Propranolol for Intractable Hemolysis After Open Heart Operation Yutaka Okita, MD, Shigehito Miki, MD, Kenji Kusuhara, MD, Yuichi Ueda, MD, Takafumi Tahata, MD, and Kazuo Yamanaka, MD Department of Cardiovascular Surgery, Tenri Hospital, Tenri, Japan
Postoperative intravascular hemolysis occurring in 2 patients was alleviated by propranolol. One patient underwent mitral valve replacement and had development of intractable hemolysis due to a paravalvular leak. The other patient underwent ventricular septal defect closure and had hemolysis caused by the Dacron patch. Both patients were given oral propranolol, and the degree of
ntravascular hemolysis after open heart operations often results from mechanical destruction of erythrocytes due to interference between intracardiac foreign bodies and residual cardiac defects. Further operation is usually indicated in such patients unless the hemolysis spontaneously subsides. We treated 2 patients whose intractable intravascular hemolysis after open heart operation was alleviated with the use of propranolol.
Case Reports Patient 1 A 58-year-old woman with a typical history of rheumatic fever had undergone open mitral commissurotomy for mitral stenosis when she was 51 years old. Seven years later exertional dyspnea developed, and cardiac catheterization revealed moderate mitral stenosis, mild mitral regurgitation, and severe tricuspid regurgitation. At operation, a severely deformed mitral valve was replaced with a St. Jude Medical prosthesis (27 mm) using 2-0 polypropylene (Prolene; Ethicon, Somerville, NJ) continuous sutures. The annulus of the tricuspid valve was reduced from 60 mm to 40 mm using DeVega’s technique. The postoperative course was compromised by a moderate degree of low cardiac output syndrome. She left the intensive care unit on the 10th postoperative day. On the 20th postoperative day, her urine was found to be black. A weak pansystolic blowing murmur was heard at the left sternal border. The hemoglobin value was 73 g/L, the maximum serum lactate dehydrogenase level was 7,525 IU, and the plasma free hemoglobin level was 879 mg/L. There was moderate hepatic and renal dysfunction. Peripheral blood examination for hemolysis excluded intrinsic erythrocyte abnormalities. Although left ventricuAccepted for publication March 25, 1991. Address reprint requests to Dr Okita, Department of Cardiovascular Surgery, Tenri Hospital, 200 Mishirna, Tenri, Nara 632, Japan.
0 1991 by The Society of Thoracic Surgeons
hemolysis decreased substantially. Although the exact mechanism of the propranolol effect on mechanical intravascular hemolysis is unclear, propranolol is thought to reduce the shearing stress between erythrocytes and the foreign material by slowing the velocity of the circulation. (Ann Tkorac Surg 1991;52:1158-60)
lography, performed on the 39th postoperative day, did not detect a paravalvular leak around the mitral valve prosthesis, mechanical hemolysis due to a paramitral prosthetic valve leak was highly suspected, and 30 mg of propranolol (0.8 mg/kg) was prescribed on the 131st postoperative day. Six days after propranolol administration was started, her urine became clear, the lactate dehydrogenase level declined to 1,480 IU, and the plasma hemoglobin was 52 mg/L. However, the patient did not tolerate the propran0101, and her cardiac size increased and lungs became congestive. Administration of propranolol was discontinued on the 186th postoperative day. Her urine immediately became black again, and the lactate dehydrogeriase and plasma hemoglobin levels rose to 4,240 IU and 498 mg/L, respectively. A second postoperative left ventriculogram disclosed a tiny paravalvular leak. At reoperation, a 2-mm paravalvular leak was detected and closed with direct suture. Postoperatively, there was no evidence of intravascular hemolysis and she was discharged from the hospital. Her clinical course is shown in Figure 1.
Patient 2 A 2-year-old boy was diagnosed with a ventricular septal defect, coarctation of the aorta, patent ductus arteriosus, and pulmonary hypertension soon after birth. When he was 2 months old, he underwent subclavian flap relpair for coarctation, ductus ligation, and pulmonary arterial banding in our hospital. At the corrective operation, a large subarterial ventricular septal defect was closed through a main pulmonary arteriotomy with a Dacron double-velour patch (Meadox, Oakland, NJ) using eight buttressed polyester sutures (Ethibond; Ethicon). After excision of the short, narrowed, and scarred segment of the main pulmonary artery, leaving the most posterior portion, the main pulmonary artery was reconstructed with direct anastomosis using 6-0 polypropylene sutures (Prolene). 0003-4975/91/$3.50
CASE REPORT OKITA ET AL PROPRANOLOL FOR HEMOLYSIS
Ann Thorac Surg 1991;52:115&f30
MVR (SJM27M) T A P (DeVega)
P h Hb LDH
80- 8,000 60- 6,000
- 40- 4,000 60-
20 40 60 80 100 120 140 160 180 200 220 240 260 280300 320 340 360 Postoperative days
Fig I. Clinical course of patient 1 , a 58-year-old woman with mitral stenosis and minor regurgitation, tricuspid regurgitation, and minor aortic regurgitation who had undergone open mitral commissurotomy. K a t h = catheterization; CHF = congestive heart failure; Hb = hemoglobin; LDH = lactate dehydrogenase; Max = maximum; MVR = mitral valve replacement; PVL = paravalvular leakge; SJM = St. Iude Medical; TAP = tricuspid annuloplasty.)
