Use of erythropoietin to increase the volume of autologous blood donated by orthopedic patients

For patients who donate blood for autologous use and undergo major orthopedic surgery, low basal hematocrit (Hct) is the major cause of allogeneic blood exposure. To determine whether recombinant human erythropoietin (rHuEPO) could increase autologous blood procurement and reduce allogeneic blood exposure, a prospective randomized study was conducted in 50 women undergoing total hip replacement who had basal Hct < 40 percent (0.40). Patients were randomly placed in three groups: those receiving placebo, those receiving 300 U of rHuEPO per kg, and those receiving 600 U of rHuEPO per kg every 3 to 4 days for 21 days. Oral iron (125-270 mg/day) was given; in the last 24 patients, 100 mg of iron saccharate was administered intravenously at each donation. At each visit, 350 mL of blood was collected if Hct was > or = 34 percent (0.34). Patients receiving rHuEPO donated a greater amount of blood for autologous use than did patients in the placebo group (4.5 +/− 1.1 vs. 2.8 +/− 0.6 units; p < 0.05) and received a significantly lower amount of allogeneic blood (1.2 +/− 1.4 vs. 0.4 +/− 0.8 units; p < 0.05). No difference between the effects of the two doses of rHuEPO was observed. Iron support was a critical factor in the efficacy of treatment. No untoward effects were observed. The rHuEPO emerged as a safe and effective treatment, with adequate iron support, by which to increase preoperative deposit of autologous blood and to reduce exposure to allogeneic blood for patients with low basal Hct.     

The effect of recombinant human erythropoietin on the efficacy of autologous blood donation in patients with low hematocrits: a multicenter, randomized, double-blind, controlled trial

BACKGROUND: This randomized controlled study was undertaken to determine the effect of recombinant human erythropoietin (rHuEPO) on erythropoiesis, autologous blood collection, and allogeneic transfusion risk in elective surgery patients with low baseline hematocrits. STUDY DESIGN AND METHODS: Patients (n = 204) with low baseline hematocrits ( < or = 39%), scheduled for orthopedic surgery within 25 to 35 days, were seen every 3 to 4 days for 21 days. At each visit, 450 mL of blood was collected if the hematocrit was > or = 33 percent, and rHuEPO (600 U/kg) or placebo was administered intravenously. RESULTS: One hundred seventy-three patients were evaluable. The number of autologous units collected from the rHuEPO and control groups, respectively, was 4.5 +/− 1.0 and 3.0 +/− 1.1 (p < 0.001), and marrow production of red cells increased by 668 +/− 222 and 353 +/− 155 mL over and above baseline production (p < 0.05). Allogeneic blood transfusion was required by 31 percent of control and 20 percent of rHuEPO patients (p = 0.09). Excluding 8 patients who received > 6 units, 29 percent of control and 14 percent of rHuEPO patients required allogeneic blood (p = 0.015). Logistic regression modeling determined that the risk of allogeneic transfusion was reduced by rHuEPO (p = 0.025). CONCLUSION: The use of rHuEPO stimulates erythropoiesis, permits the storage of more autologous blood, and reduces allogeneic transfusion risk in patients with low hematocrits who are undergoing elective orthopedic surgery. Additional studies are necessary to determine the optimal schedules of rHuEPO administration and autologous blood collection as well as the cost-effectiveness of this strategy.     

Effectiveness of very low doses of subcutaneous recombinant human erythropoietin in facilitating autologous blood donation before orthopedic surgery

