Acta Pædiatrica ISSN 0803-5253
REGULAR ARTICLE
Healthy term and moderately preterm infants have similar cerebral oxygen saturation and cerebral blood flow volumes during early post-natal transition A Demel ([email protected])1, K Feilke1, M Sch€oning2, M Wolf3, CF Poets1, AR Franz1 1.Department of Neonatology, University Children’s Hospital Tuebingen, Tuebingen, Germany 2.Department of Neuropediatrics, University Children’s Hospital Tuebingen, Tuebingen, Germany 3.Biomedical Optics Research Laboratory, Division of Neonatology, University Hospital Zurich, Zurich, Switzerland
Keywords Cerebral blood flow volume, Cerebral oxygen saturation, Near-infrared spectroscopy, Preterm infants, Term infants Correspondence A Demel, Department of Neonatology, University Children’s Hospital Tuebingen, Calwerstr. 7, 72076 Tuebingen, Germany. Tel: +49 7071 29 84750 | Fax: +49 7071 293969 | E-mail: [email protected] Received 7 October 2014; revised 17 February 2015; accepted 8 April 2015. DOI:10.1111/apa.13023
ABSTRACT Aim: This pilot study evaluated changes in regional cerebral oxygen saturation and cerebral blood flow volume during the transitional period in healthy term and moderately preterm infants. Methods: The cohort comprised 16 preterm infants and seven full-term infants with mean gestational ages of 34 and 39 weeks, respectively. Longitudinal measurements were conducted during the first three days after birth. Regional cerebral oxygen saturation was determined bilaterally by frequency domain near-infrared spectroscopy. Flow volumes were determined in internal carotid and vertebral arteries by multiplying the time-averaged velocity by the cross-sectional area: cerebral blood flow volume was calculated as the sum of flow volumes and adjusted for brain weight. Results: Brain weight-adjusted cerebral blood flow volumes and regional cerebral oxygen saturation were similar in preterm and term infants. Regional cerebral oxygen saturation did not correlate with brain weight-adjusted cerebral blood flow volume. Right and left brain weight-adjusted internal carotid flow volumes did not correlate with right and left regional cerebral oxygen saturation. Conclusion: Our findings suggest that during the first three days after birth there was adequate cardiorespiratory adaptation, cerebral perfusion and adequate compensation through the arterial circle of Willis in both healthy term and moderately preterm infants.
INTRODUCTION Post-natal brain injury may result from inadequate cerebral perfusion and oxygenation (1). Despite advances in imaging and near-infrared spectroscopy (NIRS), a bedside method is required to reliably and continuously monitor developmental and pathological changes in perfusion and oxygenation of the brain in neonates to elucidate and eventually prevent the pathophysiology underlying brain injury. Previously, transcranial Doppler ultrasound measurements of cerebral blood flow (CBF) velocity in intracranial arteries have been applied to assess cerebral perfusion, but variable vessel diameters, which cannot be quantified transcranially, limit its clinical usefulness. In contrast, our group previously described a method to sonographically determine neonatal CBF volume (2). Changes in CBF volume may either appropriately reflect changes in demand or result from pathological disturbances and are hence difficult to interpret when evaluated alone. To assess cerebral oxygenation in preterm infants, conventional NIRS has been established to assess cerebral oxygen saturation in preterm infants. However, conventional NIRS only enables an assessment of relative changes
e330
in the chromophore concentrations and absolute values of regional cerebral oxygen saturations (rcStO2) must be interpreted with caution (3–5). Furthermore, rcStO2 alone may not be a reliable indicator of oxygen delivery to the tissue to lead to a clinical decision (6–9). In contrast, frequency domain NIRS is a technology that, by measuring the path length the light has travelled, allows us
Key Notes
This study evaluated changes in regional cerebral oxygen saturation and cerebral blood flow volume during the transitional period in healthy term and moderately preterm infants. We studied 16 preterm and seven full-term infants with mean gestational ages of 34 and 39 weeks, respectively. During the first three days after birth, there was adequate cardiorespiratory adaptation, cerebral perfusion and adequate compensation through the arterial circle of Willis in both groups.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e330–e336
Demel et al.
