Low-dose postoperative aprotinin reduces mediastinal drainage and blood product use in patients undergoing primary coronary artery bypass grafting who are taking aspirin: a prospective, randomized, double-blind, placebo-controlled trial

BACKGROUND: Although low-dose aprotinin administered after cardiopulmonary bypass has been reported to reduce mediastinal blood loss and blood product requirements in patients not taking aspirin, it is unknown whether low-dose postoperative aprotinin has any beneficial effects in patients undergoing coronary artery bypass operations who are at high risk of excessive postoperative bleeding and increased transfusion requirements because of aspirin use until just before the operation. METHODS: Fifty-five patients undergoing primary coronary artery operations with cardiopulmonary bypass who continued taking aspirin (150 mg/d) until the day before the operation were enrolled in a prospective, randomized, double-blind trial to receive a single dose of either placebo (n = 29) or 2 x 10(6) kallikrein inhibiting units of aprotinin (n = 26) at the time of sternal skin closure. RESULTS: Patients in the aprotinin group had a lower rate (28 +/- 18 vs 43 +/- 21 mL/h [mean +/- standard deviation], P <.005) and total volume of mediastinal drainage (955 +/- 615 vs 1570 +/- 955 mL, P <.007), as well as a shorter duration of mediastinal drain tube insertion (24.4 +/- 13.8 vs 31.3 +/- 16.5 hours, P <.05). In addition, a smaller proportion of patients receiving aprotinin required a blood product (31% vs 62%, P =.03), resulting in a reduction in the use of packed cells by 47% (P =.05), platelets by 77% (P =.01), fresh frozen plasma by 88% (P =.03), and total blood products by 68% (P =.01) in this group. CONCLUSIONS: These results suggest that postoperative administration of low-dose aprotinin in patients taking aspirin until just before primary coronary artery operations with cardiopulmonary bypass not only reduces the rate and total amount of postoperative mediastinal blood loss but also lowers postoperative blood product use.     

High-dose aprotinin in cardiac surgery: three years' experience in 1,784 patients.

The effect of the proteinase-inhibitor aprotinin on blood loss and homologous blood requirement in cardiac surgery was investigated. In a prospective study, 902 adult patients were treated with high-dose aprotinin (total greater than 5 x 10(6) kallikrein inactivator units [KIU]; group A), while 882 patients without aprotinin administration served as the controls (group C). Both groups were operated on between January 1987 and October 1989, and included patients with primary coronary artery bypass grafting (n = 525 group C, n = 560 group A), valve replacement (n = 292 group C, n = 264 group A), or combined procedures (n = 65 group C, n = 78 group A), as well as cardiac reoperations (n = 91 group C, n = 110 group A). The average blood loss 36 hours postoperatively in the aprotinin group was 679 +/- 419 mL, compared with 1,038 +/- 671 mL in the control group (P less than 0.05). Total homologous blood requirement was also significantly less in group A (942 +/- 1,630 mL) compared with group C (1,999 +/- 2,283 mL) (P less than 0.05), a reduction of 53%. Serum creatinine concentrations did not show intergroup differences on the first postoperative day (group A, 1.2 +/- 0.7; group C, 1.3 +/- 0.5 mg/dL) or on discharge from the intensive care unit (ICU). Thus, impairment of renal function as a consequence of aprotinin treatment was not observed. Three patients developed signs of mild circulatory depression after injection of aprotinin, which responded promptly to vasopressor therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduction of blood loss and transfusion requirement by aprotinin in posterior lumbar spine fusion.

