Gretchen A. Cress

Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants.

Objective. Although many centers have introduced more restrictive transfusion policies for preterm infants in recent years, the benefits and adverse consequences of allowing lower hematocrit levels have not been systematically evaluated. The objective of this study was to determine if restrictive guidelines for red blood cell (RBC) transfusions for preterm infants can reduce the number of transfusions without adverse consequences. Design, Setting, and Patients. We enrolled 100 hospitalized preterm infants with birth weights of 500 to 1300 g into a randomized clinical trial comparing 2 levels of hematocrit threshold for RBC transfusion. Intervention. The infants were assigned randomly to either the liberal- or the restrictive-transfusion group. For each group, transfusions were given only when the hematocrit level fell below the assigned value. In each group, the transfusion threshold levels decreased with improving clinical status. Main Outcome Measures. We recorded the number of transfusions, the number of donor exposures, and various clinical and physiologic outcomes. Results. Infants in the liberal-transfusion group received more RBC transfusions (5.2 ± 4.5 [mean ± SD] vs 3.3 ± 2.9 in the restrictive-transfusion group). However, the number of donors to whom the infants were exposed was not significantly different (2.8 ± 2.5 vs 2.2 ± 2.0). There was no difference between the groups in the percentage of infants who avoided transfusions altogether (12% in the liberal-transfusion group versus 10% in the restrictive-transfusion group). Infants in the restrictive-transfusion group were more likely to have intraparenchymal brain hemorrhage or periventricular leukomalacia, and they had more frequent episodes of apnea, including both mild and severe episodes. Conclusions. Although both transfusion programs were well tolerated, our finding of more frequent major adverse neurologic events in the restrictive RBC-transfusion group suggests that the practice of restrictive transfusions may be harmful to preterm infants.

Phlebotomy overdraw in the neonatal intensive care nursery.

Objective. Because blood loss attributable to laboratory testing is the primary cause of anemia among preterm infants during the first weeks of life, we quantified blood lost attributable to phlebotomy overdraw, ie, excess that might be avoided. We hypothesized that phlebotomy overdraw in excess of that requested by the hospital laboratory was a common occurrence, that clinical factors associated with excessive phlebotomy loss would be identified, and that some of these factors are potentially correctable. Design, Outcome Measures, and Analysis. Blood samples drawn for clinical purposes from neonates cared for in our 2 neonatal special care units were weighed, and selected clinical data were recorded. The latter included the test performed; the blood collection container used; the infants location (ie, neonatal intensive care unit [NICU] and intermediate intensive care unit); the infants weight at sampling; and the phlebotomists level of experience, work shift, and clinical role. Data were analyzed by univariate and multivariate procedures. Phlebotomists included laboratory technicians stationed in the neonatal satellite laboratory, phlebotomists assigned to the hospitals central laboratory, and neonatal staff nurses. Phlebotomists were considered experienced if they had worked in the nursery setting for >1 year. Blood was sampled from a venous or arterial catheter or by capillary stick from a finger or heel. Blood collection containers were classified as tubes with marked fill-lines imprinted on the outside wall, tubes without fill-lines, and syringes. Infants were classified by weight into 3 groups: <1 kg, 1 to 2 kg, and >2 kg. The volume of blood removed was calculated by subtracting the weight of the empty collection container from that of the container filled with blood and dividing by the specific gravity of blood, ie, 1.050 g/mL. The volume of blood withdrawn for individual laboratory tests was expressed as a percentage of the volume requested by the hospital laboratory. Results. The mean (± standard error of the mean) volume of blood drawn for the 578 tests drawn exceeded that requested by the hospital laboratory by 19.0% ± 1.8% per test. The clinical factors identified as being significantly associated with greater phlebotomy overdraw in the multiple regression model included: 1) collection in blood containers without fill-lines; 2) lighter weight infants; and 3) critically ill infants being cared for in the NICU. Because the overall R 2 of the multiple regression for these 3 clinical factors was only .24, the random factor of individual phlebotomist was added to the model. This model showed that there was a significant variation in blood overdraw among individual phlebotomists, and as a result, the overallR 2 increased to .52. An additional subset analysis involving 2 of the 3 groups of blood drawers (ie, hospital and neonatal laboratory phlebotomists) examining the effect of work shift, demonstrated that there was significantly greater overdraw for blood samples obtained during the evening shift, compared with the day shift when drawn using unmarked tubes for the group of heavier infants cared for in the NICU. Conclusion. Significant volumes of blood loss are attributable to overdraw for laboratory testing. This occurrence likely exacerbates the anemia of prematurity and may increase the need for transfusions in some infants. Attempts should be made to correct the factors involved. Common sense suggests that blood samples drawn in tubes with fill-lines marked on the outside would more closely approximate the volumes requested than those without. Conversely, the use of unmarked tubes could lead to phlebotomy overdraw because phlebotomists may overcompensate to avoid having to redraw the sample because of an insufficient volume for analysis. We were surprised to observe that the lightest and most critically ill infants experienced the greatest blood overdraw. Because the volume indicators on the outside of syringe barrels are seemingly analogous to the blood collection tubes with fill-lines, it was also unexpected to observe that blood overdraw was greater with syringes than with either marked or unmarked tubes. It is likely that this is attributable in part to the unavoidable presence of the air bubble inevitably originating in the syringe tip. Educating individual phlebotomists, nurses, and other members of the care team on reducing unnecessary blood loss, eg, ordering only essential blood tests, exercising the greatest care in the smallest infants, practice in drawing blood samples into syringes, etc, may also help. Other promising means for reducing laboratory blood loss include technologic improvements to further reduce laboratory sample volume required, more reproducible and better capillary blood sampling containers, and use of point-of-care laboratory testing in which little to no blood loss results.

