epoetin-alfa and Critical-Illness

With increasing knowledge of the risks associated with receiving blood transfusions, a new paradigm of bloodless medicine is needed. Principles of bloodless medicine include careful monitoring for obvious and hidden anemias, rapid intervention, minimizing blood losses from laboratory testing and procedures, and careful management of bleeding diatheses. As evidence is revealed and refined, standard treatment of anemia in the intensive care unit will include erythropoietin-stimulating agents, iron, folate, and vitamin B12, which will reduce risks associated with blood transfusions.

Topics: Anemia; Blood Transfusion; Bloodless Medical and Surgical Procedures; Critical Care Nursing; Critical Illness; Epoetin Alfa; Heart Failure; Hematinics; Humans; Intensive Care Units

Topics: Anemia; Critical Illness; Epoetin Alfa; Erythropoietin; Humans; Recombinant Proteins; Treatment Outcome

Evidence regarding the cost-effective use of and benefits associated with epoetin alfa in treating anemia of critically ill patients is assessed.. Anemia of critical illness is a leading cause of inadequate oxygen delivery that affects almost all patients in the intensive care unit setting after day 3. Red blood cell transfusions are commonly used to correct anemia of critical illness, but they are also associated with risks including hemolytic reactions and viral transmission. The latest evidence suggests that when a strict transfusion protocol is implemented, epoetin alfa does not decrease the transfusion requirements of critically ill patients. In the absence of a strict transfusion protocol, an average of 5.1 doses of epoetin, at a cost of $2154, is required to avoid one transfusion. Evidence is accumulating that epoetin may reduce mortality rates in trauma patients. However, important questions remain regarding the magnitude and mechanism of the potential benefit and if the benefit outweighs the risk of thromboembolism. Therefore, the reduction in transfusion-related adverse events is the only clinical outcome benefit that is well-supported by current evidence. However, the known risk of transfusion-related adverse events is low; approximately 29,000 patients would need to be treated to avoid a serious transfusion-related event. Treating these patients would cost over $25 million, and it would take over 100 years to prevent one serious event in a unit admitting 20 epoetin-eligible patients per month.. Published data suggest a prohibitive cost associated with epoetin alfa use in critically ill patients given that the only well-supported clinical benefit of this treatment is the avoidance of transfusion-related adverse events. Continued research is necessary to clarify if there is a net clinical benefit of epoetin use (especially in trauma patients) and to develop optimal blood management strategies.

Topics: Anemia; Cost-Benefit Analysis; Critical Care; Critical Illness; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Intensive Care Units; Oxygen; Randomized Controlled Trials as Topic; Recombinant Proteins; Thromboembolism

The elements and limitations of pharmacoeconomic models, types of analytic methods used in pharmacoeconomic evaluations, outcomes used in studies of anemia treatments, and comparative efficacy and cost-effectiveness of the two available erythropoietic therapies in the treatment of anemia in cancer and critical care patients are discussed.. Clinical, humanistic, and economic outcomes should be taken into consideration in pharmacoeconomic models. The validity of such models may be compromised by a lack of outcome data, unreasonable assumptions, the heterogeneity of the patient population, patient selection bias in comparative studies, and inconsistent use of instruments to measure outcomes. The degree of anemia in patients with cancer correlates with health-related quality of life (QOL). Erythropoietic therapy increases hemoglobin concentrations and QOL, reduces the need for blood transfusions, and is cost-effective for treating anemia in cancer and critical care patients. Epoetin alfa may provide a more rapid hemoglobin response and improvement in QOL at a lower cost than darbepoetin alfa. Front loading with weekly doses of either erythropoietic agent followed by a three-week-long dosing interval for maintenance treatment may be used to quickly correct anemia, improve convenience, and reduce costs.. Erythropoietic therapy for the treatment of anemia in cancer and critical care patients is cost-effective.

