PediatrCardiol 12:170-174, 1991

Pediatric Cardiology 9 Springer-Verlag New York l n c 1991

O p e n H e a r t S u r g e r y in C h i l d r e n o f J e h o v a h ' s W i t n e s s e s : E x t r e m e Hemodilution on Cardiopuimonary Bypass JOrg I. S t e i n , ~ H a n s G o m b o t z , 2 B r u n o Rigler, 3 Helfrid M e t z l e r , 2 C h r i s t a S u p p a n , ~ a n d Albrecht Beitzke ~ Departments of ~Pediatric Cardiology, 2Anesthesiology, and 3Cardiovascular Surgery, University of Graz, Graz, Austria

SUMMARY. Between January 1979 and July 1989, 15 children of Jehovah's Witnesses underwent corrective open surgery for congenital heart disease (CHD) on cardiopulmonary bypass (CPB). Ages ranged from 1.5-17 years and body weight from 9.1-63 kg, with five patients weighing less than 15 kg. Eight children were cyanotic, and two of them had had previous thoracic operations. All operations were performed in moderate to deep hypothermia using a modified version of isovolemic hemodilution with bloodless priming technique of extracorporeal circulation. Mean hematocrit levels decreased from 47.3% (36.9-70%) to 34.6% (27.2-49.1%) after hemodilution, and then to 17.9% (10.5-25.6%) during bypass. They increased again to 34.1% (24.450%) at the end of the operation and to 33.4% (25.1-40%) on day 12. All intra- and postoperative hematocrit levels were significantly lower (p < 0.001). There was one postoperative death, not related to the technique. Our results demonstrate that bloodless cardiac surgery on bypass is feasible in children as shown in this special group of children of Jehovah's Witnesses. Knowing the risks of homologous blood transfusion this technique should be used more extensively in the future. KEY WORDS: Open heart surgery - - Children - - Congenital heart disease - - Jehovah's Witnesses - - Hemodilution - - Cardiopulmonary bypass

C a r d i a c s u r g e r y in c h i l d r e n of m e m b e r s of the Jeh o v a h ' s W i t n e s s faith p r e s e n t s a special ethical a n d m e d i c a l p r o b l e m a s - - b a s e d o n their i n t e r p r e t a t i o n o f the bible [Genesis 9 : 3 - 6 , L e v i t i c u s 17:10, A c t s 15:20, 28, 29; 2 1 : 2 5 ] - - t h e y refuse b l o o d t r a n s f u s i o n s a n d e v e n a c c e p t p o s s i b l e s e v e r e d a m a g e or d e a t h . F o r this r e a s o n o p e n heart s u r g e r y o f t e n was d e l a y e d in t h e s e p a t i e n t s . A m o r e r e s t r i c t i v e a n d critical use o f h o m o l o g o u s b l o o d t r a n s f u s i o n , due to the i n c r e a s i n g c o n c e r n a b o u t the risks, t o g e t h e r with the d e v e l o p m e n t o f n e w b l o o d - s a v i n g techn i q u e s , has m a d e c o r r e c t i v e s u r g e r y p o s s i b l e for c o n g e n i t a l heart d i s e a s e ( C H D ) on c a r d i o p u l m o n a r y b y p a s s (CPB) w i t h o u t the use o f a n y b l o o d t r a n s f u s i o n in this special g r o u p as well [!, 5, 6, 8, 12, 14, 17]. Address offprint requests to." Dr. Stein, Department of Pediatric Cardiology, University Children's Hospital, Auenbruggerplatz, A-8036 Graz, Austria.

W e report 10 y e a r s ' e x p e r i e n c e of cardiac surgery in c h i l d r e n of J e h o v a h ' s W i t n e s s e s using a modified v e r s i o n of i s o v o l e m i c h e m o d i l u t i o n on C P B c o m b i n e d with h y p o t h e r m i a a n d a bloodless prime technique.

Patients and Methods From January 1979 to July 1989, open heart surgery on CPB for complete repair of CHD was performed in 15 children of Jehovah's Witnesses (11 male and four female). Clinical data are listed in Table I. Their ages ranged tYom 1.5-17 years (mean, 9.0 +- 5.5 years) and body weight from 9.1-63 kg (mean. 29.4 • 17.1 kg), with five children weighing less than 15 kg. In the group of seven patients with cyanotic lesions, the mean age was 7.8 -+ 6.3 years (1.5-17 years) and the mean body weight 28 -+ 19.5 kg (9-57 kg). Two of these children had simple transposition of the great arteries, one transposition with ventricular septal defect and pulmonic valve stenosis, and four tetralogy of Fallot. Two patients had undergone previous palliative sys-

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Table 1. Clinical data of children of Jehovah's Witnesses undergoing open heart surgery on CPB for correction of CHD

Patient No.