BACKGROUND: Clinical and pharmacokinetic data suggest that very low doses of subcutaneous recombinant human erythropoietin (rHuEPO) may be effective in a preoperative autologous blood deposit program. STUDY DESIGN AND METHODS: Fifty-two patients, scheduled for orthopedic surgery, were enrolled in a double-blind and placebo-controlled study. Patients were randomly assigned to the placebo group or to receive 30, 60, or 100 IU per kg of rHuEPO subcutaneously twice a week for 2 weeks before surgery. The dose of rHuEPO that was effective in facilitating the collection of 4 units of blood in the 2 weeks before surgery and that prevented a sharp decrease in hematocrit was determined. RESULTS: Only in patients receiving 100 IU per kg of rHuEPO did the outcome measurements differ significantly from those in the placebo group. With a higher (p < 0.01) cumulative increase in red cell volume during the study period (297 +/− 127 vs. 121 +/− 44 mL), 64 percent of those receiving 100 IU per kg of rHuEPO were able to donate 4 units of blood for autologous use, as compared with 23 percent of the placebo group (p < 0.05). Allogeneic transfusion was avoided, and the preoperative hematocrit and reticulocyte count were significantly higher in the patients receiving 100 IU per kg of rHuEPO (p < 0.05 and p < 0.01, respectively). CONCLUSION: Subcutaneously administered rHuEPO at a dose of 100 IU per kg twice a week for 2 weeks is effective in facilitating the collection of blood for autologous use and may improve the cost- benefit ratio of blood conservation interventions. Doses < or = 60 IU per kg are ineffective in facilitating such collections in this surgical setting.     

Acute normovolemic hemodilution is a cost-effective alternative to preoperative autologous blood donation by patients undergoing radical retropubic prostatectomy

BACKGROUND: Preoperative autologous blood donation is accepted as a standard of care for radical prostatectomy. Acute normovolemic hemodilution (ANH) is an alternative method for obtaining autologous blood. The cost and benefits of these two autologous blood-collection techniques are compared. STUDY DESIGN AND METHODS: Thirty consecutive patients scheduled for radical prostatectomy underwent ANH to a target hematocrit level of 28 percent. Blood was transfused in the perioperative period to maintain the hematocrit level > 25 percent. Hematocrit levels, transfusion outcomes and costs, and postoperative outcomes for these patients (hemodilution group) were compared with a matched patient cohort who preoperatively donated 3 units of blood for autologous use in prostatectomy surgery (nonhemodilution group, n = 30). RESULTS: Thirty patients underwent ANH to a hematocrit level of 28.7 +/− 1.7 percent, and 1740 +/− 346 mL (3.5 +/− 0.7 units) of blood were collected. Three (10%) of the patients in each cohort had allogeneic blood exposure. Transfusion costs were 73 percent higher for the nonhemodilution group patients than for the hemodilution group patients ($330 +/− $100 vs. $191 +/− $55, p < 0.001). No differences were found in postoperative outcomes. CONCLUSION: An integrated blood conservation program utilizing hemodilution and a defined transfusion trigger can decrease the requirement for preoperative donation of blood for autologous use in radical prostatectomy. Point-of-care autologous blood procurement is more cost-effective than preadmission donation of autologous blood units.     

A randomized trial of perioperative hemodilution versus transfusion of preoperatively deposited autologous blood in elective surgery

Hemodilution, one of several methods proposed to decrease homologous blood transfusion in elective surgery, has not been studied in a prospective controlled trial to determine if it is successful. A prospective, randomized controlled study was conducted to determine if hemodilution can serve as an alternative to preoperative autologous blood donation. Fifty patients were randomized to preoperatively deposit 3 units of autologous blood or to undergo hemodilution immediately before elective radical retropubic prostatectomy. All patients were treated under a standard protocol, including surgery performed by a single surgeon. The preoperative deposit groups received a mean of 2.44 +/− 1.0 units of blood; 2 of 25 patients required homologous blood transfusion for blood loss of 2600 mL and 1700 mL. The hemodilution group received a mean of 2.88 +/− 0.4 units of autologous blood: no hemodilution patient received homologous blood. At discharge, the mean hematocrit for the preoperative deposit group was 35.5 +/− 4.9 (0.35 +/− 0.05), and that for the hemodilution group was 31.8 +/− 4.7 (0.32 +/− 0.05) (p less than 0.001). There were no differences in perioperative morbidity in the treatment groups. The best predictor of discharge hematocrit was the initial hematocrit of the patient. It can be concluded that hemodilution can safely replace or at least augment preoperative autologous donations as a means of decreasing homologous blood transfusion in study patients. These results can be applied to any elective surgery procedure in which a 1000-mL blood loss is anticipated. Other advantages of hemodilution, including convenience, lower cost, and better preservation of all components of autologous blood, suggest that this practice deserves wider application.     

