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Extracorporeal perfusion for acute respiratory failure
Extracorporeal perfusion for acute respiratory failure Recent experience with the spiral coil membrane lung Selection criteria, clinical data, and physiological measurements obtained during five extracorporeal membrane lung perfusions for acute respiratory insufficiency are presented. Four patients died and 1 survived. A new technique of femoral artery cannulation to allow aortic arch perfusion is described. When properly monitored, this route provides improved oxygen delivery to the brain during venoarterial (VA) perfusion. The importance of monitoring the equivalent of carotid artery POi during VA perfusion is emphasized. Recognition of the effects of high cardiac output in limiting the quality of extracorporeal perfusion, plus the use of hypothermia to reduce output, are stressed. We have confirmed that perfusion can be accomplished with small quantities of heparin, so that bleeding is reduced, but thrombocytopenia and occasional hemorrhage continue to be persistent problems.
W. M. Zapol, M.D., J. Qvist, M.D., H. Pontoppidan, M.D., A. Liland, M.D., T. McEnany, M.D., and M. B. Laver, M.D., Boston, Mass.
-I—extracorporeal perfusion for acute respiratory failure has become increasingly safe and successful during the past two years due to improvements in materials and tehniques and to mounting clinical experience by perfusion teams. This article will describe the nature of the progress on four major fronts: (1) better criteria for selection of patients; (2) improved patient management and monitoring; (3) cannulation techniques permitting optimal distribution of oxygenated blood; and (4) reduction of hemorrhagic complications by precise coagulation control. We shall illustrate the importance of these factors by citing data from five recent perfusions and detailed physiological measureFrom the Departments of Anesthesia and Surgery, the Harvard Medical School, Massachusetts General Hospital, Boston, Mass. 02114. Supported by grants from the National Institutes of Health: GM 15904, GM 01273, HL 70303, and HL 16154. Received for publication July 24, 1974.
ments of a recent survivor of long-term perfusion. Methods Patient management and monitoring. All candidates for perfusion have catheters inserted for continuous monitoring of central venous, radial artery, pulmonary artery, and pulmonary capillary wedge pressures; urine output; and body temperature. Cardiac output is measured by dye or thermal dilution for computation of pulmonary vascular resistance. Chest roentgenograms are obtained. In patients without a bronchopleural fistula, functional residual capacity (FRC) is measured by helium dilution; standard pneumotachygraphy yields pressure-volume loops for computation of dynamic compliance. Management of pulmonary function must include therapy with antibiotics, vigorous chest physiotherapy, frequent positional changes, tracheobronchial suctioning, strict attention to water balance, and management 439
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Fig. 1. Diagram of venovenous perfusion route. M.L., Membrane lung.
Fig. 2. Diagram of venoarterial perfusion route with femoral artery cannulation and distal aortic return. M.L., Membrane lung.
of cardiac failure with inotropic drugs.1 Because lung compliance is generally very low, these patients are ventilated with a volume pre-set ventilator, with positive end-expiratory pressure levels (PEEP) of 10 to 15 cm. of water. Paralysis is produced with pancuronium and sedation with morphine. Patients in acute respiratory failure with sepsis have a marked increase in cardiac output. This situation, which may set a severe limit on the quality of extracorporeal perfusion, can be improved by lowering the body temperature to between 32 and 35° C. Perfusion equipment (Figs. 1 to 4). Venous blood is drained from a large-bore cannula2* inserted through the common femoral vein into the right atrium for venoarterial (VA) perfusion (Figs. 2 and 4 ) . When venovenous (VV) alone (Fig. 1) or venovenous with venoarterial ( W A ) per-
fusion is desired (Fig. 3), the cannula tip is positioned in the inferior vena cava at the level of the diaphragm to avoid recirculation of the returning stream of oxygenated blood into the drainage catheter. The outside diameter (O.D.) of the catheter is a minimum of 8.15 mm. and more commonly 10.35 mm. in adults. Blood is drained via silicone drainage tubing (12.7 mm. I.D.) to a servo-controlled reservoir bag (75 ml. volume). It is pumped in a nonocclusive, segmented polyurethane chamber,3 reinforced with fiberglass, by a Sarns Model 3500 roller pump through a spiral coil, silicone membrane lung.* Blood then passes through a bubble trap and past an electromagnetic flow probe to the patient. Oxygen saturation of venous blood is monitored continuously.4 A heat exchanger is not used, so that extracorporeal prime volume and
*Mr. Raymond Johnson, Peabody, Mass.
*Sci-Med Inc., Minneapolis, Minn.
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Fig. 3. Diagram of mixed venovenous and venoarterial perfusion. M.L., Membrane lung.
Fig. 4. Diagram of venoarterial arch perfusion. M.L., Membrane lung.
surface area are reduced. Instead, the entire apparatus is enclosed in a vinyl canopy and the ambient air temperature is regulated. For partial extracorporeal perfusion in adults, we use 0.5 sq. M. of membrane lung per 10 kilograms of body weight. The extracorporeal blood priming volume for a 70 kilogram adult is approximately 1,350 ml. However, if the patient progresses to total pulmonary failure, then 1 sq. M. of membrane lung per 10 kilograms is required. Membrane lungs are changed if outflow saturation falls below 90 per cent.
lateral pneumothoraces, pneumopericardium, and pneumoperitoneum. An open lung biopsy obtained 2 days before the start of perfusion showed diffuse interstitial edema, hyaline membranes, and early interstitial fibrosis. VV perfusion was initiated on the sixteenth day after the onset of pneumonia. Rather than being drained from the inferior vena cava (Fig. 1) through the common femoral vein, venous blood was drained from the right atrium via the right internal jugular vein to the extracorporeal circuit and was returned to the femoral vein. The jugular cannulation site permits passage of a large-bore cannula. Perfusion was terminated because of total loss of pulmonary function and severe right ventricular failure. At autopsy, the lungs demonstrated severe interstitial and bronchial pneumonia with marked pulmonary hemorrhage and fibrosis. Hepatomegaly and ascites were present. CASE 2. A 26-year-old woman in her sixth month of pregnancy was referred to us for perfusion after 13 days of viral pneumonia. The decision for perfusion was made because of an extremely low lung compliance and a right pneumothorax. Pa 0j was 88 torr on an Flo, of 1.0 and a Paco. of 50 torr during mechanical ventilation with 10 cm. H 2 0 PEEP prior to bypass (tidal
Case reports Patient data are summarized in Tables I and II. CASE 1. A 6-month-old boy developed viral pneumonia after a second-stage operation for megaureter. He was treated with mechanical ventilation and PEEP but required increasing concentrations of inspired oxygen (Fi 0 ,). His compliance diminished further and he developed bi-
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200
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Fig. 5. Respiratory data in Case 4. Po= for the right temporal and left radial arteries (lower curves) are measured at the Flo, indicated. During perfusion, Po2 in the left radial artery is higher than in the right temporal artery due to admixture of blood from the patient's lung with that from the membrane lung. The right temporal artery Po- is indicative of the lung's performance when tested at an Flo, of 1.0. PEEP, Positive end-expiratory pressure.
Table I. Clinical data and perfusion method Case No.
Age
1 2
6 mo. 26 yr.
Bilateral megaureter Influenza pneumonia
3
30 yr.
4
5
Primary
disease
Perfusion route
Duration of bypass (Jays)
Pulmonary
disease
4.5 3
Pyosalpinx
VV VA (femoral) VVA
37 yr.
