BACKGROUND: The impact of the permissive hypotension approach in clinically well infants on regional cerebral oxygen saturation (rScO2) and autoregulatory capacity (CAR) remains unknown. METHODS: Prospective cohort study of blinded rScO2 measurements within a randomized controlled trial of management of hypotension (HIP trial) in extremely preterm infants. rScO2, mean arterial blood pressure, duration of cerebral hypoxia, and transfer function (TF) gain inversely proportional to CAR, were compared between hypotensive infants randomized to receive dopamine or placebo and between hypotensive and non-hypotensive infants, and related to early intraventricular hemorrhage or death. RESULTS: In 89 potentially eligible HIP trial patients with rScO2 measurements, the duration of cerebral hypoxia was significantly higher in 36 hypotensive compared to 53 non-hypotensive infants. In 29/36 hypotensive infants (mean GA 25 weeks, 69% males) receiving the study drug, no significant difference in rScO2 was observed after dopamine (n = 13) compared to placebo (n = 16). Duration of cerebral hypoxia was associated with early intraventricular hemorrhage or death. Calculated TF gain (n = 49/89) was significantly higher reflecting decreased CAR in 16 hypotensive compared to 33 non-hypotensive infants. CONCLUSIONS: Dopamine had no effect on rScO2 compared to placebo in hypotensive infants. Hypotension and cerebral hypoxia are associated with early intraventricular hemorrhage or death. IMPACT: Treatment of hypotension with dopamine in extremely preterm infants increases mean arterial blood pressure, but does not improve cerebral oxygenation. Hypotensive extremely preterm infants have increased duration of cerebral hypoxia and reduced cerebral autoregulatory capacity compared to non-hypotensive infants. Duration of cerebral hypoxia and hypotension are associated with early intraventricular hemorrhage or death in extremely preterm infants. Since systematic treatment of hypotension may not be associated with better outcomes, the diagnosis of cerebral hypoxia in hypotensive extremely preterm infants might guide treatment.

Applied Mathematics and Computer Science School of Engineering Science and Technology Universidad del Rosario Bogotá Colombia

Coombe Woman and Infants University Hospital Dublin Ireland

Department of Electrical Engineering ESAT Stadius KU Leuven Leuven Belgium

Department of Neonatal Intensive Care University Hospital Antwerp Edegem Belgium

Department of Neonatology Rotunda Hospital and School of Medicine Royal College of Surgeons in Ireland Dublin Ireland

Department of Neonatology Tomas Bata University Zlín Czech Republic

Department of Neonatology University Hospital of Ostrava Ostrava Czech Republic

Department of Neonatology University Hospitals Leuven Leuven Belgium

Department of Pediatrics Division of Neonatology CHU Sainte Justine University of Montreal Montréal QC Canada

Departments of Pediatrics Pharmacology and Surgery University of Alberta Edmonton AB Canada

INFANT Research Centre University College Cork Cork Ireland

Institute for the Care of Mother and Child Prague 3rd Faculty of Medicine Charles University Prague Czech Republic

National Maternity Hospital Dublin Ireland

UCL Institute for Women's Health University College London London UK

Pediatr Res. 2021 Aug;90(2):248-249. doi: 10.1038/s41390-021-01552-0. PubMed

See more in PubMed

Adams-Chapman, I. et al. Neurodevelopmental impairment among extremely preterm infants in the neonatal research network. Pediatrics 141, e20173091 (2018). PubMed DOI PMC

Blencowe, H. et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 379, 2162–2172 (2012). PubMed DOI PMC

Levene, M. Development of audit measures and guidelines for good practice in the management of neonatal respiratory distress syndrome. Report of a Joint Working Group of the British Association of Perinatal Medicine and the Research Unit of the Royal College of Physicians. Arch. Dis. Child 67, 1221–1227 (1992). DOI

Munro, M. J., Walker, A. M. & Barfield, C. P. Hypotensive extremely low birth weight infants have reduced cerebral blood flow. Pediatrics 114, 1591–1596 (2004). PubMed DOI PMC

Borch, K., Lou, H. C. & Greisen, G. Cerebral white matter blood flow and arterial blood pressure in preterm infants. Acta Paediatr. 99, 1489–1492 (2010). PubMed DOI PMC

Miall-Allen, V. M., de Vries, L. S. & Whitelaw, A. G. Mean arterial blood pressure and neonatal cerebral lesions. Arch. Dis. Child 62, 1068–1069 (1987). PubMed DOI PMC

Tsuji, M. et al. Cerebral intravascular oxygenation correlates with mean arterial pressure in critically ill premature infants. Pediatrics 106, 625–632 (2000). PubMed DOI PMC

