Outcomes of a Quality Improvement Initiative to Prevent Unnecessary Packed Red Blood Cell Transfusions Among Extremely Low Birth-Weight Neonates.

BACKGROUND: Extremely low birth-weight (ELBW) infants frequently receive packed red blood cell (PRBC) transfusions. Recent studies have shown that more restrictive PRBC transfusion guidelines limit donor exposure and reduce transfusion-related costs without any increase in adverse clinical outcomes. PURPOSE: We developed and implemented an evidence-based PRBC transfusion guideline for ELBW infants treated in our unit and then measured provider adherence to this guideline. METHODS/SEARCH STRATEGY: We performed a retrospective review of all PRBC transfusions given to ELBW infants in 2012 (preguideline) and the first half of 2014 (postguideline). We identified the indication for each transfusion by reviewing physiological/laboratory data and the daily clinical note. We then determine whether each transfusion met criteria according to our new evidence-based guideline. FINDINGS/RESULTS: When extrapolating the newly developed protocol to 2012 data, less than 15% of transfusions among ELBW infants would have met the current evidence-based standard. Conversely, during the first 6 months of 2014, 61% of transfusions were administered in adherence to the guideline (P < 001). Using current cost estimates, this represents a projected cost savings of $31,000 in that 6-month period. IMPLICATIONS FOR PRACTICE: A multidisciplinary approach to improving PRBC transfusion practices results in potentially safer, more cost-effective care for ELBW infants. IMPLICATIONS FOR RESEARCH: Given the frequency, potential harms, and costs associated with PRBC transfusions in ELBW infants, it seems both feasible and important to pursue prospective clinical trials comparing permissive and restrictive approaches to transfusion in this vulnerable population.

Assessment of red blood cell transfusion and transfusion duration on cerebral and mesenteric oxygenation using near-infrared spectroscopy in preterm infants with symptomatic anemia.

BACKGROUND: The aim of red blood cell (RBC) transfusion is to improve tissue oxygenation and relieve anemia-related symptoms in preterm infants. We sought to assess regional cerebral (rSO2 C) and mesenteric (rSO2 M) tissue oxygenation using a near-infrared spectroscopy (NIRS) method and vital signs (heart rate, arterial oxygen saturation, mean arterial blood pressure) in symptomatic preterm infants with anemia who received RBC transfusions. STUDY DESIGN AND METHODS: Twenty-three symptomatic patients with anemia who were at least 1 month old, whose gestational age was less than 30 weeks, and whose hematocrit level was not more than 27% were involved in the transfusion group. The control group consisted of preterm infants (Hct ≥ 32) matched for gestational age and postnatal days. The transfusion group was divided into two subgroups based on transfusion duration (2 or 4 hr). Both study groups were monitored for vital signs and rSO2 C, rSO2 M, and mesenteric-cerebral oxygenation ratio (MCOR) via NIRS for 24 hours simultaneously and compared with the control group. NIRS variables and vital signs obtained before, during, and after transfusion were compared both within and between 2- and 4-hour groups. RESULTS: rSO2 C, rSO2 S, and MCOR increased during and after transfusions, while cerebral fractional oxygen extraction (FOEC) and mesenteric fractional oxygen extraction (FOEM) decreased. No significant difference was found between subgroups for NIRS measurements and vital signs. A weak correlation between hemoglobin concentration and FOEC and FOEM was found. CONCLUSION: RBC transfusion improved cerebral-mesenteric oxygenation and MCOR in symptomatic infants with anemia, independent of the transfusion duration.

Resource implications of adopting a restrictive neonatal blood transfusion policy.

BACKGROUND: Blood transfusions (BTFs) are not without risk and pose a significant financial burden on resource-limited services. In line with current international evidence, the nursery at Groote Schuur Hospital (GSH), Cape Town, South Africa, introduced a restrictive BTF protocol to minimise transfusions and manage costs. OBJECTIVE: To determine whether adopting a restrictive BTF policy results in fewer transfusions. METHODS: Data were retrospectively collected on all infants who received BTFs in the GSH nursery over a 6-month period following adoption of a restrictive BTF policy in 2010. BTF figures for a similar time period before the restrictive policy, during 2008, were obtained for comparison. RESULTS: After introduction of the restrictive BTF policy, 42 of 1 097 infants admitted (3.8%) received a total of 64 BTFs. In comparison, 102 of a total of 940 infants (10.9%) admitted during a period of the same length before introduction of the restrictive BTF policy received a total of 121 transfusions. Comparison between the number of BTFs administered before and after the restrictive policy showed a highly statistically significant difference (p<0.001). The total cost of the blood products used in the two 6-month periods was R91 870 v. R48 640, based on current prices. CONCLUSIONS: By adopting a restrictive policy, we were able to halve the number of BTFs, reduce risks associated with transfusions, and achieve significant cost benefits. Following evidence-based guidelines results in high standards of care, while also making the most effective use of resources.