Pelvic fractures and multiple
VA (arch)
4.5
Pneumonitis Pneumonitis and interstitial fibrosis Pneumonitis and gram-negative pneumonia Gram-negative pneumonia
12 yr.
intra-abdominal injuries Femoral fracture and cerebral VVA contusion
4.5
Necrotic bronchopneumonia
4
Legend: W , Venovenous. VA, Venoarterial. W A , Venovenous and venoarterial.
volume 800 ml., peak pressure 70 cm. H = 0). Coincident with femoral cannulation and after administration of heparin, she developed a tension pneumothorax on the left. A thoracostomy tube was inserted anteriorly, and a second tube in the midaxillary line was required. On the second day of VA perfusion (Fig. 2), an expanding hematoma spontaneously dissected between the left parietal pleura and chest wall. Three consecutive thoracotomies failed to achieve hemostasis despite extensive electrocautery. Perfusion was discontinued due to the enormous requirements for blood. Severe pulmonary consolidation with early fibrosis,
subpleural cystic alveolar dilation, and dissection of parietal pleura off the chest wall were found at autopsy. CASE 3. A 30-year-old woman was transferred after 15 days of mechanical ventilation for severe diffuse pneumonia with hypoxemia. After 1 week of mechanical ventilation the patient developed a left pneumothorax for which she required insertion of a thoracostomy tube. After her arrival the patient's condition deteriorated rapidly because of increasing air leakage from the left lung, and extracorporeal perfusion was instituted. Since the cardiac index was high
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Fig. 6. Case 4. A, Chest radiogram 1 day before perfusion. B, Chest radiogram on the third day of perfusion; note drainage catheter in the right atrium and aortic arch blood return catheter in the aortic arch. C, Chest radiogram 2 days after perfusion. (5.2 L. per square meter per minute) presumably because of associated sepsis, we began perfusion via the VV route (Fig. 1). Bypass was complicated by septicemia and an increasing air leak from the left lung. We positioned a Fogarty embolectomy catheter in the leaking lobar bronchus through the tracheostomy tube and succeeded in sealing the air leak when the balloon was inflated. Pulmonary artery pressure increased from 40/15 to 70/20 mm. Hg during perfusion, and VA perfusion was added to lower pulmonary blood flow (Fig. 3). As pulmonary function had deteriorated, it was necessary to maintain some VV blood return to ensure an
adequate Pao, to the brain and heart, since both were perfused with mixed venous blood ejected from the left ventricle. Pulmonary artery pressure remained at 50 to 70/20 mm. Hg despite partial VVA bypass. Total loss of transpulmonary gas exchange after 4 days of support led to the decision to cease extracorporeal perfusion. Autopsy revealed early interstitial fibrosis and severe, confluent, bilateral pneumonia with several abscesses ruptured into the pleural cavity. There was acute and chronic bilateral salpingitis with pyosalpinx. CASE 4. A 37-year-old white man was transferred 3 days after sustaining severe abdominal trauma (pelvic fractures with retroperitoneal
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DAYS Fig. 7. Case 4. Cardiac output and pulmonary vascular resistance (PVR). Dye is injected into the pulmonary artery and sampled in the right temporal artery during perfusion. Table II. Mean cardiopulmonary during perfusion
Case No.
Weight (Kg.)
1 2 3 4 5
3.5 58 55 71 30
Cardiac output (L./min.) 1.6 2.5 4.5 7.0 2.5
Bypass
flow (L./min.) 0.8 4.0 5.0 3.0 2.7
data
Total oxygen transfer of membrane lung* (c.c./min.) 45, 136, 145, 120, 110,
50 130 225 100 135
♦The first value of each pair is the initial value at the start of perfusion; the second was obtained close to termination of perfusion. hematoma). He had undergone a laparotomy to repair an inferior vena cava tear and two small bowel perforations. Postoperatively, he developed septicemia with Bacteroides, and three species of gram-negative bacteria were cultured from the trachea. Induced hypothermia (32° C.) by surface cooling effectively reduced the cardiac index from 9.6 to 4.3 L. per minute per square meter, but Pao2 remained below 35 torr (Fig. 5). We instituted VA perfusion, draining blood from the superior vena cava through the left internal jugular vein and returning blood through the femoral artery to the arch of the aorta at the level of the left subclavian artery (8.12 mm. O.D. steel spring-
reinforced cannula; Figs. 4 and 5). Fig. 6 shows the chest radiograms 1 day before perfusion, on the second day of perfusion (note position of the aortic cannula), and 1 day after bypass was completed. Hemodynamic performance was stable throughout perfusion. Fig. 7 shows the patient's cardiac output and Fig. 8 the quantity of blood flow through the membrane lung. Pulmonary vascular resistance is illustrated in Fig. 7. The proportions of oxygen delivered via the patient's lung and the membrane are shown in Fig. 9. 13:1 Xenon, injected into the extracorporeal blood return to evaluate the magnitude of intracranial blood flow, demonstrated major perfusion of the left carotid artery, with only a small amount reaching the right carotid artery. During perfusion, Po2 in the left radial artery was always higher than that in the right temporal artery. Platelet counts before bypass were 54,000 per cubic millimeter and were maintained above 20,000 per cubic millimeter during perfusion with platelet transfusions (Fig. 10). The volume of blood and plasma replacement during perfusion is illustrated in Fig. 11. Lee-White clotting time was maintained at approximately 20 minutes (Fig. 12). During perfusion, ventilation was controlled, with a tidal volume of 800 ml. at a rate of 15 breaths per minute; this required plateau inspiratory pressures of 45 to 50 cm. H 2 0. On this regimen, respiratory function improved slowly, with a rise in quasistatic compliance (measured with inspiration of more than 2 seconds) and FRC (measured with a PEEP of 15 cm. H.O) (Fig. 13). Late on the fourth day of perfusion, the Pao, was 65 torr and Paco, was 41 torr at an extracorporeal blood flow of 500 ml. per minute, an Fio, of 0.6, and peak airway pressures of 45 cm. H^O. After 110 hours of perfusion, bypass was terminated and the patient was decannulated. The patient's postperfusion course was complicated. Major problems included recurrent sepsis from intra-abdominal abscesses, urine extravasation requiring right nephrectomy, small bowel obstruction, acute gangrenous cholecystitis, and gentamicin-induced nephritis with severe renal failure. Three months after decannulation, a false aneurysm developed on the femoral artery, for which resection and insertion of a vein graft were required. Four months after perfusion, the patient was weaned from the ventilator, and 1 month later he was discharged from the hospital on maintenance hemodialysis. CASE 5. A 12-year-old boy was transferred 18
days after sustaining head trauma and 10 days after developing gram-negative pneumonia. Sixty hours of medical treatment did not improve oxygenation, and the patient was placed on VA perfusion with femoral vein and artery cannulation.
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Pulmonary gas exchange decreased during perfusion. It was necessary to insert a cannula in the internal jugular vein and perfuse by the VVA mode (Fig. 3) to maintain adequate cerebral oxygen tensions. Despite decreased peak ventilator pressure, the patient developed several tension pneumothoraces, and three thoracostomy tubes were required. Perfusion was terminated more than 30 hours after pulmonary function had ceased. Autopsy showed severe acute bilateral hemorrhagic bronchopneumonia with extensive microabscess formation and necrosis of pulmonary tissue.
