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Experimental evaluation of Gore-Tex membrane oxygenator
Experimental evaluation of Gore-Tex membrane oxygenator Experimental studies have been conducted with the Gore-Tex membrane oxygenator in mongrel dogs. On the basis of our results, we believe the oxygenator is ready for a clinical trial in adults on partial perfusion.
Kensuke Esato and Ben Eiseman, Denver, Colo.
Xreviously, w e 2 , 4 ' 5 described an effective silicone membrane oxygenator and then evaluated a new form of expanded Teflon (Gore-Tex*) membrane, more permeable to both oxygen and carbon dioxide, for use in such units. The current study evaluates the use of this membrane (Gore-Tex) in the oxygenator unitf that we originally described. Experimental studies The oxygenator. The disposable membrane oxygenator unit measures 30 by 16.2 by 10 cm. and has a priming volume of 500 ml. of blood. An inflatable shim, when inflated to 200 mm. Hg, provides a thin membrane surface (blood contact) area of 2.25 sq. M. (Fig. 1). The expanded polytetrafluoroethylene (PTFE or Teflon) is 2 ml. thick with a 0.5 /*. pore size. Circuitry and pump. As diagramed in Fig. 2, the extracorporeal circuit included a Gore-Tex membrane oxygenator, two roller pumps, and one Travenol disposable heat exchanger. The output of the arterial From the Department of Surgery, Denver General Hospital, and University of Colorado Medical Center, Denver, Colo. 80204. Supported by National Institutes of Health Grant No. HL 15873. Received for publication Aug. 9, 1974. •Manufactured by W. L. Gore and Associates, Flagstaff, Ariz. tManufactured by Travenol Laboratories, Inc., Morton Grove, 111.
690
pump in these studies ranged from 60 to 70 ml. per minute per kilogram of body weight according to the flow of the venous pump, which was maintained by the flow draining from the dog. The circuit, made of % inch I.D. silicone rubber tubing throughout, included a recirculation line between the arterial and venous reservoirs, so that the oxygenator could be replaced, if necessary, without interruption of venoarterial pumping. The component was primed with 500 ml. of lactated Ringer's solution plus 1,000 ml. of heparinized blood collected from a single donor. Experiment. Gas exchange by the oxy-
Volume 69
Gore-Tex membrane oxygenator
Number 5
691
May, 1975
FEMORAL ARTERY
HEAT EXCHANGE
ARTERIAL PUMP
Fig. 2. Circuitry for evaluation of oxygenator.
genator was evaluated by means of femoral vein-femoral artery perfusions in 10 mongrel dogs, weighing 20 to 60 kilograms. The dogs were anesthetized with sodium pentobarbital (30 mg. per kilogram of body weight), and the inferior and superior venae cavae were cannulated via the right femoral vein and the right jugular vein. Venous blood drained by gravity into the venous reservoir and was pumped through the oxygenator and heat exchanger by the Travenol pump into an arterial reservoir and then into the right femoral artery. The 10 dogs were divided into two equal groups, one ventilated with room air and the other made hypoxic in order to test the limits of oxygen and carbon dioxide transfer through the membrane. The first group of 5 dogs was mechanically ventilated with room air via a Harvard animal respirator. The second group (5 dogs) was rendered hypoxic (Po 2 50 to 60 mm. Hg in arterial blood) by using 95 per cent nitrogen and 5 per cent carbon dioxide in the endotracheal tube system of the respirator. Duration of each perfusion was 3 hours. In order to obtain high pump flow rates of 60 to 70 ml. per minute per kilogram of body weight, venous return had to be in-
Balloon Catheter
Fig. 3. Method of venous cannulation using balloon-tip Bardic cannula. SVC, Superior vena cava. 1VC, Inferior vena cava.
The Journal of
6 9 2
Esato
and
Eiseman
Thoracic and Cardiovascular Surgery
O
ANOXIC GROUP
•
NONANOXIC GROUP
2000
Blood Flow Rate
Fig. 4. Arterial saturation as function of blood flow rate. Venous saturation, 60 to 80 per cent. Hematocrit, 30 to 49 per cent.
creased by using balloon-tipped Fogarty catheters in the superior and inferior cavae. As shown in Fig. 3, these catheters blocked most of the venous return to the right atrium. Heparin, 1 to 3 mg. per kilogram, was given at the time of cannulation. Clotting time was measured before perfusion, 1 hour after the start of perfusion, and immediately after perfusion in 4 cases. The flow was measured by a probe monitoring through a BLI pulse logic flowmeter (Biotronex Laboratory, Inc., Silver Spring, Maryland). Sampling and pressure catheters were placed in the femoral artery and vein. Temperature was maintained at 37° ± 2° C. by the heat exchanger. Partial pressure of oxygen and carbon dioxide and pH were measured on blood samples at 30 minute intervals during perfusion. Hemoglobin in both whole blood and plasma and the hematocrit level were also calculated. Oxygen and carbon dioxide transfer rates were calculated by the following formula: 0 3 content (vol. %) = 1.34 x whole blood hemoglobin x 0 2 saturation (% ) 0 3 transfer rate (ml./min.) = blood flow (ml./min.) 100
(0-. content of arterial blood 0 2 content of venous blood).
