Preoperative administration of epoetin alfa to reduce transfusion requirements in elderly patients having primary total hip or knee reconstruction

Avoidance of allogeneic blood transfusion is challenging in elderly patients with multiple comorbid conditions, who need major elective orthopaedic surgery. We conducted a study comparing the safety and efficacy of preoperative recombinant human erythropoietin (epoetin alfa) in patients having major elective orthopaedic surgery and in matched historical control patients. Patients aged 70 years or more undergoing primary total knee arthroplasty (TKA) or total hip arthroplasty (THA) were given two or three doses, respectively, of epoetin alfa (40,000 IU). They also received oral iron for 14 or 21 days. Epoetin alfa increased hemoglobin (Hb) and hematocrit (HCT) levels before surgery; 74% of control patients required blood transfusion, compared with 12.5% of patients receiving epoetin alfa. No serious adverse event was attributed to study treatment. These data indicate that epoetin alfa is safe and effective and reduces the need for allogeneic blood transfusion in elderly patients having elective total joint replacement.     

Preoperative administration of epoetin alfa to total joint arthroplasty patients

Epoetin alfa is indicated to reduce allogeneic transfusions in patients undergoing major operations. This study included 40 patients undergoing total joint arthroplasty who received 600 IU/kg doses of epoetin alfa 21, 14, and 7 days preoperatively. Statistically equal matches were obtained according to preoperative hemoglobin, operation, sex, and age. After controlling for autologous donation, the average hemoglobin level on postoperative day one in the treatment group (10.93 g/dL) was significantly higher than the matched patient group (9.86 g/dL). Likewise, treated patients were transfused with significantly less blood (0.68 units/patient) compared to the matched group (1.6 units/patient). In these patients, administration of epoetin alfa was associated with significantly higher perioperative hemoglobin levels and significantly fewer transfusions than matched counterparts. The use of epoetin alfa in this heterogeneous surgical population illustrates its success in a varied population.     

Preoperative Epoetin Alfa in Colorectal Surgery: A Randomized,Controlled Study

Background Colorectal cancer patients are often anemic before surgery, and this leads to an increased requirement for allogeneic blood transfusion. This may result in transfusion-induced immunosuppression, which in turn leads to increased morbidity and possibly an increased rate of tumor relapse. We investigated the possible benefits of perioperative epoetin alfa administration in anemic patients to correct hemoglobin levels and reduce transfusion needs.Methods A total of 223 colorectal cancer patients with anemia scheduled for surgery were randomized to a group that received epoetin alfa 150 or 300 IU/kg/day subcutaneously for 12 days (day -10 to +1) or to a control group. All received iron (200 mg/day by mouth) for 10 days before surgery. Hemoglobin levels, hematocrit, and the number of blood units transfused were recorded.Results A total of 204 patients were eligible for analysis. Mean hemoglobin levels and hematocrit were significantly higher in the 300 IU/kg group than in the control group, both 1 day before surgery (hemoglobin, P = .008; hematocrit, P = .0005) and 1 day after surgery (hemoglobin, P = .011; hematocrit, P = .0008). Blood loss during and after surgery was similar in all groups. Patients who received epoetin alfa 300 IU/kg required significantly fewer perioperative transfusion units than control patients (.81 vs. 1.32; P = .016) and significantly fewer postoperative units (.87 vs. 1.33; P = .023). There were no significant differences in the number of units in the 150 IU/kg group.Conclusions Preoperative epoetin alfa (300 IU/day) increases hemoglobin levels and hematocrit in colorectal surgery patients. These effects are associated with a reduced need for perioperative and postoperative transfusions.See Appendix 1 for a list of investigators in the Hellenic Surgical Oncology Perioperative EPO Study Group.     

