Cerebral Oximetry Monitoring in Extremely Preterm Infants

Hansen, Mathias; Pellicer, Adelina; Hyttel-Sørensen, Simon; Ergenekon, Ebru; Szczapa, Tomasz; Hagmann, Cornelia; Naulaers, Gunnar; Mintzer, Jonathan; Fumagalli, Monica; Dimitriou, Gabriel; Dempsey, Eugene; Tkaczyk, Jakub; Cheng, Guoqiang; Fredly, Siv; Heuchan, Anne Marie; Pichler, Gerhard; Fuchs, Hans; Nesargi, Saudamini; Hahn, Gitte Holst; Piris-Borregas, Salvador; Širc, Jan; Alsina, Miguel; Stocker, Martin; Özkan, Hilal; Sarafidis, Kosmas; Hopper, Andrew; Karen, Tanja; Rzepecka-Węglarz, Beata; Oğuz, Şerife Suna; Arruza, Luis; Memişoğlu, Aslı; Florentino, Ruth del Rio; Baserga, Mariana; Maton, Pierre; Truttmann, Anita C.; Cuevas, Isabel de las; Agergaard, Peter; Zafra, Pamela; Bender, Lars; Lauterbach, Ryszard; Lecart, C; Buyst, Julie De; El-Khuffash, Afif; Curley, Anna; Vaccarello, Olalla Otero; Miletin, Jan; Papathoma, E; Vesoulis, Zachary; Vento, Giovanni; Cornette, Luc; Lopez, Laura Serrano; Yasa, Beril; Klamer, Anja; Agosti, Massimo; Baud, Olivier; Mastretta, Emmanuele; Çetınkaya, Merih; McCall, Karen; Zeng, Shujuan; Hatzidaki, Eleftheria; Bargiel, Agata; Marciniak, Sylwia; Gao, Xiaoyan; Lin, Huang; Chalak, Lina F.; Liu, Yang; Rao, Shashidhar; Xu, Xin; Gonzalez, Begoña L.; Wilińska, Maria; Yin, Zhinan; Sadowska-Krawczenko, Iwona; Serrano-Viñuales, Itziar; Królak‐Olejnik, Barbara; Ybarra, Marta; Morales‐Betancourt, Catalina; Korček, Peter; Teresa-Palacio, Marta; Mosca, Fabio; Hergenhan, Anja; Köksal, Nilgün; Tsoni, Konstantia; Kadri, Munaf M.; Knöpfli, Claudia; Rafińska-Ważny, Elżbieta; Akin, Mustafa; Nordvik, Tone; Zhang, Peng; Kersin, Sinem G.; Thewissen, Liesbeth; Alarcón, Ana; Healy, David; Urlesberger, Berndt; Bas, Munevver; Baumgärtner, Jana; Skylogianni, Eleni; Karadyova, Veronika; Valverde, Eva; Bergón-Sendín, Elena; Kucera, Jachym; Pisoni, Silvia; Wang, Le; Smits, Anne; Sanchez-Salmador, Rebeca; Rasmussen, Marie Isabel; Olsen, Markus Harboe; Jensen, Aksel Karl Georg; Gluud, Christian; Jakobsen, Janus Christian; Greisen, Gorm

doi:10.1056/nejmoa2207554

Cited by 22 publications

(16 citation statements)

References 26 publications

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“…A previous study showed that the burden of cerebral hypoxia was significantly higher in extremely preterm infants with IVH than those without [ 54 ]. In contrast, the recent randomized, phase 3 trial showed that intervention guided by cerebral oximetry monitoring to normalize cerebral oxygenation did not reduce severe brain injury [ 55 ]. Whether iNO therapy improved cerebral tissue hypoxia or reduced fluctuation of cerebral blood flow was not documented in this retrospective study.…”

