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Arch Dis Child Fetal Neonatal Ed 2004;89:F101-F107. doi: 10.1136/adc.2002.019760
Many previously widely accepted neonatal transfusion practices are changing as neonatologists become more aware of the risks to their patients of multiple blood product transfusions. Recent literature and research on neonatal transfusion practice are here reviewed, and practical guidelines and trigger thresholds for blood products commonly used in neonatal medicine are proposed.
Sick neonates are one of the most heavily transfused groups of patients in modern medicine. However, despite considerable research, most neonatal transfusion practice remains opinion based rather than truly evidence based. Most neonatologists would not prescribe drugs to their patients unless there was a reasonable expectation of benefit. Unfortunately, this rigour does not translate to the prescription of blood products, and as a result there exists a diversity of opinion and practice between different clinicians (1) and different institutions. (2-6) Clearly the administration of blood products conveys a finite risk of transmitting potentially serious infections (7-9) and is not without risk and cost. (7 8) It therefore remains a continuing task to define and refine the most clinically appropriate protocols for blood product use in neonates, within the constraints of the available evidence. With these goals in mind this paper reviews recent literature and research on neonatal transfusion practice and proposes practical transfusion guidelines and trigger thresholds for commonly used blood products in neonatal medicine.
RED BLOOD CELLS
Packed red blood cells (RBCs) are the most common blood product administered to sick neonates. Many previous studies (reviewed in refs (10 11)) have attempted to define their optimal use in neonates. However, rapidly changing patient populations and characteristics over the last decade, coupled with the introduction of increasingly rigorous transfusion protocols, have reduced the relevance of much of this previous work to modern neonatal practice. Progress in RBC transfusion practice therefore requires a fundamental re-evaluation of its basic aims.
At the most basic level, RBC transfusions are required for two reasons:
* to ensure adequate tissue oxygenation during intensive care periods
* after intensive care, to treat clinically significant symptomatic anaemia
However, neither clinical situation is straight-forward to define.
Ensuring adequate tissue oxygen delivery
Tissue oxygenation is influenced by the concentration and type of haemoglobin (Hb), the concentration of 2,3-diphosphoglycerate within RBCs (both factors affect the Hb-oxygen dissociation curve and thus the oxygen unloading capacity of the blood), and the cardiopulmonary function of the neonate. Apart from Hb concentration, none of these variables are easily measurable in everyday neonatal practice. In addition, assuming optimised cardiopulmonary function during intensive care, apart from altering Hb concentration by transfusion (and thereby Hb type and 2,3-diphosphoglycerate concentration by exchanging HbF for HbA RBCs), little can be done to influence these variables on an hour to hour or day to day basis. Thus RBC transfusion remains the only "haematological" treatment option available that has the potential to significantly influence tissue oxygen delivery. However, the question remains how to recognise when a neonate is developing Hb limited oxygen unloading capacity to the tissues and how to measure this accurately in everyday practice?
Methods of assessing tissue oxygenation
Peripheral fractional oxygen extraction (FOE)
Direct measurement of tissue oxygenation is not possible. However, surrogate measures have been attempted. Recently, Wardle et al (12) measured peripheral FOE by near infrared spectroscopy as a surrogate measure of the adequacy of tissue oxygen delivery in 74 neonates < 1500 g undergoing standard neonatal care. High peripheral FOE (> 0.47) was taken as a cut off point suggesting inadequate tissue oxygen delivery and thereby the potential for inadequate tissue oxygenation. This parameter was used as an RBC transfusion trigger in 37 neonates, with the remaining 37 neonates receiving RBC transfusion guided by a conventional Hb based protocol. Although there was a trend towards fewer RBC transfusions in the FOE group, this was not significant. However, neonates in the FOE group had lower median Hb during the study, and time to first transfusion from study entry was also longer. No difference in major neonatal complications was seen between the two groups, suggesting that no clinical compromise occurred in the neonates in the FOE group. Interestingly, two thirds of transfusions in the FOE group were given because of clinical concerns about low Hb or symptoms and not because of high FOE. Thus, this method of assessing trigger thresholds for RBC transfusion in preterm neonates deserves further assessment, as sticking closely to high FOE as a transfusion trigger may prove to be a practical method to further reduce RBC transfusions and donor exposure without adversely affecting outcome.
Capillary whole blood lactate
Lactate concentration has also been assessed as an indicator of tissue oxygenation and/or the need for RBC transfusion. (13-16) In the intensive care period, lactate concentrations are highly variable, probably reflecting variations in tissue perfusion rather than Hb limited oxygen unloading capacity to the tissues. Therefore, during intensive care, lactate concentrations are not useful in deciding the need for RBC transfusion. In stable neonates, these concentrations have been shown to decrease after RBC transfusions given for "symptomatic" anaemia. (13 15 16) However, even in stable preterm neonates, lactate concentrations show considerable variation during a 24 hour period, (13) and before transfusion they do not correlate with Hb or packed cell volume. (13) Thus, peripheral blood lactate concentrations may be useful in the overall assessment of tissue perfusion/oxygenation, but on their own are not a reliable indicator of the need for RBC transfusion.
In summary, with currently available techniques, there is no practical method applicable to everyday neonatal practice that accurately and reproducibly assesses tissue oxygenation.
Trends in clinical practice
As high quality methods for assessing tissue oxygenation are not available, observational clinical studies of RBC transfusion practice represent the best available evidence to guide future developments. Over the past 15 years, a number of groups have reported on this subject in preterm neonates. Most of these reports show a definite trend towards decreased use of RBC transfusions, even in the most preterm neonates. (17-20) Importantly, there is no suggestion that this results in an increased need for respiratory support or oxygen therapy or poorer weight gain or increased length of hospital stay. (3 12) In addition, there is not an increased incidence of important neonatal complications, such as intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), chronic lung disease of prematurity (CLD), or sepsis, in preterm neonates managed with …