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Discussion Perfusion criteria. The use of hypoxemia as a criterion for initiation of membrane lung perfusion is illustrated by Case 4. 5 Low Pao2 (30 to 50 torr) due to severe rightto-left intrapulmonary shunting persisted despite aggressive respiratory management, including mechanical ventilation with 100 per cent oxygen, a PEEP of 10 to 15 cm. H z O, diuresis, cardiotonics, and vigorous chest physiotherapy. Persistent hypoxemia in addition to poor quasistatic lung compliance ( < 10 ml. per centimeter of water) and diffuse bilateral opacification on the chest radiogram placed him in a group of patients whose risk of dying is extremely high." Patient 4 had a brief course of pulmonary insufficiency (4 days). Of all candidates for perfusion, patients suffering rapid progression of severe, acute respiratory failure have the greatest probability of survival if they are perfused early in the course of their disease. In the early phases of pulmonary disease, lesions may be arrested and leave sufficient functioning pulmonary tissue for recovery. Unlike Patient 4, the other patients had pulmonary disease for 2 weeks or longer. Pa 0 , above 50 torr can usually be maintained with aggressive medical respiratory management. However, if an acceptable Pao., can be obtained only by lengthy exposure to a high Fi0.2, extensive pulmonary fibrosis7 (Patients 1, 2, and 3 ) , and diffuse pulmonary sepsis8 may result. By exposure to a high Fio 2 , an adequate Pao, (50 to 100 torr) was maintained before perfusion in
OFF
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2
1 3
J 4
L 5
i 6
DAYS
Fig. 8. Case 4. Bypass blood flow during perfusion.
f j Membrane Lung 500 -
^ ^
r
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OFF
Lung
70 kg
300
1
200
1
1 2
^Natural
3
4
5
6
ill 1 1 8 i
15 16 17 18
DAYS
Fig. 9. Case 4. Oxygen transfer through the patient's lung and the membrane lung is computed by multiplying blood flow by the Van Slyke oxygen content difference.
Patients 2, 3, and 5, despite major intrapulmonary shunting, a low compliance, and radiographic evidence of diffuse bilateral infiltrates. During this therapy, they developed massive pleural air leaks requiring treatment with tube thoracostomies. Extensive necrosis of pulmonary tissues and moderate interstitial fibrosis were found at autopsy. Patient 4, treated for only 72 hours with 100 per cent oxygen, now has restricted pulmonary function and a chest radiogram characteristic of diffuse pulmonary fibrosis. He is alive 10 months after perfusion.
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Fig. 10. Case 4. Platelet counts during perfusion. Platelet counts remained low after perfusion due to antiplatelet antibodies.
ON
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g g Whole Blood f ]
Plasma Frozen Cells
*
Ol—L
I
2
3
4
5
6
7
8
9 10 II
12 13
DAYS
Fig. 11. Case 4. Blood and plasma requirements during perfusion.
These patients pose a serious challenge to our present mode of therapy. It is possible that gram-negative bacterial pneumonia alone caused the pulmonary necrosis found in Patient 5 or that viral infection in Patients 1 and 2 led to the severe pulmonary damage. However, we believe that the course of acute pulmonary disease might have been modified and fibrosis prevented if perfusion had been initiated early. Appropriate timing of perfusion permits reduction of high ventilator pressure and Fi0,.. Clinical experience with perfusion technology suggests that bypass lasting 1 to 2 weeks is possible. However, it has been clearly shown 5 - 9 that severe necrosis and extensive fibrosis, once established (as in Patients 1, 2, 3, and 5 ) , is probably not reversible.
A marked increase in pulmonary vascular resistance (5 to 8 units) in the absence of hypoxemia may signify extensive destruction of pulmonary vasculature. A high resistance to flow was measured in Patients 2, 3, and 5, coincident with what appeared to be severe lung destruction. In our experience, this parameter requires careful monitoring since the associated right ventricular failure may preclude recovery. Open lung biopy may assist in the decision of whether to perfuse a patient whose pulmonary disease has persisted more than 1 week. Open biopsy may not reflect the general condition of the lungs, as a peripheral sample revealing total fibrous replacement does not indicate the number of remaining functioning alveoli; however, exposure allows the surgeon to survey a large portion of the lung surface. Advantages must be weighed against the hazards of a subsequent air leak. Open biopsy also poses the hazard of bleeding from the thoracotomy wound or from the lung during perfusion. We believe that biopsy is often not helpful in patients who have had pulmonary disease for less than 1 week. Open lung biopsy was performed in Patient 1 after pneumonia had persisted for 14 days. It showed areas of interstitial edema, hyaline membranes, and early diffuse fibrosis. One week later, at autopsy, there was severe diffuse fibrosis with no detectable normal alveolar structures. Perfusion routes. We have now used five perfusion routes (see Figs. 1 to 4). All
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methods require only one blood pump. Previously, we" reported high-flow VV perfusion (Fig. 1) in adults and children. VV or prepulmonary oxygenation has the advantage of allowing the arterial tree to distribute oxygenated blood in a uniform pattern via the left ventricle. Venous blood is drained from the inferior vena cava via the common femoral vein and oxygenated blood is returned to the superior vena cava (as initially performed in Patient 3). Two incisions (femoral and cervical) are necessary. We have adapted this technique for use in small children. For Patient 1, an infant weighing only 3.5 kilograms, the drainage catheter was placed into the right atrium via the right jugular vein." This reversal of our usual VV flow pattern was necessary to introduce a cannula into the infant's atrium, wide enough (3.76 mm. O.D.) to allow a large blood flow (150 to 211 ml. per kilogram per minute). VA perfusion decreases pulmonary blood flow (see Fig. 7 ) . If this results in a decrease of mean pulmonary artery pressure, lung regions with high pulmonary vascular resistance will receive less blood, intrapulmonary shunting may decrease, and smaller transcapillary filtration pressures can be expected. Hill3 has reported that VA perfusion decreases the mean pulmonary artery pressure; however, this was rarely observed in our four VA or VVA perfusions, possibly due to extensive destruction of the lung vasculature. Surgically, VA is more complex than VV perfusion. It requires cannulation of the arterial system with a large-bore cannula. In the past, the common femoral artery has been transected and cannulated both proximally and distally. Patient 4 developed a false aneurysm 3 months after perfusion and required a vein graft. In the future, it may be advisable to replace the cannulated segment with a vein graft when bypass is completed. The major flaw of VA bypass is the inappropriate distribution of arterialized blood, depending upon the position of the arterial cannula (Fig. 2 ) . Oxygenated blood re-
6 0 -
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447
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20
-J
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1
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2
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3
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DAYS Fig. 12. Case 4. Lee-White clotting time of Patient 4 during perfusion.