Aprotinin reduces blood loss in many orthopedic procedures. In posterior lumbar spine fusion, blood loss results primarily from large vein bleeding and also occurs after the wound is closed. Seventy-two patients undergoing posterior lumbar spine fusion were randomly assigned to large-dose aprotinin therapy or placebo. All patients donated three units of packed red blood cells (RBCs) preoperatively. Postoperative blood loss was harvested from the surgical wound in patients undergoing two- and/or three-level fusion for reinfusion. The target hematocrit for RBC transfusion was 26% if tolerated. Total (intraoperative and 24 h postoperative) blood loss, transfusion requirements, and percentage of transfused patients per treatment group were significantly smaller in the aprotinin group than in the placebo group (1935 +/- 873 vs 2809 +/- 973 mL per patient [P = 0.007]; 42 vs 95 packed RBCs per group [P = 0.001]; 40% vs 81% per group [P = 0.02]). Hematological assessments showed an identically significant (a) intraoperative increase in both thrombin-antithrombin III complexes (TAT) and in activated factor XII (XIIa) and (b) decrease in activated factor VII (VIIa), indicating a similar significant effect on coagulation in patients of both groups (P = 0.9 for intergroup comparisons of postoperative VIIa, XIIa, and TAT). Intraoperative activation of fibrinolysis was significantly less pronounced in the aprotinin group than in the placebo group (P < 0.0001 for intergroup comparison of postoperative D-dimer levels). No adverse drug effects (circulatory disturbances, deep venous thrombosis, alteration of serum creatinine) were detected. Although administered intraoperatively, aprotinin treatment dramatically reduced intraoperative and 24-h postoperative blood loss and autologous transfusion requirements but did not change homologous transfusion in posterior lumbar spine fusion. IMPLICATIONS: In our study, aprotinin therapy significantly decreased autologous, but not homologous, transfusion requirements in posterior lumbar spine fusion.     

A randomized trial of aprotinin (Trasylol) on blood loss, blood product requirement, and myocardial injury in total arterial grafting

BACKGROUND: Total arterial grafting is increasingly preferred in coronary artery bypass grafting, but it increases blood loss. Aprotinin (Trasylol; Bayer Corp, Leverkusen, Germany) reduces blood loss in cardiac surgery but has not been subjected to a randomized trial in total arterial grafting. METHODS: A single-center, randomized, double blind, placebo-controlled trial of aprotinin administration in total arterial grafting was performed. The primary outcome variable was postoperative blood loss, and the secondary outcome variable was the number of units of donor blood or coagulant products transfused. The incidence of myocardial injury was determined from serial measurements of cardiac troponin T and creatine kinase-MB and renal injury from serum creatinine. RESULTS: The placebo group (n = 34) and aprotinin group (n = 36) were similar with respect to all preoperative and intraoperative comparisons. One patient in each group underwent reexploration for bleeding. Open-label aprotinin was administered to 9 patients in the placebo group (26%) and to 2 patients in the aprotinin group (6%). There was a highly significant reduction in the median (interquartile range) blood loss in the aprotinin group compared with the placebo group (785 mL [590-1025 mL] vs 1525 mL [1175-1920 mL], respectively). Similarly, the aprotinin group demonstrated a marked reduction in the need for blood transfusion (77% vs 39%; P =.0001), the mean number of transfused blood units (2.6 vs 0.8, P <.001), and the number of patients requiring coagulant products (24% vs 3%; P <.001). There was no difference in myocardial injury in the 2 groups. Four patients in the aprotinin group had persistently elevated creatinine levels in the postoperative period (3 of whom had elevated preoperative creatinine levels and perioperative complications). CONCLUSIONS: Aprotinin significantly reduces blood loss and the need for blood component transfusion in patients undergoing total arterial grafting without increasing the risk of myocardial injury. Aprotinin should be considered routinely in patients undergoing total arterial grafting but cautiously in patients with an elevated preoperative creatinine level.     

Effect of aprotinin on postoperative blood loss in off-pump coronary artery bypass surgery

BACKGROUND AND AIM OF THE STUDY: Off-pump coronary artery bypass (OPCAB) enables a reduction in postoperative complications, particularly bleeding and transfusion. Nevertheless, a significant percentage of patients still needs transfusion. The effect of antifibrinolytic therapy on postoperative bleeding as part of OPCAB is still not widely described. The purpose of this study was to investigate the potential benefit of aprotinin in OPCAB. METHODS: We conducted a retrospective comparative study with a historical control group. Consecutive patients undergoing off-pump coronary bypass were divided in two groups: 40 patients were operated without any antifibinolytic drug (group C); 40 patients received aprotinin (group A) during surgery. Patients in group A received a bolus of 2 x 10(6) KIU during 30 minutes, followed by a continuous infusion of 0.5 x 10(6) KIU per hour until the end of surgery. The same protocol was used during the whole study period. RESULTS: Preoperative data of the two groups did not differ except for the number of grafts performed, which was higher in group A. Prothrombin time and activated clotting time increased in both groups after surgery. The use of packed red blood cells or fresh frozen plasma was not significantly different between both groups. Postoperative blood loss was significantly reduced in the aprotinin group (540 mL +/- 320 vs. 770 mL +/- 390, p = 0.006). No increase in postoperative troponin values was found in group A. CONCLUSIONS: Aprotinin significantly reduced postoperative blood loss without reducing the transfusion rate. Aprotinin was not associated with any increase in postoperative complications.     