Content (volumes per cent) of carbon dioxide is calculated by the Singer-Hasting nomogram. C0 2 transfer rate (ml./min.) = blood flow (ml./min.) 100
x (COj content of venous blood CO- content of arterial blood).
Results The effect of blood flow on arterial saturation is shown in Fig. 4. Fig. 5 demonstrates the relationship between blood flow and oxygen transfer rate. As the flow increases, oxygen transfer rate increases. At a blood flow of 3,000 ml. per minute, the oxygen transfer rate is about 180 ml. per minute. The oxygen transfer is statistically a linear function of blood flow rate at the limited condition (y = 0.93 ± 0.03). Fig. 6 illustrates the variation of arterial saturation with venous saturation at the condition in which blood flow ranged from 40 to 80 ml. per minute per kilogram of body weight and hematocrit was 30 to 49 per cent. In the anoxic group, a linear relationship existed between venous and arterial saturations (y = 0.84 ± 0.06). This input saturation had to remain above 70 per cent for the output saturation to stay
Volume 69
Gore-Tex membrane oxygenator
Number 5
693
May, 1975
O Anoxic Group • Nonanodc Group
i O
Blood Flow Rate
ml/min
Fig. 5. Effect of blood flow rate on oxygen transfer rate. Venous saturation, 60 to 80 per cent. Hematocrit, 30 to 49 per cent.
about 95 per cent. Alternately stated, complete oxygenation could not be achieved with venous saturations below 75 to 80 per cent in the animals ventilated with high concentrations of nitrogen and carbon dioxide. On the contrary, total arterial oxygen saturation was achieved in the animals ventilated with room air, even when central venous oxygen was 35 per cent. This can be explained by the lower blood flow rate in the nonanoxic group. Variation of oxygen transfer with venous saturation is shown in Fig. 7: There was greater transfer when the venous blood was desaturated. At a venous saturation of 70 per cent, oxygen transfer rate is about 5 vol. per cent. Fig. 8 shows the effect of blood flow on carbon dioxide transfer rate at the limited range in which venous PcOj is from 30 to 60 mm. Hg and ApH (difference between arterial and venous value) is below 0.05. With increased blood flow rate, carbon dioxide transfer rate increases (y = 0.279 + 0.19). At a blood flow of 3,000 ml. per minute, carbon dioxide transfer rate is about 200 ml. per minute. There is no significant difference in carbon dioxide transfer between anoxic and nonanoxic groups. The effect of venous Pco, on carbon dioxide
&
90 r - 0.84 + 0.06
3
(/)
e:
5
O Anoxic Group • Nonanoxic Group
< ^
an -
L
J-
>L
Venous Saturation (%)
Fig. 6. Variation of arterial saturation with venous saturation. Blood flow, 40 to 80 ml. per minute per kilogram. Hematocrit, 30 to 49 per cent.
transfer rate and APcOj (difference between arterial and venous value) with blood flows between 1,200 and 4,000 ml. per minute is illustrated in Fig. 9. There is significant positive correlation between APcoL. and venous Pcro. (y = 0.67 ± 0.10). As venous
The Journal of
694
Esato and Eiseman
Thoracic and Cardiovascular Surgery
O ANOXIC GROUP 0 NONANOXIC CROUP
O Anoxic Group • Nonanoxic Group
E E
o
(J Q_
a ■ io (0 0
rr >
o
0)
a c 1° I-
CM
o u
cP
^
o
o
00
Venous PCO2
o •
_L
J
m m Hg
Fig. 9. Effect of venous blood Pco ; on carbon dioxide transfer rate and change in Pco-. Blood flow rate, 1,200 to 4.000 ml. per minute. 25
SO
75
loo
Venous Saturation %
Fig. 7. Variation of oxygen transfer rate with venous saturation. Blood flow, 40 to 80 ml. per minute per kilogram. Hematocrit, 30 to 49 per cent.
O ANOXIC GROUP •
NONANOXIC GROUP
0.279 + 0.19
ID
rr
CM
o o
1
looo
2000
Blood Flow Rate
X
3000
J
4000
ml/min
Fig. 8. Effect of blood flow rate on Pco.., transfer rate. Venous Pco5, 30 to 60 mm. Hg. pH, below 0.05.