45
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-
BYPASS
OFF
i
I
30
^ 8 is
15 0 2000
1—
J
1500
/ ^ ^ ~ ^
1000 500 0
1
1
1
1
1
1
1
DAYS
Fig. 13. Case 4. Effective (quasistatic) compliance and functional residual capacity (FRC) of Patient 4.
turned to the distal aorta is distributed to the kidneys, mesenteric bed, and lower limbs. We have frequently observed the combination of a high cardiac index, an intrapulmonary shunt greater than 50 per cent, and a small difference in arteriovenous oxygen content in severe acute respiratory failure. In these circumstances, the modest increase in venous oxygen saturation afforded by VA partial perfusion is inadequate to provide sufficiently high arterial oxygen tensions to the heart and brain. Our modification of the VA technique, i.e., "mixed" venovenous and venoarterial perfusion (Fig. 3), served to improve oxygenation of the heart and brain in Patients 3 and 5 by returning some oxygenated blood to the superior vena cava. Like VV but unlike VA perfusion, this technique has the disadvantage of requiring two incisions. In addition,
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it necessitates insertion of a flowmeter to measure blood flow to each route. To better distribute oxygenated blood, we have modified classic VA perfusion by passing the femoral artery cannula into the aortic arch to the level of the left subclavian artery (Fig. 4). VA arch perfusion requires an extremely large-bore spring-reinforced cannula to minimize flow resistance and allow a single roller pump to be used. By injecting a bolus of radioactive xenon, we have documented the contribution of aortic arch perfusion to cerebral oxygenation.1" Since the heart is proximal to the extracorporeal perfusion zone in VA arch perfusion, it may be necessary to add VV perfusion if severe pulmonary failure prevents oxygenation of mixed venous blood. Others have used the right axillary artery for return of bypassed blood.10 Because this vessel accommodates only a small catheter, high pump pressures are required which increase the mechanical danger of extracorporeal perfusion. In addition, the proximity of the artery to the brachial plexus increases the hazard of sepsis following prolonged cannulation. Respiratory management and monitoring. Vigorous chest physiotherapy, tracheal suctioning, and frequent postural changes are necessary to foster pulmonary healing.1 During perfusion, the Fi 02 is lowered to 0.6 or less. In our experience, appropriate oxygenation has not been possible without mechanical ventilation with a PEEP of 10 to 15 cm. H 2 0 during extracorporeal perfusion. However, extracorporeal gas exchange allows us to decrease the tidal volume and lower the peak inspiratory pressure to below 45 cm. H 2 0 . In this manner, we avoid or reduce the magnitude of a bronchopleural fistula. Patient 4 responded successfully to these methods (Figs. 6 and 13). Patient 1, in whom PEEP was discontinued after perfusion began, rapidly developed complete pulmonary consolidation and a marked decrease in pulmonary compliance. At present there is little reason to believe that "putting the lung to rest" is desirable. Because bypass blood can approach the
root of the aorta during VA arch perfusion, it is important to determine the precise origin of blood at an arterial sampling site. This is particularly important for computation of the alveolar-arterial oxygen tension difference (A-aDo2) and the patient's cardiac output (see Fig. 5). In order to determine the origin of the blood at a particular peripheral arterial line (e.g., left radial artery), dye is injected into the pulmonary artery and dilution curves are drawn from the artery. Appearance of a "normal" dye-dilution curve indicates that the artery is perfused via the left ventricle. In Cases 3, 4, and 5, we found it valuable to cannulate the right temporal artery to follow the course of carotid artery Po 2 . FRC was measured by helium dilution to evaluate the progress of lung function. FRC increased in Patient 4 concomitantly with decreases in A-aDo2 (Fig. 13) and slow radiographic clearing of infiltrates (Fig. 6, C). Improvement of quasistatic lung compliance was slow (Fig. 13). Radiography, FRC, and compliance are not affected by changes in extracorporeal blood flow or cardiac output, whereas the A-aDo2 and V D / V T are. Therefore, they represent objective and valuable methods for evaluation of pulmonary function during partial extracorporeal perfusion. Management of coagulation. We follow Hill's11 example and maintain the Lee-White clotting time at about 15 to 20 minutes by continuously infusing bovine lung heparin (10 to 50 units per kilogram per hour). During perfusion, levels of fibrin-split products, fibrinogen concentration, and prothrombin time are monitored daily. We transfuse fresh-frozen plasma and red cells to maintain the hematocrit around 30 per cent (see Fig. 11). All cellular solutions are ultrafiltered.14 Despite extensive electrocautery at cannulation sites, minor bleeding occurred during perfusion in several patients but was readily managed by local pressure, a reduction of the heparin dose, and infusion of platelets. After perfusion, careful examination of the membrane lung has shown localized
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areas of thrombus formation, confined to less than 10 per cent of the membrane lung surface. We have not used an in-line filter during perfusion and have not found systemic arterial thrombi at autopsy. Consumption of platelets due to systemic trauma, pulmonary disease, and extracorporeal treatment of blood is significant.13 When the platelet count falls below 20,000 per cubic millimeter, minor spontaneous bleeding has occurred. To conserve platelets, membrane lungs should be changed and blood exposed to fresh surface areas of membrane only when gas transport is impaired. Wound hemorrhage did not occur when operations were performed several days prior to perfusion. At present, only active bleeding can be considered a contraindication to extracorporeal perfusion. Patient 4 had an upper gastrointestinal hemorrhage (500 ml.) during bypass which ceased following ice saline lavage. If hemorrhage continues despite platelet infusion, the clotting time may be lowered to 10 minutes. At this level, clotting will not occur in the spiral coil membrane lung if a large blood flow rate is maintained. If the patient develops disseminated intravascular coagulation and consumes plasma coagulation factors, we administer fresh-frozen plasma and increase the heparin dose. We would like to thank the physicians, technicians, and nurses of the Massachusetts General Hospital who have provided expert care for our patients.
Braslow, N.: Dual Wavelength Reflectance Oximeter for Long-Term Extracorporeal Monitoring, Annual Conference on Engineering in Medicine and Biology 12: 113, 1970. 5 Hill, J. D., de Leval, M. R., Fallat, R. J., Bramson, M. L., Eberhart, R. C., Schulte, H. D., Osborn, J. J., Barber, R., and Gerbode, F.: Acute Respiratory Insufficiency: Treatment With Prolonged Extracorporeal Oxygenation, J. THORAC CARDIOVASC SURG.
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REFERENCES 1 Pontoppidan, H., Geffin, B., and Lowenstein, E.: Acute Respiratory Failure in the Adult, Boston, 1973, Little, Brown and Company. 2 Kolobow, T., and Zapol, W.: A New ThinWalled Nonkinking Catheter for Peripheral Vascular Cannulation, Surgery 68: 625, 1970. 3 Kolobow, T., and Zapol, W.: Partial and Total Extracorporeal Respiratory Gas Exchange With the Spiral Membrane Lung: Mechanical Devices for Cardiopulmonary Assistance: in Bartlett, R. H., Drinker, P., and Galletti, P. M., editors: Advances in Cardiology, Basel, 1971, S. Karger, AG, p. 112. 4 Vurek, G. G., Friauf, W. S., Perry, K., and
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551, 1972. Ashbaugh, D. G., and Petty, T. L.: Sepsis Complicating the Acute Respiratory Distress Syndrome, Surg. Gynecol. Obstet. 135: 865, 1972. Nash, G., Blennerhassett, J. B., and Pontoppidan, H.: Pulmonary Lesions Associated With Oxygen Therapy and Artificial Ventilation, N. Engl. J. Med. 276: 368, 1967. Finder, E., LaForce, M., and Huber, G. L.: Prevention of Oxygen Toxicity in the Lung, Chest 62: 365, 1972. Zapol, W., Pontoppidan, H., McCullough, N., Schmidt, V., Bland, J., and Kitz, R.: Clinical Membrane Lung Support for Acute Respiratory Insufficiency, Trans. Am. Soc. Artif. Intern. Organs 18: 553, 1972. Kanarek, D., Zapol, W., Ahluwalia, B., Qvist, J., Hales, C , and Liland, A.: Radionuclide Imaging of the Circulatory Distribution of Membrane Lung Perfusion, Trans. Am. Soc. Artif. Intern. Organs 20: 1974. In press. Hill, J. D., O'Brien, T. G., Murray, J. J., Dontigny, L., Bramson, M. L., Osborn, J. J., and Gerbode, F.: Prolonged Extracorporeal Oxygenation for Acute Post-traumatic Respiratory Failure (Shock-Lung Syndrome), N. Engl. I. Med. 286: 629, 1972. Hatterslea, P. G.: Activated Coagulation Time in Whole Blood, J. A. M. A. 196: 436, 1966. Bloom, S., Zapol, W., Wonders, T., Berger, S., and Salzman, E.: Platelet Destruction During 24 Hour Membrane Lung Perfusion, Trans. Am. Soc. Artif. Intern. Organs 20: 1974. In press. Patterson, R. H., Jr., and Twichell, J. B.: Disposable Filter for Microemboli: Use in Cardiopulmonary Bypass and Massive Transfusion, J. A. M. A. 215:76, 1971. White, J. J., Risemberg, H., and Haller, J. A.: Prolonged Respiratory Support in Infants With the Kolobow Spiral Coil Respirator, Mt. Sinai J. Med. N. Y. 40: 173, 1973. Soeter, J. R., Smith, G. T., Anema, R. J., Suehiro, G. T., and McNamara, J. J.: Distribution of Oxygenated Blood in Femoral and Brachtal Artery Perfusion During Venoarterial Bypass in Primates, J. THORAC. CARDIOVASC. SURG. 65: 825, 1973.
