Dexmedetomidine-induced cerebral hypoperfusion exacerbates ischemic brain injury in rats

Nakano, Takuma; Okamoto, Hirotsugu

doi:10.1007/s00540-009-0777-9

Cited by 32 publications

(23 citation statements)

References 41 publications

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“…In the developing mouse brain, dose-dependent neuroprotection with dexmedetomidine and clonidine was found [66] . Some studies, however, have shown that dexmedetomidine and clonidine induce cerebral hypoperfusion and neurotoxicity in small-animal stroke models [67] . Dean et al [68] showed a complex dose-dependent response to clonidine with low doses, but not high doses, being neuroprotective after hypoxic brain injury in preterm fetal sheep.…”

Section: Discussionmentioning

confidence: 99%

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

Ezzati¹,

Kawano²,

Rocha‐Ferreira³

et al. 2017

Dev Neurosci

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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; these may have been exacerbated by an interaction with either isoflurane or low body temperature. Hypothermia + dexmedetomidine treatment was neurotoxic following HI in our piglet NE model, suggesting that caution is vital if dexmedetomidine is combined with cooling following NE.

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Section: Discussionmentioning

confidence: 99%

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

Ezzati¹,

Kawano²,

Rocha‐Ferreira³

et al. 2017

Dev Neurosci

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“…Dexmedetomidine activates all three sub-types of a 2 adrenoceptors, which are present in high concentrations in vascular smooth muscle, as well as in key arousal areas of the central nervous system, such as the locus ceruleus [6]. The activation of a 2A receptors by dexmedetomidine exerts neuroprotective effects [7][8][9], while the activation of a 2B receptors constricts cerebral vessels and decreases cerebral blood flow (CBF) [6,10,11].…”

Section: Introductionmentioning

confidence: 99%

Effects of dexmedetomidine on cerebral blood flow in critically ill patients with or without traumatic brain injury: A prospective controlled trial

Wang

Fang

et al. 2013

Brain Injury

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“…Despite its potential benefits, dexmedetomidine can have deleterious effects on cardiovascular and cerebrovascular functions which mandate close hemodynamic monitoring during infusion. Nakano recently reported that dexmedetomidine-induced cerebral hypoperfusion exacerbated ischemic brain injury in rats [28]. Hypotension was observed in 10 of 39 (26%) neurosurgical patients treated with dexmedetomidine infusions for sedation during intubation in the ICU [21].…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Controls Agitation and Facilitates Reliable, Serial Neurological Examinations in a Non-Intubated Patient with Traumatic Brain Injury

et al. 2010

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Given the large numbers of alcohol-dependent patients who suffer a traumatic brain injury and subsequently develop agitation and alcohol withdrawal in hospital, dexmedetomidine offers a novel strategy to facilitate sedation without neurological or respiratory depression. As this case report demonstrates, dexmedetomidine is an emerging treatment option for agitation in patients who require reliable, serial neurological testing to monitor the course of their traumatic brain injury.

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Dexmedetomidine-induced cerebral hypoperfusion exacerbates ischemic brain injury in rats

Abstract: Hypertension following the administration of high-dose dexmedetomidine is associated with cerebral hypoperfusion and the exacerbation of ischemic brain injury, possibly through alpha-2-induced cerebral vasoconstriction.

Cited by 32 publications

References 41 publications

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

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

Effects of dexmedetomidine on cerebral blood flow in critically ill patients with or without traumatic brain injury: A prospective controlled trial

Dexmedetomidine Controls Agitation and Facilitates Reliable, Serial Neurological Examinations in a Non-Intubated Patient with Traumatic Brain Injury

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