Preoperative autologous donation versus cell salvage in the avoidance of allogeneic transfusion in patients undergoing radical retropubic prostatectomy

There are many methods for preventing allogeneic blood administration during radical retropubic prostatectomy, and many of these methods have been compared with each other, but no studies have compared preoperative autologous donation (PAD) and cell salvage (CS). In this study, we evaluated these two methods in patients undergoing radical retropubic prostatectomy. In a prospective cohort model, allogeneic exposure in patients from one surgeon who routinely had his patients donate blood before surgery was compared with that in patients from a different surgeon who predominantly used CS. Fifty patients were enrolled in the study: 26 in the PAD group and 24 in the CS group. No difference in allogeneic exposure was seen between the two groups. A significant difference was seen in the volume of red blood cells lost (891 +/- 298 mL versus 1134 +/- 358 mL in the PAD and CS groups, respectively). We conclude that PAD and CS are equivalent in their ability to avoid allogeneic transfusion. Larger surgical blood loss in the CS group would suggest that in a more rigorously designed study, CS might provide better allogeneic avoidance than PAD. IMPLICATIONS: In this prospective cohort study, cell salvage and preoperative autologous donation were compared with respect to their ability to avoid allogeneic transfusion. There was a suggestion that cell salvage might offer better allogeneic transfusion avoidance.     

急性血小板分离回输对体外循环心脏直视手术患者的血液保护效果

目的 评价急性血小板(Plt)分离回输对体外循环(CPB)心脏直视手术患者的血液保护效果.方法 择期拟在CPB下行心脏直视手术患者30例,ASA分级Ⅱ或Ⅲ级,年龄41～63岁,体重52～72 kg.采用随机数字表法,将患者随机分为2组(n=15):对照组(C组)和急性Plt分离组(APP组).APP组在麻醉诱导后行APP,提取富Plt血浆,于CPB结束鱼精蛋白中和肝索后回输,C组不行APP.于麻醉诱导前、术后1、24和48h时记录Hb、Plt、PT、APTT及Fib.记录CPB时间、主动脉阻断时间、术后引流量和输血情况.结果 APP组急性Plt分离处理的全血容量为(1285±185) ml,采集富Plt血浆(192±38) ml,其中Plt计数(817±282)×10/L,占全身血容量Plt总数(21±3)％,Plt分离时间(35±10) min.与C组比较,APP组术后1h时Plt升高,术后24h内引流量、异体红细胞、Plt输注量和异体Ph输注率降低(P＜0.05或0.01),其余指标差异无统计学意义(P＞0.05).结论 急性Plt分离回输对CPB心脏直视手术患者具有血液保护作用.     

High-dose aprotinin modulates the balance between proinflammatory and anti-inflammatory responses during coronary artery bypass graft surgery

OBJECTIVE: To rule out the effect of high-dose aprotinin in respect to the balance of proinflammatory and anti-inflammatory mediators induced by cardiopulmonary bypass (CPB). DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: University-affiliated cardiac center. PARTICIPANTS: Twenty patients scheduled for coronary artery bypass graft surgery. INTERVENTIONS: In group A patients (n = 10), high-dose aprotinin was administered (2 x 106 KIU pre-CPB, 2 x 10(6) KIU in prime, 500,000 KIU/hr during CPB). In group C patients (n = 10), placebo was used instead. Proinflammatory interleukin (IL)-6, anti-inflammatory IL-1-receptor antagonist, and clinical parameters were measured 8 times perioperatively. The values are presented as mean +/- SEM. MEASUREMENTS AND MAIN RESULTS: Four hours after CPB, IL-6 concentration reached the maximum value, being significantly lower in group A patients as compared with group C patients (615 +/- 62 pg/mL v 1,409 +/- 253 pg/mL; p = 0.019). On the first postoperative day, the concentration of IL-6 in group A patients remained lower (219 +/- 24 pg/mL v 526 +/- 123 pg/mL; p = 0.015). In contrast, IL-1-receptor antagonist concentration was higher in group A patients as compared with group C patients after CPB (13,857 +/- 4,264 pg/mL v 5,675 +/- 1,832 pg/mL; p = 0.03). Total postoperative blood loss was lower in group A patients as compared with group C patients (648 +/- 64 mL v 1,284 +/- 183 mL; p = 0.002). CONCLUSIONS: High-dose aprotinin treatment reduced the inflammatory reaction and postoperative blood loss. The anti-inflammatory reaction was significantly enhanced in these patients, which suggests that the physiologic reaction of the organism to reduce the deleterious effects from CPB is more pronounced by using high-dose aprotinin.     

