Clinical practice of allogenic red blood cell transfusion and fluid bolus therapy in neonates

Abstract

This thesis by publication comprises of seven chapters encompassing several aspects of allogenic red blood cell (RBC) transfusion practice, fluid bolus therapy and the use of these products utilised in both. The work aims to improve the evidence-base on which clinical and research decisions are made around both of these therapies and the products, namely RBCs and 0.9% sodium chloride, utilised within neonatal units. It includes two systematic reviews and meta-analyses to address uncertainties in neonatal transfusion practice, an in-vitro study designed to provide information to inform clinical transfusion practice and an observational, cross-sectional study to further understand the use of fluid bolus therapy in neonates. To place these studies in their broader context, an introductory chapter (Chapter 1) is provided. The first study (Chapter 2) provides contemporary data on blood usage in neonatal units. Without recent data on the use of blood products, it is challenging to design accurate clinical studies. Prior to this study, knowledge of neonatal transfusion practices was limited to local cohort or survey-based studies. This study found blood product use remains common in neonates born before 30 weeks' gestation. The second study (Chapter 3) provides, for the first time, a systematic review of the known published adverse effects and associations of neonatal allogenic RBC transfusion. The review did not find any significant differences in a range of clinical outcomes between neonates exposed to restrictive and liberal RBC transfusion practices. The predominance of nonrandomised and observational studies was highlighted in this relatively highly-transfused population group. Chapter 4 provides a systematic review of published studies examining washing RBCs prior to transfusion in neonates. It is possible that modification of RBCs prior to transfusion, through washing with 0.9% sodium chloride, may reduce adverse effects related to neonatal allogenic RBC transfusion. The review found insufficient evidence to support or refute the use of washed RBCs to prevent the development of significant neonatal morbidities or mortality. This review provided key data to support the development of a randomised study in this area. Transfusion guidelines advise against the co-infusion of RBCs with solutions other than 0.9% sodium chloride. This study (Chapter 5) evaluates the impact of co-infusion with dextrosecontaining fluids on markers of RBC quality in an in-vitro setting. The study found the invitro characteristics of RBCs co-infused with 0.9% sodium chloride or 10% dextrose were not adversely impacted, arguing against the recommendation not to co-infuse. These findings led to practice changes in several neonatal units in Australia and Canada. Intravenous fluid bolus therapy for suspected haemodynamically compromised neonates is an apparent common intervention in neonatal units. Despite this, the volume and type of fluid used, as well as the timing and indications for this practice are not well described or understood. The NeoBolus study (Chapter 6) provides a contemporary description of clinical practice in relation to the types and specific indications for use of fluid therapy, including blood products, in neonates with suspected haemodynamic compromise. The data generated will provide key information to develop a randomised study in the area. In summary, this work provides a number of insights into neonatal transfusion practice and fluid bolus therapy, key to improving the evidence-base and identifying future directions for research in these areas.