Topics: Anemia; Cost-Benefit Analysis; Critical Care; Critical Illness; Darbepoetin alfa; Economics, Pharmaceutical; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Anemia and the need for red blood cell transfusions are common among patients admitted to intensive care units. Erythropoietin has been used to decrease the need for transfusions; however, its ability to improve clinical outcomes is unknown. We evaluated the effect of erythropoietin-receptor agonists on clinically important outcomes, including mortality, length of stay in hospital or intensive care unit, ventilator use, transfusion requirements and major adverse events.. To identify relevant studies, we searched electronic databases covering 1950 to 2007 (MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the Scopus database). We also searched conference proceedings and grey literature sources. We selected all randomized controlled trials involving critically ill patients that compared an erythropoietin-receptor agonist with a placebo or no intervention. No language restrictions were considered. Data were extracted using a standardized extraction template. We used a fixed effects model to calculate all summary measures of treatment effects.. Of 673 identified records, 9 studies that investigated erythropoietin alpha met the eligibility criteria and were included in our analysis. Erythropoietin, compared with placebo or no intervention, had no statistically significant effect on overall mortality (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.71-1.05, I2 = 0%). The treatment and control groups did not differ in the length of stay in hospital or intensive care unit, or in the duration of mechanical ventilation, in the 3 studies that reported these outcomes. Erythropoietin, compared with placebo, significantly reduced the odds of a patient receiving at least 1 transfusion (OR 0.73, 95% CI 0.64-0.84, I2 = 54.7%). The mean number of units of blood transfused per patient was decreased by 0.41 units in the erythropoietin group (95% CI 0.10-0.74, I2 = 79.2%). Most of the included studies were performed before the widespread adoption of a restrictive transfusion strategy. Only 1 study provided detailed reports of adverse events, and none of the studies systematically evaluated all patients for venous thromboembolism.. At this time, we do not recommend the routine use of erythropoietin-receptor agonists in critically ill patients. The reduction in red blood cell transfusions per patient was very small, and there is insufficient evidence to determine whether this intervention results in clinically important benefits with acceptable risks.

Topics: Anemia; Critical Illness; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Randomized Controlled Trials as Topic; Receptors, Erythropoietin; Recombinant Proteins

Anemia occurs in virtually all critically ill patients receiving long-term mechanical ventilation and has been associated with increased mortality and poor outcomes. Allogeneic RBC transfusions are routinely administered to critically ill anemic patients, especially during lengthy stays in ICUs or in long-term acute care facilities. Although RBC transfusions are a physiologically rational approach to raising hemoglobin levels, they may increase the risk of complications and have been associated with higher mortality in critically ill patients. Treatment with epoetin alfa, an erythropoiesis-stimulating agent, as a means of reducing transfusion requirements has been studied in the critically ill and in patients receiving long-term mechanical ventilation. Promising results have been reported, including a potential survival benefit, although larger and more definitive studies are needed in order to establish whether raising hemoglobin levels affects clinical outcomes in patients receiving mechanical ventilation.

Topics: Anemia; Blood Banks; Comorbidity; Critical Illness; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Hemoglobins; Humans; Recombinant Proteins; Respiration, Artificial; Respiratory Insufficiency; Time Factors; Ventilator Weaning

To discuss the controversies regarding the use of epoetin alfa (EPO) for reducing red blood cell (RBC) transfusions in critically ill patients with anemia.. A MEDLINE search (1966-July 2003) was conducted using the search terms anemia; critical illness; erythropoietin; epoetin alfa; and erythropoietin, recombinant. References of selected articles were reviewed for studies that may have been missed by the computerized search.. Studies pertaining to the use of EPO for anemia of critical illness with an emphasis on data obtained from controlled trials.. Anemia is a common complication in patients admitted to the intensive care unit (ICU). Two prospective, randomized studies have demonstrated decreased transfusion requirements associated with EPO administration in medical/surgical patients who were in the ICU for at least 3 days and had hematocrit concentrations <38%. No differences were found in length of stay or mortality. A multicenter trial found that a restrictive strategy of RBC transfusion (hemoglobin goal 7-9 g/dL) was associated with in-hospital mortality lower than that with a more liberal approach, which calls into question the 38% hematocrit goal in the EPO trials. Furthermore, preliminary results from an economic analysis of EPO use in the ICU setting have demonstrated that EPO is not cost-effective.. Given the controversies surrounding EPO administration in critically ill patients, institutions are encouraged to develop EPO guidelines to help ensure the most appropriate use of this expensive product. Additional studies regarding patients most likely to benefit from EPO therapy, the most effective dosing regimen, and use of adjunctive therapies are needed.

