losartan-potassium and Critical-Illness

Sepsis-induced acute kidney injury (SI-AKI), a common critically ill, represents one of the leading causes of global death. Emerging evidence reveals autophagy as a pivotal modulator of SI-AKI. Autophagy affects the cellular processes of renal lesions, including cell death, inflammation, and immune responses. Herein, we conducted a systematic and comprehensive review on the topic of the proposed roles of autophagy in SI-AKI. Forty-one relevant studies were finally included and further summarized and analyzed. This review revealed that a majority of included studies (24/41, 58.5%) showed an elevation of the autophagy level during SI-AKI, while 22% and 19.5% of the included studies reported an inhibition and an elevation at the early stage but a declination of renal autophagy in SI-AKI, respectively. Multiple intracellular signaling molecules and pathways targeting autophagy (e.g. mTOR, non-coding RNA, Sirtuins family, mitophagy, AMPK, ROS, NF-Kb, and Parkin) involved in the process of SI-AKI, exerting multiple biological effects on the kidney. Multiple treatment modalities (e.g. small molecule inhibitors, temsirolimus, rapamycin, polydatin, ascorbate, recombinant human erythropoietin, stem cells, Procyanidin B2, and dexmedetomidine) have been found to improve renal function, which may be attributed to the elevation of the autophagy level in SI-AKI. Though the exact roles of autophagy in SI-AKI have not been well elucidated, it may be implicated in preventing SI-AKI through various molecular pathways. Targeting the autophagy-associated proteins and pathways may hint towards a new prospective in the treatment of critically ill patients with SI-AKI, but more preclinical studies are still warranted to validate this hypothesis.

Topics: Acute Kidney Injury; Autophagy; Critical Illness; Epigenesis, Genetic; Erythropoietin; Humans; Prospective Studies; Sepsis

Erythropoietin (EPO) is a 34kD pleiotropic cytokine that was first identified as being essential for red blood cell (RBC) production. It is now recognized however that EPO is produced by many tissues. It plays a key role in the modulation of the response to injury, inflammation, and tissue hypoxia via the inhibition of apoptosis. Large clinical trials in the critically ill failed to demonstrate a role for EPO as an RBC transfusion sparing agent; however, improved clinical outcomes, attributable to EPO role in tissue protection are observed in critically ill trauma patients. Further research to confirm or refute these observations is required.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Apoptosis; Cell Proliferation; Critical Illness; Erythrocyte Transfusion; Erythropoietin; Female; Humans; Male; Middle Aged; Wounds and Injuries

The aim was to investigate the efficacy and safety of erythropoietin (EPO) to prevent acute kidney injury (AKI) in patients with critical illness or perioperative care.. Randomized controlled trials comparing EPO with placebo for AKI prevention in adult patients with critical illness or perioperative care were searched in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Web of Science, and Clinical Trials.gov until October 2014. The outcomes of interest included the incidence of AKI, dialysis requirement, mortality, and adverse event. Fixed effect model was used to calculate the pooled risk ratio (RR) and 95% confidence interval (CI) for eligible studies.. Ten randomized controlled trials involving 2759 participants were identified and included in the analysis. Compared with placebo, EPO administration did not reduce the incidence of AKI (RR, 0.97; 95% CI, 0.79-1.19; P = 0.782), dialysis requirement (RR, 0.72; 95% CI, 0.31-1.70; P = 0.457), or mortality (RR, 0.96; 95% CI, 0.78-1.18; P = 0.705). Moreover, EPO had no effect on the risk of adverse events, but estimations of RR were difficult due to their relatively infrequent occurrence.. This meta-analysis suggests that prophylactic administration of EPO in patients with critical illness or perioperative care does not prevent AKI, dialysis requirement, or mortality.

Topics: Acute Kidney Injury; Adult; Aged; Critical Illness; Erythropoietin; Female; Humans; Incidence; Male; Middle Aged; Odds Ratio; Postoperative Complications; Preoperative Care; Randomized Controlled Trials as Topic; Renal Dialysis; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

This article describes the incidence and etiology of anemia in critically ill children. In addition, the article details the pathophysiology and clinical ramifications of anemia in this population. The use of transfused packed red blood cells as a therapy for anemia in critically ill patients is also discussed, including the indications for and complications associated with this practice as well as potential reasons for these complications. Finally, the article lists some therapeutic practices that may lessen the risks associated with transfusion, and briefly discusses the use of blood substitutes.

Topics: Acute Lung Injury; Anemia; Blood Substitutes; Blood Transfusion; Child; Child, Preschool; Critical Illness; Erythropoietin; Hemodilution; Humans; Immunomodulation; Infant; Infant, Newborn; Infant, Premature; Iron; Phlebotomy; Risk Factors; Transfusion Reaction; Treatment Outcome

Topics: Acute Lung Injury; Adult; Anemia; Blood Preservation; Blood Specimen Collection; Brain Injuries; Critical Illness; Erythrocyte Transfusion; Erythropoietin; Hemorrhage; Humans; Myocardial Ischemia; Nervous System Diseases; Sepsis; Shock; Stroke; Subarachnoid Hemorrhage

Erythropoietin (EPO) belongs to a group of pharmacological agents with multifunctional effects. EPO was originally acknowledged as the main regulator of erythropoiesis, but it also exhibits several extra haematopoietic properties, such as promoting the maintenance of homeostasis of cells under stress. These pleiotropic effects have been extensively investigated in preclinical models including models of ischaemic-reperfusions injuries, inflammation, neuroprotection, neovascularisation and wound healing. Promising effects of EPO have especially been reported in models of ischaemic-reperfusions injuries. The mechanisms by which EPO exerts these organ-protective effects are not completely understood, although anti-apoptotic, anti-inflammatory and anti-oxidative properties have been described. Activation of the EPO receptor initiates several intracellular signalling systems, such as, phosphatidylinositol 3-kinase, STAT5, mitogen-activated protein kinase and nuclear factor-kappa B. These pathways are recognized as involved in the cellular response to stress and regulation of apoptosis. Although EPO has been demonstrated to be effective in animal models, the effect has not been clearly demonstrated in clinical trials. This MiniReview gives a brief introduction to the pleiotropic effects of EPO, the evidence of organ protection in animal models, and discusses the disappointing results obtained from recent clinical trials.

Topics: Animals; Apoptosis; Critical Illness; Disease Models, Animal; Erythropoietin; Hematopoiesis; Humans; Immunomodulation; Neuroprotective Agents; Oxidative Stress; Randomized Controlled Trials as Topic; Receptors, Erythropoietin

Anemia is common in the intensive care unit, and may be associated with adverse consequences. However, current options for correcting anemia are not without problems and presently lack convincing efficacy for improving survival in critically ill patients. In this article we review normal red blood cell physiology; etiologies of anemia in the intensive care unit; its association with adverse outcomes; and the risks, benefits, and efficacy of various management strategies, including blood transfusion, erythropoietin, blood substitutes, iron therapy, and minimization of diagnostic phlebotomy.

Topics: Anemia; Critical Care; Critical Illness; Erythrocyte Transfusion; Erythrocytes; Erythropoietin; Hematinics; Humans; Intensive Care Units; Iron; Trace Elements

There is a high prevalence of anaemia among patients admitted to the intensive care unit (ICU), and it may have a negative effect on patient's outcome. The most common treatment for anaemia in the ICU patient is allogeneic blood transfusion (ABT), yet it has been found to be a risk factor associated with an increased risk of morbidity and mortality in critical care patients. As a reduction of erythropoietin secretion and action is observed in most ICU patients, the administration of (rHuEPO) has emerged as a therapeutic option. Unfortunately, the results from different studies show that rHuEPO treatment results in a small reduction of ABT requirements when "restrictive" transfusion criteria are applied, which has only been supported by three of the studies. Yet this did not result in a decreased mortality rate, except for patients with a diagnosis on admission of trauma in two studies, even though one study reported a dose-dependent increase of thrombotic vascular events among patients without thromboprophylaxis. Altogether, clinical data suggest a role for rHuEPO in the treatment of anaemia in trauma patients, especially in those sustaining neurotrauma, whereas for non-trauma patients without an approved indication, rHuEPO administration is an expensive approach, does not seem to improve outcome, and might result in serious adverse effects. Consequently, more basic and clinical studies are required to ascertain which patients are more likely to benefit from these treatments, as well as to identify the optimal doses and administration schedules, and iron administration.

Topics: Anemia; Critical Illness; Erythropoietin; Humans; Recombinant Proteins

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

Erythropoietin (Epo) is a peptide hormone that stimulates erythropoiesis. There are several agents in clinical use and in development that either act as ligands for the cell surface receptors of Epo or promote Epo production, which stimulates erythropoiesis. These are known as erythropoietic agents. The agents already in use include epoetin alfa, epoetin beta, and darbepoetin alfa. Newer agents under active investigation include continuous erythropoietin receptor activator (CERA) or proline hydroxylase inhibitors that increase hypoxia-inducible factor-1 (HIF-1), thereby stimulating Epo production and iron availability and supply. Erythropoietic agents have been shown to promote neuronal regeneration and to decrease post-stroke infarct size in mouse models. They have also been reported to shorten survival when used to treat anemia in many cancer patients and to increase thromboembolism. In contrast, rapid decrease of Epo levels as observed in astronauts and high-altitude dwellers upon rapid descent to sea level leads to the decrease of erythroid mass, a phenomenon known as "neocytolysis." The relative decrease in the serum Epo level is known to occur in some subjects with otherwise unexplained anemia of aging. Anemia by itself is a predictor of poor physical function in the elderly and is a significant economic burden on society. One out of every five persons in the United States will be elderly by 2050. Erythropoietic agents, by preventing and treating otherwise unexplained anemias of the elderly and anemia associated with other disease conditions of the elderly, have the potential to improve the functional capacity and to decrease the morbidity and mortality in the elderly, thereby alleviating the overall burden of medical care in society.

Topics: Aged; Anemia; Animals; Critical Illness; Erythropoiesis; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Mice; Peptides; Peptides, Cyclic; Polyethylene Glycols; Receptors, Erythropoietin; Recombinant Proteins

Blood transfusions and blood products are often given as a life-saving measure in patients with critical illness. However, some patients, such as Jehovah's Witnesses, may refuse their administration due to religious beliefs. Jehovah's Witnesses accept most available medical treatments, but not blood transfusions or blood products due to their religion's interpretation of several passages from the Bible. Since recombinant human erythropoietin (rHuEPO) became available, several cases have been reported in which rHuEPO was successfully administered to critically ill Jehovah's Witnesses. Administration of rHuEPO in combination with other blood conservation techniques has been shown to increase hemoglobin levels and survival in patients who experienced trauma, burns, general surgery, or gastrointestinal hemorrhage. We performed a literature search of the MEDLINE and International Pharmaceutical Abstracts databases of rHuEPO therapy in the Jehovah's Witness population. Fourteen cases were identified in which rHuEPO was administered to Jehovah's Witnesses who required the drug for critical care resuscitation as an alternative to blood products. In each clinical situation, rHuEPO enhanced erythropoiesis; however, time to the start of treatment, dosages, route of administration, and treatment duration varied widely. Supplementation with adjunctive agents, such as iron, folic acid, and vitamin B12, was also beneficial. Use of rHuEPO in Jehovah's Witnesses may provide an alternative to blood transfusions or blood products. Other alternatives, such as hemoglobin-based oxygen carriers and perfluorocarbons, are also being explored.