Wong, F. Y. et al. Impaired autoregulation in preterm infants identified by using spatially resolved spectroscopy. Pediatrics 121, e604–e611 (2008). PubMed DOI PMC

Batton, B. et al. Blood pressure, anti-hypotensive therapy, and neurodevelopment in extremely preterm infants. J. Pediatr. 154, 351–357 (2009). e351. PubMed DOI PMC

Sassano-Higgins, S., Friedlich, P. & Seri, I. A meta-analysis of dopamine use in hypotensive preterm infants: blood pressure and cerebral hemodynamics. J. Perinatol. 31, 647–655 (2011). PubMed DOI PMC

Eriksen, V. R., Hahn, G. H. & Greisen, G. Dopamine therapy is associated with impaired cerebral autoregulation in preterm infants. Acta Paediatr. 103, 1221–1226 (2014). PubMed DOI PMC

Durrmeyer, X. et al. Abstention or intervention for isolated hypotension in the first 3 days of life in extremely preterm infants: association with short-term outcomes in the EPIPAGE 2 cohort study. Arch. Dis. Child. Fetal Neonatal Ed. 102, 490–496 (2017). PubMed DOI PMC

Dempsey, E. M., Al Hazzani, F. & Barrington, K. J. Permissive hypotension in the extremely low birthweight infant with signs of good perfusion. Arch. Dis. Child Fetal Neonatal Ed. 94, F241–F244 (2009). PubMed DOI PMC

Dempsey, E. M. et al. Management of hypotension in preterm infants (The HIP Trial): a randomised controlled trial of hypotension management in extremely low gestational age newborns. Neonatology 105, 275–281 (2014). PubMed DOI PMC

Papile, L. A., Burstein, J., Burstein, R. & Koffler, H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J. Pediatr. 92, 529–534 (1978). PubMed DOI PMC

Wong, F. Y., Nakamura, M., Alexiou, T., Brodecky, V. & Walker, A. M. Tissue oxygenation index measured using spatially resolved spectroscopy correlates with changes in cerebral blood flow in newborn lambs. Intensive Care Med. 35, 1464–1470 (2009). PubMed DOI PMC

Caicedo, A. et al. Decomposition of near-infrared spectroscopy signals using oblique subspace projections: applications in brain hemodynamic monitoring. Front. Physiol. 7, 515 (2016). PubMed DOI PMC

Caicedo, A. et al. Detection of cerebral autoregulation by near-infrared spectroscopy in neonates: performance analysis of measurement methods. J. Biomed. Opt. 17, 117003 (2012). PubMed DOI PMC

Hahn, G. H., Heiring, C., Pryds, O. & Greisen, G. Applicability of near-infrared spectroscopy to measure cerebral autoregulation noninvasively in neonates: a validation study in piglets. Pediatr. Res. 70, 166–170 (2011). PubMed DOI PMC

Schreiber, T. & Schmitz, A. Surrogate time series. Phys. D 142, 346–382 (2000). DOI

Kleiser, S., Nasseri, N., Andresen, B., Greisen, G. & Wolf, M. Comparison of tissue oximeters on a liquid phantom with adjustable optical properties. Biomed. Opt. Express 7, 2973–2992 (2016). PubMed DOI PMC

van Bel, F., Lemmers, P. & Naulaers, G. Monitoring neonatal regional cerebral oxygen saturation in clinical practice: value and pitfalls. Neonatology 94, 237–244 (2008). PubMed DOI PMC

Harrell, F. Regression Modeling Strategies (Springer, 2001).

The International Neonatal Network. The CRIB (clinical risk index for babies) score: a tool for assessing initial neonatal risk and comparing performance of neonatal intensive care units. Lancet 342, 193–198 (1993). DOI

Zhang, J., Penny, D. J., Kim, N. S., Yu, V. Y. H. & Smolich, J. J. Mechanisms of blood pressure increase induced by dopamine in hypotensive preterm neonates. Arch. Dis. Child. Fetal Neonatal Ed. 81, F99–F104 (1999). PubMed DOI PMC

Rennie, J. M. Cerebral blood flow velocity variability after cardiovascular support in premature babies. Arch. Dis. Child 64, 897–901 (1989). PubMed DOI PMC

Seri, I., Rudas, G., Bors, Z., Kanyicska, B. & Tulassay, T. Effects of low-dose dopamine infusion on cardiovascular and renal functions, cerebral blood flow, and plasma catecholamine levels in sick preterm neonates. Pediatr. Res. 34, 742–749 (1993). PubMed DOI PMC