Which may be effective to reduce blood loss after cardiac operations in cyanotic children: tranexamic acid,aprotinin or a combination?

BACKGROUND: Children with cyanotic heart disease undergoing cardiac surgery in which cardiopulmonary bypass is used are at increased risk of postoperative bleeding. In this study, the authors investigated the possibility of reducing postoperative blood loss by using aprotinin and tranexamic acid alone or a combination of these two agents. METHODS: In a prospective, randomized, blind study, 100 children undergoing cardiac surgery were investigated. In group 1 (n = 25) patients acted as the control and did not receive either study drugs. In group 2 (n = 25) patients received aprotinin (30.000 KIU.kg(-1) after induction of anesthesia, 30.000 KIU.kg(-1) in the pump prime and 30.000 KIU.kg(-1) after weaning from bypass). In group 3 (n = 25) patients received tranexamic acid (100 mg.kg(-1) after induction of anesthesia, 100 mg.kg(-1) in the pump prime and 100 mg.kg(-1) after weaning from bypass). In group 4 (n = 25) patients received a combination of the two agents in the same manner. Total blood loss and transfusion requirements during the period from protamine administration until 24 h after admission to the intensive care unit were recorded. In addition, hemoglobin, platelet counts and coagulation studies were recorded. RESULTS: Postoperative blood loss was significantly higher in the control group (group 1) compared with children in other groups who were treated with aprotinin, tranexamic acid or a combination of the two agents (groups 2, 3 and 4) during the first 24 h after admission to cardiac intensive care unit (40 +/- 18 ml.kg(-1).24 h(-1), aprotinin; 35 +/- 16 ml.kg(-1).24 h(-1), tranexamic acid; 34 +/- 19 ml.kg(-1).24 h(-1), combination; 35 +/- 15 ml.kg(-1).24 h(-1)). The total transfusion requirements were also significantly less in the all treatment groups. Time taken for sternal closure was longer in the control group (68 +/- 11 min) compared with treatment groups 2, 3 and 4, respectively (40 +/- 18, 42 +/- 11, 42 +/- 13 min, P < 0.05). The coagulation parameters were not found to be significantly different between the three groups. CONCLUSIONS: Our results suggested that both agents were effective to reduce postoperative blood loss and transfusion requirements in patients with cyanotic congenital heart disease. However, the combination of aprotinin and tranexamic acid did not seem more effective than either of the two drugs alone.     

Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose aprotinin versus autologous fresh whole blood transfusion.

Ninety patients undergoing cardiac surgery were randomly divided into three groups of 30 patients to compare the effects on bleeding and transfusion requirements of either intraoperative infusion of high-dose aprotinin (GpI) or reinfusion of autologous fresh whole blood (GpII) versus a control group (GpIII). Standardized anesthetic, perfusion, and surgical techniques were used. Platelet counts, hemoglobin concentration, hematocrit, fibrinogen, and Ivy-Nelson bleeding times determined at fixed times perioperatively did not differ among the three groups. The total loss from the chest drains was significantly reduced in GpI (328 +/- 28 mL; mean +/- SEM) as compared with the loss in GpII and GpIII (775 +/- 75 mL and 834 +/- 68 mL, respectively). There was a threefold difference in the total hemoglobin loss (GpI, 14.2 +/- 1.7 g; GpII, 50.1 +/- 5.0 g; GpIII, 45.0 +/- 5.2 g). GpI patients also received less banked blood: 250 +/- 53 mL versus 507 +/- 95 mL in GpII and 557 +/- 75 mL in GpIII. No GpI patient required transfusion of platelets or fresh frozen plasma. Fresh whole autologous blood transfusions had no significant hemostatic effect and failed to reduce the homologous blood requirement. Conversely, high-dose aprotinin reduced blood loss and transfusion requirements.     