Topics: Blood Substitutes; Critical Care; Critical Illness; Erythropoietin; Female; Hemorrhage; Humans; Jehovah's Witnesses; Male; Middle Aged; Recombinant Proteins

Acute kidney injury (AKI) frequently occurs in critically ill patients and is an independent risk factor for poor outcome. The prevention of kidney injury in intensive care remains a great challenge as specific nephroprotective therapies are still lacking. The present review summarizes recent evidence for the use of erythropoietin as a promising candidate to provide protection from AKI.. Beyond the known hematopoietic actions of erythropoietin, a number of preclinical studies demonstrated that erythropoietin possesses pleiotropic, organ-protecting properties. Preconditional and postconditional erythropoietin treatment was shown to protect from ischemic, toxic and septic AKI. Despite heterogeneities in study design and dose, erythropoietin consistently ameliorated renal injury. The mechanisms of protection remain largely unclear but may involve reduction of apoptosis, induction of cellular proliferation and tissue repair as well as mobilization of stem cells.. Animal studies revealed a physiological basis for the use of erythropoietin in AKI, which may be clinically applicable to prevent AKI in critically ill patients, but clinical studies are still lacking.

Topics: Acute Kidney Injury; Adaptor Proteins, Signal Transducing; Carrier Proteins; Critical Illness; Erythropoietin; Hematopoiesis; Humans; Intracellular Signaling Peptides and Proteins; Recombinant Proteins; Ribonucleoproteins, Small Nuclear; Risk Factors; Tumor Suppressor Proteins

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 is a common condition among medical and surgical patients admitted to the intensive care unit (ICU) and generally has a multifactorial origin. In order to avoid the deleterious effects of anemia, 40% of ICU patients receive allogenic blood transfusion (ABT). This figure increases up to 70% if the ICU stay is longer than 7 days. However, ABT is associated with a dose-dependent increase in morbidity and mortality. In contrast, the administration of exogenous erythropoietin plus iron supplements, especially iv iron, improves anemia and reduces ABT requirements, although it does not reduce mortality. To ascertain whether treatment of anemia in the critically ill with exogenous erythropoietin and iron might improve outcomes and to optimize drug administration schedules and dosage, further studies with sufficient statistical power and adequate follow-up are warranted.

Topics: Anemia; Blood Transfusion; Critical Illness; Erythropoiesis; Erythropoietin; Humans; Injections, Intravenous; Iron; Prevalence; Recombinant Proteins

Simple, sensitive and specific predictors of mortality in the critically ill remain elusive goals, and brain natriuretic peptide and venous lactate are the subjects of recent studies. The role of vasopressin in sepsis continues to be the focus of much research interest. Dose ranging studies, potential adverse effects, and selective V1 agonists are discussed below in recent trials. Finally the use of erythropoietin in the critically ill continues to be studied but many continue to urge caution for widespread use outside of clinical trials.

Topics: Animals; Critical Illness; Erythropoietin; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Vasoconstrictor Agents; Vasopressins

Critically ill patients receive an extraordinarily large number of blood transfusions. Between 40% and 50% of all patients admitted to intensive care units (ICUs) receive at least one allogeneic red blood cell (RBC) unit and average close to 5 U of RBCs during their ICU admission. RBC transfusion is not risk-free, and there is little evidence that "routine" transfusion of stored allogeneic RBCs is beneficial to critically ill patients. It is clear that most critically ill patients can tolerate hemoglobin levels as low as 7 g/dL, and therefore, a more conservative approach to RBC transfusion is warranted. Anemia of critical illness is a distinct clinical entity characterized by blunted erythropoietin (EPO) production and abnormalities in iron metabolism identical to what is commonly referred to as anemia of chronic disease. As such, the bone marrow in many of these patients responds to the administration of exogenous EPO, in spite of their underlying critical illness. The efficacy of perioperative recombinant human erythropoietin (rHuEPO) has been demonstrated in a variety of elective surgical settings. Similarly, in critically ill patients, rHuEPO therapy will also stimulate erythropoiesis. In randomized placebo-controlled trials, therapy with rHuEPO resulted in a significant reduction in allogeneic RBC transfusions. Strategies to increase the production of RBCs are complementary to other approaches to reduce blood loss in the ICU and decrease the transfusion threshold in the management of all critically ill patients.

Topics: Anemia; Blood Loss, Surgical; Chronic Disease; Critical Illness; Elective Surgical Procedures; Erythrocyte Transfusion; Erythropoietin; Humans; Iron; Recombinant Proteins

To present information regarding the use of recombinant human erythropoietin (rHuEPO) to treat anemia in intensive care unit (ICU) patients. Anemia is common in critically ill patients. Approximately 95% of patients have subnormal hemoglobin (Hb) values by day 3 of their ICU stay. ICU-associated anemia often requires replacement of red blood cells (RBCs) via transfusion. Recent surveys of ICU practice document that approximately 50% of ICU patients receive RBC transfusions. ICU-associated anemia is largely the result of the cumulative effects of blood loss and decreased RBC production. Blood loss in critically ill patients may be overt, occult, or due to phlebotomy. Decreased RBC production is the other major factor influencing the development of anemia. Decreased RBC production is due to the combined effects of abnormal iron metabolism, inappropriately low erythropoietin production, diminished response to erythropoietin, and direct suppression of RBC production. Inflammatory mediators play a pivotal role in the pathogenesis of decreased RBC production. Clinical trials have shown that, compared with nontreated subjects, rHuEPO-treated ICU patients will have increased serum erythropoietin concentrations, increased reticulocyte counts, and increased hemoglobin and hematocrit values and require fewer RBC transfusions. These clinical trials have not detected significant differences in outcomes in association with rHuEPO, however.. rHuEPO can be used to increase hemoglobin and hematocrit values and decrease the number of RBC transfusions in ICU patients. Further investigation is necessary to identify the appropriate target population of ICU patients for treatment, to clarify the appropriate dosing schedule, and to ascertain whether such therapy has a positive impact on outcomes.

Topics: Anemia; Blood Component Transfusion; Critical Illness; Erythropoietin; Humans; Intensive Care Units; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: Anemia, Iron-Deficiency; Critical Illness; Dose-Response Relationship, Drug; Drug Monitoring; Erythropoiesis; Erythropoietin; Hematinics; Humans; Recombinant Proteins; Treatment Outcome

To review of the prevalence, pathogenesis, diagnosis, and management of iron (Fe)-related anemias in critical illness.. A MEDLINE/PubMed search from 1966 to October 2005 was conducted. References from relevant articles were manually cross-referenced with additional original articles, review articles, correspondence, and chapters from selected textbooks.. Both Fe metabolism and erythropoiesis are affected by the inflammatory response that accompanies critical illness. As a result, many critically ill patients develop the anemia of inflammation, which may be compounded by an underlying Fe deficiency. Most commonly available markers of total body Fe detect Fe deficiency unreliably in the setting of inflammation. Among these tests, the serum transferrin receptor assay is relatively accurate in reflecting total body Fe, regardless of inflammation. Treatment options for Fe-related anemias in critical illness include Fe replacement and recombinant human erythropoietin therapy. The decision to implement these therapies is complex and centers on a critical evaluation of ability to affect anemia, morbidity, and mortality in critical illness and on the potential risks of therapy.. Fe deficiency anemia and the anemia of inflammation may co-exist in critical illness. Diagnosis of and differentiation between these two anemias involves careful interpretation of multiple markers of total body Fe stores. The utility of treatment with both Fe and recombinant human erythropoietin for these disorders during critical illness requires further investigation.

Topics: Anemia, Iron-Deficiency; Critical Illness; Erythropoietin; Humans; Inflammation; Iron; Recombinant Proteins; Transferrin

Topics: Anemia; Critical Illness; Erythropoietin; Humans; Kidney Failure, Chronic; Recombinant Proteins; Treatment Outcome

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

Healthy individuals are able to tolerate profound, short-term decreases in hemoglobin levels and oxygen saturation without serious consequences, but critically ill patients in respiratory failure lack the necessary reserve capacity to preserve tissue oxygenation. The development of progressive anemia in ICU patients has led to much interest and debate about transfusion practices, yet optimal hemoglobin levels and how they should be achieved remain unclear. Animal and human studies regarding critical oxygen delivery provide the rationale for optimizing hemoglobin levels and supporting cardiovascular function during respiratory failure. Theoretically, the oxygen-carrying benefit of RBCs should hasten recovery from respiratory failure, and transfusions would therefore be expected to shorten the duration of mechanical ventilation. However, evidence to the contrary has been reported. Controversies related to transfusions and their inability to improve outcomes suggest that further research regarding transfusion alternatives is needed, especially in anemic patients with respiratory failure.

Topics: Anemia; Animals; Cell Hypoxia; Comorbidity; Critical Illness; Erythrocyte Transfusion; Erythropoietin; Humans; Oxygen; Oxygen Consumption; Respiration, Artificial; Respiratory Insufficiency; Risk Factors

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

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

Topics: Anemia; Blood Loss, Surgical; Critical Illness; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Humans; Inflammation; United States

Anemia may be the most common illness of critically ill patients. The majority of critically ill patients are anemic at admission to the intensive care unit (ICU), and hemoglobin concentrations typically decline during the first 3 days of ICU stay. Hemoglobin continues to decline for patients with sepsis and higher severity of illness. This patient population may be at particular risk of adverse consequences of anemia given the cardiovascular, respiratory, and metabolic compromise frequently encountered during critical illness. The etiology of anemia of critical illness is multifactorial, resulting from phlebotomy, gastrointestinal bleeding, coagulation disorders, blood loss from vascular procedures, renal failure, nutritional deficiencies,bone marrow suppression, and impaired erythropoietin response.

Topics: Anemia; Blood Substitutes; Critical Care; Critical Illness; Erythrocyte Transfusion; Erythropoietin; Hemostatics; Humans; Phlebotomy; Point-of-Care Systems

Review the literature regarding the use of recombinant human erythropoietin (rHuEPO) to prevent red blood cell (RBC) transfusion in critically ill patients.. 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.. 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.. 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.