W. M. Zapol, M.D., J. Qvist, M.D., H. Pontoppidan, M.D., A. Liland, M.D., T. McEnany, M.D., and M. B. Laver, M.D., Boston, Mass.
-I—extracorporeal perfusion for acute respiratory failure has become increasingly safe and successful during the past two years due to improvements in materials and tehniques and to mounting clinical experience by perfusion teams. This article will describe the nature of the progress on four major fronts: (1) better criteria for selection of patients; (2) improved patient management and monitoring; (3) cannulation techniques permitting optimal distribution of oxygenated blood; and (4) reduction of hemorrhagic complications by precise coagulation control. We shall illustrate the importance of these factors by citing data from five recent perfusions and detailed physiological measureFrom the Departments of Anesthesia and Surgery, the Harvard Medical School, Massachusetts General Hospital, Boston, Mass. 02114. Supported by grants from the National Institutes of Health: GM 15904, GM 01273, HL 70303, and HL 16154. Received for publication July 24, 1974.
ments of a recent survivor of long-term perfusion. Methods Patient management and monitoring. All candidates for perfusion have catheters inserted for continuous monitoring of central venous, radial artery, pulmonary artery, and pulmonary capillary wedge pressures; urine output; and body temperature. Cardiac output is measured by dye or thermal dilution for computation of pulmonary vascular resistance. Chest roentgenograms are obtained. In patients without a bronchopleural fistula, functional residual capacity (FRC) is measured by helium dilution; standard pneumotachygraphy yields pressure-volume loops for computation of dynamic compliance. Management of pulmonary function must include therapy with antibiotics, vigorous chest physiotherapy, frequent positional changes, tracheobronchial suctioning, strict attention to water balance, and management 439
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Fig. 1. Diagram of venovenous perfusion route. M.L., Membrane lung.
Fig. 2. Diagram of venoarterial perfusion route with femoral artery cannulation and distal aortic return. M.L., Membrane lung.
of cardiac failure with inotropic drugs.1 Because lung compliance is generally very low, these patients are ventilated with a volume pre-set ventilator, with positive end-expiratory pressure levels (PEEP) of 10 to 15 cm. of water. Paralysis is produced with pancuronium and sedation with morphine. Patients in acute respiratory failure with sepsis have a marked increase in cardiac output. This situation, which may set a severe limit on the quality of extracorporeal perfusion, can be improved by lowering the body temperature to between 32 and 35° C. Perfusion equipment (Figs. 1 to 4). Venous blood is drained from a large-bore cannula2* inserted through the common femoral vein into the right atrium for venoarterial (VA) perfusion (Figs. 2 and 4 ) . When venovenous (VV) alone (Fig. 1) or venovenous with venoarterial ( W A ) per-
fusion is desired (Fig. 3), the cannula tip is positioned in the inferior vena cava at the level of the diaphragm to avoid recirculation of the returning stream of oxygenated blood into the drainage catheter. The outside diameter (O.D.) of the catheter is a minimum of 8.15 mm. and more commonly 10.35 mm. in adults. Blood is drained via silicone drainage tubing (12.7 mm. I.D.) to a servo-controlled reservoir bag (75 ml. volume). It is pumped in a nonocclusive, segmented polyurethane chamber,3 reinforced with fiberglass, by a Sarns Model 3500 roller pump through a spiral coil, silicone membrane lung.* Blood then passes through a bubble trap and past an electromagnetic flow probe to the patient. Oxygen saturation of venous blood is monitored continuously.4 A heat exchanger is not used, so that extracorporeal prime volume and
*Mr. Raymond Johnson, Peabody, Mass.
*Sci-Med Inc., Minneapolis, Minn.
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Fig. 3. Diagram of mixed venovenous and venoarterial perfusion. M.L., Membrane lung.
Fig. 4. Diagram of venoarterial arch perfusion. M.L., Membrane lung.
surface area are reduced. Instead, the entire apparatus is enclosed in a vinyl canopy and the ambient air temperature is regulated. For partial extracorporeal perfusion in adults, we use 0.5 sq. M. of membrane lung per 10 kilograms of body weight. The extracorporeal blood priming volume for a 70 kilogram adult is approximately 1,350 ml. However, if the patient progresses to total pulmonary failure, then 1 sq. M. of membrane lung per 10 kilograms is required. Membrane lungs are changed if outflow saturation falls below 90 per cent.
lateral pneumothoraces, pneumopericardium, and pneumoperitoneum. An open lung biopsy obtained 2 days before the start of perfusion showed diffuse interstitial edema, hyaline membranes, and early interstitial fibrosis. VV perfusion was initiated on the sixteenth day after the onset of pneumonia. Rather than being drained from the inferior vena cava (Fig. 1) through the common femoral vein, venous blood was drained from the right atrium via the right internal jugular vein to the extracorporeal circuit and was returned to the femoral vein. The jugular cannulation site permits passage of a large-bore cannula. Perfusion was terminated because of total loss of pulmonary function and severe right ventricular failure. At autopsy, the lungs demonstrated severe interstitial and bronchial pneumonia with marked pulmonary hemorrhage and fibrosis. Hepatomegaly and ascites were present. CASE 2. A 26-year-old woman in her sixth month of pregnancy was referred to us for perfusion after 13 days of viral pneumonia. The decision for perfusion was made because of an extremely low lung compliance and a right pneumothorax. Pa 0j was 88 torr on an Flo, of 1.0 and a Paco. of 50 torr during mechanical ventilation with 10 cm. H 2 0 PEEP prior to bypass (tidal
Case reports Patient data are summarized in Tables I and II. CASE 1. A 6-month-old boy developed viral pneumonia after a second-stage operation for megaureter. He was treated with mechanical ventilation and PEEP but required increasing concentrations of inspired oxygen (Fi 0 ,). His compliance diminished further and he developed bi-
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400-
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300 R Temporal Artery F[0 2 =10
P
°* (torrS
200
\ L. Radial Artery
100 R Temporal Artery
0 20 PEEP
(cmHsO>
10
~
0 FiOa
1.0 05
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0
10 DAYS
Fig. 5. Respiratory data in Case 4. Po= for the right temporal and left radial arteries (lower curves) are measured at the Flo, indicated. During perfusion, Po2 in the left radial artery is higher than in the right temporal artery due to admixture of blood from the patient's lung with that from the membrane lung. The right temporal artery Po- is indicative of the lung's performance when tested at an Flo, of 1.0. PEEP, Positive end-expiratory pressure.