Preoperative epoetin alfa vs autologous blood donation in primary total knee arthroplasty

This prospective randomized trial compared preoperative autologous blood donation (PAD) with epoetin alfa in patients undergoing primary total knee reconstruction. Fifty adult patients with pretreatment hemoglobin level of 100 to 130 g/L were randomized to either epoetin alfa 40,000 U at preoperative days 14 and 7 or to a standard PAD protocol. Patient characteristics and operative blood loss were similar between groups. Baseline hematological parameters for epoetin alfa vs PAD were not significantly different; however, by the day of surgery the epoetin alfa group had significantly higher hemoglobin (130 vs 114 g/L; P < .001), hematocrit (0.408 vs 0.352; P < .001), and reticulocyte count (3.4 vs 2.1 x 10(9) cells per liter; P < .001). These differences remained significant for 1 to 2 days postoperatively. There was no significant difference in the incidence of allogeneic transfusions between groups (28% for epoetin alfa vs 8% for PAD; P = .1383). Both treatments were generally well tolerated. Epoetin alfa appears to be a safe alternative to PAD in patients who are at risk for transfusion in the perioperative period following total knee arthroplasty.     

Effects of epoetin alfa on blood transfusions and postoperative recovery in orthopaedic surgery: the European Epoetin Alfa Surgery Trial (EEST)

BACKGROUND AND OBJECTIVE: Preoperative epoetin alfa administration decreases transfusion requirements and may reduce transfusion complications, such as postoperative infection due to immune suppression and thus hospitalization time. This study examined the impact of preoperative epoetin alfa administration on postoperative recovery and infection rate. METHODS: In an open randomized controlled multicentre trial in patients undergoing orthopaedic surgery, the effects of preoperative administration of epoetin alfa vs. routine care were compared in six countries. Haemoglobin (Hb) values, transfusions, time to ambulation, time to discharge, infections and safety were evaluated in patients with preoperative Hb concentrations 10-13g dL(-1) (on-treatment population: epoetin n = 460; control n = 235), from study entry until 4-6 weeks after surgery. Outcome was also compared in patients with and without transfusion. RESULTS: Epoetin-treated patients had higher Hb values from the day of surgery until discharge (P < 0.001) and lower transfusion rates (12% vs. 46%; P < 0.001). Epoetin treatment delivered no significant effect on postoperative recovery (time to ambulation, time to discharge and infection rate). However, the time to ambulation (3.8+/-4.0 vs. 3.1+/-2.2days; P < 0.001)and the time to discharge (12.9+/-6.4 vs. 10.2+/-5.0 days; P < 0.001) was longer in the transfused than in the non-transfused patients. Side-effects in both groups were comparable. CONCLUSIONS: Epoetin alfa increases perioperative Hb concentration in mild-to-moderately anaemic patients and thus reduces transfusion requirements. Patients receiving blood transfusions require a longer hospitalization than non-transfused patients.     

The role of preoperative epoetin alfa in men undergoing radical retropubic prostatectomy

PURPOSE: The safety and effects on hematocrit of recombinant human erythropoietin (epoetin alfa) were evaluated in men undergoing radical retropubic prostatectomy. MATERIALS AND METHODS: Between February 1, 1997 and November 2, 1998, 305 men with clinically localized adenocarcinoma of the prostate underwent radical retropubic prostatectomy performed by a single surgeon (H. L.). Of these men 283 with a baseline hematocrit of less than 48% received 600 IU/kg. epoetin alfa 14 days (-14) and 7 days (-7) before radical retropubic prostatectomy. Hematocrit was measured at baseline on day -14, on day -7, just before anesthesia induction on day 0, immediately postoperatively and on the day of discharge home. The number of allogeneic units transfused, and all intraoperative and postoperative complications were recorded. RESULTS: Mean hematocrit at baseline on day -14 and at induction on day 0 was 42.9% and 45.8%, respectively (p = 0.0001). The frequency of hematocrit decreasing, showing no change or increasing 0.1 to 1.9, 2.0 to 3.9 or greater than 4.0 hematocrit points was 16.5%, 0.5%, 23%, 22% and 38%, respectively. Of the men 17% had no increase in hematocrit. A weak correlation existed between baseline hematocrit and the erythropoietic response to epoetin alfa (r2 = 0.06). Mean change in hematocrit after treatment with epoetin alfa in the quartile baseline hematocrit groups 34.2 to 41.4, 41.5 to 43.2, 43.3 to 44.9 and 45.0 to 48.0 hematocrit points was 3.71, 2.45, 3.86 and 1.02 hematocrit points, respectively. Of the surgical candidates 22 (9.1%) achieved an induction hematocrit of greater than 51%. Of the 283 men receiving epoetin alfa 21 (7.4%) also received an allogeneic transfusion. The transfusion rate did not correlate with induction hematocrit. The only adverse cardiovascular event was an uncomplicated postoperative pulmonary embolus. CONCLUSIONS: Our prospective study demonstrates that epoetin alfa given preoperatively in 2 doses of 600 IU/kg. is safe for significantly increasing hematocrit in men before radical retropubic prostatectomy. It is intuitive that the significant increase in hematocrit decreases the requirement for allogeneic blood transfusion.     

