Pediatric application of Landé-Edwards membrane oxygenator

Volume 65, Number 4

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1973

THORACIC AND CARDIOVASCULAR SURGERY The Journal

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Pediatric application of Laude-Edwards membrane oxygenator Continuous perfusion and hypothermic arrest techniques J. S. Wright, F.R.A.C.S., F.A.C.S., G. C. Fisk, F.F.A.R.A.C.S., F.F.A.R.C.S., C. H. McCulloch, F.F.A.R.C.S., T. A. Torda, F.F.A.R.C.S., F.F.A.R.A.C.S., R. Stacey, and R. G. Hicks, Sydney, Australia

There is an ample literature concerning the experimental and clinical evaluation of membrane oxygenators of various types for open-heart surgery in adults and in children.v 4, 6, 7, 10, 11, 14 Experience is accruing concerning the advantages of membrane oxygenators for prolonged extracorporeal gas exchange, this application being the most likely to confirm the advantages of membrane oxygenators over others in regard to minimization of damage to the formed blood elements and lipoproteins.v 8, 9, 12, 13 From the Divisions of Cardio-Thoracic Surgery, Anesthesia, and Neurology, The Prince Henry and Prince of Wales Hospitals, Sydney, New South Wales, Australia. Received for publication Dec. 13, 1972. Address for reprints: Dr. J. S. Wright, Department of Surgery, Prince Henry Hospital, Little Bay, New South Wales 2036, Australia.

In conjunction with an extensive laboratory experience involving infant dogs and pigs, we have used the Lande-Edwards membrane oxygenator in a series of pediatric patients ranging in age from 2 days to 7 years. The majority of our clinical experience has been in the smallest age group, in which the membrane oxygenator has been employed for partial core cooling and elective hypothermic arrest. The lesser part of our experience concerns the use of the membrane oxygenator for continuous, conventional perfusion in larger children, for whom we generally employed moderate hypothermia without circulatory arrest. This report details our clinical experience and includes a statement of techniques used, physiologic and hematologic findings, and our current conclusions.

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Table I. Patients treated with hypothermic arrest No. of deaths

Lesions operated

TAPVD Tetralogy of Fallot TGA VSD PS Total

2 3 5 10 1 21

2 2 1 1 0 6

Legend: TAPVO. Total anomalous pulmonary venous drainage. TGA. Transposition of the great arteries. VSO. Ventricular septal defect. PS. Pulmonary stenosis.

Table II. Patients treated by continuous perfusion No. of deaths

Lesions operated

PS PS/ASD PS/ASD/VSD VSD MS (replacement) TGA TGA/VSD Truncus arteriosus Total

2 1 1 2 1 1 1 1 10

0 0 0 0 0 0 1 1 2

Legend: ASO. Atrial septal defect. MS. Mitral stenosis. For other abbreviations. see Table I.

Table III. A verage age and weight of patients Hypothermic arrest

Age Weight

8 mo. (2 da.-3 yr.) 6 Kg. (3-11 Kg.)

Continuous perfusion

36 mo. (9 mo.-7

yr.)

13 Kg. (7.5-17.5 Kg.)

Clinical experience and measurements

Since May of 1971, 31 children have undergone cardiopulmonary bypass for which the Lande-Edwards membrane oxygenator combined with Sarns roller pumps was used. Tables I and II detail the lesions involved and the results of operation. The age of the 21 patients subjected to the hypothermic arrest technique averaged 8 months (2 days to 3 years) and their weight averaged 6 kilograms (3 to 11 kilograms). The 10 patients who had contin-

uous perfusion with moderate hypothermia averaged 36 months of age (9 months to 7 years) and 13 kilograms in weight (7.5 to 17.5 kilograms) (Table III). Platelet counts, gas determinations, plasma hemoglobin estimations, perfusion flow rates, and mixed packed cell volume estimations were recorded at relevant intervals. Arterial and venous blood gases were estimated at 15 minute intervals during perfusion and at frequent intervals postoperatively. All patients were operated upon via a median sternotomy, with arterial and venous pressures recorded from the left groin. The electrocardiogram and electroencephalogram were monitored continuously throughout the procedure. A Pall microfilter was employed in the latter part of this series for the priming fluid and cardiotomy return. Anesthetic and respiratory management