Efficacy of preoperative donation of blood for autologous use in radical prostatectomy

To determine the amount of blood lost, the number of transfusions, and the effectiveness of preoperative autologous blood donation in radical prostatectomy, 163 patients' records from 1987 to 1991 were reviewed at four university hospitals and three community hospitals. Calculated red cell volume lost was 1003 +/− 535 mL (mean +/− SD), which corresponds to 44 +/− 18 percent (mean +/− SD) of total red cell volume. Preoperative donation of blood for autologous use reduced the rate of transfusion of allogeneic blood from 66 to 20 percent (p < 0.001). Of the patients who donated 1 to 2 units, 32 percent received allogeneic blood; 14 percent of those who donated 3 units received allogeneic blood. Donation of 4 units reduced the allogeneic transfusion rate to 11 percent. However, as the number of units donated increased (1-3 units), the units not transfused also increased (0-21%). Ninety-one (56%) of 163 patients donated fewer than 3 units. Autologous blood donation is effective in minimizing the transfusion of allogeneic blood to radical prostatectomy patients, but many patients do not donate enough blood (< 3 units). The donation of 3 units of blood for autologous use is recommended for patients who undergo radical prostatectomy.     

Preoperative recombinant human erythropoietin in anemic surgical patients

Preoperative anemia in a surgical patient predisposes to poor outcomes and allogeneic blood transfusions. As an alternative to transfusions, pharmacologic management of preoperative anemia with recombinant human erythropoietin (rHuEPO) has been well studied in many different types of surgery. rHuEPO, when used alone or in combination with preoperative autologous blood donation before elective surgery, stimulates erythropoiesis and helps to avoid or reduce the need for allogeneic blood transfusions. The clinical evidence on preoperative use of rHuEPO in orthopedic, cardiac, and cancer surgery, as well as in bloodless surgery, is reviewed.     

A phase III trial of recombinant human erythropoietin therapy in nonanemic orthopedic patients subjected to aggressive removal of blood for autologous use: dose, response, toxicity, and efficacy

BACKGROUND: Previous clinical trials have shown that the use of recombinant human erythropoietin (EPO) can facilitate autologous blood donation and reduce allogeneic blood transfusions in autologous blood donors who are anemic at first donation. However, the role of EPO therapy in nonanemic patients remains undefined. To identify this role, a randomized, controlled, multicenter dose-escalation trial was conducted in patients whose initial hematocrit was > 39 percent (0.39). STUDY DESIGN AND METHODS: EPO (150, 300, or 600 units/kg) or placebo was administered intravenously at each of six phlebotomy visits over a 3-week study period. Sixteen (14%) of 116 patients were unable to complete the treatment protocol because of adverse events (n = 11) or for personal reasons (n = 5); 2 patients (1 EPO and 1 placebo) experienced serious adverse events. RESULTS: In 91 evaluable patients, additional red cell production during the study period was 440 +/− 176, 621 +/− 215, 644 +/− 196, and 856 +/− 206 mL (mean +/− SD), respectively, for patients receiving placebo and EPO at 150, 300, and 600 units/kg (p < 0.05 for all EPO groups compared to placebo). However, the percentages of patients in each group who received allogeneic blood did not differ: 2 (9%) of 23 placebo patients and 6 (9%) of 68 EPO patients. CONCLUSION: It is concluded that, while EPO therapy increased preoperative red cell production, no clinical benefit could be demonstrated in autologous blood donors who were not anemic at first blood donation.     

Subcutaneous administration of recombinant human erythropoietin before cardiac surgery: a double-blind, multicenter trial in Japan