Table I. Clinical data and perfusion method Case No.
Age
1 2
6 mo. 26 yr.
Bilateral megaureter Influenza pneumonia
3
30 yr.
4
5
Primary
disease
Perfusion route
Duration of bypass (Jays)
Pulmonary
disease
4.5 3
Pyosalpinx
VV VA (femoral) VVA
37 yr.
Pelvic fractures and multiple
VA (arch)
4.5
Pneumonitis Pneumonitis and interstitial fibrosis Pneumonitis and gram-negative pneumonia Gram-negative pneumonia
12 yr.
intra-abdominal injuries Femoral fracture and cerebral VVA contusion
4.5
Necrotic bronchopneumonia
4
Legend: W , Venovenous. VA, Venoarterial. W A , Venovenous and venoarterial.
volume 800 ml., peak pressure 70 cm. H = 0). Coincident with femoral cannulation and after administration of heparin, she developed a tension pneumothorax on the left. A thoracostomy tube was inserted anteriorly, and a second tube in the midaxillary line was required. On the second day of VA perfusion (Fig. 2), an expanding hematoma spontaneously dissected between the left parietal pleura and chest wall. Three consecutive thoracotomies failed to achieve hemostasis despite extensive electrocautery. Perfusion was discontinued due to the enormous requirements for blood. Severe pulmonary consolidation with early fibrosis,
subpleural cystic alveolar dilation, and dissection of parietal pleura off the chest wall were found at autopsy. CASE 3. A 30-year-old woman was transferred after 15 days of mechanical ventilation for severe diffuse pneumonia with hypoxemia. After 1 week of mechanical ventilation the patient developed a left pneumothorax for which she required insertion of a thoracostomy tube. After her arrival the patient's condition deteriorated rapidly because of increasing air leakage from the left lung, and extracorporeal perfusion was instituted. Since the cardiac index was high
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Fig. 6. Case 4. A, Chest radiogram 1 day before perfusion. B, Chest radiogram on the third day of perfusion; note drainage catheter in the right atrium and aortic arch blood return catheter in the aortic arch. C, Chest radiogram 2 days after perfusion. (5.2 L. per square meter per minute) presumably because of associated sepsis, we began perfusion via the VV route (Fig. 1). Bypass was complicated by septicemia and an increasing air leak from the left lung. We positioned a Fogarty embolectomy catheter in the leaking lobar bronchus through the tracheostomy tube and succeeded in sealing the air leak when the balloon was inflated. Pulmonary artery pressure increased from 40/15 to 70/20 mm. Hg during perfusion, and VA perfusion was added to lower pulmonary blood flow (Fig. 3). As pulmonary function had deteriorated, it was necessary to maintain some VV blood return to ensure an
adequate Pao, to the brain and heart, since both were perfused with mixed venous blood ejected from the left ventricle. Pulmonary artery pressure remained at 50 to 70/20 mm. Hg despite partial VVA bypass. Total loss of transpulmonary gas exchange after 4 days of support led to the decision to cease extracorporeal perfusion. Autopsy revealed early interstitial fibrosis and severe, confluent, bilateral pneumonia with several abscesses ruptured into the pleural cavity. There was acute and chronic bilateral salpingitis with pyosalpinx. CASE 4. A 37-year-old white man was transferred 3 days after sustaining severe abdominal trauma (pelvic fractures with retroperitoneal
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ON
i~
6
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BYPASS OFF
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4
-
2
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0 20
r _
OPumpFlow —•Cardiac Output
■S
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5
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DAYS Fig. 7. Case 4. Cardiac output and pulmonary vascular resistance (PVR). Dye is injected into the pulmonary artery and sampled in the right temporal artery during perfusion. Table II. Mean cardiopulmonary during perfusion
Case No.
Weight (Kg.)
1 2 3 4 5
3.5 58 55 71 30
Cardiac output (L./min.) 1.6 2.5 4.5 7.0 2.5
Bypass
flow (L./min.) 0.8 4.0 5.0 3.0 2.7
data
Total oxygen transfer of membrane lung* (c.c./min.) 45, 136, 145, 120, 110,
50 130 225 100 135
♦The first value of each pair is the initial value at the start of perfusion; the second was obtained close to termination of perfusion. hematoma). He had undergone a laparotomy to repair an inferior vena cava tear and two small bowel perforations. Postoperatively, he developed septicemia with Bacteroides, and three species of gram-negative bacteria were cultured from the trachea. Induced hypothermia (32° C.) by surface cooling effectively reduced the cardiac index from 9.6 to 4.3 L. per minute per square meter, but Pao2 remained below 35 torr (Fig. 5). We instituted VA perfusion, draining blood from the superior vena cava through the left internal jugular vein and returning blood through the femoral artery to the arch of the aorta at the level of the left subclavian artery (8.12 mm. O.D. steel spring-
reinforced cannula; Figs. 4 and 5). Fig. 6 shows the chest radiograms 1 day before perfusion, on the second day of perfusion (note position of the aortic cannula), and 1 day after bypass was completed. Hemodynamic performance was stable throughout perfusion. Fig. 7 shows the patient's cardiac output and Fig. 8 the quantity of blood flow through the membrane lung. Pulmonary vascular resistance is illustrated in Fig. 7. The proportions of oxygen delivered via the patient's lung and the membrane are shown in Fig. 9. 13:1 Xenon, injected into the extracorporeal blood return to evaluate the magnitude of intracranial blood flow, demonstrated major perfusion of the left carotid artery, with only a small amount reaching the right carotid artery. During perfusion, Po2 in the left radial artery was always higher than that in the right temporal artery. Platelet counts before bypass were 54,000 per cubic millimeter and were maintained above 20,000 per cubic millimeter during perfusion with platelet transfusions (Fig. 10). The volume of blood and plasma replacement during perfusion is illustrated in Fig. 11. Lee-White clotting time was maintained at approximately 20 minutes (Fig. 12). During perfusion, ventilation was controlled, with a tidal volume of 800 ml. at a rate of 15 breaths per minute; this required plateau inspiratory pressures of 45 to 50 cm. H 2 0. On this regimen, respiratory function improved slowly, with a rise in quasistatic compliance (measured with inspiration of more than 2 seconds) and FRC (measured with a PEEP of 15 cm. H.O) (Fig. 13). Late on the fourth day of perfusion, the Pao, was 65 torr and Paco, was 41 torr at an extracorporeal blood flow of 500 ml. per minute, an Fio, of 0.6, and peak airway pressures of 45 cm. H^O. After 110 hours of perfusion, bypass was terminated and the patient was decannulated. The patient's postperfusion course was complicated. Major problems included recurrent sepsis from intra-abdominal abscesses, urine extravasation requiring right nephrectomy, small bowel obstruction, acute gangrenous cholecystitis, and gentamicin-induced nephritis with severe renal failure. Three months after decannulation, a false aneurysm developed on the femoral artery, for which resection and insertion of a vein graft were required. Four months after perfusion, the patient was weaned from the ventilator, and 1 month later he was discharged from the hospital on maintenance hemodialysis. CASE 5. A 12-year-old boy was transferred 18
days after sustaining head trauma and 10 days after developing gram-negative pneumonia. Sixty hours of medical treatment did not improve oxygenation, and the patient was placed on VA perfusion with femoral vein and artery cannulation.