to exactly quantify absorption and scattering coefficients and hence the absolute chromophore concentrations (10,11). Complementing NIRS with additional measures of cerebral perfusion may improve assessment of cerebral haemodynamics and increase reliability (2,12,13). CBF and cerebral blood volume have been assessed in the past by NIRS and were found to allow outcome prediction in term infants with perinatal asphyxia and in preterm infants with arterial hypotension (14,15). We propose that the combined determination of cerebral oxygenation by NIRS and cerebral blood flow by ultrasound may enable an even better evaluation of the oxygen and substrate supply to the brain. Furthermore, Boas et al. (16) supported the hypothesis that measures of blood flow and blood volume were more reliable than the evaluation of rcStO2 alone. This was a pilot study to evaluate the feasibility of a combined determination of rcStO2 and CBF volume.
PATIENTS AND METHODS Design This prospective longitudinal observational pilot study was conducted during the first three days after birth with measurements at 0–12 hours, 12–24 hours, 24–36 hours, 36–48 hours and 48–72 hours. Patients Infants were recruited at the Neonatal Intensive Care Unit of the University Children’s Hospital Tuebingen, Germany, from November 2010 to July 2011. Inclusion criteria were haemodynamically stable, healthy infants without circulatory compromise, which was defined as a mean arterial pressure higher than or equal to the minimum gestational age, a peripheral capillary refill time of less than two seconds and lack of circulatory support. Exclusion criteria were chromosomal or syndromal abnormalities, structural heart defects, infectious diseases, such as sepsis, as well as any brain injury such as periventricular leukomalacia, intraventricular haemorrhage, hydrocephalus and meningitis. The final cohort comprised 16 preterm infants with a mean gestational age of 34 weeks and a mean birthweight of 2.120 g and seven full-term infants with a mean gestational age of 39 weeks and a mean birthweight of 3.520 g (Table 1). Methods Near-infrared spectroscopy Frequency domain NIRS measurements were conducted with the Oxiplex TS 3.1 (ISS Inc., Champaign, Illinois, USA) and the data processed using its proprietary software. Its light is generated by eight laser diodes, four diodes per wavelength, intensity modulated at a frequency of 110 MHz and emitted at 834 nm and 692 nm wavelength. Photons are transmitted through an optical fibre cable to the probe. Based on the amplitude and phase shift of the intensity modulated light, concentrations of the predominant chromophores, oxygenated haemoglobin and deoxygenated haemoglobin were calculated assuming a brain water
Cerebral haemodynamics in infants
Table 1 Clinical characteristics of included participants: median (range) Clinical characteristics
Preterm infants (n = 16) Full-term infants (n = 7)
Gestational age (weeks) Head circumference (cm) Birthweight (g) Umbilical artery pH APGAR 5 minutes Gender M/F (n/n) Delivery mode (C-section/vaginal delivery) Respiratory support (no support/nCPAP)
34 (32 1/7–35 5/7) 39 6/7 (37 0/7–40 1/7) 31.3 (27.0–34.0)
35.0 (32.0–36.0)
2120 (1150–2922) 7.28 (7.21–7.39) 8 (7–10) 9/7 11/5
3520 (2360–4390) 7.26 (7.23–7.36) 9 (8–9) 2/5 5/2
5/11
7/0
nCPAP, Nasal continuous positive airway pressure.
