Aprotinin and recombinant human erythropoietin reduce the need for homologous blood transfusion in cardiac surgery

The effects of low dose aprotinin (Trasylol) and preoperative administration of recombinant human erythropoietin (EPO) were evaluated in 144 patients undergoing cardiopulmonary bypass divided into four groups. Group I (n=43) received a subcutaneous administration of EPO (18,000 U) one week before operation and intraoperative administration of low-dose aprotinin (mean; 1.38 ± 0.26 × 10⁶ kallikrein inactivator units; KIU) from extracorporeal circulation, group II (n=39) received only preoperative administration of EPO, group III (n=28) received only intraoperative administration of low-dose aprotinin (mean; 1.46 ± 0.25 X 10⁶ KIU), and group IV (n=34) were not administered either drug. Compared with group IV, the intraoperative blood loss was significantly lower in group I (p<0.01), and in group II or III (p<0.05). The postoperative drainage in 24 hours was significantly lower in groups I and III receiving aprotinin than in the other groups. The mean volume of total homologous blood transfusion and the percentage of cases not requiring a homologous blood transfusion in each group was, respectively, 74 ± 235 ml and 88.4% in group I, 282 ± 1289 ml and 87.2% in group II, 414 ± 584 ml and 60.7% in group III, and 976 ± 1931 ml and 44.1% in group IV. Significant differences were recognized between group I and group IV (p<0.05). These findings indicate that when used in combination, both drugs reduce blood loss and the need for a homologous blood transfusion more effectively than either drug alone.     

Effect of recombinant human erythropoietin on autologous blood pre-donation in open heart surgery

We have used recombinant human erythropoietin (EPO) with an autologous blood predonation in open heart surgery looking forward to preventing patient's blood level of hemoglobin and quick recovery in post-operative period. In our results, patient's value of hemoglobin (Hb) and hematocrit (Ht) decreased due to autologous blood predonation. In group A (autologous blood predonation with EPO administration), however, predonated blood volume were larger than in group B (without EPO administration), decreased value of Hb and Ht were smaller than in group B. The counts of reticulocyte were higher in group A at the operative day. Among six cases phlebotomized with EPO administration, five cases required no homologous blood transfusion for their hospital course. Postoperative recovery of patient's Ht value were earlier in preoperative blood donation group. In particular, patients who administered EPO intravenously have showed fair recovery from anemia. EPO is very effective drug to prevent patients from the developing anemia as a complication of autologous blood predonation. We conclude that autologous blood predonation with EPO administration is beneficial method to reduce homologous blood requirement in open heart surgery.     

Experience of predeposit autologous blood transfusion and medication of recombinant human erythropoietin in pediatric open heart surgery]

To avoid using the homologous blood, 11 children between the age of 5 and 15 years donated autologous blood of 10 ml/kg of body weight (upper limit 400 ml) once a week for two weeks prior to elective open heart surgery. Five of 11 children received erythropoietin (100 U/kg of body weight) intravenously three times a week for two weeks. Only one patient experienced a mild donor reaction but no adverse effects occurred in erythropoietin therapy. In all the patients cardiac operations were able to be completed without homologous blood transfusion. Patients treated with erythropoietin were not anemic despite of preoperative donation although without erythropoietin therapy patients were mildly anemic. Our experience documents safety and effectiveness of predeposit autologous blood transfusion and erythropoietin therapy in pediatrics.     

Autologous blood transfusion with recombinant human erythropoietin in heart operations

The effects of recombinant human erythropoietin (rHuEPO) on improving the anemia associated with autologous blood collection before open heart operations and on improving the postoperative anemia were studied. The study was carried out on 18 patients undergoing coronary artery bypass operations; 400 mL of autologous whole blood was taken from each patient 2 weeks before operation and was subsequently used in the operation, and rHuEPO (100 U.kg-1.day-1) was given intravenously for 2 weeks before operation and for 1 week after operation. The group in which iron preparations were also administered intravenously was designated as group I (10 patients), and the group in which rHuEPO was given alone was designated as group II (8 patients). In group III, as a control group, 11 past patients were used in whom 400 mL of autologous whole blood was collected 2 weeks before operation but neither rHuEPO nor iron preparations were given. After autologous blood collections, the hemoglobin levels improved in group I, group II, and group III, in that order, and with significant differences among them. It was shown that rHuEPO was effective in ameliorating the anemia associated with preoperative autologous blood collection, and the effect was further enhanced with intravenous supplementing iron preparations. After operation, the anemia markedly improved while rHuEPO was administered, but the hemoglobin levels decreased rapidly when the administration was terminated. Further studies are needed regarding the use of rHuEPO after operation.     

