Randomized, Placebo-Controlled, Double-Blind Study of an Ultra-Low-Dose Aprotinin Regimen in Reoperative and/or Complex Cardiac Operations

A bstract Background and aim of the study : High-dose aprotinin is an effective but costly method to reduce transfusions after cardiopulmonary bypass (CPB). Very low doses of aprotinin have been shown to be effective in primary cardiac surgery, but not in patients undergoing procedures associated with the greatest usage of allogeneic blood products after CPB. We evaluated the efficacy of ultra-low-dose aprotinin in this patient population. Methods : Aprotinin 1 million KIU or placebo was added to the priming solution of the CPB circuit of 52 patients undergoing a reoperation and/or a complex surgical procedure. Dryness of operative field, hemoglobin concentrations, coagulation parameters, chest drainage, and transfusion requirements were compared. Results : Total chest drainage was not different between groups, but fewer patients in the aprotinin group required additional protamine postoperatively (35% vs 69% for controls, p = 0.03) and fewer received fresh frozen plasma (FFP; 19% vs 46% for controls, p = 0.04). Red cell transfusion was smaller in the aprotinin group compared to placebo (median 4 and 2 units, respectively, p = 0.04). Transfusion of FFP, platelets, cryoprecipitates was not different between groups. Total number of units transfused tended to be reduced in the aprotinin group compared to control (median 2 and 7 units, respectively, p = 0.06). Conclusions : Prophylactic administration of ultra-low-dose aprotinin reduced transfusions in patients undergoing repeat operations or complex procedures. Aprotinin could be used in a more economical manner, even in this patient population at high-risk of receiving allogeneic blood products.     

Autotransfusion of washed shed mediastinal fluid decreases the requirement for autologous blood transfusion following cardiac surgery: a prospective randomized trial

Objectives: The National Blood Service issues 2.2 million units of blood per year, 10% of these (220 000) are utilized in cardiac procedures. Transfusion reactions, infection risk and cost should stimulate us to decrease this transfusion rate. We test the efficacy of autotransfusion following surgery in a prospective randomized trial. Methods: One hundred and twelve patients undergoing CABG, valve or CABG+valve procedures were randomized into two groups. Group A received washed postoperative drainage fluid and group C were controls. The indication for transfusion was a postoperative haemoglobin (Hb) <10 g/l or a PCV<30. There was no significant difference in preoperative and operative variables between the groups. Results: Twenty-eight patients in group A and 46 in group C required homologous transfusion (P=0.0008). Group A patients required 298±49 ml of banked blood per patient, group C 508±49 ml (P=0.003). There was no difference in total blood required (volume autotransfused+volume banked blood transfused) between the groups (group A 404±50 ml, group C 508±50 ml) or in mean total mediastinal fluid drainage (group A 652±51 ml, group C 686±50ml). The mean Hb concentration was significantly higher in group A on day 1 (11.2 g/dl±51 vs.10.6 g/dl±13 (P=0.002)). No morbidity was associated with autotransfusion. Conclusion: Autotransfusion can decrease the amount of homologous blood transfused following cardiac surgery. This represents a benefit to the patient and a decrease in cost to the health service.     

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.     

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.     

Antifibrinolytic therapy and perioperative blood loss in cancer patients undergoing major orthopedic surgery

BACKGROUND: Aprotinin has been reported to reduce blood loss and transfusion requirements in patients having major orthopedic operations. Data on whether epsilon amino-caproic acid (EACA) is effective in this population are sparse. METHODS: Sixty-nine adults with malignancy scheduled for either pelvic, extremity or spine surgery during general anesthesia entered this randomized, double-blind, placebo-controlled trial, and received either intravenous aprotinin (n = 23), bolus of 2 x 10(6) kallikrein inactivator units (KIU), followed by an infusion of 5 x 10(5) KIU/h, or EACA (n = 22), bolus of 150 mg/kg, followed by a 15 mg/kg/h infusion or saline placebo (n = 24) during surgery. Our goal was to determine whether prophylactic EACA or aprotinin therapy would reduce perioperative blood loss (intraoperative + first 48h) >30% when compared to placebo. RESULTS: The mean age of the study population was 52 +/- 17 yr. The groups did not differ in age, duration of surgery, perioperative blood loss or number of packed erythrocyte units transfused. When compared to the placebo group, the two treated groups had a significantly lower D-Dimer level immediately after surgery, P < 0.01. CONCLUSIONS: Under the conditions of this study, we were unable to find a clinical benefit to using aprotinin or EACA to reduce perioperative blood loss or transfusion requirements during major orthopedic surgery in cancer patients.     

