Preoperative autologous blood donations in pediatric cardiac surgery

Preoperative Autologous Blood Donations in Pediatric Cardiac Surgery Munetaka Masuda, MD, Yosito Kawachi, MD, Shouiti Inaba, MD, Kouji Matsuzaki, MD, Fumio Fukumura, MD, Shigeki Morita, MD, Ryuji Tominaga, MD, and Hisataka Yasui, MD Department of Cardiovascular Surgery and Blood Transfusion Sen,ice, Kyushu University Hospital, Kyushu University, Fukuoka, Japan

Background. Preoperative autologous blood donation is one of the most effective methods to avoid h o m o l o g o u s blood transfusion in cardiac operations. However, there have been few reports about the safety and efficacy of autologous blood donation in children. Methods. Since 1986, w e have instituted a blood conservation program including preoperative autologous blood donations in children. Eighty children as young as 3 years old (mean + SD, 8.6 --- 3.9 years) and weighing as little as 12.3 kg (29.2 +- 14.5 kg) were enrolled in the program, and 735 + 388 mL of blood was donated during an average of 3.1 --- 1.5 phlebotomies before the operations. Results. Two episodes of mild vasovagal reaction were observed in 2 patients as a complication of the phlebot-

omy. Seventy-six percent of the collected blood was stored by cryopreservation; the remaining 24% was preserved by liquid storage. Seventy-eight of these patients (97.5%) underwent operations using cardiopulmonary bypass. Seventy-five patients (94%) were operated on successfully without the need for a h o m o l o g o u s blood transfusion. As for the other 5 patients, 2 received only platelet concentrate. Conclusion. Preoperative autologous blood donation is a safe and effective method to avoid h o m o l o g o u s blood transfusion in pediatric cardiac operations.

the risk of transfusion-transmitted diseases A lthough such as a c q u i r e d i m m u n o d e f i c i e n c y s y n d r o m e ,

M a t e r i a l and M e t h o d s

hepatitis, and graft versus host disease has b e e n r e d u c e d considerably [1, 2], various risks remain and sometimes can be fatal. An increasing risk of postoperative infection also has b e e n r e p o r t e d [3]. As a result, there is increasing interest in b l o o d conservation in cardiovascular surgery to avoid the n e e d for homologous blood transfusions. Intraoperative b l o o d salvage with a cell-saver system and postoperative autotransfusion of s h e d blood have been r e p o r t e d to be effective [4]. Pharmacologic agents are also useful, such as aprotinin [5] and tranexamic acid [6] to prevent fibrinolysis caused by c a r d i o p u l m o n a r y bypass. Although such interventions help to avoid homologous blood transfusion in m a n y adults, the efficacy of these interventions is limited in children, especially w h e n c a r d i o p u l m o n a r y b y p a s s is required. In 1986, we instituted a preoperative autologous blood donation p r o g r a m for cardiovascular surgery, a n d 665 patients were enrolled in this p r o g r a m until the e n d of 1994. A m o n g these patients, 80 children (age range, 3 to 15 years) were included. In this article, we introduce our p r o g r a m and its results regarding preoperative autologous blood donation in pediatric cardiac surgery. Accepted for publication July 17, 1995. Address reprint requests to Dr Masuda, Department of Cardiovascular Surgery, Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-82,Japan. © 1995 by The Society of Thoracic Surgeons

(Ann Thorac Surg 1995;60:1694-7)

