertheless, they function satisfactorily within limits for the following reasons. Firstly, the real lung is adapted for maximal exercise, while patients on cardiopulmonary bypass are usually close to basal metabolic rate or less if hypothermia is used. Secondly, under resting conditions at sea level, there is an enormous reserve in the capacity of the lung to achieve equilibrium between pulmonary capillary blood and alveolar gas (see Figure 8.2). Therefore a subnormal diffusing capacity does not necessarily result in arterial hypoxaemia. Thirdly, it is possible to operate an artificial lung with an 'alveolar' oxygen concentration in excess of 90%, compared with 14% for real alveolar gas under normal circumstances. This greatly increases the gas transfer for a given 'diffusing capacity' of the artificial lung (page 189). Fourthly, there is no great difficulty in increasing the 'ventilation/perfusion ratio' of a membrane artificial lung above the value of about 0.8 in the normal lung at rest. Fifthly, the 'capillary transit time' of the artificial lung can be increased beyond the time of about 0.75 second in the real lung. This facilitates the approach of blood P o 2 to 'alveolar' P o 2 (see Figure 8.2). Finally, in certain types of gas-exchangers, it is possible to use countercurrent flow between gas and blood. This does not occur in the lungs of mammals. Carbon dioxide exchanges much more readily than oxygen because of its greater blood and lipid solubility. Therefore, in general, elimination of carbon dioxide does not present a major problem and the limiting factor of an artificial lung is oxygenation. 423
424
E x t r a c o r p o r e a l gas e x c h a n g e
Against these favourable design considerations, there are certain advantages of the real lung, apart from its very large surface area, which are difficult to emulate. Firstly, the pulmonary capillaries have a diameter close to that of the erythrocyte. Therefore, each erythrocyte is brought into very close contact with the alveolar gas (see Figure 1.7). Streamline flow through much wider channels in a membrane artificial lung tends to result in a stream of erythrocytes remaining at a distance from the interface. Much thought has been devoted to the creation of turbulent flow to counteract this effect. In contrast, there is a very favourable diffusion distance in a bubble oxygenator when foaming occurs. Secondly, the vascular endothelium is specially adapted to prevent undesirable changes in the formed elements of blood, particularly neutrophils and platelets. Most artificial surfaces cause clotting of blood, and artificial lungs therefore require the use of anticoagulants. Further adverse changes result from denaturation of protein (see below). Thirdly, the lung has an extensive non-respiratory function in the uptake, synthesis and biotransformation of many constituents of the blood (see Chapter 11). This function is lost when the lungs are bypassed. Fourthly, the lung is an extremely efficient filter with an effective pore size of about 10 μιη for flow rates of blood up to about 25 1/min. This is difficult to achieve with any man-made filter.
Types of extracorporeal gas exchangers With blood/gas interface Bubble oxygenators. The simplest design of extracorporeal oxygenator stems from the well-tried wash bottle of the chemist. By breaking up the gas stream into small bubbles, it is possible to achieve very large surface areas of interface. However, the smaller the bubbles, the greater the tendency for them to remain in suspension when the blood is returned to the patient. This is dangerous because of the direct access of the blood to the cerebral circulation. A compromise is to break the gas stream into bubbles ranging from 2 to 7 mm diameter, giving an effective area of 2 interface of the order of 15 m . With a mean red cell transit time of 1-2 seconds and a 'ventilation/perfusion ratio' of unity or slightly more and an oxygen concentration of more than 90%, this gives an acceptable outflow blood P o 2 with blood flow rates up to about 6 1/min (Finlayson and Kaplan, 1979). The P c o 2 of the outflowing blood must be controlled by admixture of carbon dioxide with the inflowing oxygen in the gas phase. Priming volumes range from 400 to 900 ml. Gas is passed through the blood in a reservoir of about 1 litre capacity in which foaming takes place. Blood is then passed to a second reservoir for 'debubbling' to take place with the help of an antifoaming compound (e.g. Dow Corning Medical Antifoam-A). Disc and vertical screen oxygenators. These devices have been used to film blood over a large surface area which is directly exposed to gas. This prevents the danger of bubbles remaining in the blood and there tends to be less damage to the blood. However, it is not practicable to obtain the large surface areas of a bubble oxygenator and the apparatus is troublesome to clean and maintain. These devices are now declining in popularity.