A randomized clinical trial comparing immediate versus delayed clamping of the umbilical cord in preterm infants: short-term clinical and laboratory endpoints

BACKGROUND: Most neonates less than 1.0 kg birth weight need red blood cell (RBC) transfusions. Delayed clamping of the umbilical cord 1 minute after delivery transfuses the neonate with autologous placental blood to expand blood volume and provide 60 percent more RBCs than after immediate clamping. This study compared hematologic and clinical effects of delayed versus immediate cord clamping.

Circulating RBC volume, measured with biotinylated RBCs, is superior to the Hct to document the hematologic effects of delayed versus immediate umbilical cord clamping in preterm neonates

BACKGROUND: One problem assessing the hematologic physiology of preterm infants after delivery and/or the efficacy and toxicity of therapeutic interventions affecting RBC measurements is the inability of blood Hct values to accurately reflect circulating RBC volume—owing to changes in plasma volume that influence Hct (i.e., a fall in plasma volume concentrates RBCs to increase Hct; a rise in plasma volume dilutes RBCs to decrease Hct).

Feasibility and safety of AS-3 red blood cells for neonatal transfusions☆☆☆★

OBJECTIVES Most extremely low birth weight (<1 kg) infants receive red blood cell (RBC) transfusions. RBCs stored up to 42 days can be transfused safely in small volumes to preterm infants; however, because the formulation of RBC anticoagulant/preservative solutions differs, clinical studies are required to document the safety of each solution before widespread use. Our goal was to study the feasibility and safety of AS-3 anticoagulant/preservative solution to preterm infants. STUDY DESIGN Two clinical studies were conducted in sequence: (1) a randomized trial to compare RBC transfusions given as stored (< or =42 days) AS-3 RBCs (11 infants) versus fresh (< or = 7 days) citrate, phosphate, dextrose, and adenine RBCs (10 infants) and (2) a subsequent evaluation of the safety of stored AS-3 RBCs in 33 additional preterm infants given 120 AS-3 RBC transfusions. RESULTS Results of both the randomized study and the subsequent evaluation documented that AS-3 RBCs stored < or =42 days and transfused in small volumes (15 mL/kg) were safe for RBC transfusions of preterm infants. Donor exposure was significantly reduced, clinical transfusion reactions were rare, and post-transfusion blood hematocrit, pH, and plasma Na, K, Ca, lactate, and glucose measurements were similar when AS-3 and citrate, phosphate, dextrose, and adenine RBC transfusions were compared. CONCLUSIONS AS-3 RBCs can be used safely for small-volume RBC transfusions for preterm infants.