Cyanotic patients 1 2 3 4 5 6 7 Mean + SD Range Acyanotic patients 8 9 10 11 12 13 14 15 Mean _+ SD

Sex

Age (years)

M M M M M F M

1.6 10. l 1.5 5 17.0 4.6 15.2 7.8 + 6.3 (1.5-17)

F M M M F F M M

6.4 3.6 14.1 15.8 9.2 15.4 11.6 4.3 9.8 -+ 5.1

Range All patients Mean + SD Range

(2.8-15.8) 9.0 -+ 5.5 (1.5-17)

Weight (kg)

10.4 42 9.1 19.6 45.1 14.5 57.5 28 + 19.5 (9-57) 21 14 35 63 25.5 35 38 12.4 30.2 +_ 16.6 (10-63)

Diagnosis

Previous palliation

TGA TOF TGA TOF TOF TOF TGA, VSD, PST

BAS

AST VSD part.AVSD ASD I1 ASD II PST VSD VSD

BAS BTS BTS

m

m

m

29 _+ 17.1 (9.1-63)

TGA, transposition of the great arteries: VSD, ventricular septal defect: AVSD, atrioventricular septal defect: ASD Ii, atrial septal defect (secundum); TOF, tetralogy of Fallot: AST, aortic valve stenosis: PST, pulmonary valve stenosis: BAS, balloon atrioseptostomy; BTS, Blatock-Taussig shunt.

Table 2. Anesthetic drugs and perfusion technique of ECC in

children of Jehovah's Witnesses Premedication

Induction and maintenance

Extracorporeal circulation Prime solution Oxygenator Flow rate Cardioplegia Hypothermia

Phenobarbital supp, 10 mg/kg Chloral hydrate, 30-50 mg/kg Atropine, 0.01-0.02 mg/kg Pethidine, I mg/kg Etomidate, 0.4 mg/kg Fentanyl, 10 ttg/kg Pancuronium, 150 ttg/kg I P P V w i t h O : : N : - 1:1 Enflurane or isoflurane, repeated fentanyl Heparin, 3 mg/kg Dextrose 5%, Ringer's solution, mannitol, sodium bicarbonate Harvey 1300, Shiley S070 2.2-2.5 ml/min/m: St Thomas's solution 25-26~ esophageal temperature, 20~ in circulatory arrest

temic-pulmonary shunt procedures, another two had had a balloon atrioseptostomy in the newborn period. In the group of eight patients with acyanotic lesions, the mean age was 9.8 _+ 5.1 years (2.8-15.8 years) and the mean body weight 30.2 + 16.6 kg (10-63 kg). Three had ventricular

septal defect, two a secundum type atrial septal defect, one an aortic valve stenosis, one a pulmonic valve stenosis, and one a partial form of atrioventricular septal defect, None of them had had a previous palliative procedure. Preoperative management, medication, and anesthesia were not different from other patients (Table 2). Besides careful blood-saving surgery, a modified version of isovolemic hemodilution combined with bloodless priming technique and hypothermia were used during extracorporeal circulation (ECC). After induction of anesthesia and before heparinization, 1520 ml/kg blood was drawn into communicating citrate phosphate dextrose (CPD) bloodbags under permanent control of central venous pressure, arterial blood pressure, and arterial blood gases. After adding of 200,000 U aprotinin, this CPD-blood was diluted isovolemically with Ringer's lactate and colloidal plasma fraction to a pre-ECC hematocrit of about 30%. It was then retransfused via a different vein, thus this blood was never disconnected from the patient's circulation (Fig. 1). At the end of the ECC all blood from the pericardial and pleural cavities was collected and returned to the oxygenator. The entire fluid of the ECC was then reinfused through the aortic cannula, if possible to reaching a left atrial filling pressure of 1215 mmHg. When coming off bypass, diuresis was started with furosemid and nitroglycerine was given for vasodilatation. Operations were performed in moderate to deep hypothermia with an esophageal temperature of 20-25~ and additional total circulatory arrest in two patients. All patients were ventilated for 24 h postoperatively, and catecholamines and antibiotics given routinely.

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Fig. 2. Perioperative hematocrit levels in cyanotic patients. 1, preoperative; 2, after hemodilution; 3, 4, during cardiopulmonary bypass; 5, after bypass; 6, postoperative; 7, day 1; 8, day 3; 9, day 6; I0, day 12.

Fig. 1. Diagram of ECC with modified hemodilution technique. Regular bypass connections are shown on the right, and the hemodilution circulation on the left. HLM, heart lung machine; F, filter; R, reservoir.

Data are expressed as mean + standard deviation (SD). ANOVA was used for repetitive measurements of hematocrit, where p < 0.05 was considered to be significant.