Topics: Anemia; Blood Transfusion; Critical Illness; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Injections, Intravenous; Injections, Subcutaneous; Randomized Controlled Trials as Topic; Recombinant Proteins

Many advances have improved the care of critically ill patients, but only a few have been through the use of pharmaceutical agents. Recently, the US Food and Drug Administration (FDA) approved drotrecogin alfa (activated), or recombinant human activated protein C, for the treatment of patients with a high risk of death from severe sepsis. Drotrecogin alfa (activated) has antiinflammatory, antithrombotic and fibrinolytic properties. When given as a continuous intravenous infusion, recombinant human activated protein C decreases absolute mortality of severely septic patients by 6.1%, resulting in a 19.4% relative reduction in mortality. The absolute reduction in mortality increases to 13% if the population treated is restricted to patients with an APACHE II score greater than 24, as suggested by the FDA. The most frequent and serious side effect is bleeding. Severe bleeds increased from 2% in patients given placebo to 3.5% in patients receiving drotrecogin alfa (activated). The risk of bleeding was only increased during the actual infusion time of the drug, and the bleeding risk returned to placebo levels 24 hours after the infusion was discontinued. Patients treated in the intensive care unit frequently develop anemia, usually severe enough to require at least one transfusion of red blood cells. With the recent discovery of the harmful effects of allogeneic red blood cell transfusions and the increasing shortage of available red blood cell products, emphasis has been placed on minimizing transfusions. Patients who receive exogenous recombinant human erythropoietin maintain higher hemoglobin levels, in spite of requiring fewer transfusions during their stay in the intensive care unit. Recombinant human erythropoietin appears to be effective whether it is given as 300 units/kg of body weight subcutaneously every other day or as 40,000 units subcutaneously every week. Differences in hemoglobin values were not apparent until at least one week of therapy, but they continued to diverge after that initial week. Furthermore, the incidence of adverse events was similar to that of patients receiving placebo and there was no difference in mortality, suggesting that avoidance of blood transfusions did not translate into increased survival. Thus, recombinant human erythropoietin appears to be both safe and effective in treating the anemia found in critically ill patients, but it is less clear that such treatment is cost effective, especially in the higher dose regimens

Topics: Critical Care; Critical Illness; Epoetin Alfa; Erythropoietin; Humans; Protein C; Recombinant Proteins; Shock, Septic; Vasopressins

Anemia is a common problem in critically ill patients. As a result, blood transfusions are often used in the intensive care unit (ICU) setting. However, mounting evidence shows that blood transfusions may contribute to negative outcomes, such as transfusion-related infections, organ dysfunction, and immunosuppression. Supplementation with epoetin alfa is currently used in some medical centers to manage anemia in critically ill patients.. This review discusses the risks with blood transfusions and the clinical evidence supporting the use of epoetin alfa in managing edema during critical illness.. A search was conducted in MEDLINE and Current Contents (1966-2003) using the terms epoetin alfa, recombinant human erythropoietin, and anemia. Articles addressing anemia and the use of epoetin alfa in critically ill patients were selected and assessed. From this selection, the cited references addressing the etiology of anemia in the ICU and the risks associated with blood transfusions were manually extracted and reviewed.. Several reports have shown that critically ill patients display evidence of anemia due to a blunted erythropoietin response. One large, randomized, placebo-controlled study assessed the effect of SC epoetin alfa on blood transfusions in the ICU. In this study, 40, 000 IU administered weekly for up to 4 weeks resulted in an overall transfusion reduction (9.9% absolute risk reduction; P<0.001 ). Other, smaller studies using different dosing regimens in critically ill patients have also demonstrated that epoetin alfa can decrease the need for transfusion.. The use of epoetin alfa in critically ill patients can decrease the number of blood transfusions required during hospitalization, and potentially result in transfusion avoidance. Because of the scarce amount of evidence and the diversity of dosing regimens used used, no strict recommendations can be drawn from this review.

Topics: Anemia; Critical Illness; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins; Transfusion Reaction

Achieving a higher hemoglobin (Hb) level might allow the anemic, critically ill, trauma patient to have an improved outcome during rehabilitation therapy.. Patients 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.. One 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.. No differences were observed in physical function outcomes or safety in anemic, critically ill, trauma patients treated with epoetin alfa compared with placebo.