BACKGROUND: Dose and injection times have not previously been determined for subcutaneously administered recombinant human erythropoietin that would allow sufficient deposition of blood for autologous use in cardiac surgery. STUDY DESIGN AND METHODS: A double- blind, multicenter trial of placebo (Group 1) and recombinant human erythropoietin at 12,000 IU (Group 2) and at 24,000 IU (Group 3) was performed on 114 patients at 26 institutions to determine the dosage that would permit an 800-g preoperative deposit of blood for autologous use. The test drug was administered subcutaneously on Days 21, 14, and 7 prior to operation, and oral iron preparations at 200 mg per day were given for 21 days. There were 28 patients in Group 1, 28 in Group 2, and 30 in Group 3, with 28 excluded for a violation of the protocol. RESULTS: Blood was safely drawn 14 and 7 days before operation from 22 patients in Group 1 (78.6%), from 26 in Group 2 (92.9%), and from all patients in Group 3 (p = 0.018). The hemoglobin level on the day before operation decreased by 1.1 +/− 1.1 g per dL (11 +/− 11 g/L) in Group 1 and by 0.9 +/− 0.9 g per dL (9 +/− 9 g/L) in Group 2 and rose by 0.1 +/− 0.8 g per dL (1 +/− 8 g/L) in Group 3, compared to initial levels. Allogeneic blood transfusion could be avoided in 62, 89, and 90 percent of Group 1, 2, and 3 patients, respectively (p = 0.013). CONCLUSION: The present study shows that subcutaneously administered recombinant human erythropoietin at a dose of 24,000 IU per week for 3 weeks is effective and sufficient to allow the safe deposition of 800 g of blood for autologous use in cardiac surgery.     

A cluster-randomized controlled trial of a blood conservation algorithm in patients undergoing total hip joint arthroplasty

BACKGROUND: The optimum strategy for reducing allogeneic blood transfusion in patients undergoing total hip joint arthroplasty (THJA) is unknown. STUDY DESIGN AND METHODS: The effectiveness of a comprehensive blood conservation algorithm (BCA) was evaluated by means of a cluster randomization trial. Thirty hospitals performing primary THJA were randomly assigned to implement the algorithm or to continue with usual care (UC). Subsequently, the institutional rate of allogeneic transfusion was determined for 60 consecutive patients who underwent surgery at each site. The BCA consisted of patient and provider education, hemoglobin-based recommendations for specific blood conservation strategies (recombinant human erythropoietin [rHuEPO] or autologous blood donation [ABD]) and transfusion guidelines. The main outcome measure was the institutional allogeneic transfusion rate. RESULTS: One hospital withdrew consent after randomization, resulting in 14 hospitals assigned to BCA and 15 to UC. In the BCA arm, the institutional rates of rHuEPO use and ABD participation were 20.1 and 27.1 percent compared to 0.6 and 25.8 percent, respectively, in the UC arm. The allogeneic transfusion rate was substantially reduced in hospitals assigned to the BCA group (p = 0.02; absolute risk reduction, 9.6% [26.1% UC vs. 16.5% BCA]). Multivariate analysis of patient-level data showed that assignment to the UC arm was an independent risk factor for allogeneic transfusion (p = 0.037; odds ratio, 1.8; 95% confidence interval, 1.0-3.1) when adjusted for other prognostic factors. No differences were observed in the use of autologous blood. CONCLUSION: A comprehensive approach to blood conservation was superior to UC for reducing allogeneic transfusion in patients undergoing THJA.     

The Collaborative Hospital Transfusion Study: variations in use of autologous blood account for hospital differences in red cell use during primary hip and knee surgery

BACKGROUND: Red cell use in patients undergoing Diagnosis Related Group (DRG) 209 procedures (major joint and limb reconstruction procedures of the lower extremities) has been shown to have large, unexplained interhospital variations. STUDY DESIGN AND METHODS: Abstracted records of 2590 consecutive DRG 209 patients at five university hospitals from January 1992 to December 1993 were stratified by procedure and preoperative blood deposit status. Patient characteristics and transfusion and in-hospital outcomes were compared across hospitals. RESULTS: Blood use among patients who did not preoperatively deposit blood was similar across hospitals. Significant differences were found across hospitals for total hip replacement patients in the percentage of patients preoperatively depositing blood (59-80%), percentage of patients receiving transfusion(s) (51 to > 99%), the mean number of units collected per patient (1.6-2.9), and the mean number of unused autologous units per 100 patients (1-185). No significant differences were found in the percentage of those who deposited blood and then required allogeneic units. There was little variability in length of hospital stay or in last hematocrits. Findings were similar for total knee replacement patients. CONCLUSIONS: Interhospital variations in red cell use for primary total hip and knee reconstruction are primarily due to hospital-specific differences in autologous blood collection and transfusion.     

