Early Development of the GABAergic System and the Associated Risks of Neonatal Anesthesia

Gascoigne, David A.; Serdyukova, Natalya A.; Aksenov, Daniil P.

doi:10.3390/ijms222312951

Cited by 16 publications

(10 citation statements)

References 184 publications

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“…While clinical studies to date have largely focused on the impact of anesthesia on healthy infants, much pre-clinical research should lead us to interpret these findings with caution (Ben-Ari, 2002). Many anesthetic and sedative agents are GABA antagonists and have been shown to be neurotoxic in neonates (Andropoulos, 2018;Gascoigne et al, 2021). It also follows that the variability of development of GABA synapses may also further be altered by other neuronal disruptions such as prematurity.…”

Section: Risk Of Brain Injury In Neonates Requiring Surgerymentioning

confidence: 99%

Impact of Comorbid Prematurity and Congenital Anomalies: A Review

Gunn-Charlton

2022

Front. Physiol.

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Preterm infants are more likely to be born with congenital anomalies than those who are born at full-term. Conversely, neonates born with congenital anomalies are also more likely to be born preterm than those without congenital anomalies. Moreover, the comorbid impact of prematurity and congenital anomalies is more than cumulative. Multiple common factors increase the risk of brain injury and neurodevelopmental impairment in both preterm babies and those born with congenital anomalies. These include prolonged hospital length of stay, feeding difficulties, nutritional deficits, pain exposure and administration of medications including sedatives and analgesics. Congenital heart disease provides a well-studied example of the impact of comorbid disease with prematurity. Impaired brain growth and maturity is well described in the third trimester in this population; the immature brain is subsequently more vulnerable to further injury. There is a colinear relationship between degree of prematurity and outcome both in terms of mortality and neurological morbidity. Both prematurity and relative brain immaturity independently increase the risk of subsequent neurodevelopmental impairment in infants with CHD. Non-cardiac surgery also poses a greater risk to preterm infants despite the expectation of normal in utero brain growth. Esophageal atresia, diaphragmatic hernia and abdominal wall defects provide examples of congenital anomalies which have been shown to have poorer neurodevelopmental outcomes in the face of prematurity, with associated increased surgical complexity, higher relative cumulative doses of medications, longer hospital and intensive care stay and increased rates of feeding difficulties, compared with infants who experience either prematurity or congenital anomalies alone.

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Section: Risk Of Brain Injury In Neonates Requiring Surgerymentioning

confidence: 99%

Impact of Comorbid Prematurity and Congenital Anomalies: A Review

Gunn-Charlton

2022

Front. Physiol.

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“…3,4 Given the trade-off between exposing the neonatal brain to potentially neurotoxic anesthetics, and the consequences of delaying or aborting the diagnostic procedure, sedation units are looking for the best possible solution to achieve optimal imaging. [6][7][8][9] In high-risk infants, sedation with a medication that combines minimal neurotoxicity with low risk of apnea and cardiovascular stability could be the ideal alternative.…”

Section: Introductionmentioning

confidence: 99%

“…Reported rates of successful brain imaging using this technique vary between 25–90%, 3–5 whereas procedural sedation or general anesthesia can achieve successful imaging in these high‐risk infants in up to 100% of the cases 3,4 . Given the trade‐off between exposing the neonatal brain to potentially neurotoxic anesthetics, and the consequences of delaying or aborting the diagnostic procedure, sedation units are looking for the best possible solution to achieve optimal imaging 6–9 . In high‐risk infants, sedation with a medication that combines minimal neurotoxicity with low risk of apnea and cardiovascular stability could be the ideal alternative.…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine as a sole sedative for procedural sedation in preterm and neonate infants: A retrospective analysis