Results Corrective open heart surgery for C H D was performed on CPB in all 15 children. Mean duration of operation was 290 -+ 84 min, whereas mean bypass time was 61 -+ 37 min. The time of total circulatory arrest for the two patients with simple transposition of the great arteries was 62 and 34 min, respectively. Differences in age and weight in both groups, the cyanotic and acyanotic patients, were not statistically significant. Perioperative hematocrit levels are shown in Figs. 2 and 3.

Cyanotic Patients Mean hematocrit level decreased from 55.1 _+ 9.4% (43-70.5%) to 37.6 -+ 8.2% (27.2-49.1%) after hemodilution and reached its lowest level of 18.4 _+ 6.5% (10.5-25.6%) during bypass. At the end of the operation it increased to 25.7 -+ 5.5% (19.5-36.8%), reached 38.3 -+ 7.5% (29.9-47.7%) on postoperative day I, fell again to 31.2 -+ 7% (22-39%) on day 3, and then increased slowly to 33.6 -+ 5.9% (25.140%) by day 12.

Fig. 3. Perioperative hematocrit levels in acyanotic patients. /, preoperative; 2, after hemodilution; 3, 4, during cardiopulmonary bypass; 5, after bypass: 6, postoperative: 7, day I; 8. day 3: 9. day 6; I0, day 12.

Acyanotic Patients T h e y started with a mean hematocrit level of 41.4 -+ 8.1% (36.9-45%), which decreased to 31.8 _+ 3.2% (28.2-38.4%) after hemodilution, reaching the lowest level of 17.5 -+ 4.1% (12.3-22.4%) on CPB, then increasing to 21.6 _+ 3.7% (15-25.8%) at the end of the operation. On postoperative day I, the hematocrit was 31.4 -4- 4.2% (24.8-35.9%), declined again to 28.3 _+ 5.2% (21.4-36.1%) on day 3, and slowly rose to 33.2 -+ 4.1% (26.8-39.8%) by day 12. Hematocrit levels showed no statistically significant difference between the groups but within the groups all intra- and postoperative values were significantly lower than the preoperative levels (p < 0.05). There was only one postoperative death, 1 day after a Senning operation for simple transposition. This was not related to the technique but probably due to persistent pulmonary hypertension. Hematocrit at time o f death was 47%.

Stein et al.: Hemodilution in Cardiac Surgery

Discussion The controversial issue of blood transfusion in Jehovah's Witnesses should neither be solved by excluding these patients from open heart surgery in ECC [14], nor by suing the parents, although this would be possible in extreme cases in many countries. With the increasing concern about the risks and side effects of homologous blood t r a n s f u s i o n - transfusion-transmitted acquired immunodeficiency syndrome, hepatitis, and possible immunosuppress i o n - - p e r s o n s other than J e h o v a h ' s Witnesses refuse homologous blood transfusion, but still would accept an autologous blood transfusion [9, 16-18]. We have successfully worked out a special intraoperative hemodilution technique with the CPDblood permanently connected to the patient's circulation, as demanded by the J e h o v a h ' s Witnesses [6, 7]. Aprotinin was given to reduce perioperative blood loss further by mitigating platelete dysfunction and fibrinolysis [15]. Open heart surgery on CPB without using any blood transfusion necessarily leads to lower intraand postoperative hemoglobin and hematocrit levels. To maintain sufficient oxygenation, cardiac output has to be increased, besides some other compensating mechanisms [4, 10]. Our modified hemodilution technique reduces the need for this and allows blood up to 20 ml/kg, being taken. It is welltolerated, even in small children [5]. Normovolemic hemodilution also causes low hematocrit levels, a desirable effect in cyanotic patients. This mechanism raises oxygen utilization through improved rheoiogy on CPB during hypothermia by decreasing blood viscosity and lowering peripheral resistance [13]. With our technique we reached hemocrit levels as low as 10.5% during ECC, and, like others [11], never saw any neurological complications. During the critical phase of discontinuing the bypass, hematocrit levels should be around 20%, as an adequate oxygen saturation is needed in the beating heart. During this period the pre-ECC drawn CPD-bloodbags are helpful as they contain fresh red cells and all coagulation factors. All the fluid from the ECC should be retransfused. This may lead to fluid overload but this can be avoided by cell separation, a method accepted by J e h o v a h ' s Witnesses [1, 6, 19]. Fluid restriction can also be achieved by ultrafiltration using special hemofilter systems, as in postoperative care [20]. Hemofiitration is now routinely used during ECC. In the postoperative care even more erythrocytes could be saved by retransfusion of the col-