Topics: Critical Illness; Erythropoietin; Humans; Randomized Controlled Trials as Topic; Recombinant Proteins

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

Anaemia is a common problem in critically ill patients admitted to intensive care units. Many factors can be involved in its development, including rapid alterations of iron metabolism. Maintenance of iron homeostasis is a prerequisite for many essential biological processes and a central element for the development of erythroid precursors and mature red blood cells. With the inflammatory process, iron distribution is disturbed, with decreased serum iron levels and increased iron stores. Little information is available on the precise role of alterations of iron metabolism in the development of iron anaemia in critically ill patients.

Topics: Anemia; Critical Illness; Erythrocyte Transfusion; Erythrocytes; Erythropoietin; Homeostasis; Humans; Inflammation; Intensive Care Units; Iron

Erythropoiesis usually fails during severe illness because of a blunting of the kidney-erythropoietin (EPO)-bone marrow axis. In this setting, clinical studies have shown that recombinant human erythropoietin (rhEPO), administered in pharmacological amounts, significantly reduces the need for blood transfusions. In addition to the kidney, however, EPO is also produced locally by other tissues in a paracrine-autocrine manner. Here, similar to its role in the bone marrow, EPO rescues cells from apoptosis. Additionally, EPO reduces inflammatory responses, restores vascular autoregulation, and promotes healing. The results of many studies (including a phase II clinical trial in ischemic stroke) demonstrate that rhEPO protects the brain, spinal cord, retina, heart, and kidney from ischemic and other types of injury. Although rhEPO is efficacious in the treatment of EPO-deficient anemia during illness, inadequate effort has been devoted to determining whether direct tissue protection might also result from its administration. Here, we speculate on the potential utility of EPO as a protective cytokine in the context of acute critical illness and suggest key parameters required for a proof-of-concept clinical study.

Topics: Apoptosis; Blood Cell Count; Bone Marrow; Critical Care; Critical Illness; Cytokines; Erythropoietin; Humans; Inflammation; Recombinant Proteins

Critically ill patients frequently develop anemia due to several factors. Iron-withholding mechanisms caused by inflammation contribute to this anemia. The iron metabolism imbalances described or reported in all intensive care studies are similar to the values observed in anemia of inflammation. The administration of iron could be useful in the optimization of recombinant human erythropoietin activity, but this could be at the expense of bacterial proliferation. Since there is a lack of evidence to support either oral or intravenous iron administration in intensive care patients, further studies are necessary to determine the efficacy and safety of iron supplementation in conjunction with recombinant human erythropoietin in critically ill patients. We review the mechanisms leading to iron sequestration in the presence of inflammation. The present article also reviews the literature describing the iron status in critically ill patients and explores the role of iron supplementation in this setting.

Topics: Anemia; Critical Care; Critical Illness; Dietary Supplements; Erythropoiesis; Erythropoietin; Ferritins; Humans; Inflammation; Intensive Care Units; Iron; Recombinant Proteins

The transfusion of red blood cells is still associated with possible adverse effects and a residual risk of transmission of viral and nonviral diseases. In addition, there is an increasing shortage of blood supply worldwide. These two facts together with the success experienced in the treatment of various types of anemia with recombinant human EPO, have recently led to an increasing interest in the anemia of critically ill patients. As in the anemia of chronic diseases there are several reasons that contribute to the development of anemia in patients on intensive care units: pre-existing anemia, blood loss, reduced red cell life span, impaired iron availability and a direct inhibition of erythropoiesis by inflammatory cytokines. The implications of anemia for the progression and prognosis of critical illness are still unclear and the optimal treatment, including optimal "transfusion triggers" remains controversial. Recombinant human EPO has been proven to be effective in ameliorating the anemia of critical illness in several pilot studies and is currently being tested in larger trials.

Topics: Adult; Anemia; Blood Loss, Surgical; Child; Critical Care; Critical Illness; Cytokines; Double-Blind Method; Drug Therapy, Combination; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Hemoglobins; Humans; Iron Compounds; Jehovah's Witnesses; Middle Aged; Multicenter Studies as Topic; Pilot Projects; Placebos; Randomized Controlled Trials as Topic; Recombinant Proteins; Reticulocyte Count; Time Factors; Transfusion Reaction

The use of recombinant human erythropoietin (rHuEpo) has revolutionized anemia management of early and late stages of chronic kidney disease. Darbopoietin is also now available for the treatment of anemia of chronic kidney disease. In addition, rHuEpo has been used for the treatment of anemia observed in critical illness. Unfortunately, the existing clinical studies of anemia in critically ill patients do not distinguish between those with and without acute renal failure (ARF). This review summarizes the existing experimental and clinical studies supporting the use of rHuEpo in ARF due to ischemic/nephrotoxic injury and conclusions are drawn on the rationale for further research into the use of this drug in ARF.

Topics: Acute Kidney Injury; Anemia; Animals; Critical Illness; Erythropoietin; Humans; Recombinant Proteins

Anaemia is a common finding in critically ill patients. There are often multiple causes. Obvious causes include surgical bleeding and gastrointestinal haemorrhage but many patients have no overt bleeding episodes. Phlebotomy can be a significant source of blood loss. In addition, critically ill patients have impaired erythropoiesis as a consequence of blunted erythropoietin production and direct inhibitory effects of inflammatory cytokines. The ability of a patient to tolerate anaemia depends on their clinical condition and the presence of any significant co-morbidity; maintenance of circulating volume is of paramount importance. There is no universal transfusion trigger. Current guidelines for critically ill and perioperative patients advise that at Hb values <70 g/L red blood cell transfusion is strongly indicated and at Hb values >100 g/L transfusion is unjustified. For patients with Hb values in the range 70 to 100 g/L the transfusion trigger should be based on clinical indicators. Most stable critically ill patients can probably be managed with a Hb concentration between 70 and 90 g/L. Uncertainties exist concerning the most appropriate Hb concentration for patients with significant cardio-respiratory disease.

Topics: Anemia; Critical Illness; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Humans; Recombinant Proteins

Although anemia is apparently tolerated in most patients, particularly those who are relatively healthy, the ICU population must be thought of differently. Anemia in the ICU may be due to acute blood loss, phlebotomy, or to the presence of inflammatory disease. The anemia in critically ill patients resembles anemia of chronic disease, which is believed to result from a poor endogenous erythropoietin response or erythropoietin deficiency. The risks of blood transfusions are many and ICU patients may not tolerate infusions of older, stored blood. Nonetheless, hemoglobin levels at or above 100 g/L may be important for oxygen delivery to vital organs, especially in critically ill patients with increased oxygen demands. The appropriate transfusion trigger for critically ill patients in this setting remains unknown. Blood transfusions in the ICU may not improve outcomes, and numerous studies have been published to suggest the contrary, that transfusions may actually worsen patients' outcomes in certain ICU settings. Recombinant human erythropoietin (rHuEPO, epoetin alfa) has been shown to reduce transfusion needs and increase hemoglobin levels in multiple settings and now, it appears to also do so in the ICU.

Topics: Anemia; Critical Care; Critical Illness; Erythropoietin; Humans; Risk; Transfusion Reaction

To review the literature concerning the role of recombinant human erythropoietin (rHuEPO) in reducing the need for transfusion in critically ill patients.. Articles were obtained through searches of the MEDLINE database (from 1990 to June 2001) using the key words erythropoietin, epoetin alfa, anemia, reticulocytes, hemoglobin, critical care, intensive care, critical illness, and blood transfusion. Additional references were found in the bibliographies of the articles cited. The Cochrane library was also consulted.. Controlled, prospective, and randomized studies on the use of rHuEPO in critically ill adults were selected.. Anemia is a common complication in patients requiring intensive care. It is caused, in part, by abnormally low concentrations of endogenous erythropoietin and is mainly seen in patients with sepsis and multiple organ dysfunction syndrome, in whom inflammation mediator concentrations are often elevated. High doses of rHuEPO produce a rapid response in these patients, despite elevated cytokine concentrations. There have been 3 studies on rHuEPO administration in intensive care and 1 trial in acutely burned patients. Only 2 of these studies looked at the impact of rHuEPO administration on the need for transfusion.. Few randomized, controlled trials explore the role of rHuEPO in critical care. Only 1 was a large, randomized clinical trial, but it presents many limitations. Future outcome and safety studies comparing rHuEPO with placebo must include clinical endpoints such as end-organ morbidity, mortality, transfusion criteria, and pharmacoeconomic analysis. rHuEPO appears to provide an erythropoietic response. Optimal dosage and the real impact of rHuEPO on the need for transfusion in intensive care remain to be determined. Currently, based on the evidence available from the literature, rHuEPO cannot be recommended to reduce the need for red blood cell transfusions in anemic, critically ill patients.

Topics: Anemia; Blood Transfusion; Critical Care; Critical Illness; Erythropoietin; Humans; Randomized Controlled Trials as Topic; Recombinant Proteins

The prospect of a shortage of blood for transfusions, increasing awareness of the adverse effects of transfusions, and the availability of human recombinant erythropoietin (rHuEPO) have stimulated interest in the pathogenesis of the anaemia of intensive care unit (ICU) patients. As in the anaemia of chronic illness or chronic renal failure (CRF), the anaemia of ICU patients is a multifactorial process. Blood loss, inappropriately low erythropoietin production, reduced red cell lifespan, reduced iron availability, and inhibition of erythropoiesis by cytokines all contribute to the anaemia of critical illness, although the contributions of the various elements differ depending on the disease aetiology. Evidence is accumulating that use of rHuEPO can induce stimulation of erythropoiesis in critical illness, but at doses that are usually several-fold higher than those used to define resistance to rHuEPO in the current guidelines for the management of anaemia in CRF. Available data suggest that these high doses are well tolerated, at least in the short term. These observations, as well as demonstrating the potential benefits of rHuEPO therapy in critically ill patients, have practical implications for non-ICU patients with CRF who do not respond sufficiently to the usual doses of rHuEPO. Although the risk-benefit ratio relationship for very high doses of rHuEPO needs further consideration, demonstration of rHuEPO efficacy in critical illness should result in a re-evaluation of the 'dose-response relationship' for rHuEPO in patients with less acute and severe illness, including CRF patients hyporesponsive to current dosing regimens.

Topics: Anemia; Critical Care; Critical Illness; Drug Resistance; Erythropoietin; Humans; Recombinant Proteins

Anemia is a frequent finding in patients treated in ICUs and results in a high number of red blood cell transfusions. Many patients are already admitted to ICUs with subnormal hemoglobin values. Surgery, frequent phlebotomies and overt bleeding episodes are obvious reasons for continuous blood loss during the ICU stay. However, these causes are usually not sufficient to explain the total blood consumption of critically ill patients, which may amount to several liters. Reduced red cell life span and occult gastrointestinal bleeding are possibly important contributory factors. Irrespective of the cause the erythropoietic response to anemia is severely blunted, as a consequence of an inappropriate increase in erythropoietin production, diminished iron availability and direct inhibitory effects of inflammatory cytokines. The importance of anemia for the course and outcome of critically ill patients and its optimal therapy remain to be defined. Considering red blood cell transfusions recent evidence indicates that a target range of 7-9 g/dl hemoglobin is at least as safe and may even be superior compared to a more liberal transfusion strategy. However, the optimal transfusion trigger in relation to patient comorbidity requires further investigation. Rigorous strategies of blood conservation may help to avoid transfusions. Red blood cell substitutes and recombinant erythropoietin are promising treatment options that are currently under investigation.