Usefulness of recombinant human erythropoietin in cardiac surgery with autologous blood transfusion]

The efficacy and method of administration of recombinant human erythropoietin (EPO) in adult cardiac surgical patients when given preoperatively was evaluated. We used EPO intravenously (iv) with 40 mg ferric oxide for a total of consecutive 47 patients. The patients were divided into group A (n = 14; EPO 200 IU/kg iv 3 times a week from 3 weeks prior to surgery to 2 weeks after surgery, donation of 800 ml) and group B (n = 33; EPO 200 IU/kg iv everyday from 8 days prior to surgery to 2 weeks after surgery, donation of 400 ml). Control groups were group AO (n = 11; donation of 835 +/- 33 ml from 14.8 days prior to surgery) and group BO (n = 7; donation of 406 +/- 34 ml at 7.3 days prior to surgery). All the EPO-treated patients received no homologous blood transfusion while 2 of patients in group BO received some homologous blood transfusion. A hemoglobin change between pre-donation and surgery was +0.14 +/- 1.3 (g/dl) in group A, +0.04 +/- 1.0 (g/dl) in group B, -1.7 +/- 1.3 (g/dl) in group AO and -1.0 +/- 0.6 (g/dl) in group BO. In a comparison of post-surgical hemoglobin levels between group A and group B, we demonstrated that the level in group B, +2.1 +/- 1.8 (g/dl) was significantly higher than that in group A, +11.1 +/- 1.6 (g/dl) 2 weeks after surgery. There was no evidence to show an aggravation of anemia in the pre-surgical period in EPO-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

心脏直视手术自体血回输和异体血输注对比研究

目的探讨在心脏直视手术中采用自体血回输的临床效果。方法将2002年进行心脏直视手术的患者作为观察组,采取综合自身输血措施,包括回输体外循环前经腔静脉放的肝素血,应用美国AOTOLOG自身血液回收机回收患者切口创面的血液,回输剩余机血、应用抑肽酶等。1998年进行心脏直视手术的患者作为对照组,体外循环前不放血、不进行血液回收、也不回收剩余机血,根据术中失血量输注库血。比较两组患者手术前后的出凝血状况、Hb的变化、术中失血量、术后引流量、用异体血量及术后并发症等情况。结果两组之间相比,术前与术后24小时HB、PLT、PT、术中失血量等方面差异无显著性(P>0.05);而术后引流量、输注异体血量对照组均大于观察组(P<0.01)。术后并发症对照组明显高于观察组P<0.01。结论对心脏直视手术患者采取自身输血措施,可明显减少输异体血量、术后引流量及术后并发症的发生率。     

Autologous blood transfusion with erythropoietin in heart surgery in an anemic patient]

A 78-year-old woman was diagnosed as having three-vessel coronary artery disease. A coronary artery bypass operation with autologous blood transfusion was indicated because of the irregular antibody and because homologous blood transfusion would lead to hemolytic complications. Since she had anemia (hemoglobin level, 10.7 g/dl) and autologous blood could not be collected, recombinant human erythropoietin (rHuEPO) and iron preparations were administered intravenously every day. The hemoglobin level reached 12.1 g/dl two weeks after administration, and then autologous blood was donated. The first 1200 ml of blood was stored frozen, and the last 400 ml as liquid in consideration of the blood preservation period. Surgery was performed uneventfully after 8 weeks of rHuEPO administration. No homologous blood transfusion was required during and after surgery. By using rHuEPO, it is thus possible to perform heart surgery without homologous blood transfusion even in patients with anemia, for whom blood transfusions have been considered necessary.     

Effects of recombinant human erythropoietin on thrombosis and fibrinolysis in autologous transfusion for hip surgery

Recombinant human erythropoietin (rHuEPO) is effective in allowing autologous blood donation in patients unable to donate because of anemia. As adverse effects of rHuEPO might include activation of coagulation and possibly fibrinolysis, we investigated these possibilities in the context of autologous blood donation preceding hip surgery. Thirty-seven patients who donated 800 ml of autologous blood for elective hip surgery were randomly assigned to either a group of 20 receiving preoperative treatment with rHuEPO (erythropoietin beta), 6000 U i.v. twice weekly for 3 weeks, or an untreated control group of 17. A significant increase in platelet count was associated with autologous blood donation and intraoperative blood loss with or without rHuEPO. Coagulation and fibrinolysis were increased significantly by intraoperative blood loss in both groups, but not by rHuEPO. Coagulation and fibrinolysis were not activated by rHuEPO for elective hip surgery.     