Damage to blood
425
Membrane oxygenators Two types of membrane are in use. Silicone rubber can be formed into a continuous thin uniform membrane. Rubber is a lipid and is freely permeable to oxygen, carbon dioxide and anaesthetic gases. An alternative approach is the use of membranes of polypropylene, Teflon or Polyacrylamide which contain small pores ranging from 0.1 to 5 μπι diameter (Finlayson and Kaplan, 1979). These pores tend to fill with protein which then forms a layer over the blood side of the membrane, the whole being freely permeable to the respiratory gases. However, performance declines over several hours which is not the case with a silicone rubber membrane. Microporous membranes can weep if the apparatus is primed with a protein-free solution, but in normal use can withstand a hydrostatic pressure gradient2 of the order of normal arterial blood pressure. Surface areas of the order of 10 m can be achieved. A major problem has been the mixing of blood as it flows across the membrane. The blood pathway is much thicker than the normal pulmonary capillary and a slow moving boundary layer impairs gas exchange. This has been avoided by designs which encourage mixing of the blood stream. Blood pumps Blood normally passes from the body to the oxygenator via a cannula in a major vein. After leaving the oxygenator, the pressure must be raised to permit re-entry into the patient's arterial circulation. Roller pumps are now universally used for this purpose and are adjusted to be not quite occlusive. This minimizes damage to the formed elements of the blood. There is no convincing evidence that performance is better with pulsatile blood flow.
Damage to blood Damage due to non-occlusive roller pumps is almost negligible. Damage due to oxygenators is probably far less than that which results from surgical suction in removing blood from the operative site and, during cardiac surgery, this factor tends to obscure the differences attributable to the type of oxygenator. However, during prolonged extracorporeal oxygenation for respiratory failure, the influence of the type of oxygenator becomes important and membrane oxygenators are then superior to bubble oxygenators. Protein denaturation Contact between blood and either gas bubbles or plastic surfaces results in protein denaturation and plastic surfaces become coated with a layer of protein. With membrane oxygenators this tends to be self-limiting, but bubble oxygenators cause a continuous and progressive loss of protein. This is the main factor which limits their prolonged use. Complement activation Complement activation occurs when blood comes into contact with any artificial surface and complement C5a is known to be formed after cardiopulmonary bypass
426
E x t r a c o r p o r e a l gas e x c h a n g e
surgery (Chenoweth et al., 1981). This results in margination of neutrophils on vascular endothelium, possible consequences of which are considered on page 488. Erythrocytes Damage may amount to shortened survival or actual destruction of erythrocytes due to shear forces, turbulence, foaming or the use of occlusive pumps. Surgical suction is generally more damaging than the oxygenator. Without suction, the damage to erythrocytes with membrane oxygenators is within reasonable limits for many hours and they are superior in this respect to bubble oxygenators. Released haemoglobin is initially bound to proteins but eventually saturates the receptors and is excreted through the kidneys. Red cell ghosts are now believed to be more damaging than free haemoglobin and they may need to be removed by filtration. Leucocytes and platelets Counts of these elements are usually reduced by an amount which is in excess of the changes attributable to haemodilution. Platelets are lost by adhesion and aggregation, and postoperative counts are commonly about half the preoperative value (Finlayson and Kaplan, 1979). Coagulation No oxygenator can function without causing coagulation of the blood. Anticoagulation is therefore a sine qua non of the technique and heparinization is universally employed for this purpose. This inevitably results in excess bleeding from any surgical incision.
Prolonged extracorporeal oxygenation for respiratory failure It has long been known that extracorporeal oxygenation can be maintained for a few days in patients with respiratory failure. For reasons outlined above, membrane oxygenators are superior to bubble oxygenators for this application. It was hoped that the 'resting of the lung' might permit healing and recovery in patients with the adult respiratory distress syndrome (ARDS), considered in Chapter 26. This hypothesis led to the multi-centre randomized prospective trial of extracorporeal membrane oxygenation (ECMO) for patients with ARDS (Zapol et al., 1979). Entry criteria were either: 1. Arterial P o 2 below 6.7 kPa (50 mmHg) for more than 2 hours, while breathing 100% oxygen, with positive end-expiratory pressure (PEEP) at least 0.5 kPa (5 c m H 20 ) . or 2. Arterial P o 2 below 6.7 kPa (50 mmHg) for more than 12 hours, while breathing 60% oxygen, with PEEP at least 0.5 kPa (5 c m H 2 0 ) and a shunt fraction greater than 30 per cent. Exclusion criteria included a pulmonary capillary wedge pressure of more than 3.3 kPa (25 mmHg), chronic pulmonary disease, malignancy, etc. Patients were
Extraporeal removal of carbon dioxide
427
then randomly allocated to conventional intermittent positive pressure ventilation (IPPV) or ECMO. The study was terminated after treatment of the first 90 patients when it was found that mortality was more than 90 per cent in both groups with no statistically significant difference between the two forms of treatment. There has been much discussion on the reasons for the failure of the ECMO trial but Zapol pointed out that the use of venoarterial bypass would have reduced pulmonary perfusion and pulmonary arterial pressure by about 30 per cent. Possible adverse consequences of loss of pulmonary perfusion are outlined above.