自体血小板分离联合术中自体血回输在脊柱侧弯矫形术中的价值

目的探讨自体血小板分离联合术中自体血回输技术在脊柱侧弯矫形术中的临床价值。方法 60例行脊柱侧弯手术患者随机分为三组,每组20例。Ⅰ组:术前自体血小板分离并制备富血小板血浆（PRP）,术中自体血回收,手术结束前回输PRP;Ⅱ组:仅行术中自体血回收,未进行自体血小板分离回输;Ⅲ组:未进行血液保护措施。测定Ⅰ组手动提取PRP中血小板计数（Plt）,于麻醉诱导前（T₁）、自体血小板分离后10 min（T₂）、输自体回收血及PRP前10 min（T₃）、输自体回收血及PRP后10 min（T₄）、术后24 h（T₅）、术后48 h（T₆）各时点测Hb水平、凝血功能、Plt和血小板聚集功能;比较手术时间、术中出血量、术后24、48 h切口总引流量、术中及术后48 h异体血输入量。结果三组手术时间、术中出血量差异无统计学意义;T₃、T₄时三组Plt和血小板聚集功能明显低于T₁时（P<0.01）。与Ⅰ组比较,T₅、T₆时Ⅱ、Ⅲ组凝血功能、血小板聚集功能显著降低（P<0.05）,术后24、48 h切口总引流量明显增加（P<0.01）,术中及术后48 h内输异体血总量明显增加（P<0.01）。结论自体血小板分离联合术中自体血回输可显著改善脊柱侧弯矫形术患者术后血小板聚集及凝血功能,减少术后切口引流量及异体血输注量。     

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.     

High-dose aprotinin reduces activation of hemostasis,allogeneic blood requirement,and duration of postoperative ventilation in pediatric cardiac surgery

BACKGROUND: Though multiple studies have affirmed the effectiveness of aprotinin in reducing blood loss in adult cardiac surgery, the possible benefit in pediatric cardiac surgery is controversial. METHODS: In a double-blind, randomized, and placebo-controlled study, the efficacy of aprotinin in attenuating the hemostatic and inflammatory activation during cardiopulmonary bypass in 60 patients weighing less than 10 kg was investigated. Secondary endpoints were the influence of aprotinin on the reduction of blood loss and allogeneic blood requirement, as well as postoperative oxygenation and length of mechanical ventilation. Aprotinin was administered in a high-dose of 3 x 10(4) KIU/kg plus a bolus of 5 x 10(5) KIU (not weight adjusted) added to the pump prime. RESULTS: Aprotinin plasma concentration at the end of cardiopulmonary bypass (CPB) was with 184 +/- 45 KIU/mL, within the targeted range of 200 KIU/mL. Coagulation and fibrinolysis were suppressed (F1.2 1 hour after CPB: 5.35 +/- 2.9 nmol/L vs 14.5 +/- 23.1 nmol/L; D-dimer 1 hour after CPB: 0.63 +/- 0.6 ng/mL vs 2.3 +/- 3.1 ng/mL; p < 0.05), inflammatory markers (interleukin [IL]-6, IL-8, IL-10) increased over time without significant differences between the groups, and only complement C3a activation was significantly attenuated at the end of CPB in the aprotinin group. Chest tube drainage was significantly reduced (24 hours: median 13.5 [IQR 12.2] mL/kg vs 19.4 [8.2] mL/kg; p < 0.05). All patients received one unit of packed cells to prime the heart lung machine. A second unit was needed significantly less often in the aprotinin group (13% vs 47%; p < 0.05). Postoperative oxygenation (pO2/FIO2 172 [IQR 128] mm Hg vs 127 [74]; p < 0.05) improved, and the time on ventilator was shorter in the aprotinin group (median 45 hours [IQR 94] vs 101 [IQR 74]; p < 0.05). No side effects were attributable to the use of aprotinin. CONCLUSIONS: High-dose aprotinin effectively attenuated hemostatic activation and reduced blood loss and transfusion requirement in pediatric cardiac surgery. Postoperative ventilation was also shortened in the aprotinin group.     