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iected blood from the chest drains, but this technique is not commonly accepted by J e h o v a h ' s Witnesses, and therefore was not used in our patients [3]. To avoid postoperative bleeding, closure of the sternum should not be done before complete neutralization of heparin is achieved and a normal blood pressure is established [2]. In our study hematocrit levels between patients with acyanotic and those with cyanotic lesions showed differences, but these were not statistically significant. The cyanotic children started with a higher hematocrit level and it remained slightly higher in these patients throughout the bypass and early postoperative phase. Although in this group we measured the lowest hematocrit on CPB, on day 12 the hematocrit was nearly the same in both groups. We noticed a second hematocrit decrease on the third postoperative day which may have been due to the loss of e r y t h r o c y t e s damaged during bypass. The death rate is reported to be slightly increased in this group of patients [6, 7, 12]. In our small group we had only one postoperative death, and this was not related to the technique. Mean age in our group was relatively high, knowing the trend to perform corrective open heart surgery in early childhood or even in the neonatal period. The reason was that because of the transfusion problem, open heart surgery had been delayed until it was safer. It is concluded that in children of J e h o v a h ' s Witnesses with C H D open heart surgery under ECC can be performed safely without blood transfusion by using a modified version of normovolemic hemodilution, combined with a bloodless prime technique and moderate-to-deep hypothermia. This technique will be of increasing importance in the light of the present concern about homologous blood transfusion because of the growing problems with blood-transmitted diseases.

References I. Bormann B, Boldt J~ Kling D, Weidler B, Scheld HH, Hempelmann G (1987) Combined autotransfusion in cardiac surgery: The use of acute normovolemic hemodilution before and during coronary artery surgery (aorto-coronary bypass). Dtsch Med Wochenschr 112:1887-1892

2. Carson LC, Poses RM. Spence RK, Bonavita G (1988) Severity of anemia and operative mortality and morbidity. Lancet /:727 3. Cosgrove DM, Amiot DM, Meserko JJ (1985) An improved technique for autotransfusion of shed mediastinal blood. Ann Thorac Surg 40:159-164

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4. Fahmy NR, Chandler HP, Patch DG, Lapas DG ( 19801 Hemodynamics and oxygen availability during acute hemodilution on conscious man. Anesthesiolo~,,y 53:84-88 5. Gombotz H, Metzler H, Hiotakis K, Dacar D (1985) Offene Herzoperationen bei Zeugen Jehovas. Wien Klin Wochenschr~ft 97:525-530 6. Gombotz H, Rigler B, Matzer Ch, Metzler H, Winkler G, Tscheliessnigg KH (1989) 10 Jahre Herzoperationen bei Zeugen Jehovahs. Anaesthesist 38:385-390 7. Henderson AM. Maryniak JK. Simpson LC (1986) Cardiac surgery in Jehovah's Witnesses. A review of 36 cases. Anaesthesia 41:748-752 8. Henling CE, Carmichael MJ, Keats AS, Cooley DA (1985) Cardiac operation for congenital heart disease in children of Jehovah's Witnesses. J Thorac Cardiovasc Surg 89:914920 9. Koretz RL, Stone O, Mousa M, Gitnick GL (1985) Non-A, non-B posttransfusion hepatitis--A decade later. Gastroenterology 88:1251 - 1254 10. Messmer K (1981) Compensatory mechanisms lk~r acute dilution anemia, Biblthca Haemat 47:31-33 I I. Niinikoski J, Laaksonen V, Meretoja O. Jalonen J, lngberg MV (1981) Oxygen transport to tissue under normovolemic moderate and extreme hemodilution during coronary bypass operation. Ann Thorac Surg 31:134-138

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12. Ott DA, Cooley DA (1977) Cardiovascular surgery in Jehovah's Witnesses. JAMA 238:1256-1258 13. Rand PW, Lacombe E, Hung HE (1964) Viscosity of normal human blood under normothermic and hypothermic conditions. J Appl Physiol 19:117 14. Riegler R (1985) Probleme bei Verweigerung von Bluttransfusionen. Anaesthetist 34:55-58 15. Royston D, Taylor KM, Bidstrup BP, Sapsford RN (1987) Effect of aprotinin on the need for blood transfuion after repeat open heart surgery. Lancet 2:1289 16. Schriemer PA, Longnecker DE, Mintz PD (1988) The possible immunosuppressive effects of perioperative blood transfusion in cancer patients. Anesthesiolo~,,y 68:422-425 17. Surgenor DMN (1987) The patient's blood is the safest blood. N Engl J Med 316:542-543 18. Ward JW, Holmberg SD, Allen JR (1988) Transmission of human immunodeficiency virus (HIV) by blood transfusions screened as negative for HIV antibody. N En~,,I J Med 318:473-475 19. Weigand-LOhnert C, Reinhart K (1988) Zum EinfluB der intraoperativen Autotransfusion auf die Sauerstoffaffinit~it der Erythrozyten. Anaesthesist 37:30-33 20. Zobel G, Beitzke A, Stein Jl, Trop M (1987) Continuous arteriovenous hemofiltration in children with postoperative cardiac failure. Br Heart J 58:473-476