Extracorporeal removal of carbon dioxide A radically new approach to artificial gas exchange has been developed by Gattinoni and his colleagues in Milan. In essence, he has restricted extracorporeal gas exchange to removal of carbon dioxide and maintained oxygenation by a modification of apnoeic mass movement oxygenation. The lungs are either kept motionless or are ventilated two to three times per minute (low-frequency positive-pressure ventilation with extracorporeal C 0 2 removal—LFPPV-ECC0 2R) (Gattinoni et al., 1980; Pesenti et al., 1981). The technique depends on two important differences between the exchange of carbon dioxide and oxygen. Firstly, membrane oxygenators remove carbon dioxide some 10-20 times more effectively than they take up oxygen. Secondly, the normal arterial oxygen content (20 ml/100 ml) is very close to the maximum oxygen capacity, even with 100% oxygen in the gas phase (22 ml/100 ml). Therefore, there is little scope for superoxygenation of a fraction of the pulmonary circulation to compensate for a larger fraction of the pulmonary circulation in which oxygenation does not take place. In contrast, the normal mixed venous carbon dioxide content is 52 ml/ 100 ml compared with an arterial carbon dioxide content of 48 ml/100 ml and there is therefore ample scope for removing a larger than normal fraction of carbon dioxide from a part of the pulmonary circulation to compensate for a remaining fraction which does not undergo any removal of carbon dioxide (Figure 22.1). I believe it is true to say that, although the underlying physiology is self-evident, this difference between carbon dioxide and oxygen has escaped attention in recent years. It is therefore possible to maintain carbon dioxide homoeostasis by diversion of only a small fraction of the cardiac output through an extracorporeal membrane oxygenator (Gattinoni et al., 1980). This is best illustrated by means of the Fick equation for carbon dioxide: carbon dioxide removal
=
pulmonary blood flow
Under normal circumstances, typical values might be: 240 = 6000 (52/100 - 48/100) (values in ml and ml/min) Using Gattinoni's technique with a flow through the membrane oxygenator of 1.3 1/min, typical values might be: 240 = 1300 (52/100 - 33.5/100)
428
E x t r a c o r p o r e a l gas e x c h a n g e 6 0 «—
- N o r m a l m i x e d venous b l o o d 50 " N o r m a l arterial b l o o d
Ε ο ο
2
40
I
- B l o o d leaving e x t r a c o r p o r e a l system w i t h l o w f l o w carbon d i o x i d e removal
30
Maximal oxygen content o n 100% o x y g e n at 1 atmosphere pressure
ο ο 20
N o r m a l arterial b l o o d Normal mixed venous b l o o d 10
ο
Figure 22.I Comparison of absolute contents of carbon dioxide and oxygen in blood at I atmosphere pressure. Note that there is ample reserve potential for removing carbon dioxide below the level attained in normal arterial blood. In contrast, the maximal possible oxygen content of blood at 1 atmosphere is not greatly in excess of the level in normal arterial blood. This difference makes possible the extracorporeal removal of carbon dioxide (but not the supply of oxygen) by passing a small fraction of the cardiac output through an extracorporeal gas exchanger.