For the larger infants and children undergoing continuous perfusion, conventional premedication was given 1 hour preoperatively (omnopon-hyoscine or meperidinedroperidol-hyoscine). Two modes of anesthesia were employed: (1) intravenous induction with thiopentone and relaxant (d-tubocurarine or pancuronium) followed by maintenance anesthesia with nitrous oxide-oxygen (50 per cent) and halothane or (2) induction by inhalational means supplemented by relaxants and fentanyl. By means of modest hyperventilation, Paco~ was maintained at 30 to 35 torr. Supplements of relaxant and fentanyl were added as necessary prior to or during bypass. The group of patients subjected to hypothermic arrest was anesthetized as in the previous group. When preliminary surface cooling was adopted, the infants were premedicated 1 ~ hours prior to anesthesia with meperidine, chlorpromazine, and promethazine. Similar methods for induction and maintenance were utilized, and 0.5 per cent halothane was used to maintain vasodilatation during surface cooling, which was achieved by means of a water blanket and ice packs applied immediately after indue-

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tion. Midesophageal and nasopharyngeal temperatures were monitored. As the temperature fell, the ventilatory rate was reduced, with the goal being a temperaturecorrected PaC02 of 30 to 35 torr. Acid-base corrections were rarely necessary. Any base deficit exceeding 6 mEq. per liter was corrected with bicarbonate. Postoperatively, most infants were permitted to breathe spontaneously after the relaxant had been reversed with atropine and neostigmine. They were then extubated and given appropriate oxygen therapy. Any infant exhibiting poor ventilation was supported with a Drager Spiromat respirator. No patient required tracheostomy, and few required respiratory support for more than 2 hours. Only those patients with pulmonary vascular disease or inadequate surgical correction required controlled ventilation in excess of 2 hours. Operative technique

The 1 sq. M. oxygenator was used for patients whose body weight was less than 8 kilograms, and the 3 sq. M. oxygenator was used if body weight exceeded 8 kilograms. This arbitrary selection was made on the assumption that approximately full ventilation could be maintained via the oxygenator if the proper size of venous and arterial cannulas was used. Continuous perfusion with moderate hypothermia. Conventional caval cannulation

was used with arterial return via the ascending aorta in 9 of the 10 patients in this group. In all instances, the left ventricle was decompressed and the aorta was occluded during intracardiac manipulations. The operative field was inundated with carbon dioxide gas, and maximum precautions were undertaken to minimize the possibility of gas embolization. Hypothermic arrest group. In the earlier part of this series of 21 patients, bypass was established as soon as conveniently possible, and core cooling was employed down to the temperature of circulatory arrest. In the latter part of this series, external cooling was begun in the earliest phase of anesthesia,

and thoracotomy was not performed until the midesophageal temperature was in the vicinity of 28° C Venous drainage occurred through a large, single cannula in the right atrium, and arterial return was via the ascending aorta. In all cases, the left ventricle was decompressed and, at a nasopharyngeal temperature of around 20° C, the patient was exsanguinated into a venous reservoir, both cavae were occluded, the ascending aorta was occluded proximal to the perfusion cannula, and pulmonary ventilation was suspended. At the termination of the intracardiac procedure, perfusion was recommenced prior to release of the cavae and aorta. When the central venous pressure had reached 10 to 12 mm. Hg, the cavae were released and perfusion was recommenced with the patient in a steep head-down position. Needle aspiration was applied to the pulmonary artery first and then to the aortic root; only then was the aortic clamp released. Throughout the preceding steps, the lungs were fully ventilated. When an adequate cardiac output was apparent, decannulation was performed in the usual fashion, and the operation was terminated conventionally. Between the temperatures of 37° and 30° C., 2 per cent carbon dioxide was added to the oxygen mixture; between 30° and 20° C., 5 per cent carbon dioxide was employed; on rewarming from 20° to 37° C, 100 per cent oxygen was used as the ventilating gas. Extracorporeal circuit

The plan of the extracorporeal circuit is shown in Fig. 1. It contains a common reservoir that receives blood both from the patient and from recirculation through the oxygenator. Recirculated blood is pumped from the reservoir through the heat exchanger and oxygenator and is returned to the common reservoir. After leaving the oxygenator, blood encounters a variable resistance to flow at a junction from which oxygenated blood is directed, by a separate pump, to the patient. This circuit resembles that described by Baffes and colleagues' in that the oxygenator is independent from the

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k

m

o

d Fig. 1. Diagram of extracorporeal circuit. a, Reservoir. b, Recirculating pump. c, Heat exchanger. d, Lande-Edwards membrane oxygenator. e, Pressure gauge. t. Arterial pump. g, Bubble trap. h, Variable resistance. i, Cardiotomy suction reservoir. j, Cardiotomy suction lines. k, Arterial line. I, Priming line. m, Venous line. 0, Oxygenating gas.

