Liesbeth Thewissen1, Gunnar Naulaers2, Dries Hendrikx3, Alexander Caicedo3,4, Keith Barrington5, Geraldine Boylan6, Po-Yin Cheung7, David Corcoran8, Afif El-Khuffash8, Aisling Garvey6, Jozef Macko9, Neil Marlow10, Jan Miletin11, Colm P F O'Donnell12, John M O'Toole6, Zbyněk Straňák13, David Van Laere14, Hana Wiedermannova15, Eugene Dempsey6. 1. Department of Neonatology, University Hospitals Leuven, Leuven, Belgium. liesbeth.thewissen@uzleuven.be. 2. Department of Neonatology, University Hospitals Leuven, Leuven, Belgium. 3. Department of Electrical Engineering, ESAT-Stadius, KU Leuven, Leuven, Belgium. 4. Applied Mathematics and Computer Science, School of Engineering, Science and Technology, Universidad del Rosario, Bogotá, Colombia. 5. Department of Pediatrics, Division of Neonatology, CHU Sainte-Justine, University of Montreal, Montréal, QC, Canada. 6. INFANT Research Centre, University College Cork, Cork, Ireland. 7. Departments of Pediatrics, Pharmacology and Surgery, University of Alberta, Edmonton, AB, Canada. 8. Department of Neonatology, Rotunda Hospital & School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland. 9. Department of Neonatology, Tomas Bata University, Zlín, Czech Republic. 10. UCL Institute for Women's Health, University College London, London, UK. 11. Coombe Woman and Infants University Hospital, Dublin, Ireland. 12. National Maternity Hospital, Dublin, Ireland. 13. Institute for the Care of Mother and Child, Prague Third Faculty of Medicine, Charles University, Prague, Czech Republic. 14. Department of Neonatal Intensive Care, University Hospital Antwerp, Edegem, Belgium. 15. Department of Neonatology, University Hospital of Ostrava, Ostrava, Czech Republic.
Abstract
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.
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.
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