The outflow from the membrane oxygenator would thus be 1.3 1/min with a carbon dioxide content of 33.5 ml/100 ml, corresponding to a P c o 2 of about 2 kPa (15 mmHg). This would account for removal of the whole of the normal metabolic production of carbon dioxide. Furthermore, there is no necessity for the bypass to be venoarterial and the far simpler venovenous bypass has been used by Gattinoni. As a result there is no reduction in pulmonary blood flow or pressure. With P c o 2 held constant by extracorporeal removal of carbon dioxide, there is no obstacle to the continued uptake of oxygen by mass movement apnoeic oxygenation, a process which is normally terminated after about 30 minutes by progressive increase in P c o 2 (see page 228). All that is necessary is to replace the alveolar gas with oxygen and connect the trachea to a supply of oxygen, which is then drawn into the lungs at a rate equal to the metabolic consumption of oxygen, and this
Extraporeal removal of carbon dioxide
429
should continue indefinitely. In fact, Gattinoni recommends ventilation of the lungs two to three times a minute with long end-expiratory pauses and PEEP of about 1.5 kPa (15 c m H 2 0 ) . This is clearly beneficial for preservation of compliance and airway patency but imposes minimal danger of barotrauma. The technique would seem to expose the lungs to very high concentrations of oxygen and the possibility of oxygen toxicity (Chapter 29). In practice this does not appear to have been a problem, possibly due to induction of superoxide dismutase during an earlier stage of therapy (page 490). Furthermore, the air which flows through the membrane exchanger maintains the nitrogen tension of the body and this does not appear to interfere with the uptake of oxygen. Alternatively, the oxygen concentration of the gas passing through the membrane exchanger can be increased to make a contribution to oxygenation of the arterial blood. Gattinoni et al. (1980) described the reversal of respiratory failure in three patients who fulfilled the entry criteria of the ECMO trial and might therefore have been expected to have a 90 per cent mortality. Since then, Gattinoni has described a series of 18 patients, all fulfilling the ECMO entry criteria, of whom 11 survived (Gattinoni et al., 1983). LFPPV-ECC0 2R was maintained for an average of 6 days. Reports of use of this technique in other centres are still sparse at the time of writing (Hickling, 1986; Hickling et al., 1986).
Extracorporeal gas exchange
The stimulus for the development of extracorporeal gas exchangers was cardiac surgery. Certain procedures were possible with stopped circulation, often prolonged by the induction of hypothermia. However, more intricate operations required an open heart for periods in excess of 20 minutes and this could not be achieved safely with simple cardiac arrest and hypothermia. The design of extracorporeal gas exchangers has been based on the principles of the real lung. A large interface is required between blood and gas and this has been achieved both with and without a membrane at the interface which would correspond to the alveolar/capillary membrane.
Factors in design The lungs of an adult have an interface between blood and gas of the order of 126 2 m (page 16). It is not possible to achieve this in an artificial substitute and artificial lungs can be considered to have a very low 'diffusing capacity'. Nevertheless, they function satisfactorily within limits for the following reasons. Firstly, the real lung is adapted for maximal exercise, while patients on cardiopulmonary bypass are usually close to basal metabolic rate or less if hypothermia is used. Secondly, under resting conditions at sea level, there is an enormous reserve in the capacity of the lung to achieve equilibrium between pulmonary capillary blood and alveolar gas (see Figure 8.2). Therefore a subnormal diffusing capacity does not necessarily result in arterial hypoxaemia. Thirdly, it is possible to operate an artificial lung with an 'alveolar' oxygen concentration in excess of 90%, compared with 14% for real alveolar gas under normal circumstances. This greatly increases the gas transfer for a given 'diffusing capacity' of the artificial lung (page 189). Fourthly, there is no great difficulty in increasing the 'ventilation/perfusion ratio' of a membrane artificial lung above the value of about 0.8 in the normal lung at rest. Fifthly, the 'capillary transit time' of the artificial lung can be increased beyond the time of about 0.75 second in the real lung. This facilitates the approach of blood P o 2 to 'alveolar' P o 2 (see Figure 8.2). Finally, in certain types of gas-exchangers, it is possible to use countercurrent flow between gas and blood. This does not occur in the lungs of mammals. Carbon dioxide exchanges much more readily than oxygen because of its greater blood and lipid solubility. Therefore, in general, elimination of carbon dioxide does not present a major problem and the limiting factor of an artificial lung is oxygenation. 423
424
E x t r a c o r p o r e a l gas e x c h a n g e
Against these favourable design considerations, there are certain advantages of the real lung, apart from its very large surface area, which are difficult to emulate. Firstly, the pulmonary capillaries have a diameter close to that of the erythrocyte. Therefore, each erythrocyte is brought into very close contact with the alveolar gas (see Figure 1.7). Streamline flow through much wider channels in a membrane artificial lung tends to result in a stream of erythrocytes remaining at a distance from the interface. Much thought has been devoted to the creation of turbulent flow to counteract this effect. In contrast, there is a very favourable diffusion distance in a bubble oxygenator when foaming occurs. Secondly, the vascular endothelium is specially adapted to prevent undesirable changes in the formed elements of blood, particularly neutrophils and platelets. Most artificial surfaces cause clotting of blood, and artificial lungs therefore require the use of anticoagulants. Further adverse changes result from denaturation of protein (see below). Thirdly, the lung has an extensive non-respiratory function in the uptake, synthesis and biotransformation of many constituents of the blood (see Chapter 11). This function is lost when the lungs are bypassed. Fourthly, the lung is an extremely efficient filter with an effective pore size of about 10 μιη for flow rates of blood up to about 25 1/min. This is difficult to achieve with any man-made filter.