Recombinant human erythropoietin as adjuvant treatment for autologous blood donation in elective surgery with large blood needs (> or = 5 units): a randomized study

BACKGROUND: Autologous blood transfusion presents no infectious or immunologic side effects. The aim of this randomized study was to determine the impact of recombinant human erythropoietin (rHuEPO) on the donation of 5 units of autologous blood by nonanemic patients who were candidates for elective surgery with transfusion requirements of > or = 5 units. STUDY DESIGN AND METHODS: Starting on Day -35, 420 mL of blood was taken weekly. All patients received 200 mg of iron saccharose complex intravenously at each visit and six subcutaneous injections of rHuEPO (141 U/kg) or placebo between Days -21 and -7. RESULTS: Of 50 patients, 45 completed the study (placebo, 21; rHuEPO, 24). Total red cell production was higher in the rHuEPO group (p = 0.001). Donation of 5 units was possible for 67 percent (placebo group) and 79 percent (rHuEPO group) of patients (p = 0.5). The mean number of blood units donated was 4.6 (placebo group) and 4.7 (rHuEPO group). More patients in the placebo group received allogeneic blood (9/21 [43%] vs. 6/23 [26%]), although the difference did not reach significance (p = 0.34). CONCLUSION: In nonanemic patients donating 5 units of blood, rHuEPO associated with intravenous iron increased total red cell production. However, no difference was found between the rHuEPO and placebo groups with regard to the number of units of autologous blood donated of the number of patients receiving allogeneic blood transfusion.     

Iron and erythropoietin measurement in autologous blood donors with anemia: implications for management

Background : The importance of autologous blood donation for elective surgery is recognized, and the method is being used at many hospitals. Not all patients are able to deposit a sufficient amount of blood before surgery because they cannot recover rapidly enough from phlebotomy-induced anemia. The ability to donate sufficient blood for autologous use was studied in patients who are particularly susceptible to phlebotomy-induced anemia. Study Design and Methods : Of 840 patients who donated blood for autologous use in elective surgery from November 1987 through May 1993, 20 with rheumatoid arthritis, 24 with iron deficiency anemia, and 37 aged 65 years and above with normocytic anemia were compared with 24 nonanemic elderly patients who donated a total of 1000 mL of blood for autologous use. Patients received iron sulfate orally and donated blood once a week until operation. Results : The amount of blood collected before surgery per control patient was more than that in others. Consequently, there was a tendency to allogeneic blood transfusion in patients with rheumatoid arthritis or elderly patients. The ferritin levels in controls and in patients with iron deficiency anemia during the donation period were almost within the normal range in spite of iron supplementation, which implied a good utilization of iron sulfate for erythropoiesis. On the other hand, the rise in ferritin levels in the elderly and in patients with rheumatoid arthritis suggested inappropriate iron availability for erythropoiesis and resulted in an increase in iron storage. Since an adequate endogenous erythropoietin response to phlebotomy-induced anemia was not observed in these patients, impaired erythropoietin production was considered one of the reasons for anemia. Conclusion : Patients with iron deficiency anemia are able to continue donating blood for autologous use so long as they have sufficient iron supplementation. However, the elderly or those with rheumatoid arthritis occasionally fail to donate a sufficient volume of blood before surgery as a result of phlebotomy-induced anemia, which is caused in turn by impaired erythropoietin production.     

Impact of intraoperative red blood cell salvage on transfusion requirements and outcomes in radical prostatectomy

BACKGROUND: Preoperative autologous blood donation lowers preoperative hemoglobin (Hb) levels, and the collected blood is frequently wasted. Intraoperative red blood cell (RBC) salvage provides fresher autologous blood in proportion to surgical blood loss, making cell salvage (CS) in radical prostatectomy (RP) feasible for study.
STUDY DESIGN AND METHODS: This retrospective study compared two strategies to reduce allogeneic RBC transfusion requirements in RP: preoperative autologous donation (PAD) versus CS. Patients underwent RP by one surgeon at one institution during two comparable time periods in 2005 (PAD—Group 1) and 2006 (CS—Group 2).
RESULTS: Group 1 patients (n = 40) underwent PAD, collecting 63 autologous RBC units; 36 units (57.1%) were reinfused and 27 (42.9%) were wasted. No Group 1 patient received allogeneic blood. Group 2 patients (n = 63) underwent intraoperative CS and received a mean of 287 mL of salvaged blood. In Group 2, two patients (3.2%) with preoperative Hb levels too low to permit autologous donation each received 2 units of allogeneic RBCs. Group 1 patients had significantly lower preoperative (−1.4 g/dL) and postoperative (−0.8 g/dL) Hb values compared to the CS group. There were no significant differences between groups in procedure times, length of stay, or numbers of cancer recurrences over the 24- to 36-month follow-up period.
CONCLUSION: Perioperative CS can effectively replace PAD for RP patients, offering similar avoidance of allogeneic transfusion, with greater convenience and superior postoperative Hb levels.     