Safety and efficacy of perioperative cell salvage and autotransfusion after coronary artery bypass grafting: a randomized trial

BACKGROUND: The aim of this study was to ascertain whether cell salvage and autotransfusion after first time elective coronary artery bypass grafting is associated with a significant reduction in the use of homologous blood, a clinically significant derangement of postoperative clotting profiles, or an increased risk of postoperative bleeding. METHODS: Patients were randomized to autotransfusion (n = 98) receiving autotransfused washed blood from intraoperative cell salvage and postoperative mediastinal fluid cell salvage after coronary artery bypass surgery or control (n = 102) receiving stored homologous blood only after coronary artery bypass surgery. RESULTS: There was no statistical difference between the groups in terms of demographics, comorbidity, risk stratification, or operative details. Mean volume of blood autotransfused was 367 +/- 113 mL. Patients in the autotransfusion group were significantly less likely to receive a homologous blood transfusion compared with controls (odds ratio 0.40, 95% confidence interval [CI] 0.22-0.71) and received significantly fewer units of blood per patient compared with controls (0.43 +/- 1.5 vs 0.90 +/- 2.0 U, p = 0.02). There was no difference between the groups in terms of postoperative blood loss, fluid requirements, blood product requirements, or in the incidence of adverse clinical events (p = NS chi(2)). Autotransfusion did not produce any significant derangement of thromboelastograph values or laboratory measures of clotting pathway function (prothrombin time, activated partial thromboplastin time, fibrinogen, and fibrinogen D-dimer levels) when compared with the effect of homologous blood transfusion (p = NS, repeated measures analysis of variance [MANOVA]). CONCLUSIONS: Autotransfusion is a safe and effective method of reducing the use of homologous bank blood after routine first time coronary artery bypass grafting.     

Efficacy of aprotinin in children undergoing craniofacial surgery

OBJECT: This prospective, randomized, placebo-controlled, double-blind trial was undertaken to assess the efficacy of aprotinin in reducing the need for blood transfusions in 39 children undergoing reconstructive craniofacial surgery. METHODS: Two demographically similar groups--a total of 39 patients with a mean age of 1.2 +/- 1.2 years--were studied. The efficacy of aprotinin (240 mg/m2 administered intravenously over 20 minutes, followed by infusions of 56 mg/m2/hr) was compared with that of an equal infusion of 0.9% saline (placebo). Patients in the aprotinin group received less blood per kilogram of body weight than patients in the placebo group (32 +/- 25 ml/kg compared with 52 +/- 34 m/kg, respectively; p = 0.04). Those patients in whom aprotinin was administered experienced less change in their hematocrit levels during surgery (aprotinin -33 +/- 13% compared with placebo -44 +/- 9%, p = 0.01). Each patient underwent a transfusion as per study protocol, and there was no significant change in hematocrit levels from the beginning to the end of surgery. The surgical faculty judged blood loss in patients in the aprotinin group to be significantly less than usual (p = 0.03). The use of aprotinin was also associated with reduced blood transfusion requirements during the first 3 postoperative days (p = 0.03). There was no adverse event reported in either the aprotinin or placebo group. CONCLUSIONS: Aprotinin decreased blood transfusion requirements in pediatric patients undergoing craniofacial reconstruction, thereby reducing the risks associated with exposure to banked blood components.     

Absence of beneficial effect of acute normovolemic hemodilution combined with aprotinin on allogeneic blood transfusion requirements in cardiac surgery