Preoperative Autologous Blood Donation Program C a n d i d a t e s were allowed to enroll in the p r o g r a m only when they did not d e m o n s t r a t e any severe heart failure or anoxic spells and w h e n their parents gave their consent to the phlebotomy. Blood was collected at the outpatient clinic in Kyushu University Hospital, except for 5 patients whose initial donation was done at the time of cardiac catheterization. At each phlebotomy, 100 to 400 mL of blood (about 10 mL/kg) was collected according to the patients' b o d y weight and h e m o g l o b i n level, followed by saline infusion for volume replacement. The collected blood was sent to the Fukuoka Red Cross Blood Center and then was s e p a r a t e d into r e d blood cells a n d plasma. All p l a s m a was stored as fresh frozen plasma. Two m e t h o d s were used for the storage of r e d blood cells, according to the expected storage period. For the liquid storage of red blood cells, we used either a citratep h o s p h a t e - d e x t r o s e solution (for up to 3 weeks) or a mannitol-adenine-phosphate solution (developed in Japan as a modification of s a l i n e - a d e n i n e - g l u c o s e - m a n n i t o l solution and available since 1991 [7] for long-term storage of red blood cells for up to 6 weeks). Cryopreservation of red blood cells [8] was done w h e n the expected storage p e r i o d exceeded the limit of liquid storage. The last donation was done 7 days or more before the operation. During the donation period, oral iron s u p p l e m e n t s were a d m i n i s t e r e d daily except for the patients whose h e m o globin level was more than 15 g/dL. 0003-4975/95159.50 SSDI 0003-4975(95)00715-6

Ann Thorac Surg 1995;60:1694-7

Operative M e t h o d s The operative p r o c e d u r e s were done for the following conditions: atrial septal defect with or without partial anomalous p u l m o n a r y venous drainage (n - 37); ventricular septal defect (18); endocardial cushion defect (3); complex a n o m a l y (7); coronary artery bypass grafting (1); coarctation of the aorta (2); aortic, mitral, and p u l m o n a r y valve annuloplasty (3, 2, 1); a n d aortic, mitral, a n d tricusp i d valve r e p l a c e m e n t (3, 2, 1, the last with cryosurgery). The two patients o p e r a t e d on through a left thoracotomy for coarctation of the aorta did not have c a r d i o p u l m o n a r y bypass; the rest of the patients were o p e r a t e d on using c a r d i o p u l m o n a r y bypass. The bypass circuit with a m e m brane oxygenator was p r i m e d with a crystalloid solution (800 mL for b o d y weight less than 30 kg, 1,100 mL for 30 to 40 kg, and 1,600 mL for more than 40 kg), and c a r d i o p u l m o n a r y bypass was initiated after systemic administration of 300 U/kg of heparin. The a d e q u a c y of anticoagulation t h e r a p y was m o n i t o r e d b y m e a s u r e m e n t of the activated clotting time. Additional heparin was given if the activated clotting time was less than 400 seconds. Myocardial protection was p e r f o r m e d with an intermittent infusion of crystalloid cardioplegic solution c o m b i n e d with topical cooling with ice slush. An ultrafilter was inserted in parallel with the bypass circuit for hemoconcentration. Protamine sulfate was a d m i n i s t e r e d after termination of c a r d i o p u l m o n a r y b y p a s s until the activated clotting time normalized. Tranexamic acid, 50 mg/kg, was also given before bypass, 90 minutes after the initiation of bypass, and at termination of bypass to prevent fibrinolysis [6]. The blood lost intraoperatively and blood r e m a i n i n g in the bypass circuit was collected, washed, and reinfused to the patients using a cell-saving system (Cell-Saver; Haemonetics Corporation, Braintree, MA). W e did not start the transfusion of p r e d e p o s i t e d autologous blood until neutralization of h e p a r i n with protamine, unless the hematocrit value during b y p a s s became less than 15%. All values are expressed as mean _+ s t a n d a r d deviation. The patients were divided into three s u b g r o u p s according to age (age less than 5, 6 to 10, and more than 11 years old) for further analysis.

Results Eighty children were enrolled in the p r o g r a m a n d u n d e r went operations b e t w e e n 1986 and 1994. Their ages ranged from 3 to 15 years old (mean ± s t a n d a r d deviation, 8.6 + 3.9 years), a n d b o d y weights ranged from 12.3 to 69 kg (29.2 _+ 14.5 kg). Thirty-six patients were male and 44 patients were female. They accounted for 54% of all the patients who u n d e r w e n t corrective operations concurrently b e t w e e n the ages of 3 and 15 years. Twenty patients were y o u n g e r than 5 years, 31 were 6 to 10 years old, and the r e m a i n i n g 29 were all more than 11 years of age. Forty percent of the patients had a body weight of less than 20 kg. All patients were in a New York Heart Association functional class of less than 1V before the operations. At each p h l e b o t o m y procedure, an average of 255 + 96 mL of blood was collected (176 + 40 mL in patients less