Orthopedic Surgery Transfusion Hemoglobin European Overview (OSTHEO) study: blood management in elective knee and hip arthroplasty in Europe

BACKGROUND: The purpose of this study was to assess current practices in blood management in elective orthopedic surgery in Europe. STUDY DESIGN AND METHODS: For this 225-center prospective survey, data were collected on 3996 patients. Actual perioperative blood loss was compared to preoperative estimates. Differences in Hb levels and other outcome variables for patients receiving allogeneic versus autologous transfusions were evaluated. The probability of allogeneic transfusion based on selected predictor variables was estimated. RESULTS: A total of 2640 (67%) hip and 1305 (33%) knee arthroplasty patients were evaluated. Estimated blood loss (median, 750 mL) was significantly lower than computed blood loss (median, 1944 mL). A total of 2762 (69%) patients received transfusions, including 1393 (35%) autologous-only and 1024 (25%) allogeneic-only. The probability of allogeneic transfusion decreased with increasing baseline Hb, but differentially so for men and women. Transfusion triggers were Hb levels of 8.93 +/- 1.83 g per dL for allogeneic transfusions, and 21 percent of these occurred when the Hb level was greater than 10 g per dL. Autologous blood transfusion was associated with a significantly lower rate (1%) of wound infections than allogeneic blood transfusion (4.2%). CONCLUSION: Accurate assessment of preoperative Hb levels, better estimation of perioperative blood loss, efficient use of autologous blood, adherence to transfusion guidelines, and pharmacologic alternatives contribute to effective and comprehensive blood and anemia management.     

Efficacy of recombinant human erythropoietin in critically ill patients admitted to a long-term acute care facility: a randomized, double-blind, placebo-controlled trial

CONTEXT: Anemia is common in the critically ill and results in a large number of red blood cell transfusions. Recent data have shown that red blood cell transfusions in critically ill patients can be decreased with recombinant human erythropoietin (rHuEPO) therapy during their intensive care unit stay. OBJECTIVE: To assess the efficacy of rHuEPO therapy in decreasing the occurrence of red blood cell transfusions in patients admitted to a long-term acute care facility (LTAC). DESIGN: A prospective, randomized, double-blind, placebo-controlled, multiple-center trial. SETTING: Two long-term acute care facilities. PATIENTS: A total of 86 patients who met eligibility criteria were enrolled in the study with 42 randomized to rHuEPO and 44 to placebo. INTERVENTIONS: Study drug (rHuEPO 40,000 units) or a placebo was administered by subcutaneous injection before day 7 of long-term acute care facility admission and continued weekly for up to 12 doses. MAIN OUTCOME MEASURES: The primary efficacy end point was cumulative red blood cell units transfused. Secondary efficacy end points were the percent of patients receiving any red blood cell transfusion; the percent of patients alive and transfusion independent; cumulative mortality; and change in hematologic variables from baseline. Logistic regression was used to adjust the odds ratio for red blood cell transfusion. All end points were assessed at both study day 42 and study day 84. RESULTS: The baseline hemoglobin level was higher in the rHuEPO group (9.9 +/- 1.15 g/dL vs. 9.3 +/- 1.41 g/dL, p = .02) as was the pretransfusion hemoglobin level (8.0 +/- 0.5 g/dL vs. 7.5 +/- 0.8 g/dL, p = .04). At day 84, patients receiving rHuEPO received fewer red blood cell transfusions (median units per patient 0 vs. 2, p = .05), and the ratio of red blood cell transfusion rates per day alive was 0.61 with 95% confidence interval of 0.2, 1.01, indicating a 39% relative reduction in transfusion burden for the rHuEPO group compared with placebo. There was also a trend at day 84 toward a reduction in the total units of red blood cells transfused in the rHuEPO group (113 units of placebo vs. 73 units of rHuEPO). Patients receiving rHuEPO were also less likely to be transfused (64% placebo vs. 41% rHuEPO, p = .05; adjusted odds ratio 0.47, 95% confidence interval 0.19, 1.16). Most of the transfusion benefit of rHuEPO occurred by study day 42. Increase in hemoglobin from baseline to final was greater in the rHuEPO group (1.0 +/- 2 g/dL vs. 0.4 +/- 1.7 g/dL, p < .001). Mortality rate (19% rHuEPO, 29.5% placebo, p = .17; relative risk, 0.55, 95% confidence interval 0.21-1.43) and serious adverse clinical events (38 % rHuEPO, 32% placebo, p = .65) were not significantly different between the two groups. CONCLUSIONS: In patients admitted to a long-term acute care facility, administration of weekly rHuEPO results in a significant reduction in exposure to allogeneic red blood cell transfusion during the initial 42 days of rHuEPO therapy, with little additional benefit achieved with therapy to 84 days. Despite receiving fewer red blood cell transfusions, patients treated with rHuEPO achieve a higher hemoglobin level.     