Avoiding transfusions in children undergoing cardiac surgery: a meta-analysis of randomized trials of aprotinin

Aprotinin, a potent antifibrinolytic drug, reduces the proportion of adults who receive blood transfusions during cardiac surgery, although the effect in children remains unclear. We performed a systematic review of the literature to identify all English language, randomized controlled trials of aprotinin involving children undergoing corrective or palliative cardiac surgery with cardiopulmonary bypass. All studies were assessed for methodological quality, and sources of heterogeneity were examined. We measured the effect of aprotinin on the proportion of children transfused, the volume of blood transfused, and the volume of chest tube drainage. Twelve trials enrolling 626 eligible children met the inclusion criteria. Aprotinin reduced the proportion of children who received red blood cell or whole blood transfusions during cardiac surgery by 33% (relative risk = 0.67; 95% confidence interval, 0.51 to 0.89). Aprotinin did not have a significant effect on the volume of blood transfused or on the amount of postoperative chest tube drainage. Most of the studies were of poor methodological quality and predefined transfusion triggers were infrequently used. Overall, aprotinin reduced the proportion of children who received blood transfusion during cardiac surgery with cardiopulmonary bypass. Further high-quality trials with clinically important outcomes may be warranted before aprotinin can be routinely recommended in this population.     

Aprotinin decreases exposure to allogeneic blood during primary unilateral total hip replacement

BACKGROUND: Aprotinin, a hemostatic agent, regulates fibrinolysis, modulates the intrinsic coagulation pathway, stabilizes platelet function, and exhibits anti-inflammatory properties through inhibition of serine proteases, such as trypsin, plasmin, and kallikrein. Aprotinin has been used successfully for many years in cardiac operations, and there have been preliminary investigations of its use in hip replacement operations. The objectives of this multicenter, randomized, placebo-controlled, double-blind trial were to evaluate the efficacy and safety of aprotinin as a blood-sparing agent in patients undergoing an elective primary unilateral total hip replacement and to examine its effect on the prevalence of deep-vein thrombosis in this population. METHODS: Seventy-three patients received a placebo; seventy-six patients, a low dose of aprotinin (a load of 500,000 kallikrein inhibitor units [KIU]); seventy-five, a medium dose of aprotinin (a load of 1,000,000 KIU, with infusion of 250,000 KIU per hour); and seventy-seven patients, a high dose of aprotinin (a load of 2,000,000 KIU, with infusion of 500,000 KIU per hour). The end points for the determination of efficacy were transfusion requirements and blood loss. Patients received standard prophylaxis against deep-vein thrombosis and underwent compression ultrasonography with color Doppler imaging of the proximal and distal venous systems of both legs to evaluate for the presence of deep-vein thrombosis. RESULTS: Aprotinin reduced the percentages of patients who required any form of blood transfusion (47 percent of the patients managed with a placebo needed a transfusion compared with 28 percent of those managed with low-dose aprotinin [p = 0.02],27 percent of those managed with high-dose aprotinin [p = 0.008], and 40 percent of those managed with medium-dose aprotinin [p = 0.5]). Only 6 percent (twelve) of the 212 patients treated with aprotinin required allogeneic blood compared with 15 percent (ten) of the sixty-eight patients treated with the placebo (p = 0.03). Aprotinin decreased the estimated intraoperative blood loss (p = 0.02 for the low-dose group, p = 0.04 for the medium-dose group, and p = 0.1 for the high-dose group), the measured postoperative drainage volume (p = 0.4 for the low-dose group, p = 0.006 for the medium-dose group, and p = 0.000 for the high-dose group), and the mean reduction in the hemoglobin level on the second postoperative day (thirty-four grams per liter for the placebo group, twenty-eight grams per liter for the low-dose group [p = 0.000], twenty-six grams per liter for the medium-dose group [p = 0.000], and twenty-three grams per liter for the high-dose group [p = 0.0001). The rate of deep-vein thrombosis was similar for all groups. CONCLUSIONS: We concluded that aprotinin is safe and effective for use as a hemostatic agent in primary unilateral total hip replacements. In patients who are at high risk of receiving allogeneic blood, use of aprotinin may be of particular clinical and economic benefit.     