Section: Discussionmentioning

confidence: 99%

First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study

Chang,

Liu,

Chen

et al. 2024

PLoS ONE

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Background Inhaled nitric oxide (iNO) has a beneficial effect on hypoxemic respiratory failure. The increased use of concurrent iNO and milrinone was observed. We aimed to report the trends of iNO use in the past 15 years in Taiwan and compare the first-year outcomes of combining iNO and milrinone to the iNO alone in very low birth weight preterm (VLBWP) infants under mechanical ventilation. Methods This nationwide cohort study enrolled preterm singleton infants with birth weight <1500g treated with iNO from 2004 to 2019. Infants were divided into two groups, with a combination of intravenous milrinone (Group 2, n = 166) and without milrinone (Group 1, n = 591). After propensity score matching (PSM), each group’s sample size is 124. The primary outcomes were all-cause mortality and the respiratory condition, including ventilator use and duration. The secondary outcomes were preterm morbidities within one year after birth. Results After PSM, more infants in Group 2 needed inotropes. The mortality rate was significantly higher in Group 2 than in Group 1 from one month after birth till 1 year of age (55.1% vs. 13.5%) with the adjusted hazard ratio of 4.25 (95%CI = 2.42–7.47, p <0.001). For infants who died before 36 weeks of postmenstrual age (PMA), Group 2 had longer hospital stays compared to Group 1. For infants who survived after 36 weeks PMA, the incidence of moderate and severe bronchopulmonary dysplasia (BPD) was significantly higher in Group 2 than in Group 1. For infants who survived until one year of age, the incidence of pneumonia was significantly higher in Group 2 (28.30%) compared to Group 1 (12.62%) (p = 0.0153). Conclusion Combined treatment of iNO and milrinone is increasingly applied in VLBWP infants in Taiwan. This retrospective study did not support the benefits of combining iNO and milrinone on one-year survival and BPD prevention. A future prospective study is warranted.

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Section: Discussionmentioning

confidence: 99%

First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study

Chang,

Liu,

Chen

et al. 2024

PLoS ONE

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“…23 In this study, source detector distances and light wavelengths were chosen in accordance with CW-NIRS SRS devices. Indeed, clinical instruments for CW-NIRS SRS use sensors with different source detector distances tailored to the application: for neonatal monitoring a distance of 25 mm is used, 32 for adult monitoring a distance of 40 or 50 mm is preferred, 33,34 whereas intermediate values are sometimes employed for pediatric population. Increasing source detector distance aims at boosting the photon penetration depth, 35 therefore improving sensitivity to the deeper tissues, such as brain cortex below scalp and skull or muscle below the adipose tissue.…”

Section: Robustness Of the Srs Approachmentioning

confidence: 99%

Robustness of tissue oxygenation estimates by continuous wave space-resolved near infrared spectroscopy

Amendola

Contini

et al. 2023

J. Biomed. Opt.

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Continuous wave near infrared spectroscopy (CW-NIRS) is widely exploited in clinics to estimate skeletal muscles and brain cortex oxygenation. Spatially resolved spectroscopy (SRS) is generally implemented in commercial devices. However, SRS suffers from two main limitations: the a priori assumption on the spectral dependence of the reduced scattering coefficient [μ 0s ðλÞ] and the modeling of tissue as homogeneous.Aim: We studied the accuracy and robustness of SRS NIRS. We investigated the errors in retrieving hemodynamic parameters, in particular tissue oxygen saturation (S t O 2 ), when μ 0 s ðλÞ was varied from expected values, and when layered tissue was considered.Approach: We simulated hemodynamic variations mimicking real-life scenarios for skeletal muscles. Simulations were performed by exploiting the analytical solutions of the photon diffusion equation in different geometries: (1) semi-infinite homogeneous medium and constant μ 0 s ðλÞ;(2) semi-infinite homogeneous medium and linear changes in μ 0 s ðλÞ;(3) two-layered media with a superficial thickness s 1 ¼ 5, 7.5, 10 mm and constant μ 0 s ðλÞ. All simulated data were obtained at source-detector distances ρ ¼ 35, 40, 45 mm, and analyzed with the SRS approach to derive hemodynamic parameters (concentration of oxygenated and deoxygenated hemoglobin, total hemoglobin concentration, and tissue oxygen saturation, S t O 2 ) and their relative error.Results: Variations in μ 0 s ðλÞ affect the estimated S t O 2 (up to AE10%), especially if changes are different at the two wavelengths. However, the main limitation of the SRS method is the presence of a superficial layer: errors strongly larger than 20% were retrieved for the estimated S t O 2 when the superficial thickness exceeds 5 mm.Conclusions: These results highlight the need for more sophisticated strategies (e.g., the use of multiple short and long distances) to reduce the influence of superficial tissues in retrieving hemodynamic parameters and warn the SRS users to be aware of the intrinsic limitation of this approach, particularly when exploited in the clinical environment.