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sampling time Fig, 1. Changes in the mean hemoglobin concentration throughout both the donation and postoperative periods. The upper line represents the highest value; the lower line represents the lowest value. Each number represents different sampling times: 1, at consultation; 2, lowest level during the donation; 3, before the operation; 4, end of the operation; 5, .first postoperative day; 6, third postoperative day; 7, seventh postoperative day.

than age 5, 217 -+ 46 mL for those b e t w e e n 6 and 10, and 356 + 80 mL in those older than 11). The total stored volume was 735 + 388 mL for all patients (621 _+ 233 mL for those y o u n g e r than 5, 644 -+ 284 mL for those b e t w e e n 6 a n d 10, a n d 920 + 496 mL for those older than 11). S c h e d u l e d donations were deferred seven times in 6 patients because of i n a d e q u a t e venous access and once because of anemia. A mild vasovagal reaction was observed two times in 2 patients. The total length of the preoperative donation period was 48 ± 38 days (range, 7 to 140 days), and all patients completed the donation program. Seventy-six percent of the collected blood was stored by cryopreservation. Cryopreservation was a p p l i e d more frequently than liquid storage in the y o u n g e r patients (90% in those less than 5, 83% in those between 6 and 10, a n d 53% in those older than 11). The changes in the h e m o g l o b i n level are shown in Figure 1. The h e m o g l o b i n level was quite stable during the donation period. At the time of consultation (sampling time 1), the level was 13.1 _+ 1.7 g/dL (range, 8.9 to 19.7 g/dL). The lowest h e m o g l o b i n concentration during the donation p e r i o d was 12.3 _+ 1.5 gldL (range, 9.5 to 18.6 g/dL; s a m p l i n g time 2). The h e m o g l o b i n level before operation was 12.8 _+ 1.3 g/dL (range, 10.2 to 17.6 g/dL; s a m p l i n g time 3). The c a r d i o p u l m o n a r y bypass time was 76 + 47 minutes (range, 17 to 224 minutes). The o p e r a t i v e b l e e d i n g a m o u n t e d to 177 _+ 153 m L except in 1 patient with uncontrolled b l e e d i n g (16,127 mL). The lowest h e m a t o crit value d u r i n g b y p a s s was 20% -- 3.7% (range, 14% to 30%). At the end of the operation, the h e m o g l o b i n level was 11.1 ÷ 1.7 g/dL (range, 7.2 to 17.5 g/dL; s a m p l i n g time

1696

MASUDA ET AL A U T O L O G O U S BLOOD D O N A T I O N IN CHILDREN

4 in Fig 1). The level recovered to 12.3 _+ 1.5 g/dL (range, 7.3 to 15.7 g/dL; sampling time 5 in Fig 1) on the first postoperative day and remained stable until the seventh postoperative day (12.0 ± 1.9 g/dL, range, 8.3 to 17.6 g/dL; sampling time 7 in Fig 1). Seventy-five of 80 patients (94%) were free from homologous blood transfusion during their hospital stay. There was no need for a homologous blood transfusion in 100% of those under the age of 5, in 90% of those between 6 and 10, and in 93% of those older than 11. The indications for a homologous blood transfusion were anemia associated with low cardiac output in 3 patients and thrombocytopenia in 2 patients. The latter received only platelet concentrate as a homologous blood transfusion.