BACKGROUND: The efficacy of acute normovolemic hemodilution (ANH) in decreasing allogeneic blood requirements remains controversial during cardiac surgery. METHODS: In a prospective, randomized study, 80 adult cardiac surgical patients with normal cardiac function and no high risk of ischemic complications were subjected either to ANH, from a mean hematocrit of 43% to 28%, or to a control group. Aprotinin and intraoperative blood cell salvage were used in both groups. Blood (autologous or allogeneic) was transfused when the hematocrit was less than 17% during cardiopulmonary bypass, less than 25% after cardiopulmonary bypass, or whenever clinically indicated. RESULTS: The amount of whole blood collected during ANH ranged from 10 to 40% of the patients' estimated blood volume. Intraoperative and postoperative blood losses were not different between control and ANH patients (total blood loss, control: 1,411 +/- 570 ml, n = 41; ANH: 1,326 +/- 509 ml, n = 36). Allogeneic blood was given in 29% of control patients (median, 2; range, 1-3 units of packed erythrocytes) and in 33% of ANH patients (median, 2; range, 1-5 units of packed erythrocytes; P = 0.219). Preoperative and postoperative platelet count, prothrombin time, and partial thromboplastin time were similar between groups. Perioperative morbidity and mortality were not different in both groups, and similar hematocrit values were observed at hospital discharge (33.7 +/- 3.9% in the control group and 32.6 +/- 3.7% in the ANH group; nonsignificant) CONCLUSIONS: Hemodilution is not an effective means to lower the risk of allogeneic blood transfusion in elective cardiac surgical patients with normal cardiac function and in the absence of high risk for coronary ischemia, provided standard intraoperative cell saving and high-dose aprotinin are used.     

Reduced blood loss by aprotinin in thoracic surgical operations associated with high risk of bleeding. A placebo-controlled, randomized phase IV study.

OBJECTIVE: Although the blood-saving effect of aprotinin has been well documented in cardiac surgery and lung transplantation, its use in lung surgery has received less attention. We present our experience with the intraoperative application of aprotinin in lung resections with a predicted high risk of bleeding. METHODS: Thirty-eight patients undergoing major thoracic surgical procedures were randomized into treatment and placebo groups. The treatment group (n=18) received a bolus of 2 x 10(6) kallikrein inhibitor units (KIU) of aprotinin followed by 5 x 10(5) KIU/h during surgery. The placebo group (n=20) received an isotonic saline infusion instead. RESULTS: There was no significant difference between the groups concerning diagnosis, co-morbidity, age, sex, height, and weight. The mean intraoperative blood loss in the treatment group was significantly reduced (342 vs. 808 ml, P<0024), postoperative blood loss was also reduced (623 vs. 1282 ml, P<0.0007) and the need for blood transfusion was less (14 vs. 60, n.s.). No severe side effects of aprotinin were registered. Re-thoracotomy was necessary in two patients of the placebo group because of postoperative bleeding. CONCLUSION: Aprotinin reduces the perioperative blood loss and the need for blood transfusion in thoracic surgical procedures in patients with an increased risk of bleeding.     

Acute plateletpheresis and aprotinin reduces the need for blood transfusion following Ross operation

The effect of acute intraoperative plateletpheresis (25% platelet yield) in combination with intraoperative low-dose aprotinin (2 million units) on blood conservation was investigated in 18 young adult patients undergoing elective Ross operation. The results were compared with a group of 19 similar patients without plateletpheresis (control group). The hematological and coagulation parameters at admission and discharge were statistically similar in both groups. The total blood product transfusion requirements were significantly reduced in the plateletpheresis group compared with the control group (3.2 units and 5.1 units, respectively, P=0.036). The total blood donor exposure was also reduced significantly in the plateletpheresis group compared with the control group (3.2 and 6.9 donors/patient, respectively, P<0.001). The direct costs for the hospital for the plateletpheresis procedure, including costs for all blood products, were similar to those for blood products alone in the control group. In summary, acute plateletpheresis in combination with low-dose aprotinin significantly reduces the blood product transfusions and blood donor exposures following the Ross operation; the treatment is cost-effective.     

