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
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Treatment of hypotension with dopamine in extremely preterm infants increases mean arterial blood pressure, but does not improve cerebral oxygenation.
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Hypotensive extremely preterm infants have increased duration of cerebral hypoxia and reduced cerebral autoregulatory capacity compared to non-hypotensive infants.
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Duration of cerebral hypoxia and hypotension are associated with early intraventricular hemorrhage or death in extremely preterm infants.
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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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Acknowledgements
We thank Steffen Fieuws, statistician (Interuniversity Institute for Biostatistics and Statistical Bioinformatics, KU Leuven, Leuven, Belgium) for the statistical advice and analysis of the data. We thank Margreet Koolen, Isabelle Hermans, and Julie Messiaen, research nurses at University Hospitals Leuven and the Clinical Research Facility Cork for the support during the trial. This trial was funded by the European Union’s Seventh Framework Program (FP7/2007-2013) The HIP Trial: #260777.
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L.T. conceptualized and designed the study, collected data, carried out the initial analysis, drafted the initial manuscript, and reviewed and revised the manuscript for important intellectual content. G.N. and E.D. conceptualized and designed the study, collected data, coordinated and supervised data collection, and critically reviewed and revised the manuscript for important intellectual content. D.H. and A.C. conceptualized and designed the study, performed the data analysis, and reviewed and revised the manuscript for important intellectual content. K.B., G.B., P.-Y.C., D.C., A.E.-K., A.G., J.M., N.M., J.M., C.P.F.O’D., J.M.O’T., Z.S., D.V.L., and H.W. conceptualized and designed the study, collected data, and reviewed and revised the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
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N.M. reports consultancy for Novartis and Shire, and is member of the Advisory Committee of GSK. The remaining authors declare no competing interests.
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Thewissen, L., Naulaers, G., Hendrikx, D. et al. Cerebral oxygen saturation and autoregulation during hypotension in extremely preterm infants. Pediatr Res 90, 373–380 (2021). https://doi.org/10.1038/s41390-021-01483-w
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DOI: https://doi.org/10.1038/s41390-021-01483-w
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