Types of extracorporeal gas exchangers With blood/gas interface Bubble oxygenators. The simplest design of extracorporeal oxygenator stems from the well-tried wash bottle of the chemist. By breaking up the gas stream into small bubbles, it is possible to achieve very large surface areas of interface. However, the smaller the bubbles, the greater the tendency for them to remain in suspension when the blood is returned to the patient. This is dangerous because of the direct access of the blood to the cerebral circulation. A compromise is to break the gas stream into bubbles ranging from 2 to 7 mm diameter, giving an effective area of 2 interface of the order of 15 m . With a mean red cell transit time of 1-2 seconds and a 'ventilation/perfusion ratio' of unity or slightly more and an oxygen concentration of more than 90%, this gives an acceptable outflow blood P o 2 with blood flow rates up to about 6 1/min (Finlayson and Kaplan, 1979). The P c o 2 of the outflowing blood must be controlled by admixture of carbon dioxide with the inflowing oxygen in the gas phase. Priming volumes range from 400 to 900 ml. Gas is passed through the blood in a reservoir of about 1 litre capacity in which foaming takes place. Blood is then passed to a second reservoir for 'debubbling' to take place with the help of an antifoaming compound (e.g. Dow Corning Medical Antifoam-A). Disc and vertical screen oxygenators. These devices have been used to film blood over a large surface area which is directly exposed to gas. This prevents the danger of bubbles remaining in the blood and there tends to be less damage to the blood. However, it is not practicable to obtain the large surface areas of a bubble oxygenator and the apparatus is troublesome to clean and maintain. These devices are now declining in popularity.
Damage to blood
425
Membrane oxygenators Two types of membrane are in use. Silicone rubber can be formed into a continuous thin uniform membrane. Rubber is a lipid and is freely permeable to oxygen, carbon dioxide and anaesthetic gases. An alternative approach is the use of membranes of polypropylene, Teflon or Polyacrylamide which contain small pores ranging from 0.1 to 5 μπι diameter (Finlayson and Kaplan, 1979). These pores tend to fill with protein which then forms a layer over the blood side of the membrane, the whole being freely permeable to the respiratory gases. However, performance declines over several hours which is not the case with a silicone rubber membrane. Microporous membranes can weep if the apparatus is primed with a protein-free solution, but in normal use can withstand a hydrostatic pressure gradient2 of the order of normal arterial blood pressure. Surface areas of the order of 10 m can be achieved. A major problem has been the mixing of blood as it flows across the membrane. The blood pathway is much thicker than the normal pulmonary capillary and a slow moving boundary layer impairs gas exchange. This has been avoided by designs which encourage mixing of the blood stream. Blood pumps Blood normally passes from the body to the oxygenator via a cannula in a major vein. After leaving the oxygenator, the pressure must be raised to permit re-entry into the patient's arterial circulation. Roller pumps are now universally used for this purpose and are adjusted to be not quite occlusive. This minimizes damage to the formed elements of the blood. There is no convincing evidence that performance is better with pulsatile blood flow.