Topics: Anemia; Blood Transfusion; Clinical Trials as Topic; Critical Care; Critical Illness; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Hemoglobins; Humans; Iatrogenic Disease; Inflammation Mediators; Iron; Length of Stay; Prospective Studies; Recombinant Proteins; Risk Factors; Time Factors

Topics: Anemia; Animals; Brain Injuries; Cardiac Output, Low; Critical Illness; Erythropoietin; Gene Expression Regulation; Genetic Therapy; Humans; Kidney Diseases

Anemia is a common clinical problem in critically ill patients and is associated with substantial red blood cell (RBC) transfusion requirements. However, RBC transfusion has significant risks, including adverse effects on the immune system. Although a low hemoglobin concentration may be tolerable, it may not be optimal for the critically ill patient. Thus, alternative therapies that can increase hemoglobin and avoid complications of RBC transfusion are desirable. Critically ill patients appear to have anemia identical to the anemia of chronic inflammatory disease with blunted erythropoietin production. Results of a recent randomized controlled trial in critically ill patients demonstrated that recombinant human erythropoietin (r-HuEPO, epoetin alfa) significantly reduced (by approximately 50%) the number of RBC units transfused (P <.002) and significantly increased hematocrit (P <.01) compared with placebo. There was no increase in mortality or adverse clinical events with therapy. Epoetin alfa may be an effective therapeutic approach to anemia in critically ill patients, decreasing the need for transfusion and achieving higher hemoglobin concentrations than generally attained with transfusion.

Topics: Anemia; Animals; Critical Illness; Erythrocyte Transfusion; Erythropoietin; Hemoglobins; Humans; Recombinant Proteins

Topics: Blood Transfusion; Critical Illness; Erythropoietin; Hemoglobins; Humans; Phlebotomy; Risk Factors

The Erythropoietin in Traumatic Brain Injury (EPO-TBI) trial aims to determine whether the administration of erythropoietin to patients with moderate or severe traumatic brain injury improves patient-centred outcomes.. EPO-TBI is a multicentre, blinded, randomised, parallel groups, placebo-controlled, phase III superiority trial of erythropoietin in ICU patients with traumatic brain injury conducted in Australia and New Zealand, Saudi Arabia and Europe; 606 critically ill patients aged 15 to 65 years with moderate or severe acute traumatic brain injury will be enrolled. Trial patients will receive either 40,000 IU erythropoietin or placebo by subcutaneous injection administered weekly for up to three doses during their ICU admission. The primary outcome measure is the proportion of unfavourable neurological outcomes, comprising death or severe disability, observed at 6 months following randomisation utilizing the Extended Glasgow Outcome Scale. Secondary outcomes, also assessed at 6 months following randomisation, include the probability of an equal or greater Extended Glasgow Outcome Scale level, mortality, the proportions of patients with proximal deep venous thrombosis or with composite thrombotic vascular events, as well as assessment of quality of life and cost-effectiveness. The planned sample size will allow 90% power to detect a reduction from 50% to 36% in unfavourable neurological outcomes at a two-sided alpha of 0.05.. A detailed analysis plan has been developed for EPO-TBI that is consistent with international guidelines. This plan specifies the statistical models for evaluation of primary and secondary outcomes, as well as defining covariates for adjusted analyses. Application of this statistical analysis plan to the forthcoming EPO-TBI trial will facilitate unbiased analyses of these important clinical data.. Australian New Zealand Clinical Trials Registry: ACTRN12609000827235 (22 September 2009). ClinicalTrials.gov: NCT00987454 (29 September 2009). European Drug Regulatory Authorities Clinical Trials: 2011-005235-22 (18 January 2012).

Topics: Adolescent; Adult; Aged; Australia; Brain Injuries; Clinical Protocols; Cost-Benefit Analysis; Critical Illness; Data Interpretation, Statistical; Disability Evaluation; Drug Administration Schedule; Drug Costs; Erythropoietin; Europe; Female; Humans; Injections, Subcutaneous; Injury Severity Score; Male; Middle Aged; Models, Statistical; Neuroprotective Agents; New Zealand; Prospective Studies; Quality of Life; Recovery of Function; Research Design; Saudi Arabia; Time Factors; Treatment Outcome; Young Adult

Treatment of renal anemia with erythropoietic stimulating agents sometimes increases blood pressure. It is uncertain whether this is due to direct vasoconstriction and/or increased red blood cell mass.. We conducted a post-hoc analysis of 160 critically ill patients in the EARLYARF trial with elevated urinary γ-glutamyltranspeptidase and alkaline phosphatase, indicating acute kidney injury. Patients received 2 doses of intravenous (i.v.) epoetin (500 U/kg), 24 hours apart, or placebo, in a randomized, double-blind study design. Hourly intra-arterial mean arterial pressure (MAP), and norepinephrine equivalent dose (NED: determined using equipotency conversion factors for doses of epinephrine, vasopressin, phenlyephrine, or dopamine) were extracted from clinical records. The differences between baseline and maximum MAP and NED (ΔMAP and ΔNED) over 4, 24, 72-hour, and 30-day periods following study drug administration were compared between groups.. At baseline, MAP was 78 ± 14 mmHg in the epoetin group and 81 ± 15 mmHg in the placebo group (p = 0.22). There were no differences between groups in ΔMAP (6 ± 14 versus 7 ± 14 mmHg; p = 0.53), in ΔNED, or in ΔMAP adjusted for ΔNED at 4 hours, or at any time points. A subgroup analysis of only those patients not requiring vasopressor support (n = 71) also showed no differences between epoetin and placebo for all outcomes.. We concluded that intravenous high dose epoetin does not acutely increase blood pressure, suggesting no acute vasoconstrictor effect in this setting.

Topics: Acute Kidney Injury; Adult; Aged; Blood Pressure; Critical Illness; Double-Blind Method; Erythropoietin; Female; Humans; Male; Middle Aged; Recombinant Proteins; Retrospective Studies

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

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.. 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).. A prospective, randomized, double-blind, placebo-controlled, multiple-center trial.. Two long-term acute care facilities.. A total of 86 patients who met eligibility criteria were enrolled in the study with 42 randomized to rHuEPO and 44 to placebo.. 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.. 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.. 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.. 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.

Topics: Aged; Anemia; Critical Illness; Double-Blind Method; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Iron; Length of Stay; Logistic Models; Long-Term Care; Male; Prospective Studies; Recombinant Proteins; Reticulocyte Count

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

Critically ill children with bronchiolitis often require red blood cell transfusions. Anemia normally results in increased circulating erythropoietin concentrations; however, critical illness has been associated with a blunted erythropoietin response. Treatment with erythropoietin decreases the need for red blood cell transfusion in several disease states. We hypothesized that critically ill children with bronchiolitis and anemia would have a circulating erythropoietin deficiency and that treatment with exogenous erythropoietin would increase reticulocyte count and hematocrit and reduce red blood cell transfusion requirements.. Randomized, blinded, placebo-controlled trial.. Children's hospital.. Critically ill children with bronchiolitis, anemia, and respiratory failure. Anemia was defined as a hematocrit >2 SD below normal for age.. Patients were randomized to one of two groups. In the erythropoietin group, patients received daily intravenous erythropoietin. In the control group, patients received daily intravenous placebo. Both groups were treated with elemental iron.. Blood for complete blood count, reticulocyte count, and ferritin and erythropoietin concentration was obtained at admission and discharge. Red blood cell transfusions were administered to patients with a persistent oxygen requirement and a hematocrit of <25%. Outcome variables included number of red blood cell transfusions, change in reticulocyte count, ferritin values, and circulating erythropoietin values between groups. Forty-four patients completed the study (mean 3.1 +/- 0.6 months), with a baseline hematocrit of 27.6 +/- 0.5%, ventilator days of 8.2 +/- 0.6, and pediatric intensive care unit length of stay of 9.8 +/- 0.6 days. There were no significant baseline demographic differences between the control and erythropoietin groups. Ten of 22 (45%) children in the erythropoietin group required red blood cell transfusion compared with 11 of 22 (50%) in the control group (p = nonsignificant). The increase in reticulocyte count was greater in the erythropoietin group compared with the control group (2.1 +/- 0.3% to 4.7 +/- 0.7%, p = .003 vs. 2.1 +/- 0.3% to 2.7 +/- 0.5%, p = nonsignificant).. Despite a favorable reticulocyte and circulating erythropoietin response, red blood cell transfusion requirements were not significantly diminished by erythropoietin treatment in children with bronchiolitis and respiratory failure. Erythropoietin cannot be routinely recommended for this patient population.

Topics: Anemia; Blood Transfusion; Bronchiolitis; Chi-Square Distribution; Critical Illness; Erythropoietin; Female; Humans; Infant; Male; Respiratory Insufficiency; Treatment Outcome

In a prospective observational study, we examined the temporal relationships between serum erythropoietin (EPO) levels, haemoglobin concentration and the inflammatory response in critically ill patients with and without acute renal failure (ARF).. Twenty-five critically ill patients, from general and cardiac intensive care units (ICUs) in a university hospital, were studied. Eight had ARF and 17 had normal or mildly impaired renal function. The comparator group included 82 nonhospitalized patients with normal renal function and varying haemoglobin concentrations. In the patients, levels of haemoglobin, serum EPO, C-reactive protein, IL-1beta, IL-6, serum iron, ferritin, vitamin B12 and folate were measured, and Coombs test was performed from ICU admission until discharge or death. Concurrent EPO and haemoglobin levels were measured in the comparator group.. EPO levels were initially high in patients with ARF, falling to normal or low levels by day 3. Thereafter, almost all ICU patients demonstrated normal or low EPO levels despite progressive anaemia. IL-6 exhibited a similar initial pattern, but levels remained elevated during the chronic phase of critical illness. IL-1beta was undetectable. Critically ill patients could not be distinguished from nonhospitalized anaemic patients on the basis of EPO levels.. EPO levels are markedly elevated in the initial phase of critical illness with ARF. In the chronic phase of critical illness, EPO levels are the same for patients with and those without ARF, and cannot be distinguished from noncritically ill patients with varying haemoglobin concentrations. Exogenous EPO therapy is unlikely to be effective in the first few days of critical illness.

