Clinical Performance of Microporous Polypropylene Hollow-Fiber Oxygenator Kozo Suma, M.D., Takayuki Tsuji, M.D., Yasuo Takeuchi, M.D., Kenji Inoue, M.D., Kenji Shiroma, M.D., Tetsuo Yoshikawa, M.D., and Jun Narumi, M.D. ABSTRACT A newly developed polypropylene hollow-fiber oxygenator was used from June, 979, to July, 980, in 00 patients undergoing open-heart operation. Adequate oxygenation and carbon dioxide elimination were observed throughout perfusion in spite of a relatively low ratio of oxygen flow to blood flow. Plasma hemoglobin level was maintained low after long hours of perfusion. There were no complications related to the oxygenator during or after the operation. Because of its highly efficient performance as well as small size and easy handling, this oxygenator is being used routinely during open-heart procedures in our hospital. The capillary oxygenator may be considered to be the ultimate oxygenator in the sense that its structure is very close to that of the natural lung, although the hollow fibers used as a gas exchange membrane differ greatly from true capillaries in some respects. Several attempts have been made to develop a hollow-fiber oxygenator using silicone rubber fiber or similar materials -4. However, due to thrombus formation [5] within the capillaries or blood leakage through the fibers, these oxygenators could not be employed clinically. In this paper we describe the newly developed capillary oxygenator* with microporous polypropylene hollow fibers and its clinical application in 00 patients undergoing open-heart operation. Oxygenator The oxygenator consists of microporous hollow fibers with an internal diameter of 200 p and a Terumo Corporation, Tokyo, Japan. From the Department of Cardiovascular Surgery, Tokyo Women s Medical College Hospital, Tokyo, Japan. Accepted for publication Mar 5, 98. Address reprint requests to Dr. Suma, The Department of Cardiovascular Surgery, Tokyo Women s Medical College Hospital, 2--0 Nishi-Ogu, Arakawa-ku, Tokyo, Japan. wall thickness of 25 p. The pore diameter is 650 A, and the porosity is 50% (Fig ). Each end of the 20 cm long fibers is embedded into the polyurethane end plates. The bundle of fibers is encased in a hard, cylindrical, transparent housing, which encloses the gas phase of the oxygenator. The blood flow and the oxygen flow are countercurrents. The construction of the oxygenator is depicted in Figure 2. Two types of the oxygenator were developed for different flow requirements. Type I (Fig 3) has a length of 24 cm, an outer diameter of 7.0 cm, and 3 X lo4 hollow fibers. Total capillary surface area is 3.3 m2, and priming volume is 280 ml. Type I has the same length as type I, an outer diameter of 4.5 cm, and.6 X lo4 hollow fibers. Total capillary surface area is.8 m2, and priming volume is 50 ml. Type I is suitable for blood flow of 2 to 4 L/min and type, for less than 2 L/min. Material and Method Based on extensive in vitro, in vivo, and animal experiments [6,7, the oxygenator was used in a clinical situation in June, 979. Thirty patients with heart disease requiring open-heart operation were selected for its preliminary clinical evaluation. After confirmed satisfactory results, its application was extended to an additional 70 patients seen consecutively from October, 979, to July, 980. In all patients, anesthesia was induced and maintained with Fluothane (halothane), nitrous oxide, and oxygen. The chest was opened through a median sternotomy. After heparinization, the venous blood from the venae cavae was introduced to the reservoir through the oxygenator with a venous roller pump and returned to the femoral artery with an arterial roller pump through a heat exchanger and a filter (Fig 4). Priming solutions included blood stored in acid-citrate-dextrose solution, or lac- 558 0003-4975/8/20558-05W.25 @ 98 by The Society of Thoracic Surgeons