Table IV. Perfusion times and flows

Total perfusion time (min.) Flow rate (L./min.)

Hypothermic arrest

Continuous perfusion

66 (20-200)

95 (35-205)

0.6 (0.3-0.9)

1.3 (0.7-1.7)

patient and, as a result, is not affected by fluctuations in arterial and perfusion line pressures. The variable-resistance device maintains the distending blood pressure within the membranes at between 25 and 50 mm. Hg. The heat exchanger is proximal to the membrane lung, allowing the temperature of the blood to be controlled before gas exchange. This avoids the danger of increasing oxygen tension to levels that might cause bubbles to come out of solution when the perfusate is being warmed. It enables the blood temperature in the circuit to be controlled, even when there is no circulation through the arterial line, and also allows more efficient temperature control because of the high blood-flow rate through the heat exchanger. The total priming volume of the

infant system, with a 1 sq. M. oxygenator, that is appropriate perfusion for patients weighing less than 8 kilograms is approximately 700 ml., while that of the 3 sq. M. oxygenator circuit is approximately 1,000 ml. Although all the patients described in this study were perfused by means of the circuitry described, we are presently investigating the use of a simple gravity-flow system such as that described by Carlson and associates." The advantages of this modification include the elimination of the recirculation component and a 50 per cent reduction in total priming volume of the whole circuit. Perfusion data (Table IV)

The average perfusion times in the continuous perfusion group was 95 minutes, with an average flow rate of 1.3 L. per minute. In the hypothermic arrest group, the average total perfusion time was 66 minutes, at an average flow rate of 600 ml. per minute. In the latter group (Fig. 2), the average lowest temperature reached was 19° c., the average length of cooling perfusion was 23 minutes, arrest time averaged 38 minutes,

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P

30

(IO-ISO)

w

...

Ill: ~

4(

Ill:

w ~

... ~

20

w

10

o

40

20

TIME

60

80

100

mins.

Fig. 2. Pattern of temperature changes during deep hypothermic arrest technique. In the latter part of this series, cooling and rewarming periods have not exceeded 30 minutes.

Table V. Hematologic findings Hypothermic arrest Plasma hemoglobin (mg. %) Platelets [x 103/c.mm.) Continuous perfusion Plasma hemoglobin (mg. %) Platelets (x 103/c.mm.)

Prime

Onset perfusion

End perfusion

45 (20-65)

34 (18-44) 92 (56-130)

59 (25-76) 72 (42-115)

35 (15-53 )

30 (15-50) 94 (53-140)

41 (23-70 ) 97 (43-135 )

and rewarming time averaged 43 minutes; in the more recent cases, cooling and rewarming durations have diminished due to preliminary surface cooling and accelerated rewarming by the concurrent use of an efficient warming blanket. In both groups of patients, the average mixed packed cell volume was between 30 and 32 per cent.

Hematologic findings (Table V) In the continuous perfusion group, plasma hemoglobin levels rose only slightly and platelet counts did not fall as a result of perfusion. (In 1 patient who required perfusion for more than 3 hours, the terminal plasma hemoglobin level was only 70 mg. per cent.) In the hypothermic arrest group, however, plasma hemoglobin levels rose from 34 to 59 mg. per cent at the end of bypass, while platelet counts fall, on the average, from 92,000 to 72,000 per cubic millimeter by the end of perfusion. The only modest damage to formed elements reflected

in these figures occurred despite double passages of perfusate through the membrane lung. Additionally, the smallest patients have a disproportionately high component of donor blood in the perfusion circuit and, in our experience, appear more prone to hemolysis during perfusion with other oxygenators. No macroscopic hemoglobinuria occurred in any patient during or immediately after perfusion. However, following the administration of fresh banked acid-citrate-dextrose blood postoperatively, transient mild hemoglobinuria has frequently been noted. This has not been apparent when the thoroughly filtered residue of perfusate from the extracorporeal circuit has been administered postoperatively, nor has it been experienced when, as is our present practice, small quantities of compatible blood from a parent have been administered postoperatively. No patient in the combined groups has had excessive postoperative bleeding.