PcOj is elevated, more carbon dioxide passes through the membrane and ^PcOj increases. At a venous Pco 2 of 40 mm. Hg, the decrease in PcoL. is about 6 mm. Hg. There is no statistical correlation between venous PCO;, and carbon dioxide transfer rates. Variation in gas flow through the oxygenator accounts for this lack of correlation, since differences in gas flow caused the carbon dioxide gradient across the membrane to vary. This study was carried out with the ventilation of the animal held constant at 5 L. per minute of either room air or 95 per cent nitrogen plus 5 per cent carbon dioxide, but with varying ventilation rates of 100 per cent oxygen through the oxygenator. Table I summarizes the oxygen and carbon dioxide transfer rate in each experiment. Maximum oxygen transfer was 473.6 ml. per minute at a blood flow of 4,000 ml. per minute, a venous saturation of 38 per cent, and a hematocrit of 49 per cent. Maximum carbon dioxide transfer was 304 ml. per minute at a blood flow of 4,000 ml. per minute, a Pco. of 43.3 mm. Hg, and a central venous blood pH of 7.468. By using a balloon-tipped catheter, we found maximum and minimum blood flow to be about 100 and 30 ml. per minute per
Volume 69
Gore-Tex membrane oxygenator
Number 5
695
May, 1975
Table I. Oxygen and carbon dioxide transfer in 2.25 sq. M. membrane oxygenators Oxygenator No.
Length Weight (Kg.)
of
run (hr.)
(%)
o2 transfer rale (ml./min.)
A noxic group 10.9 1,260 ±1.6 ±167 18.4 2,466 ±0.7 ±531 2,462 12.0 ±0.4 ± 74 16.7 3,036 ±1.0 ±436 3,320 17.9 ±0.8 ±229
92.50 ±5.00 90.45 ±6.05 90.31 ±3.20 44.03 ±9.77 69.20 ±11.69
12.79 ±7.91 43.75 ±19.70 38.48 ±13.02 319.47 ±78.81 199.20 ±78.22
49.77 ±4.07 51.12 ±4.32 50.09 ±4.48 53.80 ±10.38 40.79 ±2.80
112.10 ±63.50 103.60 ±56.80 121.91 ±65.54 132.00 ±113.39 127.76 ±76.66
Nonanoxic group 9.3 600 ±0.9 ± 0 12.4 1,060 ±391 ±2.3 17.9 1,140 ±1.6 ± 89 13.3 1,280 ±2.1 ±178 12.1 1,375 ±1.3 ±125
80.64 ±6.55 81.75 ±7.30 76.57 ±6.75 59.38 ±18.42 71.00 ±6.71
14.52 ±5.96 31.72 ±14.15 59.04 ±17.42 92.46 ±46.21 62.14 ±11.35
—
—
43.67 ±1.96
86.37 ±64.18
Mean flow rate Hemoglobin flow rate (L./min. 1 (Gm./dl.) (ml.,min.)
o2
1
25.0
3.0
3
2
31.0
3.0
5
3
25.0
3.0
5
4
59.0
3.0
15
5
43.0
3.0
15
6
20.0
2.5
3
7
30.0
3.0
3
8
50.0
2.5
3
9
23.0
2.5
3
10
29.5
3.0
3
tetrafluoroethylene
kilogram, respectively. Mean blood flow was 60.39 + 27.73 ml. per minute per kilogram of body weight. When the balloon is placed at the caval orifices into the right atrium, total inflow-outflow perfusion is achieved. Values of plasma hemoglobin before and immediately after the 3 hour perfusion were 20.00 ± 13.03 mg. per cent and 24.62 ± 18.46 mg. per cent, respectively. Discussion A variety of membrane oxygenator systems have been evaluated in recent years,1' i- •"■ ' "•1"' 1L'-1:| designed for short-term support during surgical cardiotomy and for the more physiological demanding, longterm needs in the treatment of cardiac failure and respiratory distress syndrome. However, clinical reports describing use of these membrane oxygenators for prolonged periods for patients with respiratory failure are rare."' " At basal conditions, the normal adult man requires 240 ml. of oxygen per minute. Complete total support would require this degree of oxygen exchange, but
Input 02 sal.
Input CO, content (vol. %)
C02 transfer rate (ml./min.)
