Xenon as an anesthetic of choice for full mouth debridement in a child with drug-resistant epilepsy: A clinical case

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INTRODUCTION

Outpatient dental care in children with epilepsy (particularly drug-resistant epilepsy) is challenging for anesthesiologists in terms of selecting appropriate anesthesia methods and agents, as well as for dentists in terms of improving treatment efficacy and quality while minimizing intervention time.

Sevoflurane is commonly used for anesthesia in children due to favorable tolerability and safety profiles, well-controlled anesthesia, no upper respiratory tract irritation, and rapid induction [1]. S. Tanaka et al. found that sevoflurane caused a dose-dependent increase in activity peaks on electroencephalogram (EEG) in children with epilepsy [2]. Seizure patterns in children without epilepsy have also been reported when using sevoflurane at a dose of 7–8 vol.% [3]. Epileptiform activity on ECG in children with epilepsy when using sevoflurane for general anesthesia is associated with cognitive impairment and delirium [2, 4]. Propofol, an intravenous sedative agent, can also cause seizures, according to ECG findings [5].

Drug resistance is reported in one-third of epilepsy patients. However, its prevalence varies depending on the location of epileptogenic activity source, causes of epilepsy, age of onset, and concomitant cognitive impairments [6]. Thus, selecting the best antispasmodic therapy can be difficult.

Xenon is a monatomic inert gas that is non-toxic, neuroprotective, and cardioprotective, and has no systemic metabolism. Moreover, it is non-teratogenic [7, 8]. Given its neuroprotective properties and lack of toxicity, xenon can be used during full mouth debridement in children with nervous system disorders.

CASE DESCRIPTION

Parents of patient N. (female, 3 years old) presented to the Dental Forte Elite clinic (Naberezhnye Chelny) for full mouth debridement. During the preoperative examination, the following diagnosis was made based on imaging and laboratory findings: Epileptic encephalopathy, genetic etiology. Drug resistant form. Psychomotor retardation. Spastic quadriplegia.

Physical examination, laboratory, and imaging findings

Magnetic resonance imaging of the brain revealed callosal agenesis. EEG revealed multiregional epileptiform activity, more pronounced in the left hemisphere, with a higher activity amplitude in the right hemisphere. Genetic testing revealed mutations in the BCKDK gene (dehydrogenase deficiency); in the NAXD gene (early-onset progressive encephalopathy, leukoencephalopathy); in the BLM gene (Bloom syndrome); and in the CPLANE 1 gene (Joubert syndrome).

According to the medical history, the patient received valproic acid, topiramate, and levetiracetam, with no effect. At the time of the study, the patient received vigabatrin 1,500 mg/day and levetiracetam 600 mg/day. The frequency of seizures reached 60 per day.

Treatment

Combination general anesthesia with xenon was used.

The following parameters were used to assess the efficacy and safety of anesthesia during surgery:

• Systolic and diastolic blood pressure, mean blood pressure, and heart rate assessed using the STAR8000C monitor (COMEN, China);
• Bispectral index (BIS) assessed using the anesthesia depth monitor MGA-06 (Triton, Russia);
• Pulmonary ventilation parameters: respiratory rate, airway pressure (Paw, mm Hg), minute ventilation (MV, L/min), expiratory volume (Vte), inspiratory volume (Vti), fraction of inspired oxygen (FiO₂), and end-tidal carbon dioxide (EtCO₂) assessed using an integrated module of the anesthesia apparatus;
• Capillary blood gases assessed using the iStat analyzer (USA);
• Cuff pressure assessed using the Portex cuff pressure monitoring device (UK).

Prior to anesthesia, the patient was premedicated with atropine 0.01 mg/kg and diazepam 0.2 mg/kg IV. Preoxygenation was performed at a gas flow rate of 5 L/min for 5 minutes with FiO₂ 100%, using the Venar Libera Screen anesthesia apparatus (Chirana, Slovakia) (TS + AGAS). Tracheal intubation was performed on the first attempt, without complications, using a 4 mm endotracheal tube (BIS 50 c.u.). Mechanical ventilation was performed in the pressure support ventilation (PSV) mode.

Xenon inhalation began immediately after tracheal intubation, at a flow rate of 2 L/min, FiO₂ 30%. Xenon was administered until the inspired xenon concentration reached 50% on the GKM-03-INSOVT analyzed (GRANAT, Russia). Following that, the flow rate was reduced to 200 mL/min, and FiO₂ was maintained at 30% in a closed-circle system. During anesthesia, the concentration of xenon in the fresh gas mixture was maintained between 40% and 45%, and the BIS-based depression of consciousness level was maintained between 40% and 60%. Ten minutes before the end of surgery, the xenon supply was switched off, with a flow rate of 2 L/min, FiO₂ 100%. Tracheal extubation was performed when the inspired xenon concentration reached 10%, without complications. The time from the end of xenon supply to tracheal extubation was 1 minute and 30 seconds. The patient opened her eyes when called by name 3 minutes after the treatment was completed. The patient went home with her parents 20 minutes after the treatment was completed. Changes in assessed parameters during anesthesia are presented in Table 1.

