Acta Pædiatrica ISSN 0803-5253

REGULAR ARTICLE

Heart rate passivity of cerebral tissue oxygenation is associated with predictors of poor outcome in preterm infants S Mitra ([email protected])1, M Czosnyka2, P Smielewski2, H O’Reilly3, K Brady4, T Austin1 1.Neonatal Unit, Rosie Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK 2.Academic Neurosurgical Unit, Department of Neurosurgery, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK 3.Neonatal Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK 4.Department of Anesthesiology and Critical Care Medicine, John Hopkins University School of Medicine, Baltimore, MD, USA

Keywords cerebral Doppler, cerebral hemodynamic changes, heart rate, near-infrared spectroscopy, premature infants Correspondence Dr Subhabrata Mitra, Neonatal Unit, Box 402, Rosie Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK. Tel: +447980729314 | Fax: +441223217064 | Email: [email protected] Received 21 December 2013; revised 2 March 2014; accepted 15 May 2014. DOI:10.1111/apa.12696

ABSTRACT Aim: Near-infrared spectroscopy (NIRS) and transcranial Doppler (TCD) allow non-invasive assessment of cerebral haemodynamics. We assessed cerebrovascular reactivity in preterm infants by investigating the relationship between NIRS- and TCD-derived indices and correlating them with severity of clinical illness. Methods: We recorded the NIRS-derived cerebral tissue oxygenation index (TOI) and TCDderived flow velocity (Fv), along with other physiological variables. Moving correlation coefficients between measurements of cerebral perfusion (TOI, Fv) and heart rate were calculated. We presumed that positivity of these correlation coefficients – tissue oxygenation heart rate reactivity index (TOHRx) and flow velocity heart rate reactivity index (FvHRx) – would indicate a direct relationship between cerebral perfusion and cardiac output representing impaired cerebrovascular autoregulation. Results: We studied 31 preterm infants at a median age of 2 days, born at a median gestational age of 26 + 1 weeks. TOHRx was significantly correlated with gestational age (R = 0.57, p = 0.007), birth weight (R = 0.58, p = 0.006) and the Clinical Risk Index for Babies II (R = 0.55, p = 0.0014). TOHRx and FvHRx were significantly correlated (R = 0.39, p = 0.028). Conclusion: Heart rate has a key influence on cerebral haemodynamics in preterm infants, and TOHRx may be of diagnostic value in identifying impaired cerebrovascular reactivity leading to adverse clinical outcome.

INTRODUCTION Brain injury in the preterm infant is a major cause of death and lifelong neurodisability. The haemodynamic changes in the days immediately following birth, in this group of infants, has been implicated in both haemorrhagic and ischaemic brain injury (1). Cerebral autoregulation is an important protective mechanism that ensures constant cerebral perfusion over a range of mean arterial blood pressures (MABP) (2). This can be assessed by continuous

Key notes

Abbreviations CBF, Cerebral blood flow; CPP, Cerebral perfusion pressure; CRIB, Clinical risk index for babies; Fv, Flow velovity; FvHRx, Flow velocity heart rate reactivity index; ICP, Intracranial pressure; MABP, Mean arterial blood pressure; MCA, Middle cerebral artery; Mx, Mean flow index; NIRS, Near-infrared spectroscopy; PaCO2, Partial pressure of carbon dioxide; PDA, Patent ductus arteriosus; SpO2, Peripheral oxygen saturation; SRS, Spatially resolved spectroscopy; TBI, Traumatic brain injury; TCD, Transcranial Doppler; TOHRx, Tissue oxygenation heart rate reactivity index; TOI, Tissue oxygenation index; TOx, Tissue oxygenation index for dynamic autoregulation.

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measurements of cerebral perfusion pressure (CPP), where CPP equals the difference between MABP and intracranial pressure (ICP). Cerebrovascular reactivity (CVR) reflects the capability of cerebrovascular smooth muscle to respond to changes in intramural pressure and is an important mechanism for maintaining constant cerebral blood flow. Loss of cerebral autoregulation has been identified as an independent predictor of poor outcome following traumatic







Impaired cerebrovascular autoregulation in preterm infants is related to poor outcome, making it important to understand the factors associated with impaired cerebrovascular control. Our study of 31 preterm infants showed that the tissue oxygenation heart rate reactivity index demonstrated a significant correlation with an early neonatal risk index score for predicting morbidity and mortality. The results suggest that heart rate influenced cerebrovascular regulation in the first few days of life.

©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2014 103, pp. e374–e382

Mitra et al.

brain injury (TBI) in children and adults (3). Both the presence and limits of autoregulation in the neonate have been much debated and remain unclear (4,5). Relying on blood pressure measurements alone to make informed clinical decisions ignores the complex circulatory control mechanisms that exist to optimise oxygen delivery to vital organs. The relationship between cerebrovascular reactivity and other important physiological variables, such as cardiac output, in preterm infants remains unexplored. The ability to obtain quantitative information on a range of circulatory parameters would, therefore, represent a significant advance in the management of these patients. Near-infrared spectroscopy (NIRS) and transcranial cerebral Doppler (TCD) ultrasound are non-invasive techniques, which have been applied widely to assess cerebral perfusion and oxygenation in newborn infants (6). A number of indices of cerebrovascular reactivity based on measurements using TCD and NIRS have been described in both children and adults (3,7,8). In this study, we describe a novel index of cerebrovascular reactivity, tissue oxygenation heart rate reactivity index (TOHRx), based on the relationship between the cerebral tissue oxygenation index (TOI) and heart rate. In premature infants, heart rate is the primary determinant of cardiac output. A positive relationship between TOI and heart rate would indicate impaired cerebrovascular reactivity. We hypothesised that the moving correlation coefficient between TOI and heart rate would, therefore, correlate with early indicators of clinical outcome.

PATIENTS AND METHODS Subject selection The parents of preterm infants admitted to the neonatal intensive care unit (NICU) at the Rosie Hospital (Cambridge University Hospitals NHS Foundation Trust) for clinical care were approached for the study. The inclusion criteria for the study were preterm infants born at ≤32 weeks’ gestation and infants born with very low birth weight (

Heart rate passivity of cerebral tissue oxygenation is associated with predictors of poor outcome in preterm infants.

Near-infrared spectroscopy (NIRS) and transcranial Doppler (TCD) allow non-invasive assessment of cerebral haemodynamics. We assessed cerebrovascular ...
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