— 43.80 ±6.09 48.20 ±10.18
—
87.80 ±63.35 135.73 ±96.42
parital perfusion is less demanding and depends on the degree of support provided. The theoretical value of a membrane oxygenator is its tolerance to blood elements as compared to the damage inflicted at a bloodair interface. The 2.25 sq. M. Gore-Tex membrane is capable of an oxygen transfer rate of about 180 ml. per minute at a blood flow of 3,000 ml. per minute; its maximum rate is 304 ml. per minute at a blood flow of 4,000 ml. per minute. We believe that an oxygen exchange of 180 ml. per minute is certainly sufficient for clinical trial of this membrane oxygenator unit in an adult on parital perfusion. Long-term studies are necessary to determine whether oxygen and carbon dioxide transfer rates are maintained. Recent reports of clinical use of such a Gore-Tex unit for total bypass during surgical cardiotomy confirm this conclusion.11 The carbon dioxide transfer characteristics of the Gore-Tex membrane unit far exceed reasonable clinical demand. At a blood flow of 3,000 ml. per minute and
The Journal of
6 96
Esato and Eiseman
Thoracic and Cardiovascular Surgery
a Pco 2 flow of between 1,200 and 4,000 ml. per minute, carbon dioxide transfer is about 200 ml. per minute. A 2.25 sq. M. Gore-Tex membrane is capable of removing total body carbon dioxide production of an adult man. Although these studies were primarily designed to evaluate the membrane oxygenator, other observations pertinent to its use for prolonged respiratory support were made. Plasma hemoglobin was unchanged during the 3 hour perfusion, a fact which suggests minimal hemolysis. The difficult problem of anticoagulation was met by intermittent heparinization (2 to 3 mg. per kilogram every 2 hours). Hill9 maintains a Lee-White clotting time of 25 to 40 minutes during prolonged clinical perfusion. To avoid ischemic changes in the leg used for femoral arterial perfusion, Hills uses a distal arterial perfusion limb. We have experimented with a side-arm prosthetic sleeve sewn to the femoral artery, which we employ in intra-aortic balloon assist. It is simpler than using a peripheral arterial catheter. The balloon-tipped catheters in the right atrium provided 70 to 80 per cent total bypass and were judged satisfactory in achieving good blood flow and thereby minimizing reliance on high concentrations of Flo. and high airway pressures for ventilation of the lung—all of which might prolong or intensify the respiratory distress syndrome.
minute, carbon dioxide transfer is 200 ml. per minute. 3. With balloon-tipped catheters used in the caval openings of the right atrium, venous gravity flow varied from 30 to 100 ml. per minute per kilogram of body weight (mean 60 ± 23 ml. per minute per kilogram of body weight) in large dogs. 4. There was no detectable hemolysis during these 3 hour perfusions. 5. The 2.25 sq. M. unit is judged applicable for clinical trial. REFERENCES 1 Awad, J. A., Matte, J., and Brassard, A.: Prolonged Extracorporeal Respiration With a Membrane Gas Exchanger, J. THORAC. CARDIOVASC. SURG. 66: 40, 1973.
2 Birnbaum, D., and Eiseman, B.: Laboratory Evaluation of a New Silicon Membrane Oxygenator,
3
4 5
6 7 8
Conclusions
A new biologically inert, expanded tetrafluoroethylene membrane (Gore-Tex) has been evaluated in dogs for use in a 2.25 sq. M. membrane oxygenator. 1. Oxygen transfer rate is 180 ml. per minute at a flow of 3,000 ml. per minute. Arterial saturation is maintained at 95 per cent with 70 per cent venous saturation. 2. Carbon dioxide transfer rate is variable: At a blood flow of 3,000 ml. per
9
J.
THORAC. CARDIOVASC. SURG.
64:
441, 1972. Boyd, J. C , Moran, J. F., and Clark, R. E.: An Analysis of the Operating Characteristics of the 0.25 M.2 Travenol Infant Membrane Oxygenator, Surgery 71: 262, 1972. Douglas, M„ Birnbaum, D., and Eiseman, B.: Biological Evaluation of a Disposable Membrane Oxygenator, Arch. Surg. 103: 89, 1971. Eiseman, B., Birnbaum, D., Leonard, R., and Martinez, E. J.: A New Gas Permeable Membrane for Blood Oxygenators, Surg. Gynecol. Obstet. 135: 732, 1972. Galletti, P. M.: Laboratory Experience With 24 Hours Partial Heart-Lung Bypass, J. Surg. Res. 5: 97, 1965. Hattersley, G. P.: Activated Coagulation Time of Whole Blood, J. A. M. A. 196: 436, 1966. Hill, J. D., Fallat, R. J., Cohn, K., Eberhart, R., Dontighy, L., Bramson, M. L., Osborn, J. J., and Gerbode, F.: Clinical Cardiopulmonary Dynamics During Prolonged Extracorporeal Circulation for Acute Respiratory Insufficiency, Trans. Am. Soc. Artif. Intern. Organs 17: 355, 1971. 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. 64: 551,
1972.
10 Hill, J. D., Bramson, M. L., Hackel, A., et al.: Laboratory and Clinical Studies During Prolonged Partial Extracorporeal Circulation Using the Bramson Membrane Lung, Circulation 38: 1939, 1968. 11 Karlson, K. E., Murphy, W. R., Kakvan, M.,
Volume 69 Number 5
Gore-Tex
membrane
oxygenator
69 7
May, 1975
Anthony, P., Cooper, G. N., Jr., Richardson P. D., and Galletti, P. M.: Total Cardiopulmonary Bypass With a New Microporous Teflon Membrane Oxygenator, Surgery 76: 935, 1974. 12 Lande, A. J., Fillmore, J. S., Subramanian, V., Tiedeman, N. R., Carlson, G. R., Block, A. J., and Lillehei, C. W.: Twenty-four Hours' Venous Arterial Perfusions of Awake Dogs With a Simple Membrane Oxygenator, Trans.