Myocardial assessment using tissue doppler imaging in preterm very low-birth weight infants before and after red blood cell transfusion.

OBJECTIVE: To investigate myocardial velocities in anemic very low-birth weight (VLBW) preterm infants, pre and post red blood cells transfusion using tissue Doppler imaging echocardiography. STUDY DESIGN: Forty-eight VLBW preterm infants34 weeks and>2 weeks old were prospectively divided: Transfused symptomatic infants (Hematocrit (Hct)<0.30 (n=32)) and non transfused asymptomatic controls (control 1, Hct >0.30 (n=9) and control 2, Hct <0.30 (n=7)). Echocardiography was performed before and 3-5 days after transfusion in the transfused, and the controls were studied at similar intervals. Non parametric tests were used for statistical analysis. RESULT: Left ventricular (LV) systolic velocity increased (transfused (4.6±0.70 vs 6.0±0.65, P<0.01)) as did LV diastolic velocities (P<0.01) without significant difference over time in each control. The percentage change in LV velocity following transfusion correlated negatively (ρ=0.36) with pre transfusion Hct. CONCLUSION: There is a significant increase in myocardial performance following transfusion, which is related to the severity of the anemia.

Economic evaluation alongside the Premature Infants in Need of Transfusion randomised controlled trial.

BACKGROUND: The Premature Infants in Need of Transfusion (PINT) Outcome Study showed no significant difference in the primary outcome of death or neurodevelopmental impairment (NDI) in extremely low birthweight (ELBW) infants. However, a post-hoc analysis expanding the definition of NDI to include borderline intellectual functioning (Mental Development Index (MDI) <85) found an improvement in outcomes in the group maintained at higher haemoglobin levels. OBJECTIVE: To determine the cost effectiveness of more frequent red blood cell transfusions (high-Hb threshold) compared with less frequent transfusions (low-Hb threshold) in ELBW infants. DESIGN/METHODS: The authors performed an economic evaluation using patient-level data collected during the PINT randomised trial. The authors measured comprehensive costs from a third-party payer's perspective over a time horizon from birth through 18-21 months corrected age. RESULTS: The average total cost in the high-Hb threshold group was CAN$149 767 compared with CAN$150 227 in the low-Hb threshold group (difference of CAN$460, p=0.96). Cost-effectiveness analysis estimated savings of CAN$6879 for every additional infant surviving without severe NDI. There was a 48% chance that the high-Hb threshold reduced costs while improving outcome and a 90% chance that it would be cost effective at a willingness-to-pay threshold of CAN$250 000 per additional survivor without severe NDI. Post-hoc analysis defining cognitive delay as MDI score <85, instead of <70, revealed savings in the high-Hb threshold group of CAN$4457 per additional survivor without NDI. Results were robust to deterministic sensitivity analyses. CONCLUSION: A high-Hb threshold for transfusion, as measured in ELBW PINT study infants through 18 months corrected gestational age, may be an economically appealing intervention. The estimates were associated with moderate statistical uncertainty that should be targeted in larger, future studies.

Is there a role for autologous/placental red blood cell transfusions in the anemia of prematurity?

Because most extremely preterm infants with birth weight less than 1000 g need red blood cell transfusions, many attempts have been made to collect, process, and store placental blood (ie, umbilical cord blood) for autologous transfusions. Although it is feasible to do this, multiple problems in doing so including insufficient volumes collected, clotting, hemolysis, bacterial contamination, failure to significantly supplant need for allogeneic transfusions, and high costs have led many to question whether, on balance, autologous/placental red blood cell transfusion offers clinically significant benefits.

Rhesus haemolytic disease of the newborn: Postnatal management, associated morbidity and long-term outcome.