Comment Since 1986, we have used a comprehensive blood conservation program, which includes the use of ultrafiltration, a cell-saving system, and tranexamic acid combined with preoperative autologous blood donations. In this program, we extended the indications for preoperative autologous blood donation to small children (3 years old) and the elderly (79 years old). Recently, we have particularly strengthened our efforts for children, because their life expectancy is long and thus they might obtain greater benefit from our program. Complications from allogenic blood transfusion are still unavoidable and can sometimes be fatal, although there has been a tremendous improvement in the detection of transfusion-mediated diseases. In the Fukuoka area, the rate of blood donors seropositive for antih u m a n T-lymphotropic virus type 1 is high (3.5%), and the seroconversion rate was still not zero despite the transfusion of screened blood 19l. Virus-mediated diseases such as liver cirrhosis (hepatitis virus C) and T-cell leukemia (human T-lymphotropic virus type 1) often present symptoms long after transfusion. The expression of irregular antibodies induced by allogenic blood transfusion might also be a problem at the time of pregnancy and delivery in women. Thus, children tend to benefit more than adults from the prevention of allogenic blood transfusion. Preoperative autologous blood donation is one of the most effective methods to avoid homologous blood transfusion. It has become popular primarily for elective operations in adults, but recently its indications have been extended to include high-risk patients such as those undergoing cardiac operations [10-20]. However, to our knowledge, there have been few reports on the safety and efficacy of preoperative autologous blood donation in children, especially in pediatric cardiac surgery. In Silvergleid's study [14], children as young as 8 years old and weighing as little as 27 kg predonated blood for elective orthopedic or plastic surgery operations. In our study, children as young as 3 years old and weighing as little as 12.3 kg were enrolled in the program before elective cardiac operations, including complex cases such as Fontan's procedure, Rastelli's procedure, and various types of valvular operations. Generally in pediatric cardiac operations, homologous

A n n Thorac S u r g 1995;60:1694-7

blood transfusion becomes necessary because primary solution of the bypass circuit and cardioplegic solution cause an overhemodilution of the blood, especially in small patients. Kawamura and associates [21] reported that the safe limit of hemodilution is 50% in ventricular septal defect and 40% in tetralogy of Fallot. The efficacy of blood conservation methods such as ultrafiltration, a cell-saving system, and pharmacologic tools is also quite limited to overcome overhemodilution during cardiopulmonary bypass. Autologous red blood cells are helpful to manage overhemodilution during bypass and to correct anemia after bypass. Autologous fresh frozen plasma is also useful to correct coagulopathy after cardiopulmonary bypass, especially in small patients in w h o m many coagulating factors are lost by the concentration and washing process of the remaining volume of bypass circuit with a cell-saving system. Although our data are retrospective and nonrandomized, 84% of the patients who underwent cardiac operations concurrently between the ages of 3 and 15 years and who did not predonate required homologous blood transfusion, whereas only 6% of the donating patients received transfusions in our hospital. One of the most difficult problems in autologous blood donation in children is how best to collect and store the blood. We tried to alleviate the patients' fear by applying local anesthetic agents to the puncture site. The Matsuzaki set (BB-2 IP-2; Kawasumi Chemical fnc, Tokyo, Japan) allows a single puncture for both drainage and infusion use, so the patients receive only a single puncture for every phlebotomy. In the case of inadequate venous access, donation should be postponed to another day to let the patients recover psychologically. When the operative indications are sure, an initial donation at the time of catheterization is recommended. For the storage of blood in children, cryopreservation is useful to prevent phlebotomy-induced anemia. Although mannitol-adenine-phosphate solution can extend the liquid preservation period to up to 6 weeks, cryopreservation is required for most patients under 10 years of age. For example, when the patient is 4 years old, a 3- to 4-week interval is necessary for each donation after the removal of a maximum of 200 mL of blood, and so the collected blood should be stored by cryopreservation. Alternatives such as the leapfrog method and switchback method are not recommended because they are cumbersome to perform on children. Supplementation with oral iron and an appropriate interval between donations helped to keep the hemoglobin level stable during the preoperative donation period. It is difficult to determine the minimum requirement of autologous blood to avoid homologous blood transfusion. There are many factors, such as body weight, hemoglobin level, and operative procedures, that affect the need for blood transfusion. The indications for blood transfusion also play an important role. The oxygencarrying capacity and cardiac output are important determinants for red blood cell transfusion. A hematocrit value of approximately 20% is acceptable during cardiopulmonary bypass [22]. Although we usually allow a hematocrit value of 20% in adults, a hematocrit value of