Am. Soc. Artif. Intern. Organs 15: 181, 1969. 13 Okada, J.: Pulmonary Support With a Membrane Oxygenator, J. Jap. Thorac. Surg. 20: 729, 1972. 14 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.
Kensuke Esato and Ben Eiseman, Denver, Colo.
Xreviously, w e 2 , 4 ' 5 described an effective silicone membrane oxygenator and then evaluated a new form of expanded Teflon (Gore-Tex*) membrane, more permeable to both oxygen and carbon dioxide, for use in such units. The current study evaluates the use of this membrane (Gore-Tex) in the oxygenator unitf that we originally described. Experimental studies The oxygenator. The disposable membrane oxygenator unit measures 30 by 16.2 by 10 cm. and has a priming volume of 500 ml. of blood. An inflatable shim, when inflated to 200 mm. Hg, provides a thin membrane surface (blood contact) area of 2.25 sq. M. (Fig. 1). The expanded polytetrafluoroethylene (PTFE or Teflon) is 2 ml. thick with a 0.5 /*. pore size. Circuitry and pump. As diagramed in Fig. 2, the extracorporeal circuit included a Gore-Tex membrane oxygenator, two roller pumps, and one Travenol disposable heat exchanger. The output of the arterial From the Department of Surgery, Denver General Hospital, and University of Colorado Medical Center, Denver, Colo. 80204. Supported by National Institutes of Health Grant No. HL 15873. Received for publication Aug. 9, 1974. •Manufactured by W. L. Gore and Associates, Flagstaff, Ariz. tManufactured by Travenol Laboratories, Inc., Morton Grove, 111.
690
pump in these studies ranged from 60 to 70 ml. per minute per kilogram of body weight according to the flow of the venous pump, which was maintained by the flow draining from the dog. The circuit, made of % inch I.D. silicone rubber tubing throughout, included a recirculation line between the arterial and venous reservoirs, so that the oxygenator could be replaced, if necessary, without interruption of venoarterial pumping. The component was primed with 500 ml. of lactated Ringer's solution plus 1,000 ml. of heparinized blood collected from a single donor. Experiment. Gas exchange by the oxy-
Volume 69
Gore-Tex membrane oxygenator
Number 5
691
May, 1975
FEMORAL ARTERY
HEAT EXCHANGE
ARTERIAL PUMP
Fig. 2. Circuitry for evaluation of oxygenator.
genator was evaluated by means of femoral vein-femoral artery perfusions in 10 mongrel dogs, weighing 20 to 60 kilograms. The dogs were anesthetized with sodium pentobarbital (30 mg. per kilogram of body weight), and the inferior and superior venae cavae were cannulated via the right femoral vein and the right jugular vein. Venous blood drained by gravity into the venous reservoir and was pumped through the oxygenator and heat exchanger by the Travenol pump into an arterial reservoir and then into the right femoral artery. The 10 dogs were divided into two equal groups, one ventilated with room air and the other made hypoxic in order to test the limits of oxygen and carbon dioxide transfer through the membrane. The first group of 5 dogs was mechanically ventilated with room air via a Harvard animal respirator. The second group (5 dogs) was rendered hypoxic (Po 2 50 to 60 mm. Hg in arterial blood) by using 95 per cent nitrogen and 5 per cent carbon dioxide in the endotracheal tube system of the respirator. Duration of each perfusion was 3 hours. In order to obtain high pump flow rates of 60 to 70 ml. per minute per kilogram of body weight, venous return had to be in-
Balloon Catheter
Fig. 3. Method of venous cannulation using balloon-tip Bardic cannula. SVC, Superior vena cava. 1VC, Inferior vena cava.
The Journal of
6 9 2
Esato
and
Eiseman
Thoracic and Cardiovascular Surgery
O
ANOXIC GROUP
•
NONANOXIC GROUP
2000
Blood Flow Rate
Fig. 4. Arterial saturation as function of blood flow rate. Venous saturation, 60 to 80 per cent. Hematocrit, 30 to 49 per cent.
creased by using balloon-tipped Fogarty catheters in the superior and inferior cavae. As shown in Fig. 3, these catheters blocked most of the venous return to the right atrium. Heparin, 1 to 3 mg. per kilogram, was given at the time of cannulation. Clotting time was measured before perfusion, 1 hour after the start of perfusion, and immediately after perfusion in 4 cases. The flow was measured by a probe monitoring through a BLI pulse logic flowmeter (Biotronex Laboratory, Inc., Silver Spring, Maryland). Sampling and pressure catheters were placed in the femoral artery and vein. Temperature was maintained at 37° ± 2° C. by the heat exchanger. Partial pressure of oxygen and carbon dioxide and pH were measured on blood samples at 30 minute intervals during perfusion. Hemoglobin in both whole blood and plasma and the hematocrit level were also calculated. Oxygen and carbon dioxide transfer rates were calculated by the following formula: 0 3 content (vol. %) = 1.34 x whole blood hemoglobin x 0 2 saturation (% ) 0 3 transfer rate (ml./min.) = blood flow (ml./min.) 100
(0-. content of arterial blood 0 2 content of venous blood).