Damage to blood Damage due to non-occlusive roller pumps is almost negligible. Damage due to oxygenators is probably far less than that which results from surgical suction in removing blood from the operative site and, during cardiac surgery, this factor tends to obscure the differences attributable to the type of oxygenator. However, during prolonged extracorporeal oxygenation for respiratory failure, the influence of the type of oxygenator becomes important and membrane oxygenators are then superior to bubble oxygenators. Protein denaturation Contact between blood and either gas bubbles or plastic surfaces results in protein denaturation and plastic surfaces become coated with a layer of protein. With membrane oxygenators this tends to be self-limiting, but bubble oxygenators cause a continuous and progressive loss of protein. This is the main factor which limits their prolonged use. Complement activation Complement activation occurs when blood comes into contact with any artificial surface and complement C5a is known to be formed after cardiopulmonary bypass
426
E x t r a c o r p o r e a l gas e x c h a n g e
surgery (Chenoweth et al., 1981). This results in margination of neutrophils on vascular endothelium, possible consequences of which are considered on page 488. Erythrocytes Damage may amount to shortened survival or actual destruction of erythrocytes due to shear forces, turbulence, foaming or the use of occlusive pumps. Surgical suction is generally more damaging than the oxygenator. Without suction, the damage to erythrocytes with membrane oxygenators is within reasonable limits for many hours and they are superior in this respect to bubble oxygenators. Released haemoglobin is initially bound to proteins but eventually saturates the receptors and is excreted through the kidneys. Red cell ghosts are now believed to be more damaging than free haemoglobin and they may need to be removed by filtration. Leucocytes and platelets Counts of these elements are usually reduced by an amount which is in excess of the changes attributable to haemodilution. Platelets are lost by adhesion and aggregation, and postoperative counts are commonly about half the preoperative value (Finlayson and Kaplan, 1979). Coagulation No oxygenator can function without causing coagulation of the blood. Anticoagulation is therefore a sine qua non of the technique and heparinization is universally employed for this purpose. This inevitably results in excess bleeding from any surgical incision.
Prolonged extracorporeal oxygenation for respiratory failure It has long been known that extracorporeal oxygenation can be maintained for a few days in patients with respiratory failure. For reasons outlined above, membrane oxygenators are superior to bubble oxygenators for this application. It was hoped that the 'resting of the lung' might permit healing and recovery in patients with the adult respiratory distress syndrome (ARDS), considered in Chapter 26. This hypothesis led to the multi-centre randomized prospective trial of extracorporeal membrane oxygenation (ECMO) for patients with ARDS (Zapol et al., 1979). Entry criteria were either: 1. Arterial P o 2 below 6.7 kPa (50 mmHg) for more than 2 hours, while breathing 100% oxygen, with positive end-expiratory pressure (PEEP) at least 0.5 kPa (5 c m H 20 ) . or 2. Arterial P o 2 below 6.7 kPa (50 mmHg) for more than 12 hours, while breathing 60% oxygen, with PEEP at least 0.5 kPa (5 c m H 2 0 ) and a shunt fraction greater than 30 per cent. Exclusion criteria included a pulmonary capillary wedge pressure of more than 3.3 kPa (25 mmHg), chronic pulmonary disease, malignancy, etc. Patients were
Extraporeal removal of carbon dioxide
427
then randomly allocated to conventional intermittent positive pressure ventilation (IPPV) or ECMO. The study was terminated after treatment of the first 90 patients when it was found that mortality was more than 90 per cent in both groups with no statistically significant difference between the two forms of treatment. There has been much discussion on the reasons for the failure of the ECMO trial but Zapol pointed out that the use of venoarterial bypass would have reduced pulmonary perfusion and pulmonary arterial pressure by about 30 per cent. Possible adverse consequences of loss of pulmonary perfusion are outlined above.