Although postoperative hemodynamics were satisfactory except for tachycardia, a harsh pansystolic murmur was heard, and his urine became dark red on the day of operation. The lactate dehydrogenase level was 3,105 IU and the plasma hemoglobin level was 1,549 mg/L. Postoperative Doppler echocardiography revealed no residual shunt and a pressure gradient of 15 mm Hg in the right ventricular outflow tract across the ventricular septal defect patch. There was no pressure gradient in the left ventricular outflow tract. Propranolol administration was started at 30 mg (2.7 mg/kg) daily, and his urine became clear on the following day. Thereafter his recovery was progressive. Propranolol administration was discontinued on the 16th postoperative day, and he was discharged on the 23rd day. His clinical course is shown in Figure 2.
Comment Mechanical destruction of erythrocytes by intracardiac foreign bodies after cardiac operations has been a wellknown phenomenon since Sayed and associates [l]reported that Teflon felt could cause hemolysis after correction of an endocardia1 cushion defect. The pathogenesis of this mechanical hemolysis, as reported by Rubinson and colleagues [Z] and Crexells and co-workers , is that the shearing stress generated between the foreign body surface and the erythrocyte destroys the erythrocyte membrane. Nevaril and associates  demonstrated experimentally that a shearing stress of more than 3,000 dynes/ cm2 increases hemolysis tremendously. Using Bernoulli’s
equation, stenosis with a pressure gradient of 50 mm Hg can generate a shearing stress of 4,000 dynes/cm*. According to Schlichting , shearing stress is directly proportional to the square of the velocity of blood passing through the stenosed area. Consequently, paravalvular leakage after artificial valve replacement has a great potential for causing hemolysis. As reported by Rogers and Sabiston , mechanical hemolysis associated with paravalvular leakage has occurred predominantly in aortic valve replacement. We  reported serious hemolytic anemia caused by paravalvular leakage in mitral valve replacement using St. Jude Medical prostheses. In a subarterial ventricular septal defect, the noncoronary and right cusps are deviated anteriorly due to conal malposition. Prosthetic patch closure of a large ventricular septal defect in the subarterial position inevitably causes infundibular stenosis . In our patient, both the pressure gradient across the patch and the surface of the Dacron patch were considered to generate a greater shearing stress on the erythrocytes. Anzai and associates  reported a similar experience. Theoretically, propranolol can reduce the velocity and quantity of blood flow and slow the intravascular mechanical hemolysis. Ishii and associates [lo] reported a patient with mechanical hemolysis who underwent mitral valve replacement. In their patient, the grade of hemolysis fluctuated according to the heart rate. We postulated that propranolol could alleviate the mechanical hemolysis in a such a patient. Unfortunately, the first patient could not tolerate the propranolol trial because of congestive heart
CASE REPORT OKITA ET AL PROPRANOLOL FOR HEMOLYSIS
Max Heart Rate A---7
>lam, ib LDH
o--< U 150 3,000 IU
Ann Thorac Surg
3 4 5 6 Postoperative days
Fig 2. Clinical course of patient 2 , a 2-year-old boy with a ventricular septal defect who had undergone subclavian pap repair and pulmonary arterial banding. (Preop = preoperation; other abbreviations are listed in Figure 1 . )
failure. However, the hemolysis did transiently respond to propranolol. Hemolysis that occurs after closure of a subpulmonary ventricular septal defect, as in o u r second patient, usually spontaneously resolves within several weeks. Propranolol certainly reduced the duration and degree of the hemolysis. Although propranolol is no substitute for repair, we believe that propranolol is sometimes effective for intractable mechanical hemolysis after an open heart operation.
References 1. Sayed HM, Dacie JV, Handley DA, Lewis M, Cleland WP. Haemolytic anemia of mechanical origin after open heart surgery. Thorax 1961;16:35&60. 2. Rubinson RM, Morrow AG, Gebel P. Mechanical destruction of erythrocytes by incompetent aortic valvular prostheses. Am Heart J 1966;71:17946. 3. Crexells C, Aerichide N, Bonny Y, Lepage G, Campeau L. Factors influencing hemolysis in valve prosthesis. Am Heart J 1972;84:161-70.
4. Nevaril CG, Lynch EC, Alfrey CP, Hellums JD. Erythrocyte damage and destruction induced by shearing stress. J Lab Clin Med 1968;71:784-90.
5. Schlichting H. Boundary layer theory. 4th ed. New York: McGraw-Hill, 1960. 6. Rogers BM, Sabiston DC. Hemolytic anemia following prosthetic valve replacement. Circulation 1969;39(Suppl 1): 155-61. 7. Okita Y, Miki S, Kusuhara K, et al. Intractable hemolysis caused by perivalvular leakage following mitral valve replacement with St. Jude Medical prostheses. Ann Thorac Surg 1988;46:89-92. 8. Ando M. Subpulmonary ventricular septal defect with ~pulmonary stenosis. Circulation 1974;50:412. 9. Anzai N, Yamada M, Hayashibe Y, Furukawa H, Hashimoto A, Ando M. Haemolysis following repair of subpulmoriary ventricular septal defect with pulmonic stenosis. Jpn Circ J 1980;4489%902. 10. Ishii K, Koga Y, Onitsuka T, et al. Hemolysis due to tachycardia after mitral valve replacement in a 1-year-old infant [in Japanese]. Shinzo 1987;19:7805-11.