Topics: Adult; Anemia; Critical Illness; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Injections, Subcutaneous; Injury Severity Score; Male; Prospective Studies; Recombinant Proteins; Reference Values; Risk Assessment; Survival Rate; Treatment Outcome; Wounds and Injuries; Wounds, Nonpenetrating; Young Adult

To describe the pharmacokinetic profiles of six different dosing regimens for epoetin alfa, and whether more rapid and robust reticulocytosis can be elicited with more frequent administration of epoetin alfa in anemic critically ill patients.. Randomized, open-label, multicenter, 28-day clinical trial.. Ten centers in the United States.. Adult (age >or=18 years) critically ill patients with hemoglobin or=7 days, with no ongoing acute blood loss.. One of six dosing epoetin alfa regimens for 15 days, as follows: 40,000 IU once weekly, subcutaneously (group A) or intravenously (IV) (group B); 15,000 IU every other day, subcutaneously (group C) or IV (group D); or 40,000 IU day 1 and 3, subcutaneously (group E) or IV (group F), followed by 15,000 IU once every other day on [corrected] days 5-15 [corrected]. Serum erythropoietin concentration, absolute reticulocyte count, and adverse events.. Of the 60 patients who were enrolled (60% men, mean age 53 years, mean Acute Physiology and Chronic Health Evaluation II score, 19.5), 30 were evaluable for both pharmacokinetics and pharmacodynamics (50%). Erythropoietin exposure was approximately ten times greater for IV dosing than for subcutaneous dosing. Mean absolute reticulocyte count peaked at day 11 or 15 in each group and appeared to be greater for subcutaneous dosing (mean peak response 149-169 x 10(9)/L) compared with IV dosing (mean peak response 138-147 x 10(9)/L) at most visits. The most frequently reported adverse events were pyrexia (18%), hypokalemia (15%), and hypophosphatemia (15%).. In this study of anemic critically ill patients treated with epoetin alfa, all dosing regimens were well tolerated and appeared to effect reticulocytosis, with a peak at day 11 or 15 in most patients. The pharmacokinetics of epoetin alfa did not predict pharmacodynamic response in anemic critically ill patients.

Topics: Adult; Anemia; Critical Illness; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Recombinant Proteins

A randomized, double-blind, placebo-controlled, multicenter trial (EPO-2, N = 1,302) in anemic critically ill patients demonstrated a 29-day survival benefit in the trauma subgroup receiving epoetin alfa (mortality 8.9% vs. 4.1%). A second similarly designed trial (EPO-3, N = 1,460) confirmed this survival benefit in the epoetin alfa-treated trauma cohort (mortality 6.7% vs. 3.5%). This analysis presents trauma cohort data from both trials for evaluation of the impact of baseline factors including trauma-specific variables on outcomes.. Patients received 40,000 U epoetin alfa or placebo weekly, for a total of 4 (EPO-2) or 3 (EPO-3) doses, starting on ICU day 3. Kaplan-Meier survival curves for the two groups were compared using the log-rank test. Univariate and multivariate Cox proportional hazard regression methods were used to evaluate relationship between baseline factors and mortality.. Demographic and trauma variables at baseline were comparable. Mortality was consistently reduced by approximately 50% in both studies (EPO-2--day 29 unadjusted HR: 0.46, 95% CI: 0.24-0.89; EPO-3--day 29 unadjusted HR: 0.51, 95% CI: 0.27-0.98.). Adjusting for baseline and trauma variables had minimal effect on hazard ratios for mortality at day 29 (EPO-2--day 29 adjusted HR: 0.50, 95% CI: 0.26-0.97; EPO-3--day 29 adjusted HR: 0.38, 95% CI: 0.19-0.74) and day 140 (EPO-3--adjusted HR: 0.39, 95% CI: 0.21-0.72). In EPO-3, there appeared to be an increase in clinically relevant thrombovascular events in the epoetin alfa treated group (16.4% vs. 12.5%, RR: 1.3, 95% CI: 0.93-1.85) but not in EPO-2 (11.1% vs. 13.3%, RR: 0.84, 95% CI: 0.56-1.28).. Epoetin alfa demonstrated a survival advantage in both of the critically ill trauma patient cohorts of two prospective, randomized clinical trials, which was not affected by baseline factors including trauma-specific variables. A definitive study in trauma subjects is warranted.

Topics: Blood Transfusion; Comorbidity; Critical Illness; Double-Blind Method; Epoetin Alfa; Erythropoietin; Humans; Kaplan-Meier Estimate; Proportional Hazards Models; Recombinant Proteins; Wounds and Injuries