 

Table 1. Changes in assessed parameters during anesthesia

Parameter	Before induction of anesthesia	Induction of anesthesia	After tracheal intubation	Anesthesia maintenance			Before tracheal extubation	Before transfer to recovery ward
				after 30 min	after 60 min	after 90 min
SpO2, %	99	99	99	99	99	99	99	99
HR, bpm	120	130	140	130	125	125	130	115
Blood pressure, mm Hg: systolic diastolic mean	100 50 67	105 60 75	105 55 72	100 50 67	90 55 67	95 50 65	90 50 63	90 50 63
Respiratory rate, bpm	20	22	25	27	30	26	27	25
Xeex, %	—	—	—	45	45	50	45	0
BIS, c.u.	98	75	40	45	50	45	50	92
pH	—	—	7.2	—	—	—	7.2	—
pCO2, mm Hg	—	—	45	—	—	—	44	—
pO2, mm Hg	—	—	89	—	—	—	95	—
HCO3, mmol/L	—	—	24.4	—	—	—	23.1	—
BE, mol/L	—	—	–2	—	—	—	–3	—
tCO2, mmol/L	—	—	25	—	—	—	26	—
EtCO2, mm Hg	—	44	42	44	43	44	44	—
Minute ventilation, L/min	—	4	3.2	3.4	3.5	3.4	3.3	—
TV, mL	—	100	90	95	90	95	90	—
Paw, mm Hg	—	20	15	16	17	16	15	—
Cuff pressure, cm of water	—	—	19	18	19	19	20	—

Note: SpO₂, oxygen saturation; HR, heart rate; Xe_ex, expiratory xenon concentration; pCO₂, carbon dioxide partial pressure; pO₂, oxygen partial pressure; HCO₃, plasma bicarbonate; BE, base deficit; tCO₂, total carbon dioxide; EtCO₂, end-tidal carbon dioxide; TV, tidal volume; Paw, airway pressure.

 

Outcome and follow-up findings

The treatment duration was 1 hour and 50 minutes, the anesthesia duration was 2 hours, and the total xenon consumption was 10 L. During anesthesia, all assessed parameters were within the reference range for age; there were no seizures.

A neurologist documented seizure syndrome at the end of the second day after anesthesia. The patient resumed levetiracetam and vigabatrin therapy on the day of anesthesia, at the doses specified above.

DISCUSSION

Xenon plays a vital role in regulating and inhibiting glutamate transport. Impaired glutamate transport leads to acute neuron damage, seizures, and epilepsy [9, 10]. Thus, xenon can significantly decrease neuron damage caused by overexcitation [11]. Hyperactivation of NMDA receptors caused by elevated glutamate levels may result in neurotoxicity and neuron damage, which plays a critical role in the development and progression of seizure syndrome [8]. It was recently found that xenon activates the TREK-1 gene, which is thought to be associated with Ca²⁺ channel activation, decreased glutamate release, and excitotoxicity inhibition [12]. New evidence suggests that xenon decreases glutamate levels, inhibits NMDA receptors, and reduces oxidative stress caused by neuroexcitotoxicity [13]. Of special concern are drug-resistant epileptic syndromes, which are now frequently treated using surgical methods, such as frontal temporal lobectomy, limited temporal resection, extratemporal neocortical resection, and vagal nerve stimulation. However, the results are not always conclusive [14]. Given the mechanisms of action of xenon, its use for anesthesia in patients with various forms of epilepsy, including drug-resistant epilepsy, appears relevant and significant.

CONCLUSION

Xenon, as a safe, effective, and environmentally safe gas, can become a promising, innovative alternative option for anesthesia in epilepsy patients, particularly in drug-resistant epilepsy. The presented clinical case demonstrates that xenon has high anticonvulsant efficacy during and shortly after anesthesia in a pediatric patient with drug-resistant epilepsy.

ADDITIONAL INFORMATION

Funding source. The authors state that there is no external funding for the search and analytical work and the preparation of the manuscript.

Competing interests. The authors declare that they have no competing interests.

Authors’ contribution. D.M. Khaliullin — general anesthesia, literature review, writing an article; V.V. Lazarev — writing, editing an article; I.A. Shugailov — writing, editing an article; E.S. Gracheva — conducting treatment, writing an article.

Consent for publication. Written consent was obtained from the patient for publication of relevant medical information and all of accompanying images within the manuscript.

作者简介

Dinar Khaliullin

Dental Forte Elite LLC

Email: dr170489@yandex.ru
ORCID iD: 0000-0003-2771-3134
SPIN 代码: 7165-1859

MD, Cand. Sci. (Medicine)

俄罗斯联邦, Republic of Tatarstan, Naberezhnye Chelny

Vladimir Lazarev

The Russian National Research Medical University named after N.I. Pirogov; V.F. Voyno-Yasenetsky Scientific and Practical Center of Specialized Medical Care for Children

编辑信件的主要联系方式.
Email: lazarev_vv@inbox.ru
ORCID iD: 0000-0001-8417-3555
SPIN 代码: 4414-0677

MD, Dr. Sci. (Medicine), Professor

俄罗斯联邦, Moscow; Moscow

Igor Shugailov

Russian Medical Academy of Continuous Professional Education

Email: 9978753@mail.ru
ORCID iD: 0000-0001-5304-6078
SPIN 代码: 5681-7569

MD, Dr. Sci. (Medicine), Professor

俄罗斯联邦, Moscow

Elena Gracheva

Good Dental LLC

Email: murzic_elena@icloud.com
ORCID iD: 0000-0002-2758-8065
俄罗斯联邦, Republic of Tatarstan, Naberezhnye Chelny

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