Desmopressin does not reduce bleeding and transfusion requirements in congenital heart operations

Background. Desmopressin (DDAVP) has been evaluated in many randomized clinical trials as a means to reduce blood loss and transfusion of allogeneic blood in cardiac operation requiring cardiopulmonary bypass. Desmopressin reduces blood loss in adult patients with excessive bleeding after cardiac operation. Its usefulness in patients undergoing complex congenital heart repair with cardiopulmonary bypass is unproved.

Methods. Sixty patients younger than 40 years of age scheduled for complex congenital heart operation (44 redo, 16 primary) were enrolled in this prospective, randomized, double-blind trial. Desmopressin 0.3 μg/kg or placebo was administered 10 minutes after protamine administration. Transfusion requirements and postoperative blood loss were recorded. Differences were analyzed using analysis of variance with a p value of 0.05 or less used to denote statistical significance.

Results. There were no differences in demographic or surgical characteristics between the DDAVP or placebo groups. There was no difference in blood loss and transfusion requirements between the DDAVP and placebo groups. During the intraoperative postinfusion time period, the median blood loss for redo patients was 343 versus 357 mL/m² for placebo versus DDAVP, respectively, and for primary patients, the median blood loss was 277 versus 228 mL/m².

Conclusions. The prophylactic use of DDAVP to reduce excessive bleeding or transfusion requirements in patients undergoing complex congenital heart operations is not warranted.     

Blood loss management in high-risk patients undergoing total knee arthroplasty: a comparison of two techniques

Although it is well known that patients with preoperative hemoglobin levels <13.0 g/dL are at a higher risk for requiring postoperative transfusions, the ideal blood management strategy for this group of patients remains unclear. This study compared preoperative autologous donation with preoperative administration of epoetin alfa as a method to maximize perioperative hemoglobin levels and minimize blood transfusions in these high-risk patients undergoing total knee arthroplasty (TKA). Results show that both preoperative autologous donation and epoetin alfa were successful in decreasing the need for allogeneic blood transfusions following TKA in high-risk patients. Epoetin alfa was more effective in maximizing perioperative hemoglobin levels.     

Use of erythropoietin in two-stage reimplantation total hip arthroplasty

This study was done to quantify the effect of epoetin alfa on the transfusion requirements of patients having two-stage reimplantation for infected total hip arthroplasties. This prospective study included 30 consecutive patients treated with a two-stage reimplantation procedure during a 2-year period at one institution. Each patient received a standard dose of epoetin alpha (40,000 units) subcutaneous in the interval between resection and reimplantation. Transfusions were administered only when warranted by clinical symptoms and were not governed by predetermined hemoglobin levels. When compared with a control group of similar patients, the hemoglobin levels before reimplantation were significantly higher (14.0 g/dL versus 11.8 g/dL) and the median allogeneic blood requirements were significantly lower (0 units/patient [range, 0-6] versus 4.3 units per patient [range, 0-9]). Epoetin alfa used in the interval between the resection and reimplantation stage significantly increased the hemoglobin levels and decreased the rate of transfusion for patients having two-stage reimplantation total hip arthroplasty.     

