Efficacy of Two Different Dosage Schedules for Administering Recombinant Human Erythropoietin (r-EPO) to Very Low Birth Weight (VLBW) Infants † 1379

Introduction:Although r-EPO has been effective in reducing transfusions in VLBW infants, effective dosage schedules have varied in both dose and frequency. To understand the effect of dose frequency, we compared absolute reticulocytes (abs-Retic) between 2 and 5 times/week dosage using the same r-EPO weekly dose, 500U/kg. Study Design: 80 VLBW infants were stratified into <28 weeks and 28-30 weeks gestational age groups and randomized to either 2 or 5 doses/week; 72 completed 4 weeks and 30(<28wks) completed 8 weeks of study. The primary outcome variable was abs-Retics at 4 weeks in all infants, and at 8 weeks in those <28 wks. To further estimate the effect of dose, secondary outcome variables were examined. These were hematocrits, transfusions, iatrogenic blood losses, and infections. Multiple regression analysis was used to evaluate the effect of dose frequency on secondary outcome variables. Results: By 4 weeks, abs-Retics were 27% higher and by 8 weeks 44% higher in the infants given r-EPO 5 times a week (p=0.046 and p=0.03)(see Table). Hematocrits and transfusions per infant were not different between the groups. 79% of the variance in the amount transfused could be accounted for by iatrogenic blood loss, and the latter primarily associated with days ventilated (65%) and days of antibiotics (3%). Episodes of sepsis and necrotizing enterocolitis were significantly associated with decreased abs-Retics and increased transfusions. Conclusions: (1) More frequent administration of r-EPO produced a better response in erythropoiesis using the same weekly dose. (2) The effect of the increased erythropoiesis on transfusions was overshadowed by the impact of iatrogenic blood losses on transfusions during mechanical ventilation and evaluation for sepsis.Speculation: The most effective use of r-EPO in VLBW infants may be to provide more frequent dosage during mechanical ventilation along with strategies to reduce iatrogenic blood losses, and to adjust to less frequent dosage as iatrogenic blood losses decrease.

Table 1 No caption available.