Content (volumes per cent) of carbon dioxide is calculated by the Singer-Hasting nomogram. C0 2 transfer rate (ml./min.) = blood flow (ml./min.) 100
x (COj content of venous blood CO- content of arterial blood).
Results The effect of blood flow on arterial saturation is shown in Fig. 4. Fig. 5 demonstrates the relationship between blood flow and oxygen transfer rate. As the flow increases, oxygen transfer rate increases. At a blood flow of 3,000 ml. per minute, the oxygen transfer rate is about 180 ml. per minute. The oxygen transfer is statistically a linear function of blood flow rate at the limited condition (y = 0.93 ± 0.03). Fig. 6 illustrates the variation of arterial saturation with venous saturation at the condition in which blood flow ranged from 40 to 80 ml. per minute per kilogram of body weight and hematocrit was 30 to 49 per cent. In the anoxic group, a linear relationship existed between venous and arterial saturations (y = 0.84 ± 0.06). This input saturation had to remain above 70 per cent for the output saturation to stay
Volume 69
Gore-Tex membrane oxygenator
Number 5
693
May, 1975
O Anoxic Group • Nonanodc Group
i O
Blood Flow Rate
ml/min
Fig. 5. Effect of blood flow rate on oxygen transfer rate. Venous saturation, 60 to 80 per cent. Hematocrit, 30 to 49 per cent.
about 95 per cent. Alternately stated, complete oxygenation could not be achieved with venous saturations below 75 to 80 per cent in the animals ventilated with high concentrations of nitrogen and carbon dioxide. On the contrary, total arterial oxygen saturation was achieved in the animals ventilated with room air, even when central venous oxygen was 35 per cent. This can be explained by the lower blood flow rate in the nonanoxic group. Variation of oxygen transfer with venous saturation is shown in Fig. 7: There was greater transfer when the venous blood was desaturated. At a venous saturation of 70 per cent, oxygen transfer rate is about 5 vol. per cent. Fig. 8 shows the effect of blood flow on carbon dioxide transfer rate at the limited range in which venous PcOj is from 30 to 60 mm. Hg and ApH (difference between arterial and venous value) is below 0.05. With increased blood flow rate, carbon dioxide transfer rate increases (y = 0.279 + 0.19). At a blood flow of 3,000 ml. per minute, carbon dioxide transfer rate is about 200 ml. per minute. There is no significant difference in carbon dioxide transfer between anoxic and nonanoxic groups. The effect of venous Pco, on carbon dioxide
&
90 r - 0.84 + 0.06
3
(/)
e:
5
O Anoxic Group • Nonanoxic Group
< ^
an -
L
J-
>L
Venous Saturation (%)
Fig. 6. Variation of arterial saturation with venous saturation. Blood flow, 40 to 80 ml. per minute per kilogram. Hematocrit, 30 to 49 per cent.
transfer rate and APcOj (difference between arterial and venous value) with blood flows between 1,200 and 4,000 ml. per minute is illustrated in Fig. 9. There is significant positive correlation between APcoL. and venous Pcro. (y = 0.67 ± 0.10). As venous
The Journal of
694
Esato and Eiseman
Thoracic and Cardiovascular Surgery
O ANOXIC GROUP 0 NONANOXIC CROUP
O Anoxic Group • Nonanoxic Group
E E
o
(J Q_
a ■ io (0 0
rr >
o
0)
a c 1° I-
CM
o u
cP
^
o
o
00
Venous PCO2
o •
_L
J
m m Hg
Fig. 9. Effect of venous blood Pco ; on carbon dioxide transfer rate and change in Pco-. Blood flow rate, 1,200 to 4.000 ml. per minute. 25
SO
75
loo
Venous Saturation %
Fig. 7. Variation of oxygen transfer rate with venous saturation. Blood flow, 40 to 80 ml. per minute per kilogram. Hematocrit, 30 to 49 per cent.
O ANOXIC GROUP •
NONANOXIC GROUP
0.279 + 0.19
ID
rr
CM
o o
1
looo
2000
Blood Flow Rate
X
3000
J
4000
ml/min
Fig. 8. Effect of blood flow rate on Pco.., transfer rate. Venous Pco5, 30 to 60 mm. Hg. pH, below 0.05.