Erythropoietin and preoperative autologous blood donation in the prevention of hepatitis C infection:necessity or luxury?

BACKGROUND: Prevention of exposure to allogeneic blood transfusion during surgery is an important financial issue when recombinant human erythropoietin (rHuEPO) is used in addition to preoperative blood donation. STUDY DESIGN AND METHODS: The aim of this study was to carry out a cost-effectiveness analysis of the use of rHuEPO in preoperative blood donation in orthopedic surgery. The study, based on a decision tree analysis of the use of rHuEPO, was conducted from the perspective of the French health care system. The efficacy criterion was the number of hepatitis C infections prevented. The decision tree analysis was constructed as follows: the residual risk of hepatitis C infection was 8.26 per million units transfused, and the chance node was defined according to the number of units transfused. RESULTS: With the use of rHuEPO in preoperative blood donation, 0.30562 cases of hepatitis C infection per 100,000 patients were prevented. The incremental cost of one prevented hepatitis C infection amounted to $888,000,000 (US). CONCLUSION: Despite the limitations of our model, the cost-effectiveness ratio was so large that variations only slightly modified the size of the result. From the societal perspective, it was not cost-effective to add rHuEPO to preoperative blood donation.     

Anemia in the critically ill

The anemia of critical illness is a distinct clinical entity with characteristics similar to that of chronic disease anemia. Several solutions to the processes of anemia, such as blunted erythropoietin production and erythropoietin response and abnormalities in iron metabolism have been developed. The transfusion of RBCs provides immediate correction of low hemoglobin levels, which may be of value in patients with life-threatening anemia. Avoidance of RBC and blood component transfusion, however, is becoming increasingly important as data of adverse clinical outcomes in critically ill patients become clearer. Although the optimal hemoglobin in critically ill patients is not determined, this organ system has a generous reserve. Short-term compensated anemia is tolerated well, while exogenous erythropoietin allows patients to achieve higher hemoglobin concentrations without exposure to transfused blood/blood components. A recent randomized trial enrolled over 1300 critically ill patients to receive either 40,000 units of exogenous erythropoietin or placebo. These authors found that patients randomized to erythropoietin received significantly less allogeneic RBC transfusions and had significantly greater increases in hemoglobin. Although no differences were found between groups in gross clinical outcomes (ie, death, renal failure, myocardial infarction), this study did not have the power to identify small differences in outcomes. This and other studies of exogenous erythropoietin therapy in critically ill patients clearly demonstrate that the bone marrow in many of these patients will respond to the administration of erythropoietin despite their illness, suggesting a blunted production of erythropoietin rather than a blunted response to erythropoietin. Exogenous erythropoietin therefore represents a therapeutic option for treating anemia in critical illness. Acute events in medicine and surgery often lead to many patients becoming anemic. Solutions to this process of anemia should be focused on preventing such events. Anemia after surgery represents an area for prevention. Blood conservation strategies can be performed with adequate results. Monk et al randomized 79 patients undergoing radical prostatectomy to preoperative autologous donation (PAD), preoperative exogenous erythropoietin therapy plus ANH immediately following induction of general anesthesia, and ANH alone. This study concluded that all three techniques resulted in similar hemostasis outcomes (eg, bleeding and transfusion rates), but ANH alone was the least expensive, and ANH plus exogenous erythropoietin and ANH alone resulted in a higher ICU hematocrit compared with PAD. Regardless of these prophylactic strategies, patients still become anemic after surgery or during critical illness. This acute event anemia usually is treated with RBC transfusion; however, autologous blood recovery (cell salvage systems) has been shown to be effective in patients with acute bleeding-related anemia, and this may reduce patients' exposure to allogeneic blood in these patients. There are no universally accepted treatment guidelines for managing anemia, and practice differs between clinicians, hospitals, regions, and countries. Transfusion medicine is evolving and incorporating many new pharmacological agents into the armamentarium of anemia and bleeding therapy. Accumulating evidence suggests that anemia in critically ill patients is common and correlated with poor outcomes. The management of anemia can improve outcomes; however, the optimal management of anemia is not performed universally. New approaches, continued research, and an understanding of anemia may result in more consistent and improved outcomes for critically ill patients.     