Autologous blood transfusion with recombinant human erythropoietin in heart surgery--studies on the volume of preoperative donation and postoperative administration]

Recombinant human erythropoietin (rHuEPO) was administered to 42 elective heart surgery patients, and the volume of autologous blood donated within the preoperative short period and effects of improving anemia by postoperative rHuEPO administration were studied. rHuEPO (100 U/kg/day) and chondroitin sulfate-iron (40 mg/day) were given intravenously for preoperative 14 days, and each 400 ml of autologous blood was donated on the 14th and 4th day before operation. Reticulocytes increased significantly 3 days after administration (p less than 0.01). The hemoglobin level, 13.4 +/- 1.0 g/dl before the first donation, returned to 13.4 +/- 1.1 g/dl just before operation. 800 ml of autologous blood, needed for usual open heart surgery, may possibly have been donated within 14 days without making patients anemic by intravenous rHuEPO administration. For postoperative rHuEPO administration, the patients were divided into 3 groups: Group I (10 cases): given for 14 days, Group II (12 cases): for 7 days, Group III (20 cases): no administration. Reticulocytes decreased rapidly after termination of rHuEPO administration in each group, and on the 7th day after termination, they returned to the level before administration. The hemoglobin level in Group I was maintained after termination of rHuEPO, and was +2.2 +/- 1.1 g/dl on the 21st postoperative day compared with the level of 1st postoperative day. The hemoglobin level in Group II fell after termination and was +0.9 +/- 0.7 g/dl on the 21st day, this being comparable to the level of Group III. There were significant differences between Group I and II (p less than 0.05), and between Group I and III (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of recombinant human erythropoietin therapy on ambulatory blood pressure and heart rate in chronic haemodialysis patients.

Systemic hypertension as assessed by causal blood pressure measurements is a frequently reported side-effect of recombinant human erythropoietin (rHuEpo) treatment. We investigated the effect of rHuEpo treatment on the 24-h ambulatory blood pressure and heart rate profiles of 13 chronic haemodialysis patients. After 3-4 months of rHuEpo therapy it was found that the mean haematocrit had increased from 24.5 +/- 1.0% to 32.0 +/- 1.1% (P less than 0.005), while body-weight and control of uraemia as assessed by routine laboratory data remained unchanged. Despite gradual and incomplete correction of anaemia by use of low doses of rHuEpo, increases in the ambulatory systolic and diastolic blood pressure were found. The greatest increases affected day-time systolic blood pressure and night-time diastolic blood pressure, and these increases were significant (P less than 0.05). As a result, pulse pressure increased during day-time (P less than 0.05) while the night-time decline in diastolic blood pressure disappeared. An increase in peripheral resistance after partial correction of renal anaemia might explain these observations. rHuEpo therapy increased the percentage of abnormal ambulatory blood pressure measurements (defined as systolic blood pressure greater than 140 mmHg and/or diastolic blood pressure greater than 90 mmHg) from 33% to 52% (P less than 0.05) while in contrast, mean casual prehaemodialytic and posthaemodialytic blood pressure values remained unchanged. We conclude that changes in 24-h blood pressure profiles should be carefully assessed by ambulatory blood pressure monitoring in haemodialysis patients treated with rHuEpo, since these changes are likely to be missed when only causal blood pressures are measured.     

Predonation and transfusion in open heart surgery]

The efficacy of predonation of autologous blood in reducing the use homologous blood during open heart surgery was investigated. Between January 1997, and February 1998, predonation and transfusion was studied in 100 consecutive open heart operations (CABG, 77; valve surgery, 17; ASD, 5; myxoma, 1). The guidelines for autologous predonation were as follows: an age < 70 years, a weight > 40 kg and a hemoglobin > 12 g/dl. Patients in NYHA class IV or undergoing emergency operation were excluded. The blood loss during operation ranged from 195 to 1,850 ml (mean; 670 ml), being from 305 to 1,850 ml (723 ml) for CABG, from 260 to 1,020 ml (493.5 ml) for valve surgery and from 195 to 570 ml (342 ml) for ASD. The blood loss was not significantly dependent on sex or age and did not differ elective and emergent operations. Only 36.6% of patients with autologous predonation needed homologous transfusion versus 63.4% of those without predonation. Homologous transfusion was done in only 5% of the those with predonation of 800 ml versus 69% at 400 ml and 71% at 200 ml. In conclusion, autologous blood transfusion is effective for reducing the homologous blood requirement. It also seems that predonation of 800 ml may be sufficient to allow open heart surgery without blood transfusion.     

Autologous blood donation with recombinant human erythropoietin for abdominal aortic aneurysm surgery

n = 12) who did not bank any autologous blood, and a donation group (n = 13) who did bank more than 800 ml of autologous blood with the use of erythropoietin. The hematocrit (Ht) level of the control group decreased from 41.1% ± 1.2% before the operation to 36.2% ± 0.9% just afterwards (P > 0.01). In the donation group, however, the Ht did not change significantly during either the donation period or the perioperative period. The postoperative period before oral food intake and natural defecation were both significantly shorter in the donation group than in the control group. The first day of mobilization was also earlier in the donation group. In conclusion, autologous blood donation using erythropoietin for AAA surgery is therefore considered to promote the early recovery of patients. (Received for publication on Mar. 10, 1999; accepted on Jan. 7, 2000)     

High dose aprotinin to reduce blood loss in patients undergoing redo open heart surgery.