559 Suma et al: Microporous Polypropylene Hollow-Fiber Oxygenator Fig. Scanning electron microscopic view of the inner surface of the hollow fiber. (~7,00 before 30% reduction). tated Ringer s solution with 5% dextrose to obtain 20% hemodilution, or both solutions. Normothermia or moderate hypothermia was used depending on the type of operation. During perfusion, simultaneous blood samples from the inlet and outlet of the oxygenator were taken every fifteen minutes and analyzed at 37 C for ph, partial pressure of oxygen (PO,), and partial pressure of carbon dioxide (Pco,) with a Corning 75 blood ph gas analysis system. Plasma hemoglobin values were determined by the Bing and Baker benzidine method Fig 2. Construction of the hollow-fiber oxygenator. before and after the termination of bypass. The pressure difference across the oxygenator was monitored throughout bypass. Eighteen patients weighing from 4.8 to 7 kg were perfused with the type I oxygenator. Sixty-eight patients weighing from 5 to 60 kg were perfused with the type I oxygenator, and 4 patients weighing from 38 to 78 kg were perfused with two type I oxygenators in parallel. The operative procedures performed are listed in Table. In each patient, a Kolobow membrane oxygenator was connected in parallel with the hollow-fiber oxygenator as a standby unit. However, the need to use it did not arise in any patient. As shown in Tables 2 and 3, adequate Po,, Pco,, and ph levels were maintained during perfusion with an average ratio of oxygen flow to blood flow of 0.54. Base excess also was maintained within normal range. Increase in free plasma hemoglobin averaged 6.6 mgldl during perfusion of one hour or less, 33.7 mgldl during one to two hours of perfusion, and 52.5 mgldl during two to three hours of perfusion in spite of rather extensive use of cardiotomy suction. The overall average was 29.0 mgldl for the entire group. Hemostasis after heparin neutralization with protamine sulfate was quite satisfactory, probably due to better maintained platelet function. Urine output was within normal limits during perfusion in all of the patients. Among the 00 patients, there were 4 deaths. The causes of death were not related to the oxygenator and perfusion system. Three pa-
~~~ 560 The Annals of Thoracic Surgery Vol 32 No 6 December 98 Fig 3. Type I hollow-fiber oxygenator..- t > 7 p\w I * Fig 4. Circuit for perfusion with the hollow-fiber oxygenator. (P = pump; 0 = oxygenator; F = filter; R = reservoir; H = heat exchanger; Vent. = venting.) tients (an infant with total anomalous pulmonary venous connection, an infant with transposition of the great arteries, and an adult with mitral stenosis) died of postoperative congestive heart failure. Another patient who underwent mitral valve replacement died of uncontrollable bleeding from the fragile left atrium. Postoperatively there were no pulmonary, renal, or neurological complications in patients who survived the operation. Table. Lesions and Operative Procedures Lesions and Operative Procedures Atrial septal defect Ventricular septal defect Endocardia cushion defect Tetralogy of Fallot Pulmonary stenosis Total anomalous pulmonary venous connection Epstein's disease Transposition of the great arteries Aortic valvuloplasty Aortic valve replacement Open mitral valvotomy Mitral valve replacement Aortic and mitral valve replacement Aortocoronarv bvdass No. of Patients 3 24 3 2 Comment Microporous polypropylene hollow fibers have several characteristics that make them suitable for use in oxygenators. The fibers are mechanically strong and rigid, so that they can be easily packed as a bundle in an extremely dense manner. This means that a greater effective surface area for gas transfer per unit volume of the oxygenator is obtained. The mechanical strength of polypropylene also allows use of the 3 6 9 6
56 Suma et al: Microporous Polypropylene Hollow-Fiber Oxygenator Table 2. Perfusion Data Obtained during Open-Heart Operation Variable Mean f SD Range Patient age (yr) Patient body weight (kg) Bypass time (min) Blood flow rate (mllmin) Oxygen flowlblood flow ratio Plasma hemoglobin increase (mgldl) Maximum pressure difference across oxygenator (mm Hg) SD = Standard deviation. 7.3 f 8. 0.3-69 30.2 k 7.5 4.8-78 74 f 66 23-496 2,520 f 970 300-4500 0.54 k 0.2 0.20-.67 29.0 f 29.5 0.3-50.2 6 f 5 30-335 Table 3. Results of Blood Analysis during Perfusion Variable 5 Minutes after Initiation of Total Bypass (mean f SD)a After Rewarming and before Termination of Total Bypass (mean f SD)a PH 7.46 f 0.8 7.4 f 0.32 (7.05-7.68) (7.9-7.54) Po2 (mm Hg) 467 f 62 434 f 74 (242-582) (27-565) Pcoz (mm Hg) 29 f 5 38 f 6 (5-45) (23-55) Base excess -2.8 f 3.3 0.2 f 2.8 (mmolell) (-0.0-7.0) (-6.0-9.0) anumbers in parentheses show the range. SD = standard deviation; Po2 = partial pressure of oxygen; Pco2 = partial pressure of carbon dioxide. oxygenator for longer periods without a decrease in gas transfer efficiency. Moreover, uniform-sized pores can be made in the fibers. Since polypropylene is hydrophobic, no fluid leakage occurs through the pores as long as the pore size is sufficiently small. Because the fibers adhere to potting materials such as polyurethane, they