PcOj is elevated, more carbon dioxide passes through the membrane and ^PcOj increases. At a venous Pco 2 of 40 mm. Hg, the decrease in PcoL. is about 6 mm. Hg. There is no statistical correlation between venous PCO;, and carbon dioxide transfer rates. Variation in gas flow through the oxygenator accounts for this lack of correlation, since differences in gas flow caused the carbon dioxide gradient across the membrane to vary. This study was carried out with the ventilation of the animal held constant at 5 L. per minute of either room air or 95 per cent nitrogen plus 5 per cent carbon dioxide, but with varying ventilation rates of 100 per cent oxygen through the oxygenator. Table I summarizes the oxygen and carbon dioxide transfer rate in each experiment. Maximum oxygen transfer was 473.6 ml. per minute at a blood flow of 4,000 ml. per minute, a venous saturation of 38 per cent, and a hematocrit of 49 per cent. Maximum carbon dioxide transfer was 304 ml. per minute at a blood flow of 4,000 ml. per minute, a Pco. of 43.3 mm. Hg, and a central venous blood pH of 7.468. By using a balloon-tipped catheter, we found maximum and minimum blood flow to be about 100 and 30 ml. per minute per
Volume 69
Gore-Tex membrane oxygenator
Number 5
695
May, 1975
Table I. Oxygen and carbon dioxide transfer in 2.25 sq. M. membrane oxygenators Oxygenator No.
Length Weight (Kg.)
of
run (hr.)
(%)
o2 transfer rale (ml./min.)
A noxic group 10.9 1,260 ±1.6 ±167 18.4 2,466 ±0.7 ±531 2,462 12.0 ±0.4 ± 74 16.7 3,036 ±1.0 ±436 3,320 17.9 ±0.8 ±229
92.50 ±5.00 90.45 ±6.05 90.31 ±3.20 44.03 ±9.77 69.20 ±11.69
12.79 ±7.91 43.75 ±19.70 38.48 ±13.02 319.47 ±78.81 199.20 ±78.22
49.77 ±4.07 51.12 ±4.32 50.09 ±4.48 53.80 ±10.38 40.79 ±2.80
112.10 ±63.50 103.60 ±56.80 121.91 ±65.54 132.00 ±113.39 127.76 ±76.66
Nonanoxic group 9.3 600 ±0.9 ± 0 12.4 1,060 ±391 ±2.3 17.9 1,140 ±1.6 ± 89 13.3 1,280 ±2.1 ±178 12.1 1,375 ±1.3 ±125
80.64 ±6.55 81.75 ±7.30 76.57 ±6.75 59.38 ±18.42 71.00 ±6.71
14.52 ±5.96 31.72 ±14.15 59.04 ±17.42 92.46 ±46.21 62.14 ±11.35
—
—
43.67 ±1.96
86.37 ±64.18
Mean flow rate Hemoglobin flow rate (L./min. 1 (Gm./dl.) (ml.,min.)
o2
1
25.0
3.0
3
2
31.0
3.0
5
3
25.0
3.0
5
4
59.0
3.0
15
5
43.0
3.0
15
6
20.0
2.5
3
7
30.0
3.0
3
8
50.0
2.5
3
9
23.0
2.5
3
10
29.5
3.0
3
tetrafluoroethylene
kilogram, respectively. Mean blood flow was 60.39 + 27.73 ml. per minute per kilogram of body weight. When the balloon is placed at the caval orifices into the right atrium, total inflow-outflow perfusion is achieved. Values of plasma hemoglobin before and immediately after the 3 hour perfusion were 20.00 ± 13.03 mg. per cent and 24.62 ± 18.46 mg. per cent, respectively. Discussion A variety of membrane oxygenator systems have been evaluated in recent years,1' i- •"■ ' "•1"' 1L'-1:| designed for short-term support during surgical cardiotomy and for the more physiological demanding, longterm needs in the treatment of cardiac failure and respiratory distress syndrome. However, clinical reports describing use of these membrane oxygenators for prolonged periods for patients with respiratory failure are rare."' " At basal conditions, the normal adult man requires 240 ml. of oxygen per minute. Complete total support would require this degree of oxygen exchange, but
Input 02 sal.
Input CO, content (vol. %)
C02 transfer rate (ml./min.)
— 43.80 ±6.09 48.20 ±10.18
—
87.80 ±63.35 135.73 ±96.42
parital perfusion is less demanding and depends on the degree of support provided. The theoretical value of a membrane oxygenator is its tolerance to blood elements as compared to the damage inflicted at a bloodair interface. The 2.25 sq. M. Gore-Tex membrane is capable of an oxygen transfer rate of about 180 ml. per minute at a blood flow of 3,000 ml. per minute; its maximum rate is 304 ml. per minute at a blood flow of 4,000 ml. per minute. We believe that an oxygen exchange of 180 ml. per minute is certainly sufficient for clinical trial of this membrane oxygenator unit in an adult on parital perfusion. Long-term studies are necessary to determine whether oxygen and carbon dioxide transfer rates are maintained. Recent reports of clinical use of such a Gore-Tex unit for total bypass during surgical cardiotomy confirm this conclusion.11 The carbon dioxide transfer characteristics of the Gore-Tex membrane unit far exceed reasonable clinical demand. At a blood flow of 3,000 ml. per minute and
The Journal of
6 96
Esato and Eiseman
Thoracic and Cardiovascular Surgery
a Pco 2 flow of between 1,200 and 4,000 ml. per minute, carbon dioxide transfer is about 200 ml. per minute. A 2.25 sq. M. Gore-Tex membrane is capable of removing total body carbon dioxide production of an adult man. Although these studies were primarily designed to evaluate the membrane oxygenator, other observations pertinent to its use for prolonged respiratory support were made. Plasma hemoglobin was unchanged during the 3 hour perfusion, a fact which suggests minimal hemolysis. The difficult problem of anticoagulation was met by intermittent heparinization (2 to 3 mg. per kilogram every 2 hours). Hill9 maintains a Lee-White clotting time of 25 to 40 minutes during prolonged clinical perfusion. To avoid ischemic changes in the leg used for femoral arterial perfusion, Hills uses a distal arterial perfusion limb. We have experimented with a side-arm prosthetic sleeve sewn to the femoral artery, which we employ in intra-aortic balloon assist. It is simpler than using a peripheral arterial catheter. The balloon-tipped catheters in the right atrium provided 70 to 80 per cent total bypass and were judged satisfactory in achieving good blood flow and thereby minimizing reliance on high concentrations of Flo. and high airway pressures for ventilation of the lung—all of which might prolong or intensify the respiratory distress syndrome.