Aprotinin and tranexamic acid for high transfusion risk cardiac surgery

BACKGROUND: Studies have shown that aprotinin and tranexamic acid can reduce postoperative blood loss after cardiac operation. However, which drug is more efficacious in a higher risk surgical group of patients, has yet to be defined in a randomized study. METHODS: With informed consent, 80 patients undergoing elective high transfusion risk cardiac procedures (repeat sternotomy, multiple valve, combined procedures, or aortic arch operation) were randomized in a double-blind fashion, to receive either high dose aprotinin or tranexamic acid. Patient and operative characteristics, chest tube drainage and transfusion requirements were recorded. RESULTS: There was no significant difference between the 2 treatment groups with respect to age, cardiopulmonary bypass time, complications (myocardial infarction, stroke, death), chest tube drainage (6, 12, or 24 hours), blood transfusions up to 24 hours postoperatively, total allogeneic blood transfusions for entire hospital stay, or induction/postoperative hemoglobin levels. However, multiple regression analysis revealed a positive relationship between cardiopulmonary bypass time and 24 hour blood loss in the tranexamic acid group (p = 0.001), unlike the aprotinin group where 24 hour blood loss is independent of cardiopulmonary bypass time (p = 0.423). CONCLUSIONS: Overall, there was no significant difference in blood loss, or transfusion requirements, when patients received either aprotinin or tranexamic acid for high transfusion risk cardiac operation. Aprotinin, when given as an infusion in a high-dose regimen, was able to negate the usual positive effect of cardiopulmonary bypass time on chest tube blood loss.     

High-dose aprotinin in cardiac surgery: is high-dose high enough? An analysis of 8281 cardiac surgical patients treated with aprotinin

In this retrospective analysis we tested the hypothesis that aprotinin doses of more than 6 x 10(6) kallikrein inhibiting units (KIU) per patient may be more effective in reducing bleeding compared with the high-dose regimen of 5-6 x 10(6) KIU aprotinin. The aprotinin doses administered for 8281 adult cardiac surgical patients were correlated to body weight and time of operation and calculated in KIU per kg body weight and minute of operation. Linear and logistic regression models were designed to detect potential associations between dose and postoperative bleeding, transfusion, and other covariates. The 6-h chest tube drainage in the lowest quartile dosing group was 447 +/- 319 mL (mean +/- sd) compared with 360 +/- 290 mL in the highest quartile dosing group (P < 0.001). The proportion of patients requiring allogeneic blood transfusion was reduced from 55% to 47% comparing the lowest with the highest dosing group (P < 0.01). Aprotinin dose was also an independent predictor for rethoracotomy for surgical hemostasis (1.9% in the highest quartile to 2.4% in the lowest dosing quartile; P < 0.01). The risk of renal failure requiring dialysis (2.3% in the highest dosing group vs 3.3% in the lowest dosing group; P < 0.01) or impairment of renal function (creatinine increase of >or=2 mg/dL postoperatively, 6.4% in the highest dosing group vs 10.0% in the lowest dosing group; P < 0.01) was lower with higher doses of aprotinin. Thus, there was no association between aprotinin dose and renal function. Our results support the hypothesis that a more individualized aprotinin regimen with potentially higher doses may optimize the effectiveness of aprotinin therapy in cardiac surgery.     