A prospective randomized comparison of three blood conservation strategies for radical prostatectomy.

BACKGROUND: Preoperative autologous blood donation is a standard of care for elective surgical procedures requiring transfusion. The authors evaluated the efficacy of alternative blood-conservation strategies including preoperative recombinant human erythropoietin (rHuEPO) therapy and acute normovolemic hemodilution (ANH) in radical retropubic prostatectomy patients. METHODS: Seventy-nine patients were prospectively randomized to preoperative autologous donation (3 U autologous blood); rHuEPO plus ANH (preoperative subcutaneous administration of 600 U/kg rHuEPO at 21 and 14 days before surgery and 300 U/kg on day of surgery followed by ANH in the operating room); or ANH (blinded, placebo injections per the rHuEPO regimen listed previously). Transfusion outcomes, perioperative hematocrit levels, postoperative outcomes, and blood-conservation costs were compared among the three groups. RESULTS: Baseline hematocrit levels were similar in all groups (43%+/-2%). On the day of surgery hematocrit decreased to 34% +/-4% in the preoperative autologous donation group (P < 0.001), increased to 47%+/-2% in the rHuEPO plus ANH group (P < 0.001), and remained unchanged at 43%+/-2% in the ANH group. Allogeneic blood exposure was similar in all groups. The rHuEPO plus ANH group had significantly higher hematocrit levels compared with the other groups throughout the hospitalization (P < 0.001). Average transfusion costs were significantly lower for ANH ($194+/-$192) compared with preoperative autologous donation ($690+/-$128; P < 0.001) or rHuEPO plus ANH ($1,393+/-$204, P < 0.001). CONCLUSIONS: All three blood-conservation strategies resulted in similar allogeneic blood exposure rates, but ANH was the least costly technique. Preoperative rHuEPO plus ANH prevented postoperative anemia but resulted in the highest transfusion costs.     

Reduction in Requirements for Allogeneic Blood Products: Nonpharmacologic Methods

Background. Various strategies have been proposed to decrease bleeding and allogeneic transfusion requirements during and after cardiac operations. This article attempts to document the usefulness, or lack thereof, of the nonpharmacologic methods available in clinical practice.

Methods. Blood conservation methods were reviewed in chronologic order, as they become available to patients during the perisurgical period. The literature in support of or against each strategy was reexamined critically.

Results. Avoidance of preoperative anemia and adherence to published guidelines for the practice of transfusion are of paramount importance. Intraoperatively, tolerance of low hemoglobin concentrations and use of autologous blood (predonated or harvested before bypass) will reduce allogeneic transfusions. The usefulness of plateletpheresis and retransfusion of shed mediastinal fluid remains controversial. Intraoperatively and postoperatively, maintenance of normothermia contributes to improved hemostasis.

Conclusions. Several approaches have been shown to be effective. An efficient combination of methods can reduce, and sometimes abolish, the need for allogeneic blood products after cardiac operations, inasmuch as all those involved in the care of cardiac surgical patients adhere thoughtfully to existing transfusion guidelines.     

The role of antithrombin III in the perioperative management of the patient with unstable angina

Background. To evaluate the effectiveness of intraoperative administration of antithrombin III (AT III) to improve anticoagulation and preserve the hemostatic mechanisms during cardiopulmonary bypass (CPB) in patients with unstable angina under heparin treatment.

Methods. We divided 22 patients, scheduled for coronary artery bypass grafting, into two groups. Group A (11 patients) received 3000 International Units (IU) of AT III concentrates plus heparin before aortic cannulation. Group B (11 patients) received only heparin. Blood drainage, allogeneic blood transfusions, and intraoperative activated coagulation time were recorded. Also, AT III, thrombin-antithrombin complex (TAT), fragment 1.2 (F 1.2), and -dimers were measured during the operation and the first postoperative day.