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Table VI. Gas exchange (end of perfusion) Hypothermic arrest

Continuous perfusion

Arterial Po, (mm. Hg ) Arterial Pea,

306 (\60-440)

(mm. Hg)

(20-63 ) 7.37 (7.18-7.62)

239 (\ 38-300) 42 (33-60) 7.38 (7.31-7.47)

I

pH

41

Gas exchange (Table VI) Throughout this series of cases, no difficulty was experienced in gas exchange or pH control. In both groups, the Pas, was easily maintained between 200 and 300 mrn. Hg, and the Paco" was maintained at an average of approximately 40 mm, Hg. In both groups, adequate pH control was easily attained. Surgical results Initial surgical results in our patients were disappointing. We believe this was because of the complexity of the lesions, the condition of the patient before operation, or, most importantly, technical problems with the development of the surgical procedure. Of the first 15 patients perfused with membrane oxygenators, several were ill selected, and reparative procedures were less than adequate. Eight of that group survived and are now well. Of the subsequent 16 patients treated, 1 has died, so that of a total of 31 patients perfused with the Lande-Edwards membrane oxygenator, there are 23 survivors (75 per cent). The largest mortality rate occurred in our initial experience with the hypothermic arrest technique. No significant early postoperative problems have been experienced in regard to renal, cerebral, coagulation, or respiratory function. Discussion The theoretical and practical advantages of using a membrane oxygenator rather than a bubble or film oxygenator for prolonged cardiopulmonary bypass are well docu-

merited." 3, 5, 7, 10. 12, 15, 16 We believe that the expense involved in using the LandeEdwards disposable membrane oxygenator can be justified both for complicated operations to correct congenital cardiac defects in infants and small children and for extracorporeal circulation in any operation in infants under the age of 6 months. The system we have described combines the advantages of a disposable system, a small priming volume which is reasonably related to the blood volume of the patient, and the low blood trauma of the membrane oxygenator. This study has indicated that the LandeEdwards membrane lung is capable of providing adequate gas exchange at satisfactory flow rates during total and subtotal cardiopulmonary bypass. The degree of blood destruction was shown to be low, and priming volumes are small compared with other perfusion systems." We have noted . that the blood-gas control is simpler and more accurate since both gas composition and blood flow rates through the lung can be altered; controlling the rate of blood flow is important if multiple circulations through the lung are employed. A further advantage is that temperature regulation is achieved prior to gas exchange, reducing the possibility of gas coming out of solution. The employment of the recirculation circuit allows the temperature of the extracorporeal perfusate to be regulated during circulatory arrest (Fig. 1). We have found that the priming volume of the Laude-Edwards circuit as described, with all connections, is about two thirds that of a disposable bubble oxygenator. The absence of a direct blood-gas interface has advantages beyond those of avoiding blood damage. The membrane lung acts as an excellent filter during bypass, confirmed by the fact that ultrasonic counts are reduced from approximately 18,000 per minute when a bubble oxygenator is employed to less than 2,000 per minute with the Laude-Edwards membrane oxygenator. In fact, in the absence of open cardiotomy suctioning, the

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sonar counts have been shown to be less than 100 per minute.' A reflection of the atraumatic characteristics of the membrane lung, and perhaps of its filtering qualities, has been the absence of particulate material in tubing and bubble traps at the end of prolonged perfusion, unlike that experienced with bubble and film oxygenators. At present, it appears that an arterial filter is not necessary with the membrane lung. In operation of the extracorporeal circuit, the membrane lung requires no external drive unit, thus simplifying and reducing the bulk of the pump equipment. Because the lung is of fixed volume, alterations in gas flow or venous return are reflected immediately in the venous reservoir, which reduces delay in adjustments. While the assessment of neurologic function after open-heart surgery remains difficult in the absence of gross deficits, we have experienced no neurologic problems in any of our surviving patients in whom the membrane lung has been employed. This finding has not been dependent on perfusion time, as appears true with bubble and film oxygenators. Conclusions The disposable Laude-Edwards membrane oxygenator, employed in infants and small children for either continuous perfusion or hypothermic arrest techniques, provides safe, adequate exchange of oxygen and carbon dioxide with negligible morbidity and deaths related to its use. Cardiopulmonary support has been provided for 60 to 200 minutes with no evidence of excessive blood damage or neurologic, renal, or pulmonary insufficiency. In what we believe to be the first application of the Lande-Edwards lung to hypothermic arrest procedures in neonates, the membrane lung has been shown to have particular advantages related to its low priming volume, its compactness, and its simple operation. We are grateful to Mrs. M. Ryan, who' prepared the manuscript for publication, and to the

