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Biomedical subjects

Andrew Gettinger

Publications and source records attributed to Andrew Gettinger.

6 recordsLinked to original sources

Transfusion therapy in the intensive care unit.

PURPOSE OF REVIEW: Transfusion therapy in the intensive care unit is an ever-growing field, with new understanding of potential complications, new drug therapies to reduce the need for transfusion, and new additions in component therapy. In addition to the risks of sepsis, ABO blood group mismatch, and other complications associated with transfusion, the intensivist needs to be familiar with alternative therapies to minimize transfusion. RECENT FINDINGS: Transfusion-related acute lung injury and immunosuppression are two newly recognized complications in transfusion. Transfusion-related acute lung injury can lead to respiratory failure in an acute respiratory distress syndrome-like picture, often necessitating intubation and critical care services. Immunosuppression following transfusion has been linked to cytokine and complement activation. Recombinant erythropoietin (rHuEPO, Epogen, Procrit), by maximizing red cell counts, and aprotinin (Trasylol), by inhibiting fibrinolysis, are two old drugs being used with increasing frequency in a new setting: the intensive care unit. A new component therapy, recombinant factor VIIa (rFVIIa, NovoSeven), assists in turning on the extrinsic pathway of the coagulation cascade. SUMMARY: Recognizing early signs of transfusion-related acute lung injury may aid in the treatment and reporting of this entity. Realizing the mechanism and severity of immunosuppression associated with transfusion may alter transfusion triggers in the intensive care unit. rHuEPO and aprotinin are now being used with increasing frequency to increase red cell counts and minimize the need for transfusion. Recombinant factor FVIIa targets coagulation cascade activation which helps to reduce the number of units of blood products transfused in the actively bleeding patient.

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

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

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The CRIT Study: Anemia and blood transfusion in the critically ill--current clinical practice in the United States.

OBJECTIVE: To quantify the incidence of anemia and red blood cell (RBC) transfusion practice in critically ill patients and to examine the relationship of anemia and RBC transfusion to clinical outcomes. DESIGN: Prospective, multiple center, observational cohort study of intensive care unit (ICU) patients in the United States. Enrollment period was from August 2000 to April 2001. Patients were enrolled within 48 hrs of ICU admission. Patient follow-up was for 30 days, hospital discharge, or death, whichever occurred first. SETTING: A total of 284 ICUs (medical, surgical, or medical-surgical) in 213 hospitals participated in the study. PATIENTS: A total of 4,892 patients were enrolled in the study. MEASUREMENTS AND MAIN RESULTS: The mean hemoglobin level at baseline was 11.0 +/- 2.4 g/dL. Hemoglobin level decreased throughout the duration of the study. Overall, 44% of patients received one or more RBC units while in the ICU (mean, 4.6 +/- 4.9 units). The mean pretransfusion hemoglobin was 8.6 +/- 1.7 g/dL. The mean time to first ICU transfusion was 2.3 +/- 3.7 days. More RBC transfusions were given in study week 1; however, in subsequent weeks, subjects received one to two RBC units per week while in the ICU. The number of RBC transfusions a patient received during the study was independently associated with longer ICU and hospital lengths of stay and an increase in mortality. Patients who received transfusions also had more total complications and were more likely to experience a complication. Baseline hemoglobin was related to the number of RBC transfusions, but it was not an independent predictor of length of stay or mortality. However, a nadir hemoglobin level of <9 g/dL was a predictor of increased mortality and length of stay. CONCLUSIONS: Anemia is common in the critically ill and results in a large number of RBC transfusions. Transfusion practice has changed little during the past decade. The number of RBC units transfused is an independent predictor of worse clinical outcome.

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Transfusion practice in the critically ill.

BACKGROUND: Anemia in the critically ill patient population is common. This anemia of critical illness is a distinct clinical entity characterized by blunted erythropoietin production and abnormalities in iron metabolism identical to what is commonly referred to as the anemia of chronic disease. FINDINGS: As a result of this anemia, critically ill patients receive an extraordinarily large number of blood transfusions. Between 40% and 50% of all patients admitted to intensive care units receive at least one red blood cell unit, and the average is close to five red blood cell units during their intensive care unit stay. There is little evidence that "routine" transfusion of stored allogeneic red blood cells is beneficial for critically ill patients. Most critically ill patients can tolerate hemoglobin levels as low as 7 mg/dL, so a more conservative approach to red blood cell transfusion is warranted. CONCLUSION: Practice strategies should be directed toward a reduction of blood loss (phlebotomy) and a decrease in the transfusion threshold in critically ill patients.

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Anemia and blood transfusion in trauma patients admitted to the intensive care unit.

BACKGROUND: Anemia is a common occurrence in the intensive care unit (ICU). Although resuscitation, including the use of blood, is a mainstay of early treatment of trauma victims, the safety and efficacy of red blood cell (RBC) transfusion has come under scrutiny recently. The issue of blood use in critically injured patients requires evaluation. METHODS: This was a post hoc analysis of a subset of trauma patients (> or =18 years in age) from a prospective, multicenter, observational, cohort study in the United States. Patients were enrolled within 48 hours after ICU admission and followed for up to 30 days, or until hospital discharge or death. RESULTS: Five hundred seventy-six patients from 111 ICUs in 100 hospitals were enrolled between August 2000 and April 2001. At baseline, mean age was 44.1 +/- 20.2 years, 73.6% were men, and mean APACHE II score was 16.9 +/- 8.2. Mean baseline hemoglobin was 11.1 +/- 2.4 g/dL and patients remained anemic throughout the study either with or without transfusion; 55.4% of patients were transfused (mean, 5.8 +/- 5.5 units) during the ICU stay and 43.8% of patients had an ICU length of stay > or = 7 days. Mean pretransfusion hemoglobin was 8.9 +/- 1.8 g/dL. Mean age of RBCs transfused was 20.1 +/- 11.4 days. As compared with the full study population, patients in the trauma subset were more likely to be transfused and received an average of 1 additional unit of blood. CONCLUSION: Anemia is common in critically injured trauma patients and persists throughout the duration of critical illness. These patients receive a large number of RBC transfusions during their ICU course with aged blood.

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Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial.

CONTEXT: 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. OBJECTIVE: 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. DESIGN: A prospective, randomized, double-blind, placebo-controlled, multicenter trial conducted between December 1998 and June 2001. SETTING: A medical, surgical, or a medical/surgical intensive care unit (ICU) in each of 65 participating institutions in the United States. PATIENTS: 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. INTERVENTION: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

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