Results. Group A patients had fewer transfusions and had less chest-tube drainage. In group A, AT III levels increased after AT III concentrates administration and were always higher than in group B. In group B, F 1.2 and TAT increased significantly more after CPB and at the end of operation. Differences in -dimers between the groups were not significant.

Conclusions. Intraoperative administration of AT III concentrates allowed adequate anticoagulation during CPB and attenuated the coagulative cascade activation and the consequent consumptive coagulopathy.     

Use of perflubron emulsion to decrease allogeneic blood transfusion in high-blood-loss non-cardiac surgery: results of a European phase 3 study

BACKGROUND: This single-blind randomized study in general surgery evaluated the efficacy of perflubron emulsion (PFC) as an artificial oxygen carrier being used to augment preoperative acute normovolemic hemodilution to reduce and avoid transfusion of both allogeneic erythrocytes and erythrocytes from preoperative autologous donation compared with standard of care. METHODS: Subjects (N = 492) with hemoglobin concentrations of 12-15 g/dl undergoing noncardiac surgical procedures with 20 ml/kg or greater expected blood loss were randomized into two groups. Control patients were transfused intraoperatively at a hemoglobin concentration less than 8.0 +/- 0.5 g/dl or at protocol-defined, physiologic triggers. PFC-treated patients first underwent acute normovolemic hemodilution to hemoglobin of 8.0 +/- 0.5 g/dl, followed by dosing with perflubron emulsion (1.8 g/kg). When hemoglobin reached less than 6.5 +/- 0.5 g/dl, an additional 0.9-g/kg dose was given. PFC patients were transfused at hemoglobin less than 5.5 +/- 0.5 g/dl or at predefined physiologic triggers. After surgery, hemoglobin was maintained at 8.5 +/- 0.5 g/dl or greater in all patients until discharge. Efficacy endpoints included the number of allogeneic and preoperative autologous donation units transfused and the percentage of subjects avoiding transfusion. RESULTS: Both groups had similar hemoglobin concentrations at screening (13.5 +/- 1.0 g/dl) and at discharge: 10.8 +/- 1.2 g/dl (PFC) and 11.1 +/- 1.3 g/dl (control). At 24 h, more patients in the PFC group avoided allogeneic and preoperative autologous donation erythrocyte transfusions (53% vs. 43%, < 0.05), and fewer erythrocytes were transfused (1.5 +/- 4.8 vs. 2.1 +/- 3.9 units; median, 0 vs. 1 unit; P = 0.013). By day of discharge, these differences were not significant in the intent-to-treat population, but overall there were less allogeneic and preoperative autologous donation erythrocyte transfusions in the PFC group (696 vs. 846 units). In the protocol-defined target population (n = 330 subjects with blood loss > or = 20 ml/kg), significantly greater avoidance of any erythrocyte transfusion was maintained through day of hospital discharge (26% vs. 16% in the PFC and control groups, respectively; P < 0.05), and there was also a significant reduction in the number of erythrocyte units transfused (3.4 +/- 2.9 vs. 4.9 +/- 2.4 units; median 2 vs. 4 units; P < 0.001). Adverse events rates were similar in the PFC (86%) and control (81%) groups; however, more serious adverse events were reported in the PFC group (32%) than in controls (21%; P < 0.05). Overall mortality was 3%, and the difference between groups (PFC, 4% vs. controls, 2%) was not statistically significant. CONCLUSIONS: Augmented acute normovolemic hemodilution with PFC reduces transfusion needs in patients undergoing noncardiac surgical procedures with blood loss 20 ml/kg or greater.     

