Regional Oxygenation and Perfusion Monitoring to Optimize Neonatal Packed Red Blood Cell Transfusion Practices: A Systematic Review
Introduction
Blood transfusions are commonplace in neonatal intensive care units around the world, and, historically, the threshold for their administration was very low. However, in recent years, the debate has intensified around “at what threshold should anaemic preterm infants receive packed red blood cell (pRBC) transfusion?” The quest to answer this question has led to trials comparing restrictive versus liberal transfusion thresholds [1,2]. To date, the question remains unanswered as these trials have not shown differences in short- or long-term developmental outcomes.
Significant variation in neonatal transfusion practices is reported [3,4]. Serious adverse events following pRBC transfusions include peripheral intravenous catheter related extravasation injuries, transmission of infectious diseases [5], transfusion-associated circulatory overload [5], transfusion-related organ injury [6,7], transfusion-associated graft-versus-host disease [5], transfusion-related immunomodulation [8], and acute hemolysis [5]. Fortunately, modern transfusion practices have led to a reduction in adverse events [5]. Thresholds for transfusion in contemporary practice are based primarily on hemoglobin (Hb) or haematocrit (Hct) measurement, as well as clinical features such as the need for respiratory support with or without supplemental oxygen, tachycardia, episodes of apnoea or desaturation, and sub-optimal postnatal growth [3]. In addition to patient's clinical status and supportive laboratory investigations, incorporating monitoring of regional oxygenation using near infrared spectroscopy (NIRS) and/or perfusion using ultrasound could offer a better approach in determining the threshold for transfusion. This could lead to an optimal benefit from pRBC transfusion and promote personalized transfusion medicine practice.
Ultrasound-based perfusion monitoring has been used as a surrogate marker of organ perfusion [9,10]. Ultrasound is routinely used to identify intraventricular haemorrhage, and for cardiovascular assessment in preterm infants [11], [12], [13], [14]. NIRS provides a sophisticated form of bedside, non-invasive and continuous regional oxygenation and oxygen-extraction monitoring by quantifying oxy and deoxy-Hb. Typically, the distribution of blood in tissues is 75% venous, 20% arterial and 5% capillary compartments [15], [16], [17]. As NIRS predominantly measures the venous oxygen pool, it provides an indirect measure of regional oxygen-extraction. NIRS monitoring is used to identify cerebral hypoxia and hyperoxia, and hypocarbia-related changes to cerebral oxygenation [18,19].
Traditionally, a diagnosis of anemia and the decision on administration of pRBC transfusion is primarily based on Hb or Hct measurement from a blood test. Reliance on Hb or Hct for diagnosing anemia is due to its widespread availability and accuracy. In addition, limited progress has been made on using changes in regional oxygenation and perfusion to non-invasively identify anemic preterm infants. We could not find any literature comprehensively reviewing both NIRS and ultrasound-based monitoring in the management of anemic preterm infants which has the potential for application of personalized transfusion practice. This comprehensive systematic review aims to present the current evidence on the effect of pRBC transfusion on regional oxygenation and ultrasound-based perfusion in anemic preterm infants, address limitations of the current evidence, highlight challenges in incorporating bedside use of NIRS and ultrasound monitoring to individualize pRBC transfusion practices, and recommend directions for generating high quality evidence in the future.
Section snippets
Methods
We followed the recommendations from the PRISMA-S reporting guideline [20]. 2 searches were conducted, the first in October 2020 and an update in March 2021. Using Ovid platform, we searched MEDLINE from 1946 onwards, Embase Classic + Embase from 1947 and the Maternity and Infant Care database from 1971 to January 2021. Additionally, https://www.ClinicalTrials.gov, Current Controlled Trials (https://www.isrctn.com/), Australian New Zealand Clinical Trials Registry (https://www.anzctr.org.au),
Results
We identified 44 studies that met the inclusion criteria. Most were prospective, observational studies, one was a pilot randomised controlled trial (RCT), and one was a sub-study of a large RCT [21]. 17 studies performed NIRS monitoring only (Table 1), either for a single region or combination of regions (cerebral, splanchnic, renal, hepatic, forearm, inter-scapular and leg) [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38]. Fifteen studies
Discussion
Prior systematic review has focused only on the role of NIRS in detection and management of anaemic patients of all ages not just newborn infants [64]. This systematic review provides a comprehensive summary of evidence by combining both NIRS and ultrasound-based monitoring for anaemic preterm infants. In this review, the current evidence demonstrates that changes in regional oxygenation as measured by NIRS and changes in organ perfusion as measured by pulsed Doppler ultrasound can be
Conclusions
In summary, regional oxygenation and ultrasound-based perfusion monitoring enable identification of at-risk stable anaemic preterm infants, and offers a promising strategy for individualizing transfusion practice. However, there is a dearth of evidence on their usability for triggering pRBC transfusion, due to a lack of normative values in determining the critical O2 point and heterogeneity of reported studies. Further research is required before serial regional oxygenation and ultrasound-based
Acknowledgments
Independent librarian for assisting with literature search and SuperScript Writing and Editing for professional proofreading.
Conflict of interest
None.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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