Postoperatively administered aprotinin or epsilon aminocaproic acid after cardiopulmonary bypass has limited benefit

BACKGROUND: Intraoperative antifibrinolytic treatment with aprotinin and epsilon aminocaproic acid (EACA) has been shown to be effective prophylaxis in the reduction of excessive bleeding after cardiopulmonary bypass operations. This study investigated the effectiveness of both drugs when used as a postoperative treatment of patients showing early signs of increased bleeding. METHODS: In a double-blind, randomized study, 69 patients with chest drainage of 100 mL or more 1 hour after bypass were treated with aprotinin, EACA, or placebo. RESULTS: In the first 24 hours postoperatively, neither drug significantly reduced chest drainage or blood transfusion requirements compared with placebo. Median (interquartile) cumulative chest drainage volumes for the first 24 hours postoperatively for the aprotinin, EACA, and placebo groups were 525 (340, 750), 575 (450, 762), and 650 (550, 800) mL, respectively. Among the study patients, 4 undergoing valve operation and treated with aprotinin showed a trend toward less bleeding during the first 12 hours postoperatively compared with 5 valve operation patients who received placebo (p = 0.06). Among all patients, the treatment with aprotinin or EACA failed to reduce levels of D-dimer compared with placebo after treatment, indicating that fibrinolysis was not significantly inhibited. CONCLUSIONS: Aprotinin or EACA administered in the early postoperative period was ineffective in reducing postoperative bleeding with the exception of a small group of patients having valve operations in whom aprotinin treatment may have shown some benefit.     

Aprotinin in major orthopedic surgery: a systematic review of randomized controlled trials

Aprotinin therapy is a promising strategy for reducing blood loss and blood transfusion requirements. The efficacy and safety of aprotinin in orthopedic surgery, however, remain controversial. We searched electronic databases for randomized controlled trials on the efficacy and safety of the use of aprotinin in orthopedic surgery. Thirteen trials that included a total of 506 patients who underwent major orthopedic surgery were analyzed. The pooled intraoperative and perioperative blood loss was significantly less in the aprotinin-treated patients than in the control patients (weighted mean difference [WMD] for intraoperative blood loss = -229 mL, 95% confidence interval [CI] = -367 to -91 mL, P = 0.0011; WMD for perioperative blood loss = -557 mL; 95% CI = -860 to -254 mL; P < 0.0001). The pooled amounts of red blood cell (RBC) units (U) transfused intraoperatively and perioperatively were significantly less in the aprotinin-treated patients than in the control patients (WMD for intraoperative RBC U = -1.1 U; 95% CI = -1.7 to -0.4 U; P = 0.0001; WMD for perioperative RBC U = -1.1 U; 95% CI = -1.7 to -0.5 U; P < 0.0001). Aprotinin was not associated with an increased incidence of deep vein thrombosis (odds ratio = 0.39; 95% CI = 0.14 to 1.05, P = 0.061). The authors conclude that aprotinin reduces the intraoperative and perioperative blood loss and allogeneic blood transfusion requirement and may not be associated with increased risk of deep vein thrombosis in the presence of pharmacological or mechanical prophylaxis in patients undergoing major orthopedic surgery.     