Ann Thorac Surg 1995;60:1694 7

15% is also a c c e p t a b l e in s i m p l e cases s u c h as atrial septal defect a n d v e n t r i c u l a r septal defect w h e n v e n o u s o x y g e n saturation, as m o n i t o r e d by O x y - S a t (Baxter H e a l t h c a r e C o r p o r a t i o n , Irvine, CA), is satisfactory. In this series, only 3 patients (3.8°,4.) r e q u i r e d a r e d b l o o d cell c o m p o n e n t t r a n s f u s i o n b e c a u s e of a n e m i a c o m b i n e d w i t h a s e v e r e l y low cardiac output. Based on this h i g h success rate, w e c o n s i d e r that the s t o r e d r e d cell v o l u m e in o u r series was satisfactory. T h e i n d i c a t i o n for a u t o l o g o u s b l o o d t r a n s f u s i o n is q u i t e different f r o m that for h o m o l o g o u s b l o o d t r a n s f u sion. At the initial stage of this p r o g r a m , we tried to store as m u c h a u t o l o g o u s b l o o d as possible a n d t r a n s f u s e d all d o n a t e d b l o o d to the patients, w h i c h c a u s e d p o l y c y t h e mia in 2 patients. A f t e r w a r d , w e c h a n g e d o u r policy and d e t e r m i n e d that the p r e d o n a t e d a u t o l o g o u s b l o o d s h o u l d not be t r a n s f u s e d to the p a t i e n t s w h e n the h e m o g l o b i n level is g r e a t e r t h a n 15 g/dL. T h a n k s to o u r e x p e r i e n c e with preoperative autologous blood donation, including n e a r l y 600 adults, w e can n o w accurately p r e d i c t the b l o o d r e q u i r e m e n t . As a result, in principle, all d o n a t e d b l o o d is t r a n s f u s e d b a c k to the patients. R e c e n t a d v a n c e s in pediatric cardiac s u r g e r y h a v e h e l p e d to l o w e r the age for correction of cardiac a n o m alies. In our institute, half of the c h i l d r e n w h o u n d e r g o cardiac o p e r a t i o n s are less t h a n 3 years old. This m e a n s that less t h a n half of the c h i l d r e n qualify for p r e o p e r a t i v e a u t o l o g o u s b l o o d d o n a t i o n . In addition, m o s t of o u r cases w e r e s i m p l e c o n g e n i t a l m a l f o r m a t i o n s b e c a u s e such m a l f o r m a t i o n s t e n d to h a v e g o o d o p e r a t i v e indications in the age range studied, although c o m p l e x anomalies w e r e also i n c l u d e d in our series. Further efforts to lower the indicated age for blood donation are thus r e q u i r e d to enable smaller children to benefit from our blood-saving program. In this study, 2 p a t i e n t s w h o u n d e r w e n t Rastelli's p r o c e d u r e r e q u i r e d o n l y p l a t e l e t c o n c e n t r a t e for the h o m o l o g o u s b l o o d transfusion. To i m p r o v e o u r p r o g r a m , w e are n o w c o n s i d e r i n g the i n t r o d u c t i o n of p r e o p e r a t i v e d o n a t i o n of a u t o l o g o u s platelets [23]. In conclusion, preoperative autologous blood donation in pediatric cardiac operations is c o n s i d e r e d to be a safe and effective m e t h o d to avoid h o m o l o g o u s blood transfusion and m a y also p r e v e n t transfusion-transmitted diseases. We wish to thank Mrs Youko Kominami for her technical assistance, Miss Junko Ohkubo for her assistance with the data collection, and Mr Brian Quinn (English Medical Editor, Kyushu University) for comments on the manuscript.

Addendum After we submitted this report, 2 children successfully underwent a cardiac operation using only predonated autologous blood. One patient was a 5-year-old boy, who underwent a Fontan procedure for tricuspid atresia; the other was a 2-year-old boy, who underwent a correction of pulmonary arterial branch stenosis after an arterial switch operation for transposition of the great arteries. The latter patient was the youngest in our series up to now.

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