Dexmedetomidine Combined with Therapeutic Hypothermia Is Associated with Cardiovascular Instability and Neurotoxicity in a Piglet Model of Perinatal Asphyxia

Ezzati, M, Kawano, G, Rocha-Ferreira, E, Alonso-Alconada, D, Hassell, J, Broad, K, Fierens, I, Fleiss, B, Price, D, Kaynezhad, P, Anderson, B, Hristova, M, Tachtsidis, I, Golay, X, Gressens, P, Sanders, R and Robertson, N 2017, 'Dexmedetomidine Combined with Therapeutic Hypothermia Is Associated with Cardiovascular Instability and Neurotoxicity in a Piglet Model of Perinatal Asphyxia', Developmental Neuroscience, vol. 39, no. 14, pp. 156-170.


Document type: Journal Article
Collection: Journal Articles

Title Dexmedetomidine Combined with Therapeutic Hypothermia Is Associated with Cardiovascular Instability and Neurotoxicity in a Piglet Model of Perinatal Asphyxia
Author(s) Ezzati, M
Kawano, G
Rocha-Ferreira, E
Alonso-Alconada, D
Hassell, J
Broad, K
Fierens, I
Fleiss, B
Price, D
Kaynezhad, P
Anderson, B
Hristova, M
Tachtsidis, I
Golay, X
Gressens, P
Sanders, R
Robertson, N
Year 2017
Journal name Developmental Neuroscience
Volume number 39
Issue number 14
Start page 156
End page 170
Total pages 15
Publisher S. Karger AG
Abstract The selective α2-adrenoreceptor agonist dexmedetomidine has shown neuroprotective, analgesic, anti-inflammatory, and sympatholytic properties that may be beneficial in neonatal encephalopathy (NE). As therapeutic hypothermia is only partially effective, adjunct therapies are needed to optimize outcomes. The aim was to assess whether hypothermia + dexmedetomidine treatment augments neuroprotection compared to routine treatment (hypothermia + fentanyl sedation) in a piglet model of NE using magnetic resonance spectroscopy (MRS) biomarkers, which predict outcomes in babies with NE, and immunohistochemistry. After hypoxia-ischaemia (HI), 20 large White male piglets were randomized to: (i) hypothermia + fentanyl with cooling to 33.5°C from 2 to 26 h, or (ii) hypothermia + dexmedetomidine (a loading dose of 2 μg/kg at 10 min followed by 0.028 μg/kg/h for 48 h). Whole-brain phosphorus-31 and regional proton MRS biomarkers were assessed at baseline, 24, and 48 h after HI. At 48 h, cell death was evaluated over 7 brain regions by means of transferase-mediated d-UTP nick end labeling (TUNEL). Dexmedetomidine plasma levels were mainly within the target sedative range of 1 μg/L. In the hypothermia + dexmedetomidine group, there were 6 cardiac arrests (3 fatal) versus 2 (non-fatal) in the hypothermia + fentanyl group. The hypothermia + dexmedetomidine group required more saline (p = 0.005) to maintain blood pressure. Thalamic and white-matter lactate/N-acetylaspartate did not differ between groups (p = 0.66 and p = 0.21, respectively); the whole-brain nucleotide triphosphate/exchangeable phosphate pool was similar (p = 0.73) over 48 h. Cell death (TUNEL-positive cells/mm2) was higher in the hypothermia + dexmedetomidine group than in the hypothermia + fentanyl group (mean 5.1 vs. 2.3, difference 2.8 [95% CI 0.6-4.9], p = 0.036). Hypothermia + dexmedetomidine treatment was associated with adverse cardiovascular events, even within the recommended clinical sedative plasma level; t
Subject Central Nervous System
Neurology and Neuromuscular Diseases
Cell Physiology
Keyword(s) Dexmedetomidine
Hypothermia
Magnetic resonance spectroscopy
Neonatal encephalopathy
DOI - identifier 10.1159/000458438
Copyright notice © 2017 S. Karger AG, Basel
ISSN 0378-5866
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