Topics: Acute Kidney Injury; Acute-Phase Reaction; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Transfusion; Critical Illness; Erythropoietin; Female; Hemoglobins; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Outpatients; Prospective Studies; Reference Values; Time

Anemia is common in critically ill patients and results in a large number of red blood cell (RBC) transfusions. Recent data have raised the concern that RBC transfusions may be associated with worse clinical outcomes in some patients.. To assess the efficacy in critically ill patients of a weekly dosing schedule of recombinant human erythropoietin (rHuEPO) to decrease the occurrence of RBC transfusion.. A prospective, randomized, double-blind, placebo-controlled, multicenter trial conducted between December 1998 and June 2001.. A medical, surgical, or a medical/surgical intensive care unit (ICU) in each of 65 participating institutions in the United States.. A total of 1302 patients who had been in the ICU for 2 days and were expected to be in the ICU at least 2 more days and who met eligibility criteria were enrolled in the study; 650 patients were randomized to rHuEPO and 652 to placebo.. Study drug (40 000 units of rHuEPO) or placebo was administered by subcutaneous injection on ICU day 3 and continued weekly for patients who remained in the hospital, for a total of 3 doses. Patients in the ICU on study day 21 received a fourth dose.. The primary efficacy end point was transfusion independence, assessed by comparing the percentage of patients in each treatment group who received any RBC transfusion between study days 1 and 28. Secondary efficacy end points identified prospectively included cumulative RBC units transfused per patient through study day 28; cumulative mortality through study day 28; change in hemoglobin from baseline; and time to first transfusion or death.. Patients receiving rHuEPO were less likely to undergo transfusion (60.4% placebo vs 50.5% rHuEPO; P<.001; odds ratio, 0.67; 95% confidence interval [CI], 0.54-0.83). There was a 19% reduction in the total units of RBCs transfused in the rHuEPO group (1963 units for placebo vs 1590 units for rHuEPO) and reduction in RBC units transfused per day alive (ratio of transfusion rates, 0.81; 95% CI, 0.79-0.83; P =.04). Increase in hemoglobin from baseline to study end was greater in the rHuEPO group (mean [SD], 1.32 [2] g/dL vs 0.94 [1.9] g/dL; P<.001). Mortality (14% for rHuEPO and 15% for placebo) and adverse clinical events were not significantly different.. In critically ill patients, weekly administration of 40 000 units of rHuEPO reduces allogeneic RBC transfusion and increases hemoglobin. Further study is needed to determine whether this reduction in RBC transfusion results in improved clinical outcomes.

Topics: Anemia; APACHE; Critical Illness; Double-Blind Method; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Respiration, Artificial; Treatment Outcome

The purpose of this article was to determine the prevalence of iron, vitamin B12, and folate deficiency and to evaluate the erythropoietin (EPO) response to anemia in a cohort of long-term intensive care unit (ICU) patients.. All patients admitted to three academic medical center multidisciplinary ICUs were screened for eligibility into a randomized trial of EPO for the treatment of ICU anemia. On their second or third ICU day, patients enrolled in this trial had EPO levels drawn and were screened for iron, B12, and folate deficiency. Weekly EPO levels were obtained throughout patients' ICU stay.. A total of 184 patients were screened for iron, B12, and folate deficiency. Sixteen patients (9%) were iron deficient by study criteria, 4 (2%) were B12 deficient, and 4 (2%) were folate deficient. Mean hemoglobin and reticulocyte percents of the remaining 160 patients were 10.3 +/- 1.2 g/dL and 1.66 +/- 1.09%, respectively. In most patients, serum iron and total iron binding capacity levels were very low, whereas ferritin levels were very high. Mean and median day 2 EPO levels were 35.2 +/- 35.6 mIU/mL and 22.7 mIU/mL, respectively (normal = 4.2-27.8). Serial EPO levels in most persistently anemic patients remained within the normal range.. In this cohort, screening for iron, B12, and folate deficiency identified potentially correctable abnormalities in more than 13% of patients and should be considered in those who are anticipated to have long ICU stays. Even at an early point of critical illness, most patients had iron studies consistent with anemia of chronic disease (ACD), as well as a blunted EPO response that may contribute to this ACD-like anemia of critical illness.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; APACHE; Cohort Studies; Critical Illness; Deficiency Diseases; Erythropoiesis; Erythropoietin; Female; Folic Acid; Humans; Intensive Care Units; Iron; Iron Deficiencies; Male; Middle Aged; Recombinant Proteins; Vitamin B 12

Critically ill patients often are anemic, which may impair oxygen delivery. Transfusion of red cells and supplementation with vitamins or iron are the usual therapeutic strategies, whereas only sporadic data are available on the use of epoetin alfa in these patients. We investigated endogenous erythropoietin (EPO) production and the response to epoetin alfa in anemic intensive care unit (ICU) patients.. Randomized, open trial.. Multidisciplinary ICU in a single secondary care center.. Thirty-six critically ill patients admitted to the ICU who became anemic (hemoglobin concentration, <11.2 g/dL or <12.1 g/dL in case of cardiac disease) were randomized to one of three study groups.. All patients received folic acid (1 mg) daily. The control group received no additional therapy, the iron group received 20 mg of iron saccharate intravenously (iv) daily for 14 days. The EPO group received iv iron and epoetin alfa (300 IU/kg) subcutaneously on days 1, 3, 5, 7, and 9.. Blood and reticulocyte counts were measured daily for 22 days. Serum EPO, C-reactive protein, serum transferrin receptor, and iron variables were measured on days 0, 2, 6, 10, and 21. Blood loss and red cell transfusions were recorded. Serum EPO concentrations were inappropriately low for the degree of anemia at baseline, with no difference between patients with and without renal failure. Exogenous administration of EPO increased EPO concentrations from 23+/-13 to a maximum of 166+/-98 units/L on day 10 (p < .05). Reticulocyte count increased exclusively in the EPO group from 56+/-33 x 10(9)/L to a maximum of 189+/-97 on day 13 (p < .05). Serum transferrin receptor rose only in the EPO group from 3.7+/-1.4 to 8.6+/-3.1 mg/L on day 10 (p < .05) and remained elevated on day 21, indicating an increase in erythropoiesis. Hemoglobin concentration and platelet count remained identical in the three study groups.. Endogenous EPO concentrations are low in critically ill patients. The bone marrow of these patients is able to respond to exogenous epoetin alfa, as shown by elevated concentrations of reticulocytes and serum transferrin receptors.

Topics: Adult; Aged; Aged, 80 and over; Critical Illness; Erythropoiesis; Erythropoietin; Female; Humans; Intensive Care Units; Iron; Male; Middle Aged; Prospective Studies; Recombinant Proteins

To determine whether the administration of recombinant human erythropoietin (rHuEPO) to critically ill patients in the intensive care unit (ICU) would reduce the number of red blood cell (RBC) transfusions required.. A prospective, randomized, double-blind, placebo-controlled, multicenter trial.. ICUs at three academic tertiary care medical centers.. A total of 160 patients who were admitted to the ICU and met the eligibility criteria were enrolled in the study (80 into the rHuEPO group; 80 into the placebo group).. Patients were randomized to receive either rHuEPO or placebo. The study drug (300 units/kg of rHuEPO or placebo) was administered by subcutaneous injection beginning ICU day 3 and continuing daily for a total of 5 days (until ICU day 7). The subsequent dosing schedule was every other day to achieve a hematocrit (Hct) concentration of >38%. The study drug was given for a minimum of 2 wks or until ICU discharge (for subjects with ICU lengths of stay >2 wks) up to a total of 6 wks (42 days) postrandomization.. The cumulative number of units of RBCs transfused was significantly less in the rHuEPO group than in the placebo group (p<.002, Kolmogorov-Smirnov test). The rHuEPO group was transfused with a total of 166 units of RBCs vs. 305 units of RBCs transfused in the placebo group. The final Hct concentration of the rHuEPO patients was significantly greater than the final Hct concentration of placebo patients (35.1+/-5.6 vs. 31.6+/-4.1; p<.01, respectively). A total of 45% of patients in the rHuEPO group received a blood transfusion between days 8 and 42 or died before study day 42 compared with 55% of patients in the placebo group (relative risk, 0.8; 95% confidence interval, 0.6, 1.1). There were no significant differences between the two groups either in mortality or in the frequency of adverse events.. The administration of rHuEPO to critically ill patients is effective in raising their Hct concentrations and in reducing the total number of units of RBCs they require.

Topics: Critical Illness; Double-Blind Method; Erythrocyte Transfusion; Erythropoietin; Female; Hematocrit; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Survival Rate; Treatment Outcome

Topics: Angiotensin-Converting Enzyme 2; COVID-19; Critical Illness; Erythropoietin; Extracellular Traps; Hemoglobin Subunits; Humans; Immunity, Innate; Neutrophils; Reactive Oxygen Species; RNA Viruses; SARS-CoV-2

Topics: Adult; Anemia; Blood Transfusion; Critical Care; Critical Illness; Erythropoietin; Humans

Topics: COVID-19; Critical Illness; Erythropoietin; Humans; Recombinant Proteins; SARS-CoV-2

An 80-year-old man with multiple comorbidities presented to the emergency department with tachypnea, tachycardia, fever, and critically low O

Topics: Aged, 80 and over; Anemia; Antiviral Agents; Betacoronavirus; Biomarkers; Clinical Laboratory Techniques; Convalescence; Coronavirus Infections; COVID-19; COVID-19 Testing; Critical Illness; Erythropoietin; Fever; Humans; Iran; Male; Pandemics; Pneumonia, Viral; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; SARS-CoV-2; Tachycardia; Tachypnea; Tomography, X-Ray Computed; Treatment Outcome

Topics: Adult; Anemia; Critical Care; Critical Illness; Erythropoietin; Humans; Medicine

Blood transfusions in anemic patients frequently are used for critically ill patients as a life-saving therapeutic maneuver. Jehovah's Witness (JW) patients typically refuse blood transfusions due to religious beliefs. Numerous clinical reports, in a wide spectrum of medical specialties, have shown no greater morbidity or mortality in JW patients or others who refused transfusions compared to those patients who accept transfusions. We report our experience with two JW patients who presented with severe anemia and life-threatening pancreatitis. Despite undergoing percutaneous drainages by interventional radiology (IR) for complex pancreatic collections (and other IR drainages), neither patient suffered any adverse effect from the IR procedures, even though they refused blood transfusions. Our experience suggests that IR procedures also may be successful with this more limited blood product protocol.