can be fixed firmly without distortion, thus eliminating the possibility of thrombus formation or hemolysis, which might be caused by a turbulent blood stream. Also, reduced blood trauma with this oxygenator was demonstrated in the animal experiments in which the increase of plasma free hemoglobin averaged only 26 mgldl and the thrombocyte count did not decrease after four hours of pump run L7. The hollow-fiber oxygenator shares several advantages with the conventional membrane oxygenator. These advantages include less blood trauma, less protein denaturation, lower incidence of bubble and solid particle embolization, absence of the need for antifoaming agents, and the capability of controlling oxygen and carbon dioxide exchange separately. The efficiency of gas exchange is expected to be higher in the hollow-fiber oxygenator in which blood is divided into capillary-like channels, eliminating blood stagnation and thereby increasing the effective gas exchange area. The previous experiments indicated an oxygen transfer rate of 30 ml/min/m2 at a flow rate of 500 mllmin, which was higher than that of the conventional membrane oxygenators 8, 9. However, several precautions are necessary when using this oxygenator. The pressure in the gas phase should not be allowed to increase more than that in the blood phase so as to prevent the oxygen microbubbles from diffusing into the blood phase through the pores. This might happen if the gas outflow port is obstructed. If the pressure difference across the
562 The Annals of Thoracic Surgery Vol 32 No 6 December 98 oxygenator exceeds 300 mm Hg, there is the possibility that a considerable number of fibers will be occluded by coagulated blood. However, these situations have not been experienced to date, although the maximum pressure difference did exceed 300 mm Hg in 2 patients. In our previous animal experiments, the number of obliterated fibers during four hours of pump run averaged only 95, ranging from 0 to 248, among.6 x 04 fibers [6]. The oxygenator edema found in the microporous membrane oxygenator [lo] and caused by water vapors from the blood phase has not been encountered in this oxygenator. This might be attributed to the smaller pore size in the polypropylene hollow fibers. From the practical viewpoint, the oxygenator is easy to handle and can be set up quickly. Priming the oxygenator takes fifteen minutes less time compared with the conventional membrane oxygenator, partly because the air bubbles can be removed easily from the hollow fibers. Although the consolidation of a blood reservoir, a heat exchanger, and an oxygenator as a unit is under development, satisfactory results with the hollow-fiber oxygenator in 00 patients indicate that this oxygenator is suitable, efficient, and safe for use in cardiopulmonary bypass in open-heart operations. The oxygenator is now used routinely in our hospital. In addition, due to its maintained gas transfer efficiency, it has a promising future for long-term use as a respiratory support device. References. de Filippi RP, Tompkins FC Jr, Porter JH, et al: The capillary membrane blood oxygenator: in vitro and in vivo gas exchange measurements. Trans Am SOC Artif Intern Organs 4236, 968 2. Mam GH: A capillary membrane oxygenator utilizing gas dispersed in oil. Trans Am SOC Artif Intern Organs 6:38, 970 3. Dutton RC, Mather RW, Walker SN, et al: Development and evaluation of a new hollow-fiber membrane oxygenator. Trans Am SOC Artif Intern Organs 7:33, 97 4. Kaye MP, Pace JB, Blatt SJ, et al: Use of capillary membrane oxygenator for total cardiopulmonary bypass in calves. J Surg Res 4:58, 973 5. Dutton RC, Edmunds H Jr: Formation of platelet aggregate emboli in a prototype hollow-fiber membrane oxygenator. J Biomed Mater Res 8:63, 974 6. Mori K, Fukasawa H, Hasegawa H, et al: Development and in vitro evaluation of microporous hollow-fiber oxygenator. Jpn J Artif Organs 8:602, 979 7. Tsuji T, Suma K, Takeuchi Y, et al: Animal test and clinical application of newly developed hollow-fiber oxygenator for open heart surgery. Jpn J Artif Organs 9:55, 980 8. Lefrak EA, Stevens I'M, Noon GP, et al: Current status of prolonged extracorporeal membrane oxygenation for acute respiratory failure. Chest 63:773, 973 9. Murphy W, Trudell IA, Friedman LI, et al: Laboratory and clinical experience with a microporous membrane oxygenator. Trans Am SOC Artif Intern Organs 20:278, 974 0. Beall AC Jr, Solis RT, Kakvan M, et al: Clinical experience with the Teflo disposable membrane oxygenator. Ann Thorac Surg 2:44, 976