A randomized, double-blind, placebo-controlled study to assess the effect of recombinant human erythropoietin on functional outcomes in anemic, critically ill, trauma subjects: the Long Term Trauma Outcomes Study

BackgroundAchieving a higher hemoglobin (Hb) level might allow the anemic, critically ill, trauma patient to have an improved outcome during rehabilitation therapy.MethodsPatients with major blunt trauma orthopedic injuries were administered epoetin alfa or placebo weekly both in hospital and for up to 12 weeks after discharge or until the Hb level was >12.0 g/dL, whichever occurred first. The 36-question Short Form Health Assessment questionnaire (SF-36) was used to evaluate physical function (PF) outcomes at baseline, at hospital discharge, and at several time points posthospital discharge.ResultsOne hundred ninety-two patients were enrolled (epoetin alfa [n = 97], placebo [n = 95]). Hb increased from baseline to hospital discharge in both groups (epoetin alfa: 1.2 g/dL vs placebo: 0.9 g/dL), and transfusion requirements were similar between groups. Both groups showed improvements in SF-36 PF; there were no significant differences in the average of all posthospital discharge scores (epoetin alfa: 27.3 vs placebo 30.9; P = 0.38). Thromboembolic events were similar between groups.ConclusionsNo differences were observed in physical function outcomes or safety in anemic, critically ill, trauma patients treated with epoetin alfa compared with placebo.     

急性等容血液稀释在人工关节置换术中的应用

目的评价急性等容血液稀释在人工关节置换术围手术期的治疗效果以及异体血节约程度。方法回顾分析120例初次单侧人工关节置换术患者,对照组60例未进行自体血回输,实验组60例实施自体血回输,对比两组术前以及术后第2天的血红蛋白（Hb）、红细胞压积（Hct）、白蛋白（Alb）水平和术后2 d内录输注红细胞悬液和新鲜冰冻血浆的剂量。结果实验组与对照组在年龄、性别、手术类型间无统计学差异（t年龄=2.123,t性别=2.208,t手术类型=0.138,P均大于0.05）。实验组与对照组的术后Hb、术后Hct、术前Alb间无统计学差异（t术后Hb=-0.233,t术后Hct=0.310,t术前Alb=-1.698,P均大于0.05）。实验组术前Hb（140.58±13.92）g/L、术前Hct（40.43±3.83）高于对照组术前Hb（132.15±14.50）g/L、Hct（37.97±6.19）（t术前Hb=-3.251,t术前Hct=-2.626,P均小于0.05）。实验组术后Alb水平（32.70±2.05）g/L略低于对照组（33.80±3.11）g/L（t术前Alb=-1.698,t术后Alb=2.188,P均小于0.05）。实验组围手术期人均红细胞悬液和新鲜冰冻血浆使用量分别较对照组减少1.77 IU和2.45 IU（P〈0.001）。结论急性等容血液稀释自体血回输治疗在人工关节置换围手术期能够显著降低异体红细胞悬液和新鲜冰冻血浆的用量,同时不影响术后Hb以及Hct的水平。     

脊柱手术患者急性高容量血液稀释联合控制性降压及自体血液回收的效应

目的 评价脊柱手术患者急性高容量血液稀释(AHH)联合控制性降压及自体血液回收的效应.方法 择期行脊柱手术患者30例,随机分为2组(n=15):控制性降压联合自体血液同收组(Ⅰ组)和AHH联合控制性降压及自体血液回收组(Ⅱ组),Ⅱ组手术前输注6%羟乙基淀粉130/0.4(10 mi/kg)和复方乳酸钠林格氏液10 ml/kg,速率为30 ml/min.2组均在手术开始后静脉输注尼卡地平行控制性降压,速率为1.0～6.0 μg·kg-1·min-1,在lO～15min使MAP降至65～70mm Hg,直至脊柱内固定安器安装完毕.2组术中均行自体血液回收,于脊柱内固定器安装完毕后回输.术中持续监测血液动力学参数,记录术中异体输血情况、尿最及术后引流量、异体输血量.不良反应的发生情况.结果 2组术中HR和CVP均保持稳定.与Ⅰ组比较,Ⅱ组术中异体输血免除率升高,异体输血量减少(PO.05),尿量增多(P0.05).2组均末见心、脑、肾功能异常的发生.结论 脊柱手术患考AHH联合控制性降压及自体血液回收可减免异体输血.     