To compare the effectiveness of darbepoetin alfa with epoetin alfa (recombinant human erythropoietin [rHuEPO]) for achieving transfusion independence and increasing hemoglobin concentrations in critically ill patients.. Retrospective, descriptive study.. Level I trauma center intensive care units.. Seventy-two patients who spent at least 3 days in the cardio-thoracic, medical, or surgery-trauma intensive care units and received at least one weekly dose of rHuEPO 40,000 units (33 patients) or darbepoetin alfa 100 microg (39 patients).. Number of rHuEPO and darbepoetin alfa doses, hemoglobin concentrations, and cumulative number of transfusions were recorded for up to 28 days after the first dose was given, and the data were statistically analyzed. Beginning a median of 10 days after the patients were admitted to the intensive care unit, they received a median of 3.5 doses of darbepoetin alfa or 4 doses of rHuEPO. Mean hemoglobin concentrations at which treatment with darbepoetin alfa and rHuEPO were started were 8 and 8.2 g/dl, respectively (p=0.41). Transfusion independence was achieved in 44% of patients in the darbepoetin alfa group compared with 36% of patients in the rHuEPO group (p=0.63). Patients in both groups received a mean of 2.7 units of packed red blood cells during the 28-day study period. The mean change in hemoglobin levels from baseline over time did not significantly differ between groups (p=0.75).. Patients receiving darbepoetin alfa 100 microg/week and those receiving rHuEPO 40,000 units/week for anemia of critical illness achieved similar rates of transfusion independence and increases in hemoglobin concentrations from baseline at 28 days. Compared with previously published studies, erythropoietic agents were administered late in the course of critical illness in response to low hemoglobin concentrations.

Topics: Adult; Aged; Anemia; Blood Transfusion; Critical Care; Critical Illness; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Intensive Care Units; Iron Compounds; Male; Middle Aged; Recombinant Proteins; Retrospective Studies; Time Factors; Trauma Centers; Treatment Outcome

Anemia, which is common in the critically ill, is often treated with red-cell transfusions, which are associated with poor clinical outcomes. We hypothesized that therapy with recombinant human erythropoietin (epoetin alfa) might reduce the need for red-cell transfusions.. In this prospective, randomized, placebo-controlled trial, we enrolled 1460 medical, surgical, or trauma patients between 48 and 96 hours after admission to the intensive care unit. Epoetin alfa (40,000 U) or placebo was administered weekly, for a maximum of 3 weeks; patients were followed for 140 days. The primary end point was the percentage of patients who received a red-cell transfusion. Secondary end points were the number of red-cell units transfused, mortality, and the change in hemoglobin concentration from baseline.. As compared with the use of placebo, epoetin alfa therapy did not result in a decrease in either the number of patients who received a red-cell transfusion (relative risk for the epoetin alfa group vs. the placebo group, 0.95; 95% confidence interval [CI], 0.85 to 1.06) or the mean (+/-SD) number of red-cell units transfused (4.5+/-4.6 units in the epoetin alfa group and 4.3+/-4.8 units in the placebo group, P=0.42). However, the hemoglobin concentration at day 29 increased more in the epoetin alfa group than in the placebo group (1.6+/-2.0 g per deciliter vs. 1.2+/-1.8 g per deciliter, P<0.001). Mortality tended to be lower at day 29 among patients receiving epoetin alfa (adjusted hazard ratio, 0.79; 95% CI, 0.56 to 1.10); this effect was also seen in prespecified analyses in those with a diagnosis of trauma (adjusted hazard ratio, 0.37; 95% CI, 0.19 to 0.72). A similar pattern was seen at day 140 (adjusted hazard ratio, 0.86; 95% CI, 0.65 to 1.13), particularly in those with trauma (adjusted hazard ratio, 0.40; 95% CI, 0.23 to 0.69). As compared with placebo, epoetin alfa was associated with a significant increase in the incidence of thrombotic events (hazard ratio, 1.41; 95% CI, 1.06 to 1.86).. The use of epoetin alfa does not reduce the incidence of red-cell transfusion among critically ill patients, but it may reduce mortality in patients with trauma. Treatment with epoetin alfa is associated with an increase in the incidence of thrombotic events. (ClinicalTrials.gov number, NCT00091910 [ClinicalTrials.gov].).