Department of Medical Illustration, University of New South Wales, which prepared the illustrations. REFERENCES Baffes, T. G., Palel, K. E., Jehathesan, S., and Bicoff, P.: Adaptation of Disposable Membrane Oxygenation for Clinical Total Body Perfusion. Presented at the 20th Annual Session of the American College of Cardiology, Washington, D. C., Feb. 3 to 7, 1971. 2 Bramson, M. L., Osborn, J. J., Main, F. B., O'Brien, M. F., Wright, 1. S., and Gerbode, F.: A New Disposable Membrane Oxygenator With Integral Heat Exchanger, J. THoRAe. CARDIOVASC. SURG. 58: 795, 1969. 3 Carlson, R. G., Lande, A. J., Gannon, P., and Lillehei, C. W.: Lande-Edwards Membrane Oxygenator for Heart Surgery and Respiratory Support. Presented at the Japanese Association for Thoracic Surgery, Sapporo, Japan, Sept. 28 and 29, 1972. 4 Carlson, R. G.: Personal communication. 5 Daicoff, G. R., and Miller, R. H.: Congestive Heart Failure in Infancy Treated by Early Repair of Ventricular Septal Defect, Circulation 41, 42: 110, 1970 (Supp!. 2). 6 Editorial: The Membrane Lung, Med, J. Aust. 2: 915, 1972. 7 Fisk, G. c., Wright, J. S., Stacey, R. B., Horton, D. A., Lawrence, J. C., Lawrie, G. M., and Hicks, R.: Experience With a Membrane Oxygenator for Open-Heart Surgery in Infants and Children, Med. J. Aust. 2: 932, 1972. 8 Hill, J. D., Bramson, M. L., Osborn, J. J., and Gerbode, F.: Observations and Management During Clinical Veno-Venous Bypass for Respiratory Insufficiency, Adv, Cardio!. 6: 133, 1971. 9 Hill, J. D., O'Brien, T. G., Murray, J. M., et a!.: Extracorporeal Oxygenation for PostTraumatic Respiratory Failure, N. Eng!. 1. Med. 286: 629, 1972. 10 Kirsh, M. M., Peirce, E. C., II, Gago, 0., Dufek, J., Lee, R., Jordan, F., Reinisch, J., Straker, J., Roloff, D., Rhodes, L., and Sloan, H.: Clinical Use of Peirce-General Electric Membrane Oxygenator, Ann. Thorac. Surg. 14: 140, 1972. 11 Kolobow, T., and Zapol, W. M.: Partial and Total Extracorporeal Respiratory Gas Exchange With the Spiral Membrane Lung, Adv. Cardio!. 6: 112, 1971. 12 Lande, A. J., Fillmore, S. 1., Subramanian, V. A., et a!.: 24 Hour Venous-Arterial Perfusions of Awake Dogs With a Simple Membrane Oxygenator, Trans. Am. Soc. Artif. Intern. Organs 15: 181, 1969. 13 Lande, A. J., Edwards, L., Bloch, J. H., et a!.:

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Prolonged Cardiopulmonary Support With a Practical Membrane Oxygenator, Trans. Amer. Soc. Artif. Intern. Organs 16: 352, 1970. 14 Lande, A. J., Edwards, L., Bloch, J. H., et al.: Clinical Experience With Emergency Use of Prolonged Cardiopulmonary Bypass With a Membrane Pump-Oxygenator, Ann. Thorac. Surg. 10: 409, 1970.

15 Lee, W. H., Krumhaar, D., Derry, G., et al.: Comparison of the Effects of Membrane and Non-Membrane Oxygenators in the Biochemical and Biophysical Characteristics of Blood, Surg. Forum 12: 200, 1961. 16 Sigmann, J. M., Stern, A. M., and Sloan, H. E.: Early Surgical Correction of Large Ventricular Septal Defects, Pediatrics 39: 4, 1967.