VATS is an adequate oncological operation for stage I non-small cell lung cancer

Objectives: This study was designed to determine the long-term prognosis of video-assisted thoracic surgery (VATS) vs. open lung resections for patients with pathological stage I non-small cell lung cancer (NSCLC). Materials and methods: The medical records of all patients who underwent lung resection for a pathological stage I NSCLC were reviewed for the period from 1990 to 1999, by screening of a database into which data were entered prospectively. There were 511 patients (430 males and 81 females) whose age averaged 63±10 years who underwent 515 lung resections. Our VATS experience began in 1993 with selected stage I patients, and since that date an average of one patient on four was managed with VATS. Lung resections consisted of 25 wedge resections or segmentectomies (seven VATS), 390 lobectomies (92 VATS), 19 bilobectomies (one VATS) and 81 pneumonectomies (ten VATS). Lymph node dissection was performed in all cases. Results: There were significantly more females (P=0.01) and adenocarcinoma (P=0.02) in the VATS group (n=110) when compared to the open group (n=405). Tumour size averaged 4±2 cm in the open group and 3±2 cm in the VATS group (P=0.04). The distribution of T1/T2 tumours was 97/308 and 50/60, respectively (P=0.0001). At follow-up, cancer recurrence could be documented in 117 patients, with no difference of incidence between the two groups (22.5 vs. 24.5%; P=0.64). Estimated Kaplan–Meier 5-year survival rates, including the operative mortality as well as any cancer-related and unrelated death, were 62.8% (confidence interval (CI): 56.8–68.7%) vs. 62.9% (CI: 51.4–74.4%), respectively (P=0.60). The advent of VATS did not influence the patients' survival: 5-year survival rate was 63.9% (CI: 55.3–72.5%) for the period from 1990 to 1992, and 58.8% (CI: 51.7–65.9%) for the period from 1993 to 1999 (P=0.65). Subgroups survival analysis according to the T status did not show any statistically significant difference between the two groups. Conclusions: VATS lung resection with lymph node dissection achieved a 5-year survival similar to that achieved by the conventional approach. VATS is a valuable option for the management of selected patients with an early-stage NSCLC.     

Antifibrinolytic Therapy and Perioperative Blood Loss in Cancer Patients Undergoing Major Orthopedic Surgery

Background: Aprotinin has been reported to reduce blood loss and transfusion requirements in patients having major orthopedic operations. Data on whether [epsilon] amino-caproic acid (EACA) is effective in this population are sparse.

Methods: Sixty-nine adults with malignancy scheduled for either pelvic, extremity or spine surgery during general anesthesia entered this randomized, double-blind, placebo-controlled trial, and received either intravenous aprotinin (n = 23), bolus of 2 x 106 kallikrein inactivator units (KIU), followed by an infusion of 5 x 105 KIU/h, or EACA (n = 22), bolus of 150 mg/kg, followed by a 15 mg/kg/h infusion or saline placebo (n = 24) during surgery. Our goal was to determine whether prophylactic EACA or aprotinin therapy would reduce perioperative blood loss (intraoperative + first 48h) >30% when compared to placebo.

Results: The mean age of the study population was 52 +/- 17 yr. The groups did not differ in age, duration of surgery, perioperative blood loss or number of packed erythrocyte units transfused. When compared to the placebo group, the two treated groups had a significantly lower D-Dimer level immediately after surgery, P < 0.01.     

Do patients want minimally invasive aortic valve replacement?

Objective: Access to aortic valve can be performed through small incisions. However, a considerable advantage of this approach has not been proven by randomized studies so far. We wanted to elucidate the opinion of patients when they are informed objectively about advantages and disadvantages of minimally invasive approach prior to operation. Methods: This prospective study was performed with 27 patients undergoing isolated aortic valve replacement. These patients were informed prior to operation by the same resident concerning objective data. A photograph was shown illustrating a patient with postoperative wound after a standard- and a mini-incision, respectively. After the interview the patient could decide between full and partial sternotomy. Results: After the interview 21/27 (78%) patients preferred to have a full sternotomy (group F) and 6/27 (22%) patients (group P) decided to have a partial sternotomy. Comments of group F: surgeon should have best exposure (n=15); cosmetics aspects unimportant (n=14); operation time as short as possible (n=7). Group P: cosmetic aspects important (n=6). Significant differences between groups (group F vs. group P): age (years), 69.1±1.5 vs. 49.2±7.3 (P=0.024); operation time (min), 142±7 vs. 189±15 (P=0.002); CK (IU/l), 111±11 vs. 374±114 (P=0.0007); CKMB (IU/l), 17±2 vs. 45±17 (P=0.006); ICU-stay (days), 2.6±0.2 vs. 3.2±0.2 (P=0.044). Pericardial effusion requiring drainage was observed in two patients of group P. One patient of group P suffered myocardial infarction. Conclusion: When patients are informed objectively about advantages and disadvantages of minimal invasive aortic valve surgery only a smaller number decides to have a mini incision. The patients preferring short incisions are significantly younger since cosmetic aspects are more important. Longer duration of operation may be due to longer hemostasis based on limited exposure. Air bubbles due to inadequate de-airing might be responsible for higher CK and CK-MB levels in group P.     