Topics: Adult; Aged; Critical Illness; Double-Blind Method; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Intensive Care Units; Kaplan-Meier Estimate; Length of Stay; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Respiration, Artificial; Thrombosis; Trauma Severity Indices; Wounds and Injuries

To describe the erythropoietin pharmacokinetic profile after once-weekly epoetin alfa treatment in critically ill patients. Secondary objectives were to compare pharmacodynamic and safety profiles between active treatment and placebo in these patients.. Randomized, double-blind, placebo-controlled study.. Medical, surgical, or mixed medical/surgical intensive care units.. A total of 73 anemic critically ill adults with an expected stay of >3 days and a hematocrit value of <38%.. Patients were randomized 2:1 to epoetin alfa, 40,000 IU, administered subcutaneously once weekly (n=48) or matching placebo (n=25) for up to 4 wks.. Serum erythropoietin concentration and hematologic variables (percentage reticulocytes [RETI], hemoglobin [Hb], and total red blood cell [RBC] counts) were measured, and area under the serum concentration-time curve from time 0 to the last blood sampling time at time t (t: 120, 144, or 168 hrs) postdose (AUC0-Tlast) for these three variables was determined. Mean serum erythropoietin concentrations in placebo patients were slightly higher than typical physiologic levels of erythropoietin in healthy subjects, although not appropriate for the degree of anemia in these patients. Overall, exposure of endogenous erythropoietin in the placebo group (in terms of AUC0-Tlast) was only about 20% of exposure to exogenous erythropoietin in the epoetin alfa group. Baseline hemoglobin levels were the same in both groups (9.9 g/dL). Mean change in hemoglobin level from baseline through day 29 was 1.9 g/dL and 1.6 g/dL in the epoetin alfa and placebo groups, respectively. Mean AUC(RETI)0-Tlast was higher with epoetin alfa than with placebo and was related to the AUC of erythropoietin. There were no apparent differences in AUC(Hb)0-Tlast and AUC(RBC)0-Tlast between epoetin alfa and placebo groups, which was most likely due to bleeding and transfusion events. Epoetin alfa was safe and well tolerated, with a rate of treatment-emergent complications similar to that seen with placebo.. Epoetin alfa, once weekly, augmented the erythropoietic response in critically ill patients as indicated by the increased erythropoietin levels and larger AUC(RETI)0-Tlast in treated patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Critical Illness; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Count; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; Recombinant Proteins; Retrospective Studies; Treatment Outcome

To compare the erythropoietic responses and tolerability of two recombinant human erythropoietin (EPO) regimens.. Prospective, open-label, multicenter study.. Three multidisciplinary intensive care units in Québec, Canada.. Sixty critically ill patients.. The first 30 patients received EPO 40,000 U/week (group A); the next 30 received 40,000 U twice/week (group B).. Percent change from baseline in reticulocyte count and hemoglobin concentration were evaluated in both groups on study days 7 and 14. The numbers of adverse events were also compared between the two groups. No statistically significant differences were found in the results between the two groups.. Although the study had limitations, it suggested that EPO 40,000 U twice/week did not increase or sustain stimulation of the erythropoietic response compared with EPO 40,000 U/week in critically ill patients.

Topics: Aged; Critical Illness; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Pilot Projects; Recombinant Proteins; Reticulocyte Count

The effects of various covariate factors on the pharmacokinetics of erythropoietin (EPO) in subjects who are critically ill and admitted to an intensive care unit were evaluated. Nonlinear mixed-effects modeling was used to analyze the data from 48 patients receiving subcutaneous doses of 40,000 IU/wk epoetin alfa enrolled in a randomized, double-blind, placebo-controlled, multicenter study. The pharmacokinetics of EPO follows a 1-compartment disposition model with first-order absorption and an endogenous input rate. For a patient weighing 70 kg, the typical apparent clearance (CL/F) and apparent volume of distribution (V/F) were estimated to be 1.86 L/h and 27.8 L. The interindividual variability in CL/F and V/F was estimated to be 57.2% and 83.8%. CL/F and V/F of EPO increased with body weight, as described by the following relation: CL/F = (CL/F)std*(W/W(std))0.75, and V/F = (V/F)std*(W/W(std))1.37, where W is individual weight, and W(std) is the median weight of the study population. There was a 46% drop in exposure of EPO from the first to the subsequent dosing events. The endogenous EPO production rate was found to decrease progressively with the course of the study. In addition, the modeled endogenous EPO production rate increased with body weight. The net effect of this increase on the endogenous plasma EPO levels may not be significant because EPO clearance was found to increase with body weight. All other factors investigated (eg, Sequential Organ Failure Assessment [SOFA] scores and APACHE II scores) had no significant effect on EPO pharmacokinetics. The typical population estimate of CL/F of EPO was close to previously reported values in healthy volunteers.

