Abstract
Background:
The aim of our study was to measure drug-related changes in hemodynamics and oxygen metabolism in response to different doses of an age-appropriate dobutamine formulation in hypoxic pigs. A secondary aim was to validate superior vena cava flow (SVCF) as a marker of cardiac index (CI) for subsequent clinical trials of this formulation in humans.
Methods:
Newborn pigs (n = 18) were exposed to 2-h hypoxia (10–15% oxygen) followed by reoxygenation (21–30% oxygen 4 h). After 1-h reoxygenation, pigs were randomized to: control group (no treatment), dobutamine infusion at a rate of 10–15 or 15–20 µg/kg/min. Dobutamine groups received two dobutamine doses during 30 min with a 60 min washout period between doses. Cardiovascular profile and oxygen metabolism were monitored. In four animals, an ultrasonic perivascular flow probe was placed around superior vena cava to measure SVCF.
Results:
Hypoxia significantly decreased CI, systemic vascular resistance and mean arterial blood pressure (MABP). Dobutamine doses significantly increased heart-rate, CI, and oxygen-delivery without changes in stroke-volume and MABP. Only 10–15 µg/kg/min increased oxygen consumption and peripheral tissue oxygenation measured by Near-infrared spectroscopy. A positive correlation was observed between SVCF and CI.
Conclusion:
The new pediatric dobutamine formulation improved hemodynamic status, with dose-specific differences in metabolic response. SVCF may be a useful surrogate for CI in subsequent clinical trials.
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Acknowledgements
The skilled technical assistance of Estibaliz Ruiz del Yerro is gratefully acknowledged. This study has been performed as part of the Neo-CIRCulation Project. The members of the consortium are outlined below: Chief Investigator: Adelina Pellicer, Madrid, Spain. Principal Project Co-ordinator: Heike Rabe, Brighton, UK. Local Investigators: Philip Amess, Neil Aiton, Ramon Fernandez, Liam Mahoney, Heike Rabe, Hector Rojas-Anaya, Brighton, UK; Vincent Jullien, Thomas Le Saux, Gerald Pons, Paris, France; Frank Biertz, Wolfgang Büter, Armin Koch, Hannover, Germany; Victoria Mielgo, Adolf Valls-i-Soler, Bizkaia, Spain; Wolfgang Göpel, Christoph Härtel, Lübeck, Germany; Mark Turner, Michael Weindling, Liverpool, UK; Claudia Roll, Datteln, Germany; Maria del Carmen Bravo, Fernando Cabanas, Madrid, Spain; Simon Bryson, Cheshire, UK; Alexandrina Tatu, Adrian Toma, Bucharest, Romania; Gabriela Zaharie, Cluj-Napoca, Romania; Géza Bokodi, Miklós Szabó, Budapest, Hungary; Tibor Ertl, Simone Funke, Pécs, Hungary; Ebru Ergenekon, Kivilcim Gücüyener, Şebnem Soysal, Ankara,Turkey; Olaf Dammann, Jennifer Lee, Boston, US; Neo-Circulation Expert Advisory Board: Tonse N. K. Raju, Bethesda, USA; Nicholas Evans, Sydney, Australia; Stephanie Läer, Düsseldorf, Germany; Silke Mader, Karlsfeld, Germany; Monika Seibert-Grafe, Mainz, Germany. Neo-Circulation Data Monitoring Comittee: Gorm Greisen, Copenhagen, Denmark; Lena Hellström-Westas, Uppsala, Sweden; Josef Högel, Ulm, Germany.
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Mielgo, V., Valls-i-Soler, A., Lopez-de-Heredia, J. et al. Hemodynamic and metabolic effects of a new pediatric dobutamine formulation in hypoxic newborn pigs. Pediatr Res 81, 511–518 (2017). https://doi.org/10.1038/pr.2016.257
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DOI: https://doi.org/10.1038/pr.2016.257