minute, carbon dioxide transfer is 200 ml. per minute. 3. With balloon-tipped catheters used in the caval openings of the right atrium, venous gravity flow varied from 30 to 100 ml. per minute per kilogram of body weight (mean 60 ± 23 ml. per minute per kilogram of body weight) in large dogs. 4. There was no detectable hemolysis during these 3 hour perfusions. 5. The 2.25 sq. M. unit is judged applicable for clinical trial. REFERENCES 1 Awad, J. A., Matte, J., and Brassard, A.: Prolonged Extracorporeal Respiration With a Membrane Gas Exchanger, J. THORAC. CARDIOVASC. SURG. 66: 40, 1973.
2 Birnbaum, D., and Eiseman, B.: Laboratory Evaluation of a New Silicon Membrane Oxygenator,
3
4 5
6 7 8
Conclusions
A new biologically inert, expanded tetrafluoroethylene membrane (Gore-Tex) has been evaluated in dogs for use in a 2.25 sq. M. membrane oxygenator. 1. Oxygen transfer rate is 180 ml. per minute at a flow of 3,000 ml. per minute. Arterial saturation is maintained at 95 per cent with 70 per cent venous saturation. 2. Carbon dioxide transfer rate is variable: At a blood flow of 3,000 ml. per
9
J.
THORAC. CARDIOVASC. SURG.
64:
441, 1972. Boyd, J. C , Moran, J. F., and Clark, R. E.: An Analysis of the Operating Characteristics of the 0.25 M.2 Travenol Infant Membrane Oxygenator, Surgery 71: 262, 1972. Douglas, M„ Birnbaum, D., and Eiseman, B.: Biological Evaluation of a Disposable Membrane Oxygenator, Arch. Surg. 103: 89, 1971. Eiseman, B., Birnbaum, D., Leonard, R., and Martinez, E. J.: A New Gas Permeable Membrane for Blood Oxygenators, Surg. Gynecol. Obstet. 135: 732, 1972. Galletti, P. M.: Laboratory Experience With 24 Hours Partial Heart-Lung Bypass, J. Surg. Res. 5: 97, 1965. Hattersley, G. P.: Activated Coagulation Time of Whole Blood, J. A. M. A. 196: 436, 1966. Hill, J. D., Fallat, R. J., Cohn, K., Eberhart, R., Dontighy, L., Bramson, M. L., Osborn, J. J., and Gerbode, F.: Clinical Cardiopulmonary Dynamics During Prolonged Extracorporeal Circulation for Acute Respiratory Insufficiency, Trans. Am. Soc. Artif. Intern. Organs 17: 355, 1971. 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. 64: 551,
1972.
10 Hill, J. D., Bramson, M. L., Hackel, A., et al.: Laboratory and Clinical Studies During Prolonged Partial Extracorporeal Circulation Using the Bramson Membrane Lung, Circulation 38: 1939, 1968. 11 Karlson, K. E., Murphy, W. R., Kakvan, M.,
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Gore-Tex
membrane
oxygenator
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May, 1975
Anthony, P., Cooper, G. N., Jr., Richardson P. D., and Galletti, P. M.: Total Cardiopulmonary Bypass With a New Microporous Teflon Membrane Oxygenator, Surgery 76: 935, 1974. 12 Lande, A. J., Fillmore, J. S., Subramanian, V., Tiedeman, N. R., Carlson, G. R., Block, A. J., and Lillehei, C. W.: Twenty-four Hours' Venous Arterial Perfusions of Awake Dogs With a Simple Membrane Oxygenator, Trans.
Am. Soc. Artif. Intern. Organs 15: 181, 1969. 13 Okada, J.: Pulmonary Support With a Membrane Oxygenator, J. Jap. Thorac. Surg. 20: 729, 1972. 14 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.