Topics: Algorithms; Critical Care; Critical Illness; Double-Blind Method; Drug Administration Schedule; Drug Therapy; Epoetin Alfa; Erythropoietin; Female; Humans; Injections, Subcutaneous; Inpatients; Male; Middle Aged; Models, Biological; Multivariate Analysis; Recombinant Proteins

Topics: Aged; Anemia; Aortic Aneurysm, Abdominal; Blood Loss, Surgical; Critical Illness; Epoetin Alfa; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Iron Compounds; Jehovah's Witnesses; Male; Recombinant Proteins; Salvage Therapy

Recent randomized control trials (RCTs) suggest that epoetin alfa reduces mortality in critically ill trauma patients; however, epoetin alfa is also costly and associated with adverse events. This study evaluates the cost-effectiveness of epoetin alfa in surgical trauma patients in an intensive care unit setting.. We constructed a decision analytic model to compare adjunctive use of epoetin alfa with standard care in trauma patients from the perspective of a Canadian payer. Baseline risks of events, relative efficacy, and resource use were obtained from RCTs and observational studies. One-way and probabilistic sensitivity analyses were conducted and longer time horizons explored through Markov models.. Epoetin alfa was associated with a cost per quality-adjusted life year (QALY) gained of $89,958 compared with standard care at 1 year. One-way sensitivity analyses indicated that results were sensitive to plausible ranges of mortality risk, risk of thrombosis, relative risk of mortality, relative risk of thrombosis, and quality of life estimates. Cost-effectiveness acceptability curves generated from probabilistic sensitivity analysis indicated that the probability that epoetin alfa would be considered attractive ranged from 0% to 85% over a willingness-to-pay range of $25,000 to $120,000/QALY. Consideration of lifetime time horizons reduced the cost per QALY gained to $7,203, but results were sensitive to the effect of epoetin alfa on mortality.. Although the cost per QALY gained with epoetin alfa use may fall into an acceptable range, there is significant uncertainty about its true cost-effectiveness. If data regarding long-term efficacy and safety are confirmed in future trials, epoetin alfa could potentially be cost-effective in this population.. Economic analysis, level I.

Topics: Cost-Benefit Analysis; Critical Care; Critical Illness; Drug Costs; Epoetin Alfa; Erythropoietin; Humans; Models, Econometric; Monte Carlo Method; Recombinant Proteins; Risk

Topics: Anemia; Critical Illness; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins

Anemia is a common comorbid condition among patients admitted to the intensive care unit (ICU). Darbepoietin alfa and epoetin alfa are erythropoiesis-stimulating agents (ESAs) used to manage anemia in the ICU, although neither drug has an indication in critically ill patients.. This study describes ESA practice patterns in anemic, critically ill patients admitted to the ICU.. A total of 19 hospitals participated in this US multicenter, retrospective, observational study of adult patients not receiving chronic hemodialysis who were admitted to the ICU for >or=24 hours between February 2005 and September 2005 and who received >or=1 dose of darbepoietin alfa or epoetin alfa. Data on ESA doses, dosing frequencies, hemoglobin levels, and red blood cell (RBC) transfusions were abstracted from electronic medical records.. A total of 438 patients were included in the analysis, of whom 201 (46%) were treated with darbepoietin alfa and 237 (54%) were treated with epoetin alfa. In the respective groups, similar proportions were male (121/201 [60%] and 126/237 [53%]) and white (146/195 [75%] and 140/184 [76%]); age was also similar (mean [SD], 62 [19] and 60 [18] years). The mean (SD) dose during the first week of ICU stay was 96.5 (40.5) microg with darbepoietin alfa and 33,439 (23,508) U with epoetin alfa. The most commonly prescribed dosing frequency with darbepoietin alfa was once weekly (88.1% of all prescribed doses), with a mean (SD) number of injections of 1.8 (1.75). With epoetin alfa, the most common dosing frequencies were 3 times weekly (35.9%), 1-time dosing (28.5%), and once weekly (24.0%), with a mean (SD) number of injections of 2.9 (4.2). In both groups, the duration of therapy was

Topics: Adult; Aged; Aged, 80 and over; Anemia; Cohort Studies; Critical Illness; Darbepoetin alfa; Drug Utilization Review; Epoetin Alfa; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Patient Admission; Recombinant Proteins; Retrospective Studies; Time Factors; United States

Topics: Adrenal Cortex Hormones; Anemia; Critical Illness; Drug Interactions; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Receptors, Erythropoietin; Recombinant Proteins