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Pulmonary gas exchange decreased during perfusion. It was necessary to insert a cannula in the internal jugular vein and perfuse by the VVA mode (Fig. 3) to maintain adequate cerebral oxygen tensions. Despite decreased peak ventilator pressure, the patient developed several tension pneumothoraces, and three thoracostomy tubes were required. Perfusion was terminated more than 30 hours after pulmonary function had ceased. Autopsy showed severe acute bilateral hemorrhagic bronchopneumonia with extensive microabscess formation and necrosis of pulmonary tissue.
ON
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Discussion Perfusion criteria. The use of hypoxemia as a criterion for initiation of membrane lung perfusion is illustrated by Case 4. 5 Low Pao2 (30 to 50 torr) due to severe rightto-left intrapulmonary shunting persisted despite aggressive respiratory management, including mechanical ventilation with 100 per cent oxygen, a PEEP of 10 to 15 cm. H z O, diuresis, cardiotonics, and vigorous chest physiotherapy. Persistent hypoxemia in addition to poor quasistatic lung compliance ( < 10 ml. per centimeter of water) and diffuse bilateral opacification on the chest radiogram placed him in a group of patients whose risk of dying is extremely high." Patient 4 had a brief course of pulmonary insufficiency (4 days). Of all candidates for perfusion, patients suffering rapid progression of severe, acute respiratory failure have the greatest probability of survival if they are perfused early in the course of their disease. In the early phases of pulmonary disease, lesions may be arrested and leave sufficient functioning pulmonary tissue for recovery. Unlike Patient 4, the other patients had pulmonary disease for 2 weeks or longer. Pa 0 , above 50 torr can usually be maintained with aggressive medical respiratory management. However, if an acceptable Pao., can be obtained only by lengthy exposure to a high Fi0.2, extensive pulmonary fibrosis7 (Patients 1, 2, and 3 ) , and diffuse pulmonary sepsis8 may result. By exposure to a high Fio 2 , an adequate Pao, (50 to 100 torr) was maintained before perfusion in
OFF
BYPASS
11—
2
1 3
J 4
L 5
i 6
DAYS
Fig. 8. Case 4. Bypass blood flow during perfusion.
f j Membrane Lung 500 -
^ ^
r
ON
BYPASS
OFF
Lung
70 kg
300
1
200
1
1 2
^Natural
3
4
5
6
ill 1 1 8 i
15 16 17 18
DAYS
Fig. 9. Case 4. Oxygen transfer through the patient's lung and the membrane lung is computed by multiplying blood flow by the Van Slyke oxygen content difference.
Patients 2, 3, and 5, despite major intrapulmonary shunting, a low compliance, and radiographic evidence of diffuse bilateral infiltrates. During this therapy, they developed massive pleural air leaks requiring treatment with tube thoracostomies. Extensive necrosis of pulmonary tissues and moderate interstitial fibrosis were found at autopsy. Patient 4, treated for only 72 hours with 100 per cent oxygen, now has restricted pulmonary function and a chest radiogram characteristic of diffuse pulmonary fibrosis. He is alive 10 months after perfusion.
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Fig. 10. Case 4. Platelet counts during perfusion. Platelet counts remained low after perfusion due to antiplatelet antibodies.
ON
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I
OFF
1
g g Whole Blood f ]
Plasma Frozen Cells
*
Ol—L
I
2
3
4
5
6
7
8
9 10 II
12 13
DAYS
Fig. 11. Case 4. Blood and plasma requirements during perfusion.
These patients pose a serious challenge to our present mode of therapy. It is possible that gram-negative bacterial pneumonia alone caused the pulmonary necrosis found in Patient 5 or that viral infection in Patients 1 and 2 led to the severe pulmonary damage. However, we believe that the course of acute pulmonary disease might have been modified and fibrosis prevented if perfusion had been initiated early. Appropriate timing of perfusion permits reduction of high ventilator pressure and Fi0,.. Clinical experience with perfusion technology suggests that bypass lasting 1 to 2 weeks is possible. However, it has been clearly shown 5 - 9 that severe necrosis and extensive fibrosis, once established (as in Patients 1, 2, 3, and 5 ) , is probably not reversible.
A marked increase in pulmonary vascular resistance (5 to 8 units) in the absence of hypoxemia may signify extensive destruction of pulmonary vasculature. A high resistance to flow was measured in Patients 2, 3, and 5, coincident with what appeared to be severe lung destruction. In our experience, this parameter requires careful monitoring since the associated right ventricular failure may preclude recovery. Open lung biopy may assist in the decision of whether to perfuse a patient whose pulmonary disease has persisted more than 1 week. Open biopsy may not reflect the general condition of the lungs, as a peripheral sample revealing total fibrous replacement does not indicate the number of remaining functioning alveoli; however, exposure allows the surgeon to survey a large portion of the lung surface. Advantages must be weighed against the hazards of a subsequent air leak. Open biopsy also poses the hazard of bleeding from the thoracotomy wound or from the lung during perfusion. We believe that biopsy is often not helpful in patients who have had pulmonary disease for less than 1 week. Open lung biopsy was performed in Patient 1 after pneumonia had persisted for 14 days. It showed areas of interstitial edema, hyaline membranes, and early diffuse fibrosis. One week later, at autopsy, there was severe diffuse fibrosis with no detectable normal alveolar structures. Perfusion routes. We have now used five perfusion routes (see Figs. 1 to 4). All
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methods require only one blood pump. Previously, we" reported high-flow VV perfusion (Fig. 1) in adults and children. VV or prepulmonary oxygenation has the advantage of allowing the arterial tree to distribute oxygenated blood in a uniform pattern via the left ventricle. Venous blood is drained from the inferior vena cava via the common femoral vein and oxygenated blood is returned to the superior vena cava (as initially performed in Patient 3). Two incisions (femoral and cervical) are necessary. We have adapted this technique for use in small children. For Patient 1, an infant weighing only 3.5 kilograms, the drainage catheter was placed into the right atrium via the right jugular vein." This reversal of our usual VV flow pattern was necessary to introduce a cannula into the infant's atrium, wide enough (3.76 mm. O.D.) to allow a large blood flow (150 to 211 ml. per kilogram per minute). VA perfusion decreases pulmonary blood flow (see Fig. 7 ) . If this results in a decrease of mean pulmonary artery pressure, lung regions with high pulmonary vascular resistance will receive less blood, intrapulmonary shunting may decrease, and smaller transcapillary filtration pressures can be expected. Hill3 has reported that VA perfusion decreases the mean pulmonary artery pressure; however, this was rarely observed in our four VA or VVA perfusions, possibly due to extensive destruction of the lung vasculature. Surgically, VA is more complex than VV perfusion. It requires cannulation of the arterial system with a large-bore cannula. In the past, the common femoral artery has been transected and cannulated both proximally and distally. Patient 4 developed a false aneurysm 3 months after perfusion and required a vein graft. In the future, it may be advisable to replace the cannulated segment with a vein graft when bypass is completed. The major flaw of VA bypass is the inappropriate distribution of arterialized blood, depending upon the position of the arterial cannula (Fig. 2 ) . Oxygenated blood re-
6 0 -
ON
BYPASS
r
447
OFF
fc 40 h ^
20
-J
0
L
J
1
I
2
I
3
I
4
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5
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6
DAYS Fig. 12. Case 4. Lee-White clotting time of Patient 4 during perfusion.