Leister

Yücetepe

Ulrichs

et al. 2022

Pediatric Anesthesia

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Background: Many different sedation concepts for magnetic resonance imaging have been described for prematurely and term-born infants, ranging from "no sedation" to general anesthesia. Dexmedetomidine is an alpha-2 receptor agonist that is frequently used to sedate older children, because the anesthesiologist can easily adjust sedation depth, the patient maintains spontaneous breathing, and awakens rapidly afterwards. Aims:The present study evaluates whether dexmedetomidine could safely be used as the sole sedative for prematurely and term-born infants less than 60 weeks postconceptional age undergoing diagnostic procedures. Methods:We performed a retrospective monocentric analysis of n = 39 prematurely and term-born infants (<60 weeks postconceptional age or a body weight <5 kg) who were sedated with dexmedetomidine for an MRI at a German university hospital from August 2016 to November 2018.Results: Successful imaging was achieved in all cases. The median initial bolus of dexmedetomidine administered over 10 min was 1.39 μg kg −1 body weight (range 0.34-3.64 μg kg −1 ), followed with a continuous infusion at a median rate of 1.00 μg kg −1 h −1 (range 0.5-3.5 μg kg −1 h −1 ); however, 3 patients (7%) needed some additional sedation (ketamine or propofol). All patients, including 10 infants who had previously required respiratory support, underwent the procedure without any relevant desaturation or apnea. Bradycardia was observed in up to 15 out of 39 cases (38.5%), but only four (10.3% in total and 26.7% of bradycardia) required atropine. Conclusions:These results indicate that dexmedetomidine can be safely used for procedural sedation in the high-risk cohort of prematurely and term-born infants less than 60 weeks postconceptional age. Apnea during procedural sedation and subsequent stay in the recovery room is avoided, but bradycardia remains a relevant risk that may require treatment. K E Y W O R D S apnea, bradycardia, dexmedetomidine, prematurely and term-born infants less than 60 weeks postconceptional age, procedural sedation How to cite this article: Leister N, Yücetepe S, Ulrichs C, et al. Dexmedetomidine as a sole sedative for procedural sedation in preterm and neonate infants: A retrospective analysis. Pediatr

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“…A shift in excitatory-inhibitory balance (EIB) in the brain toward excitation is a very common clinical and pathophysiological phenomenon, which can present in adulthood or as a result of disturbed development, due to the functional deficiency of inhibitory interneurons ( Gascoigne et al, 2021 ). This phenomenon manifests as neuronal hypersynchronization during the resting state, a process which affects normal neuronal and neurovascular interactions ( Staley, 2015 ; van Vliet and Marchi, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…The clinical characteristics of a shift in EIB, range from autism ( Rubenstein and Merzenich, 2003 ) to epilepsy ( Kaeser and Regehr, 2014 ), depending on its severity. Typically, this state has a very long duration (months and years) ( Berg, 2011 ; Gascoigne et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Brain tissue oxygen dynamics while mimicking the functional deficiency of interneurons

Aksenov

Doubovikov²,

Serdyukova³

et al. 2022

Front. Cell. Neurosci.

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The dynamic interaction between excitatory and inhibitory activity in the brain is known as excitatory-inhibitory balance (EIB). A significant shift in EIB toward excitation has been observed in numerous pathological states and diseases, such as autism or epilepsy, where interneurons may be dysfunctional. The consequences of this on neurovascular interactions remains to be elucidated. Specifically, it is not known if there is an elevated metabolic consumption of oxygen due to increased excitatory activity. To investigate this, we administered microinjections of picrotoxin, a gamma aminobutyric acid (GABA) antagonist, to the rabbit cortex in the awake state to mimic the functional deficiency of GABAergic interneurons. This caused an observable shift in EIB toward excitation without the induction of seizures. We used chronically implanted electrodes to measure both neuronal activity and brain tissue oxygen concentrations (PO2) simultaneously and in the same location. Using a high-frequency recording rate for PO2, we were able to detect two important phenomena, (1) the shift in EIB led to a change in the power spectra of PO2 fluctuations, such that higher frequencies (8–15 cycles per minute) were suppressed and (2) there were brief periods (dips with a duration of less than 100 ms associated with neuronal bursts) when PO2 dropped below 10 mmHg, which we defined as the threshold for hypoxia. The dips were followed by an overshoot, which indicates either a rapid vascular response or decrease in oxygen consumption. Our results point to the essential role of interneurons in brain tissue oxygen regulation in the resting state.

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Early Development of the GABAergic System and the Associated Risks of Neonatal Anesthesia

Cited by 16 publications

References 184 publications

Impact of Comorbid Prematurity and Congenital Anomalies: A Review

Impact of Comorbid Prematurity and Congenital Anomalies: A Review

Dexmedetomidine as a sole sedative for procedural sedation in preterm and neonate infants: A retrospective analysis

Brain tissue oxygen dynamics while mimicking the functional deficiency of interneurons

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