content of 90% (10,11,17,18). Total haemoglobin concentration was calculated as the sum of deoxygenated haemoglobin and oxygenated haemoglobin concentrations and rcStO2 as oxygenated haemoglobin divided by total haemoglobin concentration. The soft probe with four emitter–detector distances of 1.5, 2.0, 2.5 and 3.0 cm was applied to the infant’s skull, held by the examiner’s hand with gentle pressure during sleep in a supine position by rotating the head
REGULAR ARTICLE
Healthy term and moderately preterm infants have similar cerebral oxygen saturation and cerebral blood flow volumes during early post-natal transition A Demel ([email protected])1, K Feilke1, M Sch€oning2, M Wolf3, CF Poets1, AR Franz1 1.Department of Neonatology, University Children’s Hospital Tuebingen, Tuebingen, Germany 2.Department of Neuropediatrics, University Children’s Hospital Tuebingen, Tuebingen, Germany 3.Biomedical Optics Research Laboratory, Division of Neonatology, University Hospital Zurich, Zurich, Switzerland
Keywords Cerebral blood flow volume, Cerebral oxygen saturation, Near-infrared spectroscopy, Preterm infants, Term infants Correspondence A Demel, Department of Neonatology, University Children’s Hospital Tuebingen, Calwerstr. 7, 72076 Tuebingen, Germany. Tel: +49 7071 29 84750 | Fax: +49 7071 293969 | E-mail: [email protected] Received 7 October 2014; revised 17 February 2015; accepted 8 April 2015. DOI:10.1111/apa.13023
ABSTRACT Aim: This pilot study evaluated changes in regional cerebral oxygen saturation and cerebral blood flow volume during the transitional period in healthy term and moderately preterm infants. Methods: The cohort comprised 16 preterm infants and seven full-term infants with mean gestational ages of 34 and 39 weeks, respectively. Longitudinal measurements were conducted during the first three days after birth. Regional cerebral oxygen saturation was determined bilaterally by frequency domain near-infrared spectroscopy. Flow volumes were determined in internal carotid and vertebral arteries by multiplying the time-averaged velocity by the cross-sectional area: cerebral blood flow volume was calculated as the sum of flow volumes and adjusted for brain weight. Results: Brain weight-adjusted cerebral blood flow volumes and regional cerebral oxygen saturation were similar in preterm and term infants. Regional cerebral oxygen saturation did not correlate with brain weight-adjusted cerebral blood flow volume. Right and left brain weight-adjusted internal carotid flow volumes did not correlate with right and left regional cerebral oxygen saturation. Conclusion: Our findings suggest that during the first three days after birth there was adequate cardiorespiratory adaptation, cerebral perfusion and adequate compensation through the arterial circle of Willis in both healthy term and moderately preterm infants.
INTRODUCTION Post-natal brain injury may result from inadequate cerebral perfusion and oxygenation (1). Despite advances in imaging and near-infrared spectroscopy (NIRS), a bedside method is required to reliably and continuously monitor developmental and pathological changes in perfusion and oxygenation of the brain in neonates to elucidate and eventually prevent the pathophysiology underlying brain injury. Previously, transcranial Doppler ultrasound measurements of cerebral blood flow (CBF) velocity in intracranial arteries have been applied to assess cerebral perfusion, but variable vessel diameters, which cannot be quantified transcranially, limit its clinical usefulness. In contrast, our group previously described a method to sonographically determine neonatal CBF volume (2). Changes in CBF volume may either appropriately reflect changes in demand or result from pathological disturbances and are hence difficult to interpret when evaluated alone. To assess cerebral oxygenation in preterm infants, conventional NIRS has been established to assess cerebral oxygen saturation in preterm infants. However, conventional NIRS only enables an assessment of relative changes
e330
in the chromophore concentrations and absolute values of regional cerebral oxygen saturations (rcStO2) must be interpreted with caution (3–5). Furthermore, rcStO2 alone may not be a reliable indicator of oxygen delivery to the tissue to lead to a clinical decision (6–9). In contrast, frequency domain NIRS is a technology that, by measuring the path length the light has travelled, allows us
Key Notes
This study evaluated changes in regional cerebral oxygen saturation and cerebral blood flow volume during the transitional period in healthy term and moderately preterm infants. We studied 16 preterm and seven full-term infants with mean gestational ages of 34 and 39 weeks, respectively. During the first three days after birth, there was adequate cardiorespiratory adaptation, cerebral perfusion and adequate compensation through the arterial circle of Willis in both groups.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e330–e336
Demel et al.
