Preoperative Recombinant Human Erythropoietin Research Articles

Effect of preoperative recombinant human erythropoietin administration on inflammatory lung injury due to cardiopulmonary bypass

Objective To discuss the effects of preoperative use of recombinant human erythropoietin (rHuEPO) on inflammatory lung injury patients after cardiopulmonary bypass (CPB) under extracorporeal circulation. Methods A total of 54 patients who were scheduled to receive elective open cardiac operations under CPB were enrolled. They were divided into two groups(n=27). rHuEPO group: patients were titrated intravenously with rHuEPO (100 IU/kg, diluted into 50 ml normal saline) for consecutive three days at the same time period before operation. Control group: equivalent normal saline in place of rHuEPO was given to patients via venous injection. Peak airway pressure (Ppeak), plateau pressure (Pplat), and pulmonary dynamic compliance (Cdyn) were well monitored and recorded before CPB (T1), immediately after chest closure (T2), and 2, 4 h and 6 h after surgery (T3, T4, and T5). At T1, T2, T5, and 12, 24, 48 h, and 72 h after surgery (T6, T7, T8, and T9), arterial oxygenation indices (OI) were also recorded. Furthermore, at pre-rHuEPO treatment (T0), T1, T2, T5, T6, T7, T8, and T9, the plasma levels of the tumor necrosis factor (TNF)-α and interleukin (IL)-1β and IL-10 were measured. The time of mechanical ventilation and stay in intense care unit (ICU), discharge time and hospitalization stay were also recorded. Results Compared with the control group, Cdyn in the rHuEPO group at T2-T5 were significantly increased (P<0.05), whereas Ppeak and Pplat were decreased (P<0.05). OI values of rHuEPO group at T2 and T5-T9 were significantly higher than that of control group(P<0.05). It was demonstrated that at any time point after closing chest, the plasma concentrations of TNF-α, IL-1β, and IL-10 in both groups were relatively elevated compared with those before, while the concentrations of TNF-α and IL-1β in the rHuEPO group were lower than those in control group (P<0.05). Compared with the control group, patients receiving rHuEPO treatment underwent an apparent reduction in both mechanical ventilation and staying time in ICU (P<0.05). Conclusions Preoperative rHuEPO administration can attenuate the inflammatory lung injury after CPB via the anti-inflammation pathway and ameliorate pulmonary functions. Key words: Recombinant human erythropoietin; Cardiopulmonary bypass; Lung injury; Inflammatory response

Effects of Preoperative Intravenous Erythropoietin Plus Iron on Outcome in Anemic Patients After Cardiac Valve Replacement

Preoperative anemia is a risk factor for postoperative morbidity and in-hospital mortality in cardiac surgery. However, it is not known whether treatment of anemia before cardiac surgery by administering recombinant human erythropoietin (rhEPO) plus iron improves postoperative outcomes and decreases red blood cell transfusions in these patients. In 1998 a collection of consecutive data for patients who underwent valve replacement was initiated and the inclusion criterion was anemia. Treatment with rhEPO was given at a dose of 500 IU/kg/day every week for 4 weeks and the fifth dose 48 hours before valve replacement. During each rhEPO session, patients received intravenous iron sucrose supplementation. The intervention cohort (2006 to 2011) included 75 patients and the observation cohort was composed of 59 patients who did not receive any treatment (1998 to 2005). Multivariable logistic regression analysis showed that administration of combined therapy was independently associated with decreased postoperative morbidity (odds ratio [OR] 0.13, 95% confidence interval [CI] 0.03 to 0.59 p = 0.008) and in-hospital mortality (OR 0.16, 95% CI 0.28 to 0.95 p = 0.04) after adjusting for logistic European System for Cardiac Operative Risk Evaluation score, type of intervention, time of cardiopulmonary bypass, and year of surgery. Individually, this treatment also decreased postoperative renal failure (OR 0.23, 95% CI 0.06 to 0.88, p = 0.03). Rate of red blood cell transfusion decreased from 93% in the observation cohort to 67% in the intervention cohort as did days of hospitalization (median, 15 days, 10 to 27, versus 10 days, 8 to 14, respectively, p = 0.01 for all comparisons). In conclusion, administration of intravenous rhEPO plus iron in anemic patients before valve replacement improves postoperative survival, decreases blood transfusions, and shortens hospitalization.