Intraoperative use of platelet-plasmapheresis in vascular surgery

STUDY OBJECTIVE: To determine, in a pilot study, whether pheresis of plasma and platelets before surgical blood loss, with reinfusion of the autologous plasma and platelets after completion of the aortic reconstruction, will result in decreased bleeding and decreased transfusion of allogenic blood components in patients undergoing elective aortic reconstruction. DESIGN: Randomized study. SETTING: University medical center. INTERVENTIONS: Patients were randomized to perioperative (acute) platelet plasmapheresis (APP group) versus conventional blood component therapy (control group). In the APP group, blood was withdrawn after induction of anesthesia, to sequester approximately 300 mL of platelet rich plasma (PRP); platelet poor plasma (PPP) and red blood cells (RBC) were sequestered as well. An autotransfusion device was used to collect and re-infuse autologous RBC during the course of the operation in both groups. After completion of the aortic reconstruction, autologous PRP and PPP were re-infused in the APP group. Blood loss, volume of blood component transfusions, and preoperative and postoperative hemoglobin (Hb), hematocrit (Hct), platelet, international normalized ratio (INR), and activated partial thromboplastin time (aPTT) were recorded. MEASUREMENTS AND MAIN RESULTS: There was no difference between groups in demographics, preoperative laboratory values, or surgical procedures, although more patients were treated for aneurysms (73% vs. 60%) and fewer for occlusive disease (20% vs. 40%) in the control versus APP group. Also, there were no differences between the control and APP groups in duration of operation, blood loss, volume of colloid infused, or volume of allogenic RBC and plasma transfused. Patients in the APP group received a greater volume of crystalloid solution (9.1 +/- 3.4 L vs. 6.8 +/- 3.0 L; p = 0.002), but fewer units of allogenic platelets than the control group (0.7 +/- 1.0 units vs. 0.2 +/- 0.4 units; p < 0.04). There were no differences in postoperative Hb, Hct, INR, aPTT, or fibrinogen. The platelet count was lower in the APP group than in the control group (123 +/- 40 x 10(3)/mm(3) vs. 182 +/- 51 x 10(3)/mm(3); p = 0.004). CONCLUSIONS: Perioperative platelet plasmapheresis led to fewer allogenic platelet transfusions in patients undergoing elective aortic reconstruction. However, there was no decrease in blood loss and no reduction in transfusion of allogenic RBC or plasma. Perioperative platelet plasmapheresis is not recommended for routine use in elective aortic reconstruction.     

Fibrinolytic inhibitors in off-pump coronary surgery: a prospective, randomized, double-blind TAP study (tranexamic acid, aprotinin, placebo).

OBJECTIVE: To evaluate and compare hemostatic effects of tranexamic acid vs. aprotinin vs. placebo in off-pump coronary artery bypass (OPCAB) surgery and, in addition, to assess the safety of fibrinolytic inhibitors therapies. METHODS: In a prospective, randomized, double-blind study finally 91 patients undergoing OPCAB were investigated (group A, n=32, tranexamic acid 1g before skin incision and continuously 200mg/h; group B, n=29, aprotinin 1,000,000IU before skin incision and 250,000IU/h; group C, n=30, placebo). RESULTS: Highly significant inter-group differences were found in cumulative blood loss within 4h (geometric means [95% confidence intervals]-group A: 89.3 [72.7, 109.8] mL, group B: 72.3 [49.2, 106.3] mL and group C: 192.3 [151.8, 243.5] mL) (P<0.001), within 8h (group A: 152.1 [120.7, 191.6] mL, group B: 130.3 [88.1, 192.8] mL and group C: 283.8 [226.0, 356.3] mL) (P=0.001), and within 24h postoperatively (group A: 410.3 [337.6, 498.6] mL, group B: 345.8 [256.0, 398.2] mL and group C: 619.8 [524.3, 732.8] mL) (P<0.001). At all time points, placebo group C was significantly distinct from the groups treated with fibrinolytic inhibitors (groups A and B). However, no differences between groups A and B were found. Both mean hemoglobin and hematocrit values 24h postoperatively were different between the groups (P=0.018 and P=0.077, respectively), acheiving the lowest value in group C. Number of re-transfuzed patients was highest in group C, but without statistical significance (either packed red blood cells, P=0.119 or fresh-frozen plasma, P=0.118). We observed one postoperative myocardial infarction in aprotinin treated group B and one temporary postoperative myocardial ischemia in placebo group C, no cerebrovascular or pulmonary embolism was noticed. Treated groups A and B did not demonstrate postoperative increase in mean levels of myocardial enzymes, compared with group C. Significantly higher mean values of D-dimer were found in group C 24h postoperatively (P<0.001). CONCLUSIONS: Both tranexamic acid and aprotinin seem to be similarly effective in the reduction of postoperative blood loss in OPCAB. Tranexamic acid appears to be cost-effective and safe alternative to aprotinin.