45
ON
-
BYPASS
OFF
i
I
30
^ 8 is
15 0 2000
1—
J
1500
/ ^ ^ ~ ^
1000 500 0
1
1
1
1
1
1
1
DAYS
Fig. 13. Case 4. Effective (quasistatic) compliance and functional residual capacity (FRC) of Patient 4.
turned to the distal aorta is distributed to the kidneys, mesenteric bed, and lower limbs. We have frequently observed the combination of a high cardiac index, an intrapulmonary shunt greater than 50 per cent, and a small difference in arteriovenous oxygen content in severe acute respiratory failure. In these circumstances, the modest increase in venous oxygen saturation afforded by VA partial perfusion is inadequate to provide sufficiently high arterial oxygen tensions to the heart and brain. Our modification of the VA technique, i.e., "mixed" venovenous and venoarterial perfusion (Fig. 3), served to improve oxygenation of the heart and brain in Patients 3 and 5 by returning some oxygenated blood to the superior vena cava. Like VV but unlike VA perfusion, this technique has the disadvantage of requiring two incisions. In addition,
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it necessitates insertion of a flowmeter to measure blood flow to each route. To better distribute oxygenated blood, we have modified classic VA perfusion by passing the femoral artery cannula into the aortic arch to the level of the left subclavian artery (Fig. 4). VA arch perfusion requires an extremely large-bore spring-reinforced cannula to minimize flow resistance and allow a single roller pump to be used. By injecting a bolus of radioactive xenon, we have documented the contribution of aortic arch perfusion to cerebral oxygenation.1" Since the heart is proximal to the extracorporeal perfusion zone in VA arch perfusion, it may be necessary to add VV perfusion if severe pulmonary failure prevents oxygenation of mixed venous blood. Others have used the right axillary artery for return of bypassed blood.10 Because this vessel accommodates only a small catheter, high pump pressures are required which increase the mechanical danger of extracorporeal perfusion. In addition, the proximity of the artery to the brachial plexus increases the hazard of sepsis following prolonged cannulation. Respiratory management and monitoring. Vigorous chest physiotherapy, tracheal suctioning, and frequent postural changes are necessary to foster pulmonary healing.1 During perfusion, the Fi 02 is lowered to 0.6 or less. In our experience, appropriate oxygenation has not been possible without mechanical ventilation with a PEEP of 10 to 15 cm. H 2 0 during extracorporeal perfusion. However, extracorporeal gas exchange allows us to decrease the tidal volume and lower the peak inspiratory pressure to below 45 cm. H 2 0 . In this manner, we avoid or reduce the magnitude of a bronchopleural fistula. Patient 4 responded successfully to these methods (Figs. 6 and 13). Patient 1, in whom PEEP was discontinued after perfusion began, rapidly developed complete pulmonary consolidation and a marked decrease in pulmonary compliance. At present there is little reason to believe that "putting the lung to rest" is desirable. Because bypass blood can approach the
root of the aorta during VA arch perfusion, it is important to determine the precise origin of blood at an arterial sampling site. This is particularly important for computation of the alveolar-arterial oxygen tension difference (A-aDo2) and the patient's cardiac output (see Fig. 5). In order to determine the origin of the blood at a particular peripheral arterial line (e.g., left radial artery), dye is injected into the pulmonary artery and dilution curves are drawn from the artery. Appearance of a "normal" dye-dilution curve indicates that the artery is perfused via the left ventricle. In Cases 3, 4, and 5, we found it valuable to cannulate the right temporal artery to follow the course of carotid artery Po 2 . FRC was measured by helium dilution to evaluate the progress of lung function. FRC increased in Patient 4 concomitantly with decreases in A-aDo2 (Fig. 13) and slow radiographic clearing of infiltrates (Fig. 6, C). Improvement of quasistatic lung compliance was slow (Fig. 13). Radiography, FRC, and compliance are not affected by changes in extracorporeal blood flow or cardiac output, whereas the A-aDo2 and V D / V T are. Therefore, they represent objective and valuable methods for evaluation of pulmonary function during partial extracorporeal perfusion. Management of coagulation. We follow Hill's11 example and maintain the Lee-White clotting time at about 15 to 20 minutes by continuously infusing bovine lung heparin (10 to 50 units per kilogram per hour). During perfusion, levels of fibrin-split products, fibrinogen concentration, and prothrombin time are monitored daily. We transfuse fresh-frozen plasma and red cells to maintain the hematocrit around 30 per cent (see Fig. 11). All cellular solutions are ultrafiltered.14 Despite extensive electrocautery at cannulation sites, minor bleeding occurred during perfusion in several patients but was readily managed by local pressure, a reduction of the heparin dose, and infusion of platelets. After perfusion, careful examination of the membrane lung has shown localized
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areas of thrombus formation, confined to less than 10 per cent of the membrane lung surface. We have not used an in-line filter during perfusion and have not found systemic arterial thrombi at autopsy. Consumption of platelets due to systemic trauma, pulmonary disease, and extracorporeal treatment of blood is significant.13 When the platelet count falls below 20,000 per cubic millimeter, minor spontaneous bleeding has occurred. To conserve platelets, membrane lungs should be changed and blood exposed to fresh surface areas of membrane only when gas transport is impaired. Wound hemorrhage did not occur when operations were performed several days prior to perfusion. At present, only active bleeding can be considered a contraindication to extracorporeal perfusion. Patient 4 had an upper gastrointestinal hemorrhage (500 ml.) during bypass which ceased following ice saline lavage. If hemorrhage continues despite platelet infusion, the clotting time may be lowered to 10 minutes. At this level, clotting will not occur in the spiral coil membrane lung if a large blood flow rate is maintained. If the patient develops disseminated intravascular coagulation and consumes plasma coagulation factors, we administer fresh-frozen plasma and increase the heparin dose. We would like to thank the physicians, technicians, and nurses of the Massachusetts General Hospital who have provided expert care for our patients.
Braslow, N.: Dual Wavelength Reflectance Oximeter for Long-Term Extracorporeal Monitoring, Annual Conference on Engineering in Medicine and Biology 12: 113, 1970. 5 Hill, J. D., de Leval, M. R., Fallat, R. J., Bramson, M. L., Eberhart, R. C., Schulte, H. D., Osborn, J. J., Barber, R., and Gerbode, F.: Acute Respiratory Insufficiency: Treatment With Prolonged Extracorporeal Oxygenation, J. THORAC CARDIOVASC SURG.
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REFERENCES 1 Pontoppidan, H., Geffin, B., and Lowenstein, E.: Acute Respiratory Failure in the Adult, Boston, 1973, Little, Brown and Company. 2 Kolobow, T., and Zapol, W.: A New ThinWalled Nonkinking Catheter for Peripheral Vascular Cannulation, Surgery 68: 625, 1970. 3 Kolobow, T., and Zapol, W.: Partial and Total Extracorporeal Respiratory Gas Exchange With the Spiral Membrane Lung: Mechanical Devices for Cardiopulmonary Assistance: in Bartlett, R. H., Drinker, P., and Galletti, P. M., editors: Advances in Cardiology, Basel, 1971, S. Karger, AG, p. 112. 4 Vurek, G. G., Friauf, W. S., Perry, K., and
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