Rhesus haemolytic disease of the newborn can lead to complications such as hyperbilirubinaemia, kernicterus and anaemia. Postnatal management consists mainly of intensive phototherapy, exchange transfusion and blood transfusion. During the last decades, significant progress in prenatal care strategies for patients with Rhesus haemolytic disease has occurred. New prenatal management options have led to a remarkable reduction in perinatal mortality. As a result of the increase in perinatal survival, attention is now shifting towards short-term and long-term morbidity. This review focuses on the management of neonatal and paediatric complications associated with Rhesus haemolytic disease, discusses postnatal treatment options and summarizes the results of studies on short-term and long-term outcome.

Anaemia of prematurity. Epidemiology, management and costs.

Recombinant human erythropoietin (rHuEpo) has been increasingly used in preterm infants in the last 3 to 4 years. Recent studies have indicated a reduction in blood transfusion requirements in infants receiving rHuEpo. No significant adverse effects have emerged, apart from iron deficiency (if iron supplementation is inadequate), and the risk of transfusion-related infection is decreased. Nevertheless, rHuEpo is relatively expensive (a 6-week course costs approximately the same as 2 blood transfusions), so its use requires careful consideration; it is logical to target rHuEpo therapy to those babies who are most likely to be transfused. Using this strategy, 1 study involving stable growing preterm infants has shown that direct costs of blood transfusion and rHuEpo were similar, and the use of rHuEpo was recommended. In addition, use of high-dosage rHuEpo early in the course of management on the neonatal intensive care unit has been shown to reduce direct treatment costs in ill preterm infants. Further studies will continue to identify infants who are likely to benefit from rHuEpo therapy and to define its cost effectiveness in more detail.

Is the use of recombinant human erythropoietin in anaemia of prematurity cost-effective?

In a double-blind placebo-controlled study we showed a 3-fold decrease in blood transfusions (BTFs) given to preterm infants with anaemia of prematurity who received recombinant erythropoietin. However, only 50% of placebo recipients required a BTF. Data from the placebo group indicated that either mean daily weight gain < or = 7.5 g/day before study entry or haematocrit < or = 50% at birth was associated with BTFs (P < 0.001). We calculated that giving erythropoietin to patients in the treatment group with either of these variables prevented 24 of 28 BTFs and that it would cost R184 to prevent 1 BTF. The cost of each BTF was R187 (blood filtered to remove white cells and reduce cytomegalovirus transmission). Therefore, the costs of the two treatments were similar, but as the risk of transmitting infection is lower with erythropoietin, we recommend its use in selected preterm infants.

A cost analysis comparing erythropoietin and red cell transfusions in the treatment of anemia of prematurity.

BACKGROUND: Anemia of prematurity is invariably observed in very low birth weight infants and may become symptomatic enough to be treated with packed red cell transfusions. Recently, treatment of this condition with recombinant human erythropoietin has been advocated. STUDY DESIGN AND METHODS: To compare the costs of training symptomatic anemia in hospitalized premature infants with transfusions alone or with erythropoietin plus red cell transfusions as needed, cost estimates were derived from local hospital and published cost data. Decision analysis and sensitivity analysis were applied to a "base case." The base case was derived from results of a multicenter erythropoietin trial in the United States in which premature infants received 500 U of erythropoietin per kg of body weight each week. Because erythropoietin treatment began on average at 3 weeks of life, when infants were clinically stable, they had already received 3.5 red cell transfusions. During the 6-week treatment period, erythropoietin-treated infants received significantly fewer additional transfusions: a mean of 1.6 versus 1.1. RESULTS: The base-case cost in 1993 dollars for treating anemia in hospitalized premature infants with erythropoietin and transfusions was $1,326. This was nearly twice the cost of conventional treatment with transfusions alone ($721). If the 6-week treatment period alone is considered, erythropoietin is 3.6 times more costly: $840 versus $235. CONCLUSION: The largest available US study using erythropoietin to treat anemia in premature infants has demonstrated a small, but significant, reduction in transfusion needs. However, this study's cost data alone do not justify the widespread use of erythropoietin in premature infants. When this issue is probed in great depth, sensitivity analyses demonstrate that major reductions in erythropoietin's cost and/or improvements in its effectiveness quite possibly will make its use economically more attractive.

Recombinant human erythropoietin vs transfusions in the treatment of anemia of prematurity. A cost-benefit analysis.