Red blood cell (RBC) survival determined in humans using RBCs labeled at multiple biotin densities

BACKGROUND: Safe, accurate methods permitting simultaneous and/or repeated measurement of red blood cell (RBC) survival (RCS) are important to investigate pathophysiology and therapy of anemia. Methods using chromium 51 (51Cr)‐labeled RBCs are unacceptable for infants, children, and pregnant women. We report RCS measured in vivo using RBCs labeled with several densities of biotin (BioRBCs).

Acute physiological effects of packed red blood cell transfusion in preterm infants with different degrees of anaemia

Objective The safe lower limit of haematocrit or haemoglobin that should trigger a red blood cell (RBC) transfusion has not been defined. The objective of this study was to examine the physiological effects of anaemia and compare the acute responses to transfusion in preterm infants who were transfused at higher or lower haematocrit thresholds. Methods The authors studied 41 preterm infants with birth weights 500–1300 g, who were enrolled in a clinical trial comparing high (‘liberal’) and low (‘restrictive’) haematocrit thresholds for transfusion. Measurements were performed before and after a packed RBC transfusion of 15 ml/kg, which was administered because the infants haematocrit had fallen below the threshold defined by study protocol. Haemoglobin, haematocrit, RBC count, reticulocyte count, lactic acid and erythropoietin were measured before and after transfusion using standard methods. Cardiac output was measured by echocardiography. Oxygen consumption was determined using indirect calorimetry. Systemic oxygen transport and fractional oxygen extraction were calculated. Results Systemic oxygen transport rose in both groups following transfusion. Lactic acid was lower after transfusion in both groups. Oxygen consumption did not change significantly in either group. Cardiac output and fractional oxygen extraction fell after transfusion in the low haematocrit group only. Conclusions These studys results demonstrate no acute physiological benefit of transfusion in the high haematocrit group. The fall in cardiac output with transfusion in the low haematocrit group shows that these infants had increased their cardiac output to maintain adequate tissue oxygen delivery in response to anaemia and, therefore, may have benefitted from transfusion.

Posttransfusion 24-hour recovery and subsequent survival of allogeneic red blood cells in the bloodstream of newborn infants.

BACKGROUND:  The feasibility, efficacy, and safety of transfusing stored allogeneic RBCs has been demon‐strated for small‐volume transfusions given to infants. We measured the posttransfusion recovery and intravascular survival of allogeneic RBCs stored up to 42 days to further elucidate their efficacy.

Alloimmunization in preterm infants after repeated transfusions of WBC-reduced RBCs from the same donor

BACKGROUND: Preterm infants are among the most heavily transfused of patient groups, yet multiply transfused infants only rarely produce alloantibodies against RBC or WBC antigens. It is not known whether rates of alloimmunization might be increased by repeated exposure to RBCs and WBCs from the same donor, as in limited‐donor‐exposure programs, or whether infants might benefit from WBC‐reduced RBC components as a means of diminishing the risk of possible alloimmunization.

Neonatal laboratory blood sampling: comparison of results from arterial catheters with those from an automated capillary device.

Purpose: To compare neonatal laboratory results from capillary blood samples drawn using the Tenderfoot automated capillary sampling device with those drawn through arterial catheters. Design: Prospective, paired comparisons of laboratory results from capillary and arterial blood. Sample: Twenty-one infants being cared for in an NICU and having indwelling arterial catheters through which a variety of predominantly glucose-containing fluids were being administered. Main Outcome Variables: Statistical comparisons of paired capillary and arterial results of pH, PO2, PCO2, lactate, sodium, potassium, ionized calcium, and hematocrit. Results: No capillary-arterial differences were observed for pH, PCO2, lactate, or sodium. Although capillary results were slightly, but significantly (p <.01), higher for potassium (+0.4 mEq/liter), ionized calcium (+0.47 mg/dl), and hematocrit (+4 percent), these differences fell within acceptable Clinical Laboratories Improvement Act (CLIA) performance criteria. Markedly lower PO2 (−30.2 mmHg) and glucose (−61 mg/dl) values were observed with capillary sampling. With the exception of results for PaO2 and plasma glucose, capillary blood drawn using the Tenderfoot automated device yields laboratory results comparable to those from blood drawn from arterial catheters as assessed by CLIA performance criteria.