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Cerebrovascular And Cardiovascular Responses To Cardio-Respiratory Events In Preterm Infants During The Transitional Period.

Silvia Martini1, Luigi Corvaglia1, Giulia Frabboni1, Viviana Perrone1, Marek Czosnyka2, Peter Smielewski2, Francesca Vitali1, Arianna Aceti1, Giacomo Faldella1, Topun Austin3 
1 Neonatal Intensive Care Unit, St. Orsola-Malpighi University Hospital, Bologna, Italy  2 Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK  3 Neonatal Intensive Care Unit, Cambridge University Hospitals, Cambridge, UK 
Introduction 
Intermittent episodes of hypoxemia and/or bradycardia, also defined as cardio-respiratory events (CRE) are very frequent in preterm infants and may result in transient hypoxia and hypoperfusion to target organs, with possible clinical implications. The hemodynamic instability that characterizes the first 72 hours of life place preterm infants at high risk of complications and may contribute to enhance fluctuations in perfusion and oxygenation induced by CRE. In this study we aimed to explore whether different CRE types occurring in preterm infants during the transitional period determine different cardiovascular and cerebrovascular changes. 
Methods 
Non-invasively ventilated newborns (gestational age <32 weeks, birth weight <1500 g) admitted to the Neonatl Intensive Care Unit of St. Orsola-Malpighi Hospital (Bologna, Italy) underwent continuous simultaneous monitoring of systemic and cerebral haemodynamic parameters by near infrared spectroscopy, pulse oximetry and electrical velocimetry during the first 72 hours of life. The following parameters were evaluated: cerebral oxygenation (CrSO2), cerebral fraction of oxygen extraction (cFTOE), cerebral total haemoglobin index (cTHI), arterial oxygen saturation (SpO2), heart rate (HR), cardiac output (CO), heart contractility (ICON), systemic vascular resistances (SVR). CO was indexed for the infants’ weight, whereas SVR were adjusted for their body surface area. The monitoring data were recorded via ICM+ software (Cambridge Enterprise Ltd, UK). CRE ≥10 sec were clustered into isolated desaturation (ID, SpO2<85%), isolated bradycardia (IB, HR<100 bpm or <70% baseline) and combined desaturation/bradycardia (DB). Percentage changes (%Δ) of the recorded parameters between pre-event baseline and event nadir were analysed and compared among ID, IB and DB by Kruskal-Wallis test. Significance level was set at p<0.05. No funds were perceived for the present study. The study protocol was approved by the Ethics Committee of St. Orsola-Malpighi Hospital (Bologna, Italy). 
Results 
A total of 625 events from 24 neonates (mean gestational age 30±2 weeks) were analysed. Of these, ID were 385 (61.6%), IB 67 (10.7%) and DB 173 (27.7%). IB and BD led to a significant decrease in %ΔCOI and increase in %ΔSVRI increase compared to ID. A slight, but significant decrease in %ΔICON was also observed during BD compared to IB (Figure 1). As shown in Figure 2, %ΔcTOI significantly differed between CRE types, with the greatest reduction during DB, followed by ID and IB. DB resulted in a significant decrease in %ΔcTHI compared to ID, whereas %ΔcFTOE reached significantly lower values in the presence of desaturation, either with or without bradycardia. 
Conclusions 
Cardiovascular and cerebrovascular responses to CRE differ significantly in relation to the event type, with possible clinical implications in terms of end-organ perfusion. In particular, the occurrence of bradycardia results in a transient CO decrease and SVR increase that, in the presence of concomitant hypoxia, may further reduce brain perfusion and O2 supply, consistently with the greatest cTOI and THI reduction observed during DB. Moreover, cFTOE was significantly reduced during ID and DB compared to IB, suggesting a transient reduction in O2 delivery with no compensatory increase of O2 extraction. Eventually, the cardiovascular ad cerebrovascular effects of IB, ID and DB observed in the present study suggest different physiology mechanisms underlying these CRE, which may thus benefit from a tailored response by nursing or medical staff. 
References 
1. Di Fiore JM, Poets CF, Gauda E, Martin RJ, MacFarlane P.Cardiorespiratory events in preterm infants: interventions and consequences. J Perinatol. 2016;36:251-8 
2. Schmid MB, Hopfner RJ, Lenhof S, Hummler HD, Fuchs H. Cerebral oxygenation during intermittent hypoxemia and bradycardia in preterm infants. Neonatology 2015;107:137-46. 
3. Walter LM, Ahmed B, Odoi A, Cooney H, Horne RSC, Wong FY. Bradycardias are associated with more severe effects on cerebral oxygenation in very preterm infants than in late preterm infants. Early Hum Dev 2018;127:33-41 
Figures 
Figure 1. Percentage changes of cardiac output (COI), heart contractility (ICON) and systemic vascular resistances induced by different cardio-respiratory events: isolated desaturations (ID), isolated bradycardias (IB) and a combination of the two (DB). 
Figure 1. Percentage changes of cardiac output (COI), heart contractility (ICON) and systemic vascular resistances induced by different cardio-respiratory events: isolated desaturations (ID), isolated bradycardias (IB) and a combination of the two (DB).
Figure 2. Percentage changes of cerebral oxygenation (COI), cerebral total haemoglobin index (cTHI) and cerebral fraction of oxygen extraction (cFTOE) induced by different cardio-respiratory events: isolated desaturations (ID), isolated bradycardias (IB) and a combination of the two (DB). 
Figure 2. Percentage changes of cerebral oxygenation (COI), cerebral total haemoglobin index (cTHI) and cerebral fraction of oxygen extraction (cFTOE) induced by different cardio-respiratory events: isolated desaturations (ID), isolated bradycardias (IB) and a combination of the two (DB).

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