OBJECTIVE: To evaluate the costs relative to the benefits of using recombinant human erythropoietin (rHuEPO) therapy as an alternative to red blood cell (RBC) transfusions in infants with anemia of prematurity. DESIGN: A cost-benefit analysis of rHuEPO therapy was performed based on its use in very-low-birth-weight premature infants. SETTING AND PATIENTS: Data were drawn from published studies or were provided by the University of Iowa Hospitals and Clinics, Iowa City. MAIN OUTCOME MEASURES: Costs and benefits were analyzed as a comparison of incurred costs to averted costs. Incurred and averted costs of rHuEPO therapy and RBC transfusions included direct product costs and estimates of costs of adverse events. The analysis was viewed in terms of net savings. Sensitivity analysis was performed. RESULTS: The base case analysis yielded a net loss of $299.48 per infant. A 54% reduction in the direct product costs of rHuEPO therapy yielded a break-even point. No other variations in the sensitivity analysis resulted in a net savings. CONCLUSION: Using assumptions based on the current state of clinical research, it appears that routine use of rHuEPO with supplemental RBC transfusions would not generate any cost savings as an alternative to RBC transfusions alone. As further evidence is compiled on the efficacy of rHuEPO therapy in very-low-birth-weight premature infants, the true costs may be better established.

The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth-weight infants. European Multicentre Erythropoietin Study Group.

BACKGROUND: Anemia of prematurity is characterized by low reticulocyte counts and inadequate erythropoietin response, for which many very-low-birth-weight infants receive multiple blood transfusions. We investigated whether early treatment of such infants with recombinant human erythropoietin would reduce their need for transfusions. METHODS: We performed a controlled, blinded trial in 241 infants with very low birth weights at 12 centers in six European countries. When three days old, the infants were randomly assigned either to the epoetin group or to the control group. Those in the epoetin group received 250 IU of epoetin beta per kilogram of body weight subcutaneously three times a week from day 3 to day 42 (for a total of 17 doses); those in the control group did not receive this drug. Infants in both groups received oral iron (2 mg per day) from day 14 onward. RESULTS: The control infants needed a mean of 1.25 transfusions each, as compared with 0.87 transfusion for epoetin-treated infants (P = 0.013). The median cumulative volume of blood transfused per kilogram per day was 0.41 ml in the control group (first quartile, 0 ml; third quartile, 0.8 ml) and 0.09 ml in the epoetin group (first quartile, 0 ml; third quartile, 0.8 ml) (P = 0.044). The rate of success, defined as an absence of need for transfusions and a hematocrit that never fell below 32 percent, was 4.1 percent in the control group and 27.5 percent in the epoetin group (P = 0.008). Epoetin was most beneficial in boys with birth weights of 1200 g or more and a base-line hematocrit of 48 percent or more. No toxic effects were observed in the epoetin group; as compared with the control group, the epoetin group had an increased incidence of septicemia (14 vs. 7 episodes, P not significant) and reduced weight gain (520 vs. 571 g, P = 0.02). CONCLUSIONS: Infants with very low birth weights have less need of transfusions if given epoetin beta during the first six weeks of life (250 IU per kilogram three times a week). We recommend early epoetin treatment for all such infants, but further studies of nutrition and iron supplementation during treatment are needed.

Determination of red-cell mass in assessment and management of anaemia in babies needing blood transfusion.

A new method for the rapid determination of red-blood-cell mass (RCM) in infants needing blood transfusion is described. RCM is estimated from the fall in the baby's fetal haemoglobin level resulting from transfusion of a known mass of adult-haemoglobin-containing red cells. In severe blood loss and refractory anaemias in preterm infants, in addition to the red-cell deficit, the plasma volume is low, leading to a falsely high haematocrit of about 0.30, which conceals a deficiency of 50-70% in circulating red cells. Red-cell transfusion in such infants based on haematocrit often fails to restore RCM to normal, leading to repeated transfusions. The frequency of transfusions may be reduced by giving enough red cells fully to correct the deficiency based on RCM estimation.

Assessment of anemia in newborn infants.

In this article a practical approach to the assessment of anemia in newborn infants is developed using the classic pathophysiologic approach with special emphasis on factors such as growth and blood sampling that must be considered if an accurate assessment of anemia in this age group is to be made.