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“…10 However, achieving improved neurodevelopmental outcomes by targeting optimal Csat levels in preterm infants remains controversial. [11][12][13] As a patientspecific indicator of brain perfusion, cerebral NIRS measures may be associated with neurodevelopmental outcomes and may better guide transfusion thresholds than Hgb values.…”

Section: Introductionmentioning

confidence: 99%

“…A higher burden of cerebral hypoxia has been associated with severe intracranial hemorrhage and abnormal electroencephalography findings . However, achieving improved neurodevelopmental outcomes by targeting optimal Csat levels in preterm infants remains controversial . As a patient-specific indicator of brain perfusion, cerebral NIRS measures may be associated with neurodevelopmental outcomes and may better guide transfusion thresholds than Hgb values.…”

Section: Introductionmentioning

confidence: 99%

Tissue Oxygenation Changes After Transfusion and Outcomes in Preterm Infants

Chock,

Kirpalani,

Bell

et al. 2023

JAMA Netw Open

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ImportancePreterm infants with varying degrees of anemia have different tissue oxygen saturation responses to red blood cell (RBC) transfusion, and low cerebral saturation may be associated with adverse outcomes.ObjectiveTo determine whether RBC transfusion in preterm infants is associated with increases in cerebral and mesenteric tissue saturation (Csat and Msat, respectively) or decreases in cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE, respectively) and whether associations vary based on degree of anemia, and to investigate the association of Csat with death or neurodevelopmental impairment (NDI) at 22 to 26 months corrected age.Design, Setting, and ParticipantsThis was a prospective observational secondary study conducted among a subset of infants between August 2015 and April 2017 in the Transfusion of Prematures (TOP) multicenter randomized clinical trial at 16 neonatal intensive care units of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Preterm neonates with gestational age 22 to 28 weeks and birth weight 1000 g or less were randomized to higher or lower hemoglobin thresholds for transfusion. Data were analyzed between October 2020 and May 2022.InterventionsNear-infrared spectroscopy monitoring of Csat and Msat.Main Outcomes and MeasuresPrimary outcomes were changes in Csat, Msat, cFTOE, and mFTOE after transfusion between hemoglobin threshold groups, adjusting for age at transfusion, gestational age, birth weight stratum, and center. Secondary outcome at 22 to 26 months was death or NDI defined as cognitive delay (Bayley Scales of Infant and Toddler Development-III score &lt;85), cerebral palsy with Gross Motor Function Classification System level II or greater, or severe vision or hearing impairment.ResultsA total of 179 infants (45 [44.6%] male) with mean (SD) gestational age 25.9 (1.5) weeks were enrolled, and valid data were captured from 101 infants during 237 transfusion events. Transfusion was associated with a significant increase in mean Csat of 4.8% (95% CI, 2.7%-6.9%) in the lower–hemoglobin threshold group compared to 2.7% (95% CI, 1.2%-4.2%) in the higher–hemoglobin threshold group, while mean Msat increased 6.7% (95% CI, 2.4%-11.0%) vs 5.6% (95% CI, 2.7%-8.5%). Mean cFTOE and mFTOE decreased in both groups to a similar extent. There was no significant change in peripheral oxygen saturation (SpO2) in either group (0.2% vs −0.2%). NDI or death occurred in 36 infants (37%). Number of transfusions with mean pretransfusion Csat less than 50% was associated with NDI or death (odds ratio, 2.41; 95% CI, 1.08-5.41; P = .03).Conclusions and RelevanceIn this secondary study of the TOP randomized clinical trial, Csat and Msat were increased after transfusion despite no change in SpO2. Lower pretransfusion Csat may be associated with adverse outcomes, supporting further investigation of targeted tissue saturation monitoring in preterm infants with anemia.Trial RegistrationClinicalTrials.gov Identifier: NCT01702805

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Cerebral Oximetry Monitoring in Extremely Preterm Infants

Cited by 22 publications

References 26 publications

First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study

First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study

Robustness of tissue oxygenation estimates by continuous wave space-resolved near infrared spectroscopy

Tissue Oxygenation Changes After Transfusion and Outcomes in Preterm Infants

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