Extracorporeal removal of carbon dioxide A radically new approach to artificial gas exchange has been developed by Gattinoni and his colleagues in Milan. In essence, he has restricted extracorporeal gas exchange to removal of carbon dioxide and maintained oxygenation by a modification of apnoeic mass movement oxygenation. The lungs are either kept motionless or are ventilated two to three times per minute (low-frequency positive-pressure ventilation with extracorporeal C 0 2 removal—LFPPV-ECC0 2R) (Gattinoni et al., 1980; Pesenti et al., 1981). The technique depends on two important differences between the exchange of carbon dioxide and oxygen. Firstly, membrane oxygenators remove carbon dioxide some 10-20 times more effectively than they take up oxygen. Secondly, the normal arterial oxygen content (20 ml/100 ml) is very close to the maximum oxygen capacity, even with 100% oxygen in the gas phase (22 ml/100 ml). Therefore, there is little scope for superoxygenation of a fraction of the pulmonary circulation to compensate for a larger fraction of the pulmonary circulation in which oxygenation does not take place. In contrast, the normal mixed venous carbon dioxide content is 52 ml/ 100 ml compared with an arterial carbon dioxide content of 48 ml/100 ml and there is therefore ample scope for removing a larger than normal fraction of carbon dioxide from a part of the pulmonary circulation to compensate for a remaining fraction which does not undergo any removal of carbon dioxide (Figure 22.1). I believe it is true to say that, although the underlying physiology is self-evident, this difference between carbon dioxide and oxygen has escaped attention in recent years. It is therefore possible to maintain carbon dioxide homoeostasis by diversion of only a small fraction of the cardiac output through an extracorporeal membrane oxygenator (Gattinoni et al., 1980). This is best illustrated by means of the Fick equation for carbon dioxide: carbon dioxide removal
=
pulmonary blood flow
Under normal circumstances, typical values might be: 240 = 6000 (52/100 - 48/100) (values in ml and ml/min) Using Gattinoni's technique with a flow through the membrane oxygenator of 1.3 1/min, typical values might be: 240 = 1300 (52/100 - 33.5/100)
428
E x t r a c o r p o r e a l gas e x c h a n g e 6 0 «—
- N o r m a l m i x e d venous b l o o d 50 " N o r m a l arterial b l o o d
Ε ο ο
2
40
I
- B l o o d leaving e x t r a c o r p o r e a l system w i t h l o w f l o w carbon d i o x i d e removal
30
Maximal oxygen content o n 100% o x y g e n at 1 atmosphere pressure
ο ο 20
N o r m a l arterial b l o o d Normal mixed venous b l o o d 10
ο
Figure 22.I Comparison of absolute contents of carbon dioxide and oxygen in blood at I atmosphere pressure. Note that there is ample reserve potential for removing carbon dioxide below the level attained in normal arterial blood. In contrast, the maximal possible oxygen content of blood at 1 atmosphere is not greatly in excess of the level in normal arterial blood. This difference makes possible the extracorporeal removal of carbon dioxide (but not the supply of oxygen) by passing a small fraction of the cardiac output through an extracorporeal gas exchanger.
The outflow from the membrane oxygenator would thus be 1.3 1/min with a carbon dioxide content of 33.5 ml/100 ml, corresponding to a P c o 2 of about 2 kPa (15 mmHg). This would account for removal of the whole of the normal metabolic production of carbon dioxide. Furthermore, there is no necessity for the bypass to be venoarterial and the far simpler venovenous bypass has been used by Gattinoni. As a result there is no reduction in pulmonary blood flow or pressure. With P c o 2 held constant by extracorporeal removal of carbon dioxide, there is no obstacle to the continued uptake of oxygen by mass movement apnoeic oxygenation, a process which is normally terminated after about 30 minutes by progressive increase in P c o 2 (see page 228). All that is necessary is to replace the alveolar gas with oxygen and connect the trachea to a supply of oxygen, which is then drawn into the lungs at a rate equal to the metabolic consumption of oxygen, and this
Extraporeal removal of carbon dioxide
429
should continue indefinitely. In fact, Gattinoni recommends ventilation of the lungs two to three times a minute with long end-expiratory pauses and PEEP of about 1.5 kPa (15 c m H 2 0 ) . This is clearly beneficial for preservation of compliance and airway patency but imposes minimal danger of barotrauma. The technique would seem to expose the lungs to very high concentrations of oxygen and the possibility of oxygen toxicity (Chapter 29). In practice this does not appear to have been a problem, possibly due to induction of superoxide dismutase during an earlier stage of therapy (page 490). Furthermore, the air which flows through the membrane exchanger maintains the nitrogen tension of the body and this does not appear to interfere with the uptake of oxygen. Alternatively, the oxygen concentration of the gas passing through the membrane exchanger can be increased to make a contribution to oxygenation of the arterial blood. Gattinoni et al. (1980) described the reversal of respiratory failure in three patients who fulfilled the entry criteria of the ECMO trial and might therefore have been expected to have a 90 per cent mortality. Since then, Gattinoni has described a series of 18 patients, all fulfilling the ECMO entry criteria, of whom 11 survived (Gattinoni et al., 1983). LFPPV-ECC0 2R was maintained for an average of 6 days. Reports of use of this technique in other centres are still sparse at the time of writing (Hickling, 1986; Hickling et al., 1986).