Hemorrhage and the Use of Blood Products After Adult Cardiac Operations: Myths and Realities

Background. Several patient-, procedure-, and prescriber-related factors are thought to influence the decision to administer allogeneic blood products. We reexamine a number of assertions applied commonly to the practice of transfusion in cardiac operations.

Methods. More than 50 original articles including a total of more than 10,000 patients from 70 centers were reviewed. Data from 5,426 patients operated on between 1990 and 1994 at the Montreal Heart Institute are presented.

Results. From our review of the literature, we conclude that postoperative mediastinal fluid drainage averages 917 mL and that aspirin therapy increases drainage by less than 300 mL in most studies, which should not increase use of blood products, insofar as a strict transfusional protocol is adhered to. Across centers, transfusions can vary eightfold for the same postoperative drainage. Data from our institution show that postoperative mediastinal drainage per se is not influenced by reoperation or by the type of operation. However, total blood losses and transfusion requirements remain increased in reoperative and complex procedures. Excessive mediastinal drainage resulting in increased transfusions occurs in 29% of patients.

Conclusions. Exposure to allogeneic transfusions remains institution dependent. Constant reevaluation of local practice is essential to implement efficient blood conservation strategies.     

Use of Perflubron Emulsion to Decrease Allogeneic Blood Transfusion in High-blood-loss Non-Cardiac Surgery: Results of a European Phase 3 Study

Background: This single-blind randomized study in general surgery evaluated the efficacy of perflubron emulsion (PFC) as an artificial oxygen carrier being used to augment preoperative acute normovolemic hemodilution to reduce and avoid transfusion of both allogeneic erythrocytes and erythrocytes from preoperative autologous donation compared with standard of care.

Methods: Subjects (N = 492) with hemoglobin concentrations of 12-15 g/dl undergoing noncardiac surgical procedures with 20 ml/kg or greater expected blood loss were randomized into two groups. Control patients were transfused intraoperatively at a hemoglobin concentration less than 8.0 +/- 0.5 g/dl or at protocol-defined, physiologic triggers. PFC-treated patients first underwent acute normovolemic hemodilution to hemoglobin of 8.0 +/- 0.5 g/dl, followed by dosing with perflubron emulsion (1.8 g/kg). When hemoglobin reached less than 6.5 +/- 0.5 g/dl, an additional 0.9-g/kg dose was given. PFC patients were transfused at hemoglobin less than 5.5 +/- 0.5 g/dl or at predefined physiologic triggers. After surgery, hemoglobin was maintained at 8.5 +/- 0.5 g/dl or greater in all patients until discharge. Efficacy endpoints included the number of allogeneic and preoperative autologous donation units transfused and the percentage of subjects avoiding transfusion.

Results: Both groups had similar hemoglobin concentrations at screening (13.5 +/- 1.0 g/dl) and at discharge: 10.8 +/- 1.2 g/dl (PFC) and 11.1 +/- 1.3 g/dl (control). At 24 h, more patients in the PFC group avoided allogeneic and preoperative autologous donation erythrocyte transfusions (53%vs. 43%, P < 0.05), and fewer erythrocytes were transfused (1.5 +/- 4.8 vs. 2.1 +/- 3.9 units; median, 0 vs. 1 unit;P = 0.013). By day of discharge, these differences were not significant in the intent-to-treat population, but overall there were less allogeneic and preoperative autologous donation erythrocyte transfusions in the PFC group (696 vs. 846 units). In the protocol-defined target population (n = 330 subjects with blood loss >= 20 ml/kg), significantly greater avoidance of any erythrocyte transfusion was maintained through day of hospital discharge (26%vs. 16% in the PFC and control groups, respectively;P < 0.05), and there was also a significant reduction in the number of erythrocyte units transfused (3.4 +/- 2.9 vs. 4.9 +/- 2.4 units; median 2 vs. 4 units;P < 0.001). Adverse events rates were similar in the PFC (86%) and control (81%) groups; however, more serious adverse events were reported in the PFC group (32%) than in controls (21%;P < 0.05). Overall mortality was 3%, and the difference between groups (PFC, 4%vs. controls, 2%) was not statistically significant.     