Topics: Adult; Anemia; Anti-Bacterial Agents; Critical Illness; Drainage; Erythropoietin; Female; Humans; Jehovah's Witnesses; Male; Middle Aged; Pancreatitis; Radiology, Interventional; Recombinant Proteins; Religion and Medicine; Tomography, X-Ray Computed; Treatment Outcome; Treatment Refusal

Associations among inflammatory cytokines, erythropoietin (EPO), and anemia in critically ill septic patients remain unclear. This study tested the hypothesis that elevated inflammatory cytokines and decreased EPO would be associated with iron-restricted anemia while accounting for operative blood loss, phlebotomy blood loss, and red blood cell (RBC) transfusion volume.. Prospective observational cohort study of 42 critically ill septic patients was conducted. Hemoglobin (Hb) at sepsis onset and hospital discharge were used to calculate ΔHb. Operative blood loss, phlebotomy blood loss, and RBC transfusion volume were used to calculate adjusted ΔHb (AdjΔHb) assuming that 300 mL RBC is equal to 1 g/dL Hb. Patients with AdjΔHb of greater than 0 (positive AdjΔHb, n = 18) were compared with patients with AdjΔHb of less than or equal to 0 (negative AdjΔHb, n = 24).. Plasma tumor necrosis factor α, granulocyte colony-stimulating factor, interleukin (IL)-6, IL-8, EPO, erythrocyte mean corpuscular volume, and serum transferrin receptor were measured on days 0, 1, 4, 7, and 14. Patients with negative AdjΔHb had significantly higher day 14 levels of IL-6 (37.4 vs. 15.2 pg/mL, p < 0.05), IL-8 (39.1 vs. 18.2 pg/mL, p = 0.01), and granulocyte colony-stimulating factor (101.3 vs. 60.5 pg/mL, p = 0.01), but not EPO. On linear regression analysis, lower AdjΔHb was associated with higher day 14 levels of IL-6 (r = 0.22, p < 0.01), IL-8 (r = 0.10, p = 0.04), stromal cell-derived factor 1 (r = 0.14, p = 0.02), and tumor necrosis factor α (r = 0.13, p = 0.02), but not EPO. Patients with negative AdjΔHb had significantly lower mean corpuscular volume on days 4 (89.6 vs. 93.2 fL/cell, p = 0.04), 7 (92.3 vs. 94.9 fL/cell, p = 0.04), and 14 (92.1 vs. 96.0 fL/cell, p = 0.03) but similar serum transferrin receptor levels.. Persistent elevation of inflammatory cytokines was associated with iron-restricted anemia among critically ill septic patients, occurring in the absence of systemic iron deficiency, independent of endogenous EPO.. Prognostic study, level II.

Topics: Aged; Anemia; Critical Illness; Cytokines; Erythropoietin; Female; Humans; Inflammation; Male; Middle Aged; Prospective Studies; Sepsis

Topics: Anemia; Critical Illness; Erythropoietin; Humans; Iron

Hemorrhagic shock (HS) still has a high mortality rate and none of the known resuscitative regimens completely reverse its adverse outcomes. This study investigated the effects of different models of resuscitative therapy on the healing of organ damage in a HS model. Male Wistar rats were randomized into six groups: Sham, without HS induction; HS, without resuscitation; HS+Blood, resuscitation with the shed blood; HS+Blood+NS, resuscitation with blood and normal saline; HS+Blood+RL, resuscitation with blood and Ringer's lactate; EPO, erythropoietin was added to the blood and RL. Blood and urine samples were obtained 3 h after resuscitation. Kidney, liver and brain tissue samples were harvested for multiple organ failure evaluation. Survival rate was the highest in the Sham, EPO and HS+Blood+RL groups compared to others. Plasma creatinine concentration, ALT, AST, urinary NAG activity and renal NGAL mRNA expression significantly increased in the HS+Blood+RL group compared to the Sham group. There was a significant increase in tissue oxidative stress markers and pro-inflammatory cytokines in HS+Blood+RL group compared to the Sham rats. EPO had more protective effects on multiple organ failure compared to the HS+Blood+RL group. EPO, as a resuscitative treatment, attenuated HS-induced organ damage. It seems that it has a potential to be attractive for clinical trials.

Topics: Animals; Anti-Inflammatory Agents; Critical Illness; Dose-Response Relationship, Drug; Erythropoietin; Male; Models, Animal; Multiple Organ Failure; Oxidative Stress; Rats; Rats, Wistar; Resuscitation; Severity of Illness Index; Shock, Hemorrhagic; Treatment Outcome; Viscera

Erythropoietin (EPO) production is stimulated by hypoxia in the kidney. Ischaemic injury plays a crucial role in the pathogenesis of acute kidney injury (AKI). However, EPO concentrations in critically ill patients complicated with AKI have not been evaluated sufficiently. This study was conducted to clarify the factors associated with plasma EPO concentrations in AKI.. This study prospectively enrolled 98 critically ill adult patients treated at the adult mixed ICU. Plasma EPO, insulin-like growth factor-binding protein-1 (IGFBP-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-6 (IL-6) and urinary N-acetyl-β-D-glucosaminidase (NAG) were measured on ICU admission.. Acute kidney injury occurred in 42 (42.9%) patients. Significantly higher plasma EPO in the AKI group was detected than in the non-AKI group (16.13 (9.87-28.47) mIU/mL versus 27.81 (10.16-106.02) mIU/mL, P < 0.05). Plasma IGFBP-1 in the AKI group was also significantly higher than in the non-AKI group (19 208 (8820-50 780) pg/mL versus 63 199 (25 289-147 489) pg/mL, P < 0.05). Plasma EPO concentration was negatively correlated with haemoglobin in the non-AKI group with statistical significance, but not in the AKI group. Multiple logistic regression analysis revealed that plasma EPO in the AKI group was associated significantly with plasma IGFBP-1 and complication of diabetes mellitus, but not the haemoglobin concentration, partial pressure of arterial oxygen (PaO2 ), and IL-6.. Not low arterial oxygen tension, haemoglobin concentration, and inflammation evaluated by IL-6 but plasma IGFBP-1 was significantly associated with plasma EPO concentration in AKI, suggesting an unknown mechanism related to systemic stress conditions for EPO regulation in AKI.

Topics: Acute Kidney Injury; Adult; Aged; Biomarkers; Case-Control Studies; Chi-Square Distribution; Critical Illness; Erythropoietin; Female; Humans; Insulin-Like Growth Factor Binding Protein 1; Logistic Models; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prospective Studies; Up-Regulation

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

In recent years, several safety alerts have questioned or restricted the use of some pharmacological alternatives to allogeneic blood transfusion in established indications. In contrast, there seems to be a promotion of other alternatives, based on blood products and/or antifibrinolytic drugs, which lack a solid scientific basis. The Multidisciplinary Autotransfusion Study Group and the Anemia Working Group España convened a multidisciplinary panel of 23 experts belonging to different healthcare areas in a forum for debate to: 1) analyze the different safety alerts referred to certain transfusion alternatives; 2) study the background leading to such alternatives, the evidence supporting them, and their consequences for everyday clinical practice, and 3) issue a weighted statement on the safety of each questioned transfusion alternative, according to its clinical use. The members of the forum maintained telematics contact for the exchange of information and the distribution of tasks, and a joint meeting was held where the conclusions on each of the items examined were presented and discussed. A first version of the document was drafted, and subjected to 4 rounds of review and updating until consensus was reached (unanimously in most cases). We present the final version of the document, approved by all panel members, and hope it will be useful for our colleagues.

Topics: Anemia; Antifibrinolytic Agents; Aprotinin; Blood Coagulation Factors; Blood Transfusion; Clinical Trials as Topic; Critical Illness; Crystalloid Solutions; Erythropoietin; Hematinics; Hemorrhage; Humans; Hydroxyethyl Starch Derivatives; Iron; Isotonic Solutions; Meta-Analysis as Topic; Observational Studies as Topic; Plasma Substitutes; Recombinant Proteins; Tranexamic Acid; Transfusion Reaction

Erythropoietin (EPO) is a glycoprotein hormone produced predominantly in the kidneys. The protective effect of exogenous EPO in hypoxic-ischemic brain injury has been thoroughly examined in neonates. However, the metabolism of endogenous EPO in neonates remains unclear.. We aimed to evaluate the concentration of urinary EPO (uEPO) in critically ill neonates and to identify possible clinical and laboratory variables that may be associated with uEPO levels.. The concentrations of EPO, cystatin-C, microalbumin, and α1-microglobulin in the first available urine sample during the initial 72 h of life were measured in 103 critically ill neonates. Clinical and laboratory data were collected for each neonate.. There was a positive correlation between uEPO levels and urinary levels of cystatin-C (r = 0.265, p = 0.008), microalbumin (r = 0.422, p < 0.001), and α1-microglobulin (r = 0.421, p < 0.001). The concentration of uEPO was elevated in neonates who developed acute kidney injury (AKI) during the first week of life compared with those without AKI (p = 0.002) and was also elevated in neonates with brain injury, as demonstrated by ultrasound or magnetic resonance imaging, compared to neonates without brain injury (p = 0.008). An increased log10 uEPO level was associated with the occurrence of AKI (OR 2.70, p = 0.007) and brain injury (OR 2.33, p = 0.016).. An increased urinary EPO level in the early postnatal period is significantly associated with kidney and brain injury in critically ill neonates.

Topics: Acute Kidney Injury; Albuminuria; Alpha-Globulins; Biomarkers; Brain Injuries; Critical Illness; Cystatin C; Erythropoietin; Female; Humans; Infant, Newborn; Linear Models; Logistic Models; Magnetic Resonance Imaging; Male; Multivariate Analysis; Odds Ratio; Predictive Value of Tests; Prognosis; Risk Factors; Time Factors; Ultrasonography, Doppler, Transcranial; Up-Regulation

To investigate the relation between the need for red blood cell transfusion and serum levels of soluble-Fas, erythropoietin and inflammatory cytokines in critically ill patients with and without acute kidney injury.. We studied critically ill patients with acute kidney injury (n=30) and without acute kidney injury (n=13), end-stage renal disease patients on hemodialysis (n=25) and healthy subjects (n=21). Serum levels of soluble-Fas, erythropoietin, interleukin 6, interleukin 10, iron status, hemoglobin and hematocrit concentration were analyzed in all groups. The association between these variables in critically ill patients was investigated.. Critically ill patients (acute kidney injury and non-acute kidney injury patients) had higher serum levels of erythropoietin than the other groups. Hemoglobin concentration was lower in the acute kidney injury patients than in other groups. Serum soluble-Fas levels were higher in acute kidney injury and end-stage renal disease patients. Critically ill patients requiring red blood cell transfusions had higher serum levels of soluble-Fas (5,906±2,047 and 1,920±1,060; p<0.001), interleukin 6 (518±537 and 255+502; p=0.02) and interleukin 10 (35.8±30.7 and 18.5±10.9; p=0.02), better iron status and higher mortality rates in the first 28 days in intensive care unit. Serum soluble-Fas levels were independently associated with the number of red blood cell units transfused (p=0.02). Serum soluble-Fas behaved as an independent predictor of the need for red blood cell transfusion in critically ill patients (p=0.01).. Serum soluble-Fas level is an independent predictor of the need for red blood cell transfusion in critically ill patients with or without acute kidney injury. Further studies are warranted to reconfirm this finding.