to exactly quantify absorption and scattering coefficients and hence the absolute chromophore concentrations (10,11). Complementing NIRS with additional measures of cerebral perfusion may improve assessment of cerebral haemodynamics and increase reliability (2,12,13). CBF and cerebral blood volume have been assessed in the past by NIRS and were found to allow outcome prediction in term infants with perinatal asphyxia and in preterm infants with arterial hypotension (14,15). We propose that the combined determination of cerebral oxygenation by NIRS and cerebral blood flow by ultrasound may enable an even better evaluation of the oxygen and substrate supply to the brain. Furthermore, Boas et al. (16) supported the hypothesis that measures of blood flow and blood volume were more reliable than the evaluation of rcStO2 alone. This was a pilot study to evaluate the feasibility of a combined determination of rcStO2 and CBF volume.
PATIENTS AND METHODS Design This prospective longitudinal observational pilot study was conducted during the first three days after birth with measurements at 0–12 hours, 12–24 hours, 24–36 hours, 36–48 hours and 48–72 hours. Patients Infants were recruited at the Neonatal Intensive Care Unit of the University Children’s Hospital Tuebingen, Germany, from November 2010 to July 2011. Inclusion criteria were haemodynamically stable, healthy infants without circulatory compromise, which was defined as a mean arterial pressure higher than or equal to the minimum gestational age, a peripheral capillary refill time of less than two seconds and lack of circulatory support. Exclusion criteria were chromosomal or syndromal abnormalities, structural heart defects, infectious diseases, such as sepsis, as well as any brain injury such as periventricular leukomalacia, intraventricular haemorrhage, hydrocephalus and meningitis. The final cohort comprised 16 preterm infants with a mean gestational age of 34 weeks and a mean birthweight of 2.120 g and seven full-term infants with a mean gestational age of 39 weeks and a mean birthweight of 3.520 g (Table 1). Methods Near-infrared spectroscopy Frequency domain NIRS measurements were conducted with the Oxiplex TS 3.1 (ISS Inc., Champaign, Illinois, USA) and the data processed using its proprietary software. Its light is generated by eight laser diodes, four diodes per wavelength, intensity modulated at a frequency of 110 MHz and emitted at 834 nm and 692 nm wavelength. Photons are transmitted through an optical fibre cable to the probe. Based on the amplitude and phase shift of the intensity modulated light, concentrations of the predominant chromophores, oxygenated haemoglobin and deoxygenated haemoglobin were calculated assuming a brain water
Cerebral haemodynamics in infants
Table 1 Clinical characteristics of included participants: median (range) Clinical characteristics
Preterm infants (n = 16) Full-term infants (n = 7)
Gestational age (weeks) Head circumference (cm) Birthweight (g) Umbilical artery pH APGAR 5 minutes Gender M/F (n/n) Delivery mode (C-section/vaginal delivery) Respiratory support (no support/nCPAP)
34 (32 1/7–35 5/7) 39 6/7 (37 0/7–40 1/7) 31.3 (27.0–34.0)
35.0 (32.0–36.0)
2120 (1150–2922) 7.28 (7.21–7.39) 8 (7–10) 9/7 11/5
3520 (2360–4390) 7.26 (7.23–7.36) 9 (8–9) 2/5 5/2
5/11
7/0
nCPAP, Nasal continuous positive airway pressure.
content of 90% (10,11,17,18). Total haemoglobin concentration was calculated as the sum of deoxygenated haemoglobin and oxygenated haemoglobin concentrations and rcStO2 as oxygenated haemoglobin divided by total haemoglobin concentration. The soft probe with four emitter–detector distances of 1.5, 2.0, 2.5 and 3.0 cm was applied to the infant’s skull, held by the examiner’s hand with gentle pressure during sleep in a supine position by rotating the head