A Prospective Randomized Comparison of Three Blood Conservation Strategies for Radical Prostatectomy

Background: Preoperative autologous blood donation is a standard of care for elective surgical procedures requiring transfusion. The authors evaluated the efficacy of alternative blood-conservation strategies including preoperative recombinant human erythropoietin (rHuEPO) therapy and acute normovolemic hemodilution (ANH) in radical retropubic prostatectomy patients.

Methods: Seventy-nine patients were prospectively randomized to preoperative autologous donation (3 U autologous blood); rHuEPO plus ANH (preoperative subcutaneous administration of 600 U/kg rHuEPO at 21 and 14 days before surgery and 300 U/kg on day of surgery followed by ANH in the operating room); or ANH (blinded, placebo injections per the rHuEPO regimen listed previously). Transfusion outcomes, perioperative hematocrit levels, postoperative outcomes, and blood-conservation costs were compared among the three groups.

Results: Baseline hematocrit levels were similar in all groups (43% +/- 2%). On the day of surgery hematocrit decreased to 34% +/- 4% in the preoperative autologous donation group (P < 0.001), increased to 47% +/- 2% in the rHuEPO plus ANH group (P < 0.001), and remained unchanged at 43% +/- 2% in the ANH group. Allogeneic blood exposure was similar in all groups. The rHuEPO plus ANH group had significantly higher hematocrit levels compared with the other groups throughout the hospitalization (P < 0.001). Average transfusion costs were significantly lower for ANH ($194 +/- $192) compared with preoperative autologous donation ($690 +/- $128; P < 0.001) or rHuEPO plus ANH ($1,393 +/- $204, P < 0.001).     

Impact of Perioperative Treatment of Recombinant Human Growth Hormone on Cell Immune Function and Intestinal Barrier Function: Randomized,Double-blind,Controlled Trial

Abstract The objective of this study was to evaluate the effects of recombinant human growth hormone (GH) on cell immune function, intestinal barrier function, and outcome. A placebo-controlled randomized double-blind trial was performed, with 20 patients undergoing abdominal surgery enrolled in the study. The patients in the study group received GH (0.3 IU/kg/day) subcutaneously from day 3 before operation until day 7 after operation. The patients in the control group received placebo injections. All the patients were given isonitrogenic (0.15 g N/kg/day) and isocaloric (20 kcal/kg/day) parenteral nutrition from preoperative day 1 through postoperative day (POD) 6. The serum GH and insulin-like growth factor-1 (IGF-1) levels, intestinal permeability, peripheral CD4+/CD8+ lymphocyte subsets, and routine blood and biochemistry analyses were evaluated before and after GH treatment. In the study group a significant increase in serum levels of GH and IGF-1 was observed on PODs 3 and 7. A significant decrease in the CD4+ subset population and the CD4+/CD8+ ratio was observed in the control group on POD 7 compared with preoperative studies, whereas no change was observed in the study group. The lactulose/mannitol excretion (L/M) ratio in the control group was elevated significantly on POD 7 compared with that before operation (p = 0.01), whereas the L/M ratio in the study group did not change compared to preoperative values (p = 0.08). No adverse reactions were related to the administration. There were no differences observed in operation-related complications or postoperative hospital stays between the two groups. This small pilot study suggests that GH attenuated the depression in cellular immunity following surgical stress and possibly reduced the increase in intestinal permeability that occurs following operation. Further studies of a large group of patients are needed to determine if these changes can be translated into improved outcome in surgical patients.