Topics: Acute Disease; Adult; Biomarkers; Case-Control Studies; Critical Illness; Enzyme-Linked Immunosorbent Assay; Erythrocyte Transfusion; Erythropoietin; fas Receptor; Female; Humans; Interleukins; Male; Middle Aged

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

There is a plethora of experimental data on the potential therapeutic benefits of recombinant human erythropoietin (rhEPO) and its synthetic derivatives in critical care medicine, in particular in ischemia/reperfusion injury. Most of the recent clinical trials have not shown clear benefits, and, in some patients, EPO-aggravated morbidity and mortality was even reported. Treatment with rhEPO has been successfully used in patients with anemia resulting from chronic kidney disease, but even a subset of this patient population does not adequately respond to rhEPO therapy. The following viewpoint uses rhEPO as an example to highlight the possible pitfalls in current practice using young healthy animals for the evaluation of therapies to treat patients of variable age and underlying chronic co-morbidity.

Topics: Acute Kidney Injury; Animals; Clinical Trials as Topic; Critical Illness; Drug Resistance; Erythropoietin; Humans; Models, Animal; Recombinant Proteins; Renal Insufficiency, Chronic; Reperfusion Injury

Recent data demonstrate a possible mortality benefit in traumatically injured patients when given subcutaneous recombinant human erythropoietin (rhEPO). The purpose of this report is to examine the effect of rhEPO on mortality and transfusion in burn patients. We conducted a review of burn patients (greater than 30% total body surface area, intensive care unit [ICU] days greater than 15) treated with 40,000 u rhEPO over an 18-month period (January 2007 to July 2008). Matched historical controls were identified and a contemporaneous cohort of subjects not administered rhEPO was used for comparison (NrhEPO). Mortality, transfusions, ICU and hospital length of stay were assessed. A total of 105 patients were treated (25 rhEPO, 53 historical control group, 27 NrhEPO). Hospital transfusions (mean 13,704 +/- mL vs. 13,308 +/- mL; P = 0.42) and mortality (29.6 vs. 32.0%; P = 0.64) were similar. NrhEPO required more blood transfusions (13,308 +/- mL vs. 6827 +/- mL; P = 0.004). No difference in mortality for the rhEPO and NrhEPO (32.0 vs. 22.2%; P = 0.43) was found. Thromboembolic complications were similar in all three groups. No effect was seen for rhEPO treatment on mortality or blood transfusion requirements in the severely burned.

Topics: Adolescent; Adult; Anemia; Blood Transfusion; Burns; Critical Illness; Erythropoietin; Female; Humans; Injury Severity Score; Length of Stay; Male; Middle Aged; Recombinant Proteins; Young Adult

The aim of this study was to investigate the effect of human recombinant erythropoietin (EPO) on the microcirculation and oxygenation of critically ischemic tissue and to elucidate the role of endothelial NO synthase in EPO-mediated tissue protection. Island flaps were dissected from the back skin of anesthetized male Syrian golden hamsters including a critically ischemic, hypoxic area that was perfused via a collateralized vasculature. Before ischemia, animals received an injection of epoetin beta at a dose of 5,000 U/kg body weight with (n = 7) or without (n = 7) blocking NO synthase by 30 mg/kg body weight L-NAME (Nomega-nitro-L-arginine methyl ester hydrochloride). Saline-treated animals served as control (n = 7). Ischemic tissue damage was characterized by severe hypoperfusion and inflammation, hypoxia, and accumulation of apoptotic cell nuclei after 5 h of collateralization. Erythropoietin pretreatment increased arteriolar and venular blood flow by 33% and 37%, respectively (P < 0.05), and attenuated leukocytic inflammation by approximately 75% (P < 0.05). Furthermore, partial tissue oxygen tension in the ischemic tissue increased from 8.2 to 15.8 mmHg (P < 0.05), which was paralleled by a 21% increased density of patent capillaries (P < 0.05) and a 50% reduced apoptotic cell count (P < 0.05). The improved microcirculation and oxygenation were associated with a 2.2-fold (P < 0.05) increase of endothelial NO synthase protein expression. Of interest, L-NAME completely abolished all the beneficial effects of EPO pretreatment. Our study demonstrates that, in critically ischemic and hypoxic collateralized tissue, EPO pretreatment improves tissue perfusion and oxygenation in vivo. This effect may be attributed to NO-dependent vasodilative effects and anti-inflammatory actions on the altered vascular endothelium.

Topics: Animals; Cricetinae; Critical Illness; Erythropoietin; Humans; In Vitro Techniques; Ischemia; Male; Mesocricetus; Microcirculation; Nitric Oxide Synthase; Oxygen; Recombinant Proteins; Regional Blood Flow; Surgical Flaps

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

Anemia commonly affects critically ill patients. The causes are multifactorial and include acute blood loss, blood loss from diagnostic testing and blunted red blood cell production. Blood transfusions are frequently given to patients in intensive care units to treat low hemoglobin levels due to either acute blood loss or subacute anemia associated with critical illness. Although blood transfusion is a life-saving therapy, evidence suggests that it may be associated with an increased risk of morbidity and mortality. A number of blood conservation strategies exist that may mitigate anemia in hospital patients and limit the need for transfusion. These strategies include the use of hemostatic agents, hemoglobin substitutes and blood salvage techniques, the reduction of blood loss associated with diagnostic testing, the use of erythropoietin and the use of restrictive blood transfusion triggers. Strategies to reduce blood loss associated with diagnostic testing and the use of hemostatic agents and erythropoietin result in higher hemoglobin levels, but they have not been shown to reduce the need for blood transfusions or to improve clinical outcomes. Lowering the hemoglobin threshold at which blood is transfused will reduce the need for transfusions and is not associated with increased morbidity or mortality among most critically ill patients without active cardiac disease. Further research is needed to determine the potential roles for other blood conservation strategies.

Topics: Anemia; Blood Substitutes; Critical Illness; Deamino Arginine Vasopressin; Diagnostic Tests, Routine; Erythrocyte Transfusion; Erythropoietin; Factor VIIa; Hemostatics; Humans; Risk Factors

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

Topics: Aged; Anemia; APACHE; Critical Illness; Erythropoietin; Hematinics; Humans; Iron; 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: Anemia; Critical Illness; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans

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

Topics: Anemia; Critical Illness; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Intensive Care Units; Randomized Controlled Trials as Topic; Recombinant Proteins

Further work on the use of albumin in the intensive care unit is discussed. The interesting pilot study by Dubois and colleagues examines the potential benefits for albumin supplementation in the hypoalbuminaemic critically ill patient. Maintaining the fluid theme, we discuss recent work on factors influencing post-intensive care unit blood transfusion as well as another study on erythropoietin. Finally, a large multicentred trial comparing continuous venovenous haemofiltration with intermittent haemodialysis is outlined, the results of which pose more questions than answers.

Topics: Albumins; Blood Transfusion; Critical Illness; Erythropoietin; Fluid Therapy; Hemofiltration; Humans; Hypoalbuminemia; Renal Dialysis

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

To calculate the absolute risk reduction of transfusion-related adverse events, the number of patients needed to treat, and cost to avoid one transfusion-related adverse event by using erythropoietin in critically ill patients. Number needed to treat with sensitivity analysis.. Teaching hospital.. Hypothetical cohort of critically ill patients who were candidates to receive erythropoietin.. Using vs. not using erythropoietin to reduce the need for packed red blood cell transfusions.. We used published estimates of known transfusion risks: transfusion-related acute lung injury, transfusion-related errors, hepatitis B and C, human immunodeficiency virus, human T-cell lymphotropic virus, and bacterial contamination, stratified by severity. Based on the estimated risk and frequency of transfusions with and without erythropoietin, we calculated the absolute risk reduction of transfusion-related adverse events, the number needed to treat, and cost to avoid one transfusion-related adverse event by using erythropoietin. The estimated incidence of transfusion-related adverse event was 318 permillion units transfused for all transfusion-related adverse events, 58 per million for serious transfusion-related adverse events, and 21 per million for likely fatal transfusion-related adverse events. The routine use of erythropoietin resulted in an absolute risk reduction of 191 per million for all transfusion-related adverse events, 35 per million for serious transfusion-related adverse events, and 12 per million for likely fatal transfusion-related adverse events. The number needed to treat was 5,246 to avoid one transfusion-related adverse event, 28,785 to avoid a serious transfusion-related adverse event, and 81,000 for a likely fatal transfusion-related adverse event. The total cost was $4,700,000 to avoid one transfusion-related adverse event, $25,600,000 to avoid one serious transfusion-related adverse event, and $71,800,000 to avoid a likely fatal transfusion-related adverse event. The magnitude of these results withstood extensive sensitivity analysis.. From the perspective of avoidance of adverse events, erythropoietin does not appear to be an efficient use of limited resources for routine use in critically ill patients.

Topics: Bacterial Infections; Blood Group Incompatibility; Blood Transfusion; Cost-Benefit Analysis; Critical Illness; Erythropoietin; Health Care Costs; Humans; Incidence; Medical Errors; Morbidity; Pharmacoepidemiology; Recombinant Proteins; Risk; Transfusion Reaction; United States; Virus Diseases

Topics: Blood Transfusion; Cost-Benefit Analysis; Critical Illness; Erythropoietin; Health Care Costs; Humans; Morbidity; Recombinant Proteins; Transfusion Reaction; United States

Complex cardiac surgery often requires blood transfusion. Some patients refuse transfusion, even when it is potentially life-threatening to do so. Although recombinant human erythropoietin (rhEPO) has been used to reduce the need for blood transfusion, it has been considered ineffective in critically ill patients. The time course of hematological responses in a Jehovah's Witness patient with acute renal failure and severe cardiac disease suggests that a trial of rhEPO should be considered for salvage therapy in critically ill patients.. The authors describe successful treatment of life-threatening anemia using recombinant human erythropoietin in a critically ill Jehovah's Witness patient after cardiac surgery.