Anemia of critical illness is common among intensive care unit patients. A blood management pilot program was initiated to study the pharmacodynamic response of epoetin alfa in critically ill patients and assess the impact of the use of a standardized order set of pharmaceuticals, including epoetin alfa and intravenous iron sucrose, on the quantity of red blood cell units transfused in the adult intensive care unit.. A pre-printed order set was developed which included baseline and follow-up laboratory monitoring and pharmaceutical options for iron, either intravenous and/or oral, folic acid, ascorbic acid, cyancobalamin, and weight-based epoietin alfa. Laboratory studies included: hemoglobin/hematocrit, reticulocyte count, absolute reticulocyte count, immature reticulocyte fraction obtained at baseline, and on day three and day five; in addition, iron, total iron binding capacity, transferrin saturation, and ferritin were obtained at baseline and on day five. An average hemoglobin response of 0.8 g/dL five days after administration of epoetin alfa was demonstrated in a diverse population of critically ill patients. Patients who received intravenous iron did not have a difference in mortality as compared to those patients who did not receive intravenous iron; however, there was a significantly longer length of stay. The cost of epoetin alfa was $64,000 over 10 months (approximately 8-10 patients/month). Transfusions of RBCs in adult intensive care unit decreased over the initial five months of the pilot study.. Use of erythropoiesis stimulating agents (ESAs) in the critically ill is controversial. Implementing a standardized approach in the pharmaceutical management of anemia in the critically ill patient is possible. Limitations with the order set and standardized protocol included errors in selection of dose/weight, incomplete laboratory/monitoring, and inconsistent prospective/concurrent review to guide therapy. The determination of the cost-effectiveness of epoetin alfa therapy in anemia of critical illness was not the purpose of this project, but will be the focus of future studies.

Topics: Adult; Aged; Anemia; Baltimore; Blood; Blood Chemical Analysis; Clinical Protocols; Critical Care; Critical Illness; Drug Costs; Drug Monitoring; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Outcome and Process Assessment, Health Care; Pilot Projects; Recombinant Proteins

Topics: Critical Illness; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Hemoglobins; Humans; Recombinant Proteins; Thrombosis; Wounds and Injuries

Topics: Absorption; Critical Illness; Epoetin Alfa; Erythropoietin; Humans; Injections, Intravenous; Injections, Subcutaneous; Recombinant Proteins

Topics: Critical Illness; Data Interpretation, Statistical; Epoetin Alfa; Erythropoietin; Humans; Kaplan-Meier Estimate; Proportional Hazards Models; Recombinant Proteins

Topics: Critical Illness; Data Interpretation, Statistical; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hemoglobins; Humans; Recombinant Proteins; Wounds and Injuries

Topics: Anemia; Critical Illness; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Humans; Iron; Recombinant Proteins

Topics: Anemia; Critical Illness; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Injections, Subcutaneous; Intensive Care Units; Postoperative Hemorrhage; Recombinant Proteins; Treatment Outcome

An evidence-based epoetin alfa protocol and a multidisciplinary blood-conservation program were implemented in a medical intensive care unit (MICU) and surgical intensive care unit (SICU).. Baseline data were collected to evaluate the use of epoetin alfa and red blood cell (RBC) transfusions in our MICU and SICU. An evidence-based protocol for epoetin alfa use and a multidisciplinary blood-conservation program were designed, approved, and implemented. Preprotocol patients consisted of a convenience sample of 18 patients receiving epoetin alfa for various indications who were admitted to our MICU and SICU from January 1 to December 31, 2002. The postprotocol sample consisted of 40 patients who received epoetin alfa for the treatment of anemia due to critical illness who were admitted to the MICU and SICU from March 25 to May 23, 2003. Postprotocol data were collected and compared with baseline data. All patients seen in the MICU and SICU, during the postprotocol period, regardless of whether they were receiving epoetin alfa, were included in the multidisciplinary blood-conservation program. Postprotocol data showed statistically significant improvements in epoetin alfa dosing and monitoring and in the use of adjunctive therapy. Pharmacist-initiated blood-conservation strategies resulted in several blood-draw reductions and discontinuations. Statistically significant reductions in the number of RBC units transfused per patient and per intensive care unit (ICU) day were also observed.. An epoetin alfa protocol and a multidisciplinary blood-conservation program contributed to rational prescribing of epoetin alfa and to a reduction in the number of RBC units transfused per patient and per ICU day.

Topics: Anemia; Blood Specimen Collection; Clinical Protocols; Critical Illness; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hospital Bed Capacity, 500 and over; Hospitals, University; Humans; Intensive Care Units; Male; Middle Aged; Program Development; Quality Assurance, Health Care; Recombinant Proteins