The effect of maintenance anesthetics on neurobehavioral development of infants undergoing cleft lip and palate surgery

doi:10.19438/j.cjoms.2025.02.007

Abstract

Abstract: PURPOSE: To study the effect of different maintenance anesthetics on postoperative short-term neurobehavioral development in children undergoing cleft lip and palate surgery. METHODS: A total of 79 children under 2 years old who underwent cleft lip and palate surgery under general anesthesia were divided into inhalation anesthesia group (group IA) and combined intravenous inhalation anesthesia group (group CIIA) according to different medication methods during anesthesia maintenance. The Gesell Development Diagnosis Scale (GDDS) scores were recorded at preoperative baseline (T0), 6 months after surgery (M6) and 12 months after surgery (M12). The results included 5 functional areas of adaptability, fine motor, gross motor, language and social skills. The difference of GDDS scores between groups at each follow-up point was compared, and corrected regression analysis was performed. R 4.0.5 software was used for data analysis. RESULTS: There was no significant difference in basic characteristics and baseline GDDS scores between the two groups of patients before surgery, the induced medication and the sevoflurane concentration of maintenance during surgery between the two groups also had no significant difference. After adjusting for factors such as gender, maternal education level, BMI, family income, and anesthesia times, the fine motor ability of the combined intravenous inhalation anesthesia group was worse than that of the inhalation anesthesia group at 12 months post surgery (M12) (P< 0.05). CONCLUSIONS: Compared with inhalation anesthesia, combined intravenous and inhalation anesthesia may have a slight effect on the short-term fine motor ability of children after cleft lip and palate surgery under general anesthesia.

Key words: Cleft lip and palate repair surgery, General anesthesia, Infants, Neurobehavioral development, Gesell Development Diagnosis Scale

CLC Number:

R782.05

LIU Wen-hui, ZHOU Xun, MA Li, LI Jing-jie, LIU Jin-xing, QIU Lin. The effect of maintenance anesthetics on neurobehavioral development of infants undergoing cleft lip and palate surgery[J]. China Journal of Oral and Maxillofacial Surgery, 2025, