» Articles » PMID: 28969315

Alternative Technique or Mitigating Strategy for Sevoflurane-induced Neurodegeneration: a Randomized Controlled Dose-escalation Study of Dexmedetomidine in Neonatal Rats

Overview
Journal Br J Anaesth
Publisher Elsevier
Specialty Anesthesiology
Date 2017 Oct 4
PMID 28969315
Citations 15
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Brain injury in newborn animals from prolonged anaesthetic exposure has raised concerns for millions of children undergoing anaesthesia every yr. Alternative anaesthetic techniques or mitigating strategies are urgently needed to ameliorate potentially harmful effects. We tested dexmedetomidine, both as a single agent alternative technique and as a mitigating adjuvant for sevoflurane anaesthesia.

Methods: Neonatal rats were randomized to three injections of dexmedetomidine (5, 25, 50, or 100 µg kg -1 every 2 h), or 6 h of 2.5% sevoflurane as a single agent without or with dexmedetomidine (1, 5, 10, or 20 µg kg -1 every 2 h). Heart rate, oxygen saturation, level of consciousness, and response to pain were assessed. Cell death was quantified in several brain regions.

Results: Dexmedetomidine provided lower levels of sedation and pain control than sevoflurane. Exposure to either sevoflurane or dexmedetomidine alone did not cause mortality, but the combination of 2.5% sevoflurane and dexmedetomidine in doses exceeding 1 µg kg -1 did. Sevoflurane increased apoptosis in all brain regions; supplementation with dexmedetomidine exacerbated neuronal injury, potentially as a result of ventilatory or haemodynamic compromise. Dexmedetomidine by itself increased apoptosis only in CA2/3 and the ventral posterior nucleus, but not in prefrontal cortex, retrosplenial cortex, somatosensory cortex, subiculum, lateral dorsal thalamic nucleaus, or hippocampal CA1.

Conclusions: We confirm previous findings of sevoflurane-induced neuronal injury. Dexmedetomidine, even in the highest dose, did not cause similar injury, but provided lesser degrees of anaesthesia and pain control. No mitigation of sevoflurane-induced injury was observed with dexmedetomidine supplementation, suggesting that future studies should focus on anaesthetic-sparing effects of dexmedetomidine, rather than injury-preventing effects.

Citing Articles

A Scoping Review of the Mechanisms Underlying Developmental Anesthetic Neurotoxicity.

Borzage M, Peterson B Anesth Analg. 2024; 140(2):409-426.

PMID: 38536739 PMC: 11427602. DOI: 10.1213/ANE.0000000000006897.


Anesthesia and Sedation Exposure and Neurodevelopmental Outcomes in Infants Undergoing Congenital Cardiac Surgery: A Retrospective Cohort Study.

Simpao A, Randazzo I, Chittams J, Burnham N, Gerdes M, Bernbaum J Anesthesiology. 2023; 139(4):393-404.

PMID: 37440275 PMC: 10527982. DOI: 10.1097/ALN.0000000000004684.


Sevoflurane promotes premature differentiation of dopaminergic neurons in hiPSC-derived midbrain organoids.

Shang J, Li B, Fan H, Liu P, Zhao W, Chen T Front Cell Dev Biol. 2022; 10:941984.

PMID: 36176283 PMC: 9513420. DOI: 10.3389/fcell.2022.941984.


Dexmedetomidine Diminishes, but Does Not Prevent, Developmental Effects of Sevoflurane in Neonatal Rats.

Yang Z, Tong Y, Brant J, Li N, Ju L, Morey T Anesth Analg. 2022; 135(4):877-887.

PMID: 35759382 PMC: 9481710. DOI: 10.1213/ANE.0000000000006125.


Sevoflurane-Induced Apoptosis in the Mouse Cerebral Cortex Follows Similar Characteristics of Physiological Apoptosis.

Wang Q, Li Y, Tan H, Wang Y Front Mol Neurosci. 2022; 15:873658.

PMID: 35465098 PMC: 9024292. DOI: 10.3389/fnmol.2022.873658.


References
1.
Workman A, Charvet C, Clancy B, Darlington R, Finlay B . Modeling transformations of neurodevelopmental sequences across mammalian species. J Neurosci. 2013; 33(17):7368-83. PMC: 3928428. DOI: 10.1523/JNEUROSCI.5746-12.2013. View

2.
Lin E, Lee J, Lee C, Deng M, Loepke A . Do anesthetics harm the developing human brain? An integrative analysis of animal and human studies. Neurotoxicol Teratol. 2016; 60:117-128. DOI: 10.1016/j.ntt.2016.10.008. View

3.
Istaphanous G, Howard J, Nan X, Hughes E, McCann J, McAuliffe J . Comparison of the neuroapoptotic properties of equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in neonatal mice. Anesthesiology. 2011; 114(3):578-87. DOI: 10.1097/ALN.0b013e3182084a70. View

4.
Liu J, Yuki K, Baek C, Han X, Soriano S . Dexmedetomidine-Induced Neuroapoptosis Is Dependent on Its Cumulative Dose. Anesth Analg. 2016; 123(4):1008-17. DOI: 10.1213/ANE.0000000000001527. View

5.
Perez-Zoghbi J, Zhu W, Grafe M, Brambrink A . Dexmedetomidine-mediated neuroprotection against sevoflurane-induced neurotoxicity extends to several brain regions in neonatal rats. Br J Anaesth. 2017; 119(3):506-516. DOI: 10.1093/bja/aex222. View