Efficacy of preoperative recombinant human erythropoietin administration for reducing transfusion requirements in patients undergoing surgery for hip fracture repair. An observational cohort study

Preoperative anaemia is a major risk factor for allogeneic blood transfusion (ABT) in patients undergoing hip fracture repair. We investigated the efficacy of preoperative recombinant human erythropoietin (rHuEPO) administration for reducing ABT requirements in a series of consecutive hip fracture patients presenting with haemoglobin (Hb) between 10 g/dl and 13 g/dl. The blood conservation protocol consisted of the application of a restrictive transfusion trigger (Hb < 8 g/dl) and the perioperative administration of intravenous iron sucrose (3 x 200 mg/48 h) (group 1, n = 115). Additionally, some patients received preoperative rHuEPO (40 000 IU sc) on admission to the orthopaedic ward (group 2, n = 81). Overall, 103 of 196 patients (52.5%) received at least one ABT unit (2.1 +/- 1.0 U/patient). However, there were significant differences in perioperative ABT rates between groups (60% vs. 42%, for groups 1 and 2, respectively; P = 0.013). Postoperative Hb on postoperative days 7 and 30 was higher in group 2 than in group 1. In addition, in group 2, Hb levels were higher on postoperative day 30 than on admission (12.7 +/- 1.0 g/dl vs. 11.9 +/- 0.8 g/dl, respectively; P = 0.030). Administration of rHuEPO did not increase postoperative complications or 30-day mortality rate. Only three mild intravenous iron adverse effects were witnessed. In anaemic hip fracture patients managed with perioperative intravenous iron and restrictive transfusion protocol, preoperative administration of rHuEPO is associated with reduced ABT requirements. However, appropriate training, education and awareness are needed to avoid protocol violations and to limit further exposure to ABT and ABT-related risks.

Blood-Conservation Techniques in Craniofacial Surgery

Attempts at reducing exposure to allogeneic transfusions, using blood conservation techniques such as controlled hypotension and normovolemic hemodilution, have met with mixed results and are not always practical in small infants. Recombinant human erythropoietin (RHE), a hormone that stimulates RBC production, increases the hematocrit when administered to infants. A retrospective chart review of all patients undergoing fronto-orbital advancement for craniosynostosis by the same plastic surgeon between January 2002 and December 2002 was conducted. A subgroup of patients (10/19) received RHE as a blood-conservation strategy. Transfusion requirements were lower in the RHE group (5/10) versus the control group (9/9). Total volume of blood products transfused was statistically lower in the RHE group (154 mL RHE group versus 421 mL control) (P < 0.03). RHE combined with blood-conservation techniques was associated with a decreased need for blood transfusion, thus exposing the patient to fewer risks associated with allogeneic transfusion.

Preoperative erythropoietin in spine surgery.

Spine surgery may be associated with profuse intraoperative bleeding that often requires blood transfusions. In recent years several techniques have been developed to avoid allogenic transfusions and their potential complications to surgical patients. In this study we review and analyse the role of preoperative recombinant human erythropoietin (rHuEPO) administration in spine surgery as a blood conservation strategy. Between 1998 and 2002, a total of 250 patients scheduled for spine surgery were included in our blood-sparing program: 114 patients (group 1), operated on before rHuEPO approval (2000), underwent preoperative autologous blood donation (ABD) alone, and 136 patients operated on after rHuEPO approval (groups 2 and 3) received rHuEPO while undergoing ABD. Adding rHuEPO to ABD resulted in higher haemoglobin and haematocrit values the day of surgery, more ABD units retrieved per patient and, consequently, reduced allogenic transfusion requirements. The effectiveness of rHuEPO as the only preoperative blood conservation technique was evaluated in ten patients with a predicted blood loss of less than 30% of their total volume, scheduled for lumbar surgery. Data from these patients were matched with those from a similar group of patients who had undergone ABD. Patients receiving rHuEPO alone had higher haemoglobin levels the day of surgery than did patients in the ABD program. Neither group required allogenic transfusions. preoperative rHuEPO is useful for reducing allogenic blood requirements in elective spine surgery. In patients with an expected blood loss of around 50% of blood volume, rHuEPO improves ABD, minimising preoperative anaemia and increasing the number of ABD units collected. In patients with expected blood loss below 30% of total volume, rHuEPO administration may replace ABD.

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.

Preoperative Administration of Recombinant Human Erythropoietin in Patients Undergoing Gynecologic Surgery

The effect of preoperative recombinant human erythropoietin (r-HuEPO) in anemic women undergoing gynecologic surgery for benign diseases was evaluated in this prospective, not randomized study. One hundred and twenty women were included in the study. Sixty women were treated preoperatively with r-HuEPO at three different cumulative doses: 80,000, 120,000 and 160,000 IU. Sixty nonanemic women were not treated. Baseline hemoglobin (Hb) levels were measured. Hb levels were also measured on the day of the surgery before starting the procedure, on postoperative day 1 and on the day of discharge from the hospital. Treatment with r-HuEPO significantly increased both preoperative Hb levels and Hb levels at discharge. Conversely, Hb levels at discharge were lower than baseline levels in untreated women. The effect of r-HuEPO on Hb levels was exerted in a dose-dependent fashion. No adverse and/or side effects of treatment were observed. Preoperative treatment with r-HuEPO in selected anemic patients undergoing gynecologic surgery for benign diseases seems to be a safe and useful tool to reduce the need for red blood cell transfusions.