The effects of aprotinin on blood product transfusion associated with thoracic aortic surgery requiring deep hypothermic circulatory arrest

OBJECTIVE: To compare the effects of aprotinin on blood product use and postoperative complications in patients undergoing thoracic aortic surgery requiring deep hypothermic circulatory arrest. DESIGN: A retrospective study. SETTING: A university hospital. PARTICIPANTS: Nineteen patients who underwent elective or urgent thoracic aortic surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The total number of units of packed red blood cells, fresh frozen plasma, and platelets was significantly less in the group that received aprotinin (p = 0.01, 0.04, and 0.01). The intraoperative transfusion of packed red blood cells and platelets, collection and retransfusion of cell saver, and postoperative transfusion of fresh frozen plasma were also significantly less in the aprotinin group (p = 0.01, 0.02, 0.01, and 0.05). No patient in either group sustained renal dysfunction or a myocardial infarction. Two patients who had not received aprotinin suffered from chronic postoperative seizures, and one patient who had received aprotinin sustained a perioperative stroke. CONCLUSIONS: Low-dose aprotinin administration significantly decreases blood product transfusion requirements in the setting of thoracic aortic surgery requiring deep hypothermic circulatory arrest, and it does not appear to be associated with renal or myocardial dysfunction.     

The effect of autologous fibrin sealant (Vivostat) on morbidity after pulmonary lobectomy: a prospective randomised, blinded study

Objective: Postoperative air leakage is the most frequent complication after pulmonary surgery. The development of modern surgical techniques has been influenced strongly by the need to manage air leakage effectively during pulmonary resection. This study evaluated the effect of using an autologous fibrin sealant (Vivostat^®) during lobectomy on morbidity following surgery. Methods: This was a prospective, blinded, randomised clinical study. Patients undergoing lobectomy were enrolled into two groups (Vivostat or non-treatment control, 20 per group). Air leakage was measured over a 1-h period (using a mechanical suction pump) on the day of operation, and both air leakage and bleeding/exudation (drainage volume) were recorded every morning postoperatively until the chest tubes were removed. Personnel recording these parameters were blinded to the intervention received. Results: Compared with the control group, mean bleeding/exudate volumes were significantly reduced in the Vivostat group (day 1, 370 vs. 525 ml; total, 424 vs. 782 ml; both P<0.001), and drains were inserted for a shorter time (medians, 1 vs. 2 days, P=0.07). Significantly fewer patients had air leakage at any time in the Vivostat group (40 vs. 80%, P=0.02), and air leakage volumes were significantly lower compared with the control group (median differences: day of surgery: 0.6 l/min, P=0.01; total 0.8 l/min, P=0.03). Postoperative hospitalisation time was shorter in the Vivostat group than in the control group but the difference was not significant (0.5 days, P=0.12). Conclusions: Vivostat fibrin sealant significantly reduces post-surgical air leakage and drainage volumes following lobectomy in pulmonary surgery and is suitable for routine use in this procedure.     

心脏外科停用抑肽酶前后围术期结果比较

目的 比较2007年12月19日中国食品及药品监督管理局下令心脏外科术中停用抑肽酶前、后心脏手术围术期结果,进一步探讨在心脏外科病人应用抑肽酶的作用及安全性.方法 回顾分析停用抑肽酶前、后各6个月的病人资料,所有人选者均在体外循环下行心脏外科手术,年龄均大于18岁.2007年6月19日至2007年12月18日的手术者为抑肽酶组,入选者均在术中应用抑肽酶.2007年12月19日至2008年6月18日手术者为对照组,入选者在术中均未用抑肽酶.比较两组围术期结果.包括术后失血量、输血量、二次开胸发生率、住院病死率及心、脑、肾、肺等重大并发症的发生率.同时进行多因素Lo~tic回归分析进一步确认初步比较的结果.结果 抑肽酶组入选1699例,对照组2225例.抑肽酶组与对照组比较,术后24 h出血量[(402.5±267.3)ml对(628.1±378.2)ml,P相似文献   

Cardiac surgery with cardiopulmonary bypass: does aprotinin affect outcome?