Topics: Acute Kidney Injury; Blood Cell Count; Cardiac Surgical Procedures; Critical Care; Critical Illness; Erythropoietin; Female; Heart Diseases; Heart Valve Prosthesis Implantation; Humans; Jehovah's Witnesses; Middle Aged; Recombinant Proteins

Recombinant human erythropoietin (EPO) is used widely to treat anemia in patients with chronic kidney disease, but the benefits of EPO use in patients with acute renal failure (ARF) are unclear. In vitro and animal studies suggest that EPO may promote renal recovery and decrease mortality in ARF.. We conducted a retrospective cohort study at a tertiary-care center to evaluate the use of EPO in 187 critically ill patients with ARF requiring renal replacement therapy.. Compared with patients not administered EPO (n = 116), patients administered EPO (n = 71) were significantly more likely to have baseline chronic kidney disease, have undergone vascular surgery, and have received intermittent hemodialysis, rather than continuous renal replacement therapy. In a propensity-adjusted analysis that controlled for differences between the 2 cohorts and baseline hemoglobin level, EPO use did not decrease the transfusion of packed red blood cells. Renal recovery was not more common in patients administered EPO: the odds ratio for renal recovery in the propensity-adjusted analysis was 0.63 (95% confidence interval, 0.30 to 1.3) with EPO use. In-hospital survival was more common in the EPO-treated group, but this potential benefit was not significant in propensity-adjusted analyses.. Although EPO use was not associated with a decrease in transfusion requirements or with renal recovery in our retrospective study, 37% of critically ill patients with ARF were treated with EPO at varying doses. A randomized controlled trial is needed to evaluate the potential benefits of EPO use in patients with ARF.

Topics: Acute Kidney Injury; Adult; Aged; Anemia; APACHE; Cohort Studies; Comorbidity; Critical Care; Critical Illness; Drug Evaluation; Erythrocyte Transfusion; Erythropoietin; Female; Hospital Mortality; Humans; Male; Middle Aged; Missouri; Postoperative Complications; Recombinant Proteins; Renal Dialysis; Renal Replacement Therapy; Retrospective Studies; Risk Factors; Treatment Outcome; Vascular Surgical Procedures

During sepsis the endocrine, immune and nervous systems elaborate a multitude of biological responses. Little is known regarding the mechanisms responsible for the final circulating erythropoietin (EPO) and renin levels in septic shock. The aim of the present study was to assess the role of EPO and renin as biological markers in patients with septic shock.. A total of 44 critically ill patients with septic shock were evaluated.. Nonsurvivors had significantly higher serum EPO levels than did survivors on admission (median [minimum-maximum]; 61 [10-602] versus 20 [5-369]). A negative relationship between serum EPO and blood haemoglobin concentrations was observed in the survivor group (r = -0.61; P < 0.001). In contrast, in the nonsurvivors the serum EPO concentration was independent of the blood haemoglobin concentration. Furthermore, we observed significant relationships between EPO concentration and lactate (r = 0.5; P < 0.001), arterial oxygen tension/fractional inspired oxygen ratio (r = -0.41; P < 0.005), arterial pH (r = -0.58; P < 0.001) and renin concentration (r = 0.42; P < 0.005). With regard to renin concentration, significant correlations with lactate (r = 0.52; P < 0.001) and arterial pH (r = -0.33; P < 0.05) were observed.. Our findings show that EPO and renin concentrations increased in patients admitted to the intensive care unit with septic shock. Renin may be a significant mediator of EPO upregulation in patients with septic shock. Further studies regarding the regulation of EPO expression are clearly warranted.

Topics: Aged; Biomarkers; Critical Illness; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Hemoglobins; Humans; Intensive Care Units; Interleukin-6; Lactic Acid; Male; Middle Aged; Renin; Shock, Septic; Survivors

Erythropoietin (EPO) has been in clinical use for the treatment of anemia for over 15 years. Recently it has been demonstrated that EPO has actions other than stimulating the bone marrow. It has been suggested that due to its tissue protecting effect, EPO may be effective in improving outcome in the critically ill.

Topics: Apoptosis; Critical Care; Critical Illness; Erythropoietin; Humans; Recombinant Proteins; Treatment Outcome

To analyze whether erythropoietin treatment increases hemoglobin and decreases transfusion requirements in critically ill children.. We performed an observational, prospective study of 23 critically ill children aged between 1 month and 6 years. Recombinant human eritropoietin (rHuEPO) was administered at a dosage of 150-750 U/kg/week over 3 days. Hemogram, reticulocyte, iron metabolism, serum ferritin and transferrin were measured before treatment started and weekly thereafter.. After erythropoietin treatment, hematocrit, hemoglobin and red blood cells progressively increased, with a maximal response in the sixth week. At the end of treatment, hemoglobin increased 1.68 g/dl, hematocrit by 5 % and erythrocytes 600,000/ml/mm3. Transfusion requirements decreased from 59 transfusions at baseline to 12 in the first week of treatment and none from the sixth week. No treatment-related adverse effects were observed.. Erythropoietin can be an effective treatment for anemia in some critically ill children, decreasing the number of transfusions and increasing hemoglobin.

Topics: Anemia; Child; Child, Preschool; Critical Illness; Erythropoietin; Female; Humans; Infant; Male; Prospective Studies

Topics: Blood Transfusion; Critical Illness; Erythropoietin; Humans; Recombinant Proteins; Surgical Procedures, Operative

Topics: Anemia; Bronchiolitis; Critical Illness; Erythropoietin; Humans; Infant; Respiratory Insufficiency

Topics: Anemia; Continuity of Patient Care; Critical Illness; Erythrocyte Transfusion; Erythropoietin; Hemoglobins; Humans; Intensive Care Units; Recombinant Proteins

Topics: Anemia; Critical Illness; Erythrocyte Transfusion; Erythropoietin; Hemoglobins; Humans; Recombinant Proteins; Red-Cell Aplasia, Pure

Topics: Anemia; Critical Illness; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Intensive Care Units; Recombinant Proteins

Critically ill patients often require pharmacological support to maintain blood pressure and cardiac output, and mechanical ventilation to ensure adequate oxygenation. Current methods of measurement of oxygen delivery do not necessarily reflect tissue oxygenation. Levels of circulating erythropoietin reliably reflect the adequacy of renal oxygen supply under physiological and many pathological conditions. It is proposed that the measurement of circulating erythropoietin can be used as a measure of tissue oxygenation in critically ill patients.

Topics: Animals; Critical Illness; Erythropoietin; Humans; Models, Biological; Oxygen; Oxygen Consumption

Topics: Anemia, Hemolytic; Critical Illness; Erythropoietin; Humans

Critically ill patients often develop anaemia which can be related to a number of factors. However, the exact causes of anaemia in many patients remain unexplained. We hypothesized that the relationship between erythropoietin (EPO) and haematocrit may be altered in critically ill patients.. Serum concentrations of EPO were serially determined by the ELISA method in 36 critically ill, non-hypoxaemic patients who stayed more than 7 days in the Intensive Care Unit, including 22 patients with sepsis and 14 without. Eighteen ambulatory patients with iron-deficiency anaemia served as a control group.. Two University Hospital Intensive Care Departments.. A significant inverse correlation between serum EPO and haematocrit levels was found in the control patients (r = -0.81, p < 0.001), but not in the critically ill patients (r = -0.09, NS), except in a subgroup of non-septic patients without renal failure (r = -0.61, p < 0.01).. EPO levels can be inappropriately low in critically ill patients, so that EPO deficiency may contribute to the development of anaemia in these patients. This phenomenon is observed not only in the presence of acute renal failure, but also in the presence of sepsis.

Topics: Acute Kidney Injury; Aged; Anemia, Hemolytic; Anemia, Iron-Deficiency; Case-Control Studies; Critical Illness; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Hematocrit; Humans; Intensive Care Units; Male; Middle Aged; Regression Analysis; Respiratory Distress Syndrome; Sepsis

Topics: Critical Illness; Erythropoietin; Humans; In Vitro Techniques; Neopterin; Tumor Cells, Cultured

Topics: Anemia, Iron-Deficiency; Critical Illness; Cytokines; Erythropoietin; Humans

Topics: Aprotinin; Blood Loss, Surgical; Blood Transfusion; Blood Transfusion, Autologous; Contraindications; Critical Illness; Drainage; Erythropoietin; Evaluation Studies as Topic; Hemodilution; Hemostatics; Humans; Hypotension, Controlled; Intraoperative Care; Iron; Patient Care Planning; Plasmapheresis; Postoperative Care; Posture; Preoperative Care; Quality Control; Risk Factors; Serine Proteinase Inhibitors

To examine the endogenous erythropoietin response in critically ill children with acute anemia or acute hypoxemia.. A prospective case study of critically ill acutely anemic, and acutely hypoxemic pediatric patients compared with control groups of critically ill nonanemic and nonhypoxemic patients and with a hemoglobin and age-matched, chronically anemic patient group.. Multidisciplinary, tertiary, pediatric intensive care unit (ICU).. Critically ill patients admitted to the pediatric ICU during an 11-month period between February 1992 and March 1993 with acute anemia (n = 21), acute hypoxemia (n = 18), or neither anemia nor hypoxemia (n = 10). Outpatients with chronic anemia (n = 21) and no acute illness were also studied as a comparison group.. None.. Ages were equivalent among the groups and averaged 57.4 +/- 47.2 months (range 1 to 144). Acutely hypoxemic and critically ill control patients had normal hemoglobin levels. Acutely anemic patients had a hemoglobin level equivalent to chronically anemic outpatients, but lower (p < .001) hemoglobin levels than acutely hypoxemic and critically ill control patients. The serum erythropoietin concentrations in the acutely anemic group were significantly lower than erythropoietin values in the chronically anemic group (39.3 +/- 62.2 vs. 861 +/- 758 mU/mL, p < .001) and similar to erythropoietin concentrations in the critically ill control (13.5 +/- 10.5 mU/mL) and acutely hypoxemic (5.2 +/- 3.3 mU/mL) patient groups. Only ten of 49 critically ill patients had an erythropoietin concentration above normal, compared with 20 of 21 chronically anemic patients, whose erythropoietin concentrations were above normal.. The erythropoietin response to known physiologic stimuli is blunted in critically ill children. This blunted erythropoietin response may result in increased transfusion requirements.

Topics: Acute Disease; Analysis of Variance; Anemia; Blood Transfusion; Case-Control Studies; Child; Child, Preschool; Chronic Disease; Critical Illness; Erythropoietin; Hemoglobins; Humans; Hypoxia; Infant; Infant, Newborn; Intensive Care Units, Pediatric; Matched-Pair Analysis; Outpatients; Prospective Studies; Severity of Illness Index

Two groups of patients with terminal chronic renal failure (TCRF) treated from 1970 to 1979 (group 1) and in 1980-1989 (group 2) have been compared in respect to treatment results. All the patients underwent programmed hemodialysis performed on different equipment and according to different regimens. The results of group 2 appeared better: the lethality decreased by 18%, mean survival from 6 months to 4.5 years, up to half of the patients were able to receive hemodialysis procedures outpatiently, 30% of the patients were prepared to receive a renal transplant. The above positive shifts were achieved due to utilization of updated equipment, improved water purification, 3-stage technique of hemodialysis, antianemic drug eprex and vanalpha against osteodystrophy.

Topics: Adolescent; Adult; Aged; Combined Modality Therapy; Critical Illness; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Survival Rate