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Pediatr Res. 2015 Jun;77(6):772-8. doi: 10.1038/pr.2015.45. Epub 2015 Mar 9.

Dexmedetomidine reduces cranial temperature in hypothermic neonatal rats.

Author information

1
1] Department of Pediatrics, University of Washington, Seattle, Washington [2] Seattle Children's Hospital, Seattle, Washington.
2
Department of Pediatrics, University of Washington, Seattle, Washington.
3
1] Seattle Children's Hospital, Seattle, Washington [2] Department of Pathology, University of Washington, Seattle, Washington.
4
Department of Pharmaceutics, University of Washington, Seattle, Washington.

Abstract

BACKGROUND:

The α2-adrenergic agonist dexmedetomidine (DEX) is increasingly used for prolonged sedation of critically ill neonates, but there are currently no data evaluating possible consequences of prolonged neonatal DEX exposure. We evaluated the pharmacokinetics and histological consequences of neonatal DEX exposure.

METHODS:

DEX was administered (s.c.) to naive (uninjured) neonatal Lewis rats to provide acute (25 µg/kg, ×1) or prolonged (25 µg/kg three times daily, ×2 or ×4 d) exposure. Therapeutic hypothermia was simulated using a water-cooled blanket. Cranial temperatures were measured using an infrared thermometer. DEX concentrations were measured by LC-MS in plasma and homogenized brainstem tissue for pharmacokinetic analysis. Cortex, cerebellum, and brainstem were evaluated for evidence of inflammation or injury.

RESULTS:

Prolonged neonatal DEX exposure was not associated with renal or brain pathology or indices of gliosis, macrophage activation, or apoptosis in either hypothermic or control rats. Plasma and brain DEX concentrations were tightly correlated. DEX peaked within 15 min in brain and reduced cranial temperature from 32 to 30 °C within 30 min after injection in cooled rats.

CONCLUSION:

Prolonged DEX treatment in neonatal rats was not associated with abnormal brain histology. These data provide reassuring preliminary results for using DEX with therapeutic hypothermia to treat near-term brain injury.

PMID:
25751572
DOI:
10.1038/pr.2015.45
[Indexed for MEDLINE]

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