BACKGROUND: Aprotinin, a non-specific serine protease inhibitor, has been used for two decades to reduce perioperative blood loss and the risk for allogeneic transfusion in cardiac surgery. This study evaluated the effects of aprotinin on outcome (mortality, cardiac events, renal failure, and cerebrovascular events) in such patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Data were obtained in patients who received a strict blood conservation protocol: no antifibrinolytic therapy when at low risk (n = 854) and aprotinin (n = 1210) when at high risk for blood transfusion. Relative risk of different pre- and intra-operative variables was calculated for the different outcome variables. Backward stepwise logistic regression analysis was used to identify the independent risk factors associated with the different outcome variables. Statistical significance was accepted at P < 0.01. RESULTS: Postoperative mortality and morbidity were higher in the aprotinin group but this was related to an increased incidence of perioperative risk factors. Mortality was similar to that predicted by the Euroscore. Complex surgery was the only independent variable associated with postoperative cardiac events. Preoperative heart failure, preoperative creatinine > 1.5 mg dl(-1), urgent, and redo surgery were the independent variables associated with postoperative haemodialysis. Age > 70 yr was identified as the only independent variable associated with neurologic dysfunction. CONCLUSIONS: In the present study, patients receiving aprotinin as part of a strict blood conservation strategy represent a population at high risk for postoperative complications. For the outcome variables studied, aprotinin administration was not identified as an independent risk factor.     

Impact of postoperative blood pressure control on regression of left ventricular mass following valve replacement for aortic stenosis

Objective: Considerable left ventricular (LV) hypertrophy sometimes remains after aortic valve replacement (AVR) for aortic stenosis. For this issue, most previous studies have focused solely on transprosthetic pressure gradient, although true problem is not the pressure gradient itself but an elevated LV pressure. This study investigated the impact of blood pressure on postoperative LV mass regression, which had been overlooked in previous studies. Methods: Seventy-nine adult patients with pure aortic stenosis who were treated with AVR using bileaflet mechanical valves underwent echocardiography before surgery, around 6 months later (‘early’), and 2–3 years later (31.7±14.7 months, ‘late’). Patients were divided into two groups whether postoperative systolic blood pressure was below (n=47; N group) or above 130 mmHg (n=32; H group) following recommendation of WHO-ISH and JNC 7th report. Preoperative LV mass (g/m²) did not differ significantly (232±80 vs. 243±76, P=0.91). Results: LV mass became significantly smaller and regression was significantly more effective in N group than in H group both at ‘early’ (145±43 vs. 180±54, regression against preoperative value 34.6±19.1 vs. 19.9±26.6%, P=0.007) and ‘late’ (132±41 vs. 178±51, regression 41.1±16.0 vs. 21.0±27.0%, P<0.001) evaluations. Regression between ‘early’ and ‘late’ evaluations was significant only in N group (P=0.012). The LV mass index returned to the normal range at ‘late’ evaluation in 52.1% of N group and 12.5% of H group patients (P<0.001), and 25 out of 29 patients without residual LV hypertrophy were N group patients. Multivariate analyses revealed that preoperative LV mass index (P<0.001) and postoperative systolic blood pressure (P=0.007) showed significant influence on postoperative LV mass index, and postoperative systolic blood pressure alone significantly (P<0.001) influenced the regression ratio of the LV mass against the preoperative value. No prosthesis related variables (size, orifice area index, pressure gradient) had significant influence. Conclusions: For LV mass regression after AVR, postoperative blood pressure appeared to be more important than prosthesis selection. Controlling the systolic blood pressure below 130 mmHg was beneficial, which coincided with recommendation of WHO-ISH and JNC 7th report despite the pressure drop due to prosthesis in the aortic position.     

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.