Bouissou, A. et al. Hypotension in preterm infants with significant patent ductus arteriosus: effects of dopamine. J. Pediatr. 153, 790–794 (2008). PubMed DOI PMC

Pellicer, A. et al. Cardiovascular support for low birth weight infants and cerebral hemodynamics: a randomized, blinded, clinical trial. Pediatrics 115, 1501–1512 (2005). PubMed DOI PMC

Hyttel-Sorensen, S. et al. Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial. BMJ 350, g7635 (2015). PubMed DOI PMC

Hansen, M. L. et al. Cerebral near-infrared spectroscopy monitoring versus treatment as usual for extremely preterm infants: a protocol for the SafeBoosC randomised clinical phase III trial. Trials 20, 811 (2019). PubMed DOI PMC

Alderliesten, T. et al. Hypotension in preterm neonates: low blood pressure alone does not affect neurodevelopmental outcome. J. Pediatr. 164, 986–991 (2014). PubMed DOI PMC

Chock, V. Y., Ramamoorthy, C. & Van Meurs, K. P. Cerebral autoregulation in neonates with a hemodynamically significant patent ductus arteriosus. J. Pediatr. 160, 936–942 (2012). PubMed DOI PMC

Cunningham, S., Symon, A. G., Elton, R. A., Zhu, C. & McIntosh, N. Intra-arterial blood pressure reference ranges, death and morbidity in very low birthweight infants during the first seven days of life. Early Hum. Dev. 56, 151–165 (1999). PubMed DOI PMC

Alderliesten, T. et al. Reference values of regional cerebral oxygen saturation during the first 3 days of life in preterm neonates. Pediatr. Res. 79, 55–64 (2016). PubMed DOI PMC

Alderliesten, T. et al. Low cerebral oxygenation in preterm infants is associated with adverse neurodevelopmental outcome. J. Pediatr. 207, 109–116 (2019). e102. PubMed DOI PMC

Plomgaard, A. M. et al. No neurodevelopmental benefit of cerebral oximetry in the first randomised trial (SafeBoosC II) in preterm infants during the first days of life. Acta Paediatr. 108, 275–281 (2019). PubMed DOI PMC

Menke, J., Michel, E., Hillebrand, S., von Twickel, J. & Jorch, G. Cross-spectral analysis of cerebral autoregulation dynamics in high risk preterm infants during the perinatal period. Pediatr. Res. 42, 690–699 (1997). PubMed DOI PMC

Greisen, G. To autoregulate or not to autoregulate-that is no longer the question. Semin. Pediatr. Neurol. 16, 207–215 (2009). PubMed DOI PMC

Vesoulis, Z. A. & Mathur, A. M. Cerebral autoregulation, brain injury, and the transitioning premature infant. Front. Pediatr. 5, 64 (2017). PubMed DOI PMC

Dix, L. M. L. et al. Carbon dioxide fluctuations are associated with changes in cerebral oxygenation and electrical activity in infants born preterm. J. Pediatr. 187, 66–72 e61 (2017). PubMed DOI PMC

Wyatt, J. S. et al. Response of cerebral blood volume to changes in arterial carbon dioxide tension in preterm and term infants. Pediatr. Res. 29, 553–557 (1991). PubMed DOI PMC

Vanderhaegen, J. et al. The effect of changes in tPCO2 on the fractional tissue oxygen extraction-as measured by near-infrared spectroscopy-in neonates during the first days of life. Eur. J. Paediatr. Neurol. 13, 128–134 (2009). PubMed DOI PMC

Kaiser, J. R., Gauss, C. H. & Williams, D. K. The effects of hypercapnia on cerebral autoregulation in ventilated very low birth weight infants. Pediatr. Res. 58, 931–935 (2005). PubMed DOI PMC

Lemmers, P. M. et al. Cerebral oxygenation and brain activity after perinatal asphyxia: does hypothermia change their prognostic value? Pediatr. Res. 74, 180–185 (2013). PubMed DOI PMC

Peng, S. et al. Does near-infrared spectroscopy identify asphyxiated newborns at risk of developing brain injury during hypothermia treatment? Am. J. Perinatol. 32, 555–564 (2015). PubMed DOI PMC

Ancora, G., Maranella, E., Locatelli, C., Pierantoni, L. & Faldella, G. Changes in cerebral hemodynamics and amplitude integrated EEG in an asphyxiated newborn during and after cool cap treatment. Brain Dev. 31, 442–444 (2009). PubMed DOI PMC

Cohen, E. et al. Cerebrovascular autoregulation in preterm fetal growth restricted neonates. Arch. Dis. Child Fetal Neonatal Ed. 104, F467–F472 (2019). PubMed DOI PMC

European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update