Association of Bolus Feeding With Splanchnic and Cerebral Oxygen Utilization Efficiency Among Premature Infants With Anemia and After Blood Transfusion | Critical Care Medicine | JAMA Network Open | JAMA Network
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    1 Comment for this article
    Splanchnic tissue oxygen insufficiency after blood transfusion in preterm infants during feeds
    Sourabh Verma, MD | New York University Grossman School of Medicine, New York City, NY, United States
    We read with great interest the study by Balegar et al. examining the efficiency of splanchnic and cerebral oxygen utilization in relationship to bolus feeding among anemic premature infants receiving blood transfusion. Since Mally et al. and other neonatologists first reported a possible link between red blood cell transfusions and necrotizing enterocolitis (NEC) in premature neonates, many researchers have sought to understand the physiologic mechanisms that may be involved.

    While the pathogenesis and extent of any association remains unclear, these authors provide valuable information about splanchnic oxygenation and the potential intestinal vulnerability to ischemia in the setting of an
    anemic state and the context of a transfusion. They elegantly demonstrate how the vulnerable splanchnic circulation of a premature infant may reach an inflection point in which an already altered balance between oxygen delivery and consumption, at the tissue level, crosses a critical oxygen deficiency point after transfusion. When combined with metabolic demands on the gut during feedings, one can discern how this could potentially result in NEC.

    We commend the authors for studying both splanchnic and cerebral fractional tissue oxygen extraction (FTOE), adding data to a much-debated topic of transfusion associated necrotizing enterocolitis (TANEC). They found an adverse effect on splanchnic FTOE with no change in cerebral FTOE during feeding in the immediate hours after transfusion. However, to have a more comprehensive understanding, we suggest they examine their data further.

    We agree that a change in FTOE, rather than absolute tissue oxygen saturation may be meaningful. However, we and other researchers have found it extremely valuable to analyze the ratio between splanchnic and cerebral tissue oxygen saturations (SCOR), rather than just examining trends of individual oxygenation values as in prior published studies as hemodynamic changes between cerebral and splanchnic tissue oxygenation can vary tremendously during stress. This severity of underlying stress to the gastrointestinal tract could be further understood by evaluating SCOR values during feeding episodes before, during, and after transfusion.

    Also, severity of anemia is another factor that may predispose premature infants at risk for TANEC. Without a formal transfusion protocol in place, these authors could stratify their data based upon pre-transfusion hemoglobin levels to determine if extreme anemia had a more pronounced effects on FTOE.

    We sincerely appreciate the authors for undertaking this much-needed study, and it should make all neonatologists reflect further about when is the appropriate time to resume feeds after a transfusion.
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    Original Investigation
    February 28, 2020

    Association of Bolus Feeding With Splanchnic and Cerebral Oxygen Utilization Efficiency Among Premature Infants With Anemia and After Blood Transfusion

    Author Affiliations
    • 1Department of Neonatology, Sydney Medical School Nepean, Nepean Hospital, The University of Sydney, Kingswood, Australia
    • 2School of Biomedical Engineering, The University of Sydney, Sydney, Australia
    • 3NHMRC Clinical Trials Centre, The University of Sydney, Camperdown, Australia
    • 4The Charles Perkins Center, The University of Sydney, Sydney, Australia
    JAMA Netw Open. 2020;3(2):e200149. doi:10.1001/jamanetworkopen.2020.0149
    Key Points español 中文 (chinese)

    Question  Is there an association between feeding and splanchnic and/or cerebral oxygen utilization efficiency during anemia and/or after packed red blood cell transfusion?

    Findings  In this cohort study of 25 hemodynamically stable, bolus-fed preterm infants who received packed red blood cell transfusions, splanchnic fractional tissue oxygen extraction was adversely associated with feedings in the immediate (first 8 hours) posttransfusion period. Cerebral fractional tissue oxygen extraction was protected during the anemia and posttransfusion periods.

    Meaning  The findings suggest that enteral feeding may be associated with gut ischemia and potentially transfusion-associated necrotizing enterocolitis and reiterate cerebral autoregulation in this context.


    Importance  The pathogenesis of transfusion-associated necrotizing enterocolitis remains elusive. Splanchnic hypoperfusion associated with packed red blood cell transfusion (PRBCT) and feeding has been implicated, but studies of splanchnic tissue oxygenation with respect to feeding plus PRBCT are lacking.

    Objective  To investigate the oxygen utilization efficiency of preterm gut and brain challenged with bolus feeding during anemia and after transfusion using near-infrared spectroscopy.

    Design, Setting, and Participants  This prospective cohort study conducted from September 1, 2014, to November 30, 2016, at a tertiary neonatal intensive care unit included 25 hemodynamically stable infants with gestational age less than 32 weeks, birth weight less than 1500 g, and postmenstrual age younger than 37 weeks. Data analysis was performed from August 1, 2017, to October 31, 2018.

    Exposures  Infants received PRBCT (15 mL/kg for 4 hours) and at least 120 mL/kg daily of second hourly bolus feedings.

    Main Outcomes and Measures  Splanchnic fractional tissue oxygen extraction (FTOEs) and cerebral fractional tissue oxygen extraction (FTOEc) measures were made during 75-minute feeding cycles that comprised a 15-minute preprandial feeding phase (FP0) and 4 contiguous 15-minute postprandial feeding phases (FP1, FP2, FP3, and FP4; each 15 minutes long). The intraindividual comparisons of feeding-related changes were evaluated during the pretransfusion epoch (TE0: 4 hours before onset of transfusion) and 3 TEs after transfusion (TE1: first 8 hours after PRBCT completion; TE2: 9-16 hours after PRBCT completion; and TE3: 17-24 hours after PRBCT completion).

    Results  Of 25 enrolled infants (13 [52%] female; median birth weight, 949 g [interquartile range {IQR}, 780-1100 g]; median gestational age, 26.9 weeks [IQR, 25.9-28.6 weeks]; median enrollment weight, 1670 g [IQR, 1357-1937 g]; and median postmenstrual age, 34 weeks [IQR, 32.9-35 weeks]), 1 infant was excluded because of corrupted near-infrared spectroscopy data. No overall association was found between FTOEs and FPs in a multivariable repeated-measures model that accounted for transfusion epochs (primary analysis approach) (FP0: mean estimate, 11.64; 95% CI, 9.55-13.73; FP1: mean estimate, 12.02; 95% CI, 9.92-14.11; FP2: mean estimate, 12.77; 95% CI, 10.68-14.87; FP3: mean estimate, 12.54; 95% CI, 10.45-14.64; FP4: mean estimate, 12.98; 95% CI, 10.89-15.08; P = .16 for the FP association). However exploratory analyses of postprandial changes in FTOEs undertaken for each transfusion epoch separately found evidence of increased postprandial FTOEs during TE1 (mean [SD] FTOEs, 10.55 [5.5] at FP0 vs 13.21 [5.96] at FP4, P = .046). The primary and exploratory analyses found no association between FTOEc and feeding phases, suggesting that cerebral oxygenation may be protected.

    Conclusions and Relevance  The findings suggest that enteral feeding may be associated with gut ischemia and potentially transfusion-associated necrotizing enterocolitis. The postprandial changes in FTOEs appear to warrant further investigation in larger randomized studies.