Use of exogenous erythropoietin in critically ill patients

OBJECTIVE: Review the literature regarding the use of recombinant human erythropoietin (rHuEPO) to prevent red blood cell (RBC) transfusion in critically ill patients. DATA SOURCES: A computerized search of MEDLINE and EMBASE from 1966 through June 2003 was conducted using the terms erythropoietin, anemia, hemoglobin, critical care, intensive care, surgery, trauma, burn, and transfusion. References of selected articles were reviewed. A manual search of critical care, surgery, trauma, burn, hematology, and pharmacy journals was conducted to identify relevant abstracts. RESULTS: Six randomized studies have evaluated exogenous administration of erythropoietin to prevent RBC transfusions in critically ill patients. Studies vary with respect to rHuEPO dosage regimens, dose of concurrently administered iron, patient characteristics, and transfusion thresholds. Administration of rHuEPO rapidly produces erythropoiesis to reduce the need for RBC transfusions. The largest study conducted to date used weekly rHuEPO administration and found a modest decrease in transfusion requirements although the time to first transfusion was delayed. Reduced intensive care unit (ICU) length of stay (LOS) was shown in only one study of surgical/trauma patients. Reduced LOS after ICU discharge was found in another study of severely ill patients (APACHE II score >22). Other clinical outcomes were not altered by rHuEPO use. No adverse events were associated with rHuEPO use although studies were not designed to evaluate safety. CONCLUSIONS: rHuEPO reduces the need for transfusions. A cost-effectiveness analysis of rHuEPO for this indication is needed. Defining an optimal dosage regimen, identifying patients most likely to respond to rHuEPO, and determining risk factors for ICU associated anaemia would provide information for appropriate rHuEPO utilization.     

Methods of reducing allogeneic blood demand in orthopedic surgery

Despite advances in this field, allogeneic blood transfusion still carries a lot of risk; the availability of heterologous blood is also constantly decreasing. We describe the most popular methods for reducing the allogeneic blood requirement. Basic information is presented about the physiological mechanisms of compensation for intraoperative blood loss, which can be compromised by respiratory and cardiovascular disease or infections. Preoperative anemia (manifested by low hemoglobin levels) is statistically the most significant factor that increases the need for allogeneic blood transfusion. This paper evaluates the importance of oral and intravenous iron supplementation in the perioperative period, and the use of erythropoietin to boost Hb levels. Minimizing intraoperative blood loss also decreases the need for transfusion, and may be accomplished via meticulous hemostasis, an appropriate surgical approach, atraumatic surgical technique, reduced surgery time, and rational tourniquet use. Controlled intraoperative hypotension is a method of proven efficacy. Synthetic antifibrinolytic agents are also used to reduce perioperative blood loss; however, few clinical trials have focused on the use of such drugs in orthopedics. The use of postoperative drainage is still debatable. The allogeneic blood requirement can also be reduced by autologous blood transfusion. Autologous transfusion can be accomplished by preoperative autotransfusion, preoperative hemodilution, and intra- or postoperative blood salvage. It is currently the safest method of compensating for perioperative blood loss, avoiding all the described risks of heterologous blood transfusion.