Recently, aprotinin has been demonstrated to be effective in reducing post-operative bleeding after open heart surgery. The aim of this study was to evaluate the effectiveness of high dose aprotinin in patients undergoing redo open heart surgery in whom perioperative bleeding is generally increased. Fifty-eight patients, mean age 55 years, underwent a second open heart surgery for single valve replacement in 37 patients (mitral or aortic), for double valve replacement in 16 patients and for coronary artery by-pass grafting in 4 patients. In 30 of the 58 patients (Group A) aprotinin was infused with the following scheme: 2 million KIU in 30 minutes during induction of anesthesia, 2 million KIU in the priming volume of extracorporeal circulation and 500,000 KIU every hour until the end of the surgical procedure. The remaining 28 patients served as control group (Group B). No adverse reactions to aprotinin were observed. There was no significant difference in cardiopulmonary by-pass time and minimum temperature achieved between the two groups of patients. During the operative day blood loss was significantly lower in group A than in group B (492 +/- 336 ml vs. 628 +/- 273 ml) (p < 0.01). This difference was not significant during the following days. However 3 days after the operation a still significant difference was reported in total blood loss between group A and group B (816 +/- 507 ml vs. 1018 +/- 373 ml) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Open heart surgery for small children without homologous blood transfusion by using remote pump head system

Background

To avoid excessive hemodilution, the transfusion of a large amount of homologous blood may be required in open heart surgery for small children, which in turn, can cause a significant immunologic response.

Methods

Cardiopulmonary bypass systems with remote pump heads were used for patients weighing 5 kg or less that were undergoing ventricular septal defect repair. The procedures took place from January 1997 to August 2002. The surgery was started with bloodless prime in 122 out of 158 (77.2%) consecutive patients. Exclusion criteria were a predicted hematocrit after the initiation of bypass of less than 15%, respiratory failure or heart failure (or both), and pulmonary vascular obstructive disease.

Results

The mean age and body weight were 3.8 ± 1.8 months and 4.3 ± 0.5 kg, respectively. The priming volume was 181.0 ± 32.5 (minimum: 130) mL. The hematocrit after cardiopulmonary bypass was initiated was 16.7% ± 2.3%. Six patients required subsequent blood transfusion owing to postoperative complications that resulted in compromised hematopoiesis. In the rest, the hematocrit before discharge was 30.6% ± 3.0%. Renal and liver function tests were maintained within the normal range. Patients were extubated at 5.6 ± 2.8 hours after operation with proper oxygenation. Neurodevelopment was apparently normal. The Japanese psychomotor developmental scale assessment was given to patients without chromosomal abnormality between the ages of 1 and 3 years; the resulting score was 102.2 ± 15.4 (mean = 100 for normal population).

Conclusions

Open heart surgery was achieved without blood transfusion in the selected group of small children. The use of remote pump heads reduced the overall need for blood transfusions and possibly inflammatory reactions.     

Safety and indication of open heart surgery without blood transfusion for congenital cardiac defects in infants

Between January 1994 and June 1997, 16 cases of ventricular septal defect (VSD) and endocardial cushion defect (ECD) with pulmonary hypertension (PH), each weighing from 5 to 9 kg, underwent definitive surgery at Matsudo Municipal Hospital. We classified them into 2 groups; Group N: 8 cases without blood transfusion, Group H: 8 cases with blood transfusion. Cardiopulmonary bypass (CPB) system was a closed circuit and priming volume was 370 to 500 ml. There was no difference between the 2 groups in operative age, body weight, preoperative state, operation time, CPB time, aortic cross clamp time, bleeding and postoperative state. In Group N, CPB blood was returned to the patient as soon as possible after CPB was weaned, and postoperative hemodynamics were stable in both groups. In Group N, hematocrit (Ht) values were consistently lower than in Group H, from initiation of CPB to leaving the hospital. To accomplish safe CPB, we measured systemic venous oxygen saturation (SvO₂). In 6 cases of Group N, SvO₂ during rewarming was 48.1 ± 16.0% and Ht value was 13.2 ± 1.5%. It is thought that the safe CPB could be conducted in Group N. In addition, in Group N, respiratory index showed better values than in Group H during the postoperative period. It is thought that CPB without blood transfusion may be favorable to prevent lung injury after CPB. Retrospectively, it is thought that, to accomplish safe CPB without blood transfusion, preoperative Ht values of over 30% are desirable in patients weighing 6 kg and those of over 35% are desirable in patients weighing 5 kg.