Autologous blood transfusion in radical hysterectomy with and without erythropoietin therapy

OBJECTIVE: To investigate whether preoperative treatment with erythropoietin facilitates the collection of a sufficient amount of autologous blood in a short period of time. METHODS: Forty-one women scheduled for radical hysterectomy were randomized to preoperative autologous blood donation with or without preoperative recombinant human erythropoietin therapy. All patients were scheduled to deposit three units of blood within 2 weeks before surgery. Hemoglobin, erythrocyte volume fraction, blood cells, iron status, and hemolysis were analyzed before and after surgery. RESULTS: Hemoglobin levels decreased continuously in both groups after the first autologous donation until day 1 postoperatively. With erythropoietin therapy, the erythrocyte volume fraction and hemoglobin levels were significantly higher during precollection and day 1 after surgery. Preoperatively, the drop was 12 g/L less in the erythropoietin-treated group. The additional use of erythropoietin therapy reduced the inability of patients to predeposit blood from 17.8% to 3.4%. CONCLUSION: Most women can predeposit three units of whole blood in only 2 weeks without obtaining severe anemia. By treating women with erythropoietin, one out of seven can be prevented from a hemoglobin level below the 100 g/L limit for donation.

The effect of preoperative recombinant human erythropoietin therapy on platelets and hemostasis in patients undergoing cardiac surgery

In a double-blind, randomized, placebo-controlled trial we evaluated the effects of the administration of recombinant human erythropoietin (5 × 500 U epoetin beta/kg body weight intravenously over a 14-day period before surgery) in patients undergoing cardiac surgery and in whom autologous blood donation was contraindicated on platelet count, platelet distribution width, mean platelet volume (MPV), and certain hemostaseologic parameters. All patients received 3 × 70 IU heparin/kg per day s. c. from 2 days before operation. No thromboembolic events were associated with epoetin beta therapy during the study period. The thrombocytic parameters showed no significant changes in the placebo group before surgery, and the preoperative hematocrit increase in the epoetin beta group was accompanied with an MPV drop (in contrast to the known MPV rise in recombinant human erythropoietin-treated patients with uremia) by a mean of 0.85 fl and a platelet distribution width rise by 3.3% without a significant change in platelet count. In the epoetin beta group the coagulation time (K) of thromboelastogram (TEG) showed an increase from 4.8 to 5.4 minutes by the seventh study day and after the initiation of heparin therapy a further increase to 7.5 minutes. The higher preoperative K increase in the epoetin beta group may partly be a result of the MPV reduction, because smaller platelets are less reactive, a fact underlined by the negative correlation between the preoperative changes of MPV and reaction time of TEG ( r = −0.58, p = 0.0148). In contrast, in the placebo group the K of TEG increased only after the start of heparin therapy (from 5.1 to 6.4 minutes). The significant drop in MPV in the epoetin beta group and the higher increase in K of TEG and the other investigated hemostatic parameters do not suggest any increased thromboembolic risk during the preoperative epoetin beta therapy. Therefore this treatment seems to be a safe way for increasing mean hematocrit by approximately 0.06 within the normal range and reducing the homologous blood requirement in patients undergoing elective cardiac surgery.

Erythropoietin response to anaemia is not altered by surgery or recombinant human erythropoietin therapy

Recombinant human erythropoietin (EPO) therapy has been shown to increase red blood cell (RBC) production and facilitate autologous blood donation before elective surgery. However, recent reports have suggested that surgery and/or EPO therapy may suppress endogenous erythropoietin secretion in response to anaemia. We therefore analysed the haemoglobin/erythropoietin relationship preoperatively and postoperatively in 71 autologous blood donors subjected to aggressive phlebotomy and six treatments with either EPO (150 U/kg, n = 16, 300 U/kg, n = 18, or 600 U/kg, n = 19) or placebo (n = 18). Using data from the three preoperative study visits, the linear relationship between log erythropoietin and haemoglobin was determined for each of the 18 placebo patients. We found no significant differences in the slopes of the relationships in this group during aggressive phlebotomy. Furthermore, there was no evidence of a significant difference in the erythropoietin level recorded postoperatively for each patient to that predicted from the patient's postoperative haemoglobin level, based on the haemoglobin/log erythropoietin relationship preoperatively. Similarly, for each of the EPO-treated groups, there was no evidence of a significant difference when comparing the recorded erythropoietin level to that predicted from each patient's postoperative haemoglobin level, based on the haemoglobin/log erythropoietin relationship preoperatively. We conclude that preoperative recombinant human erythropoietin therapy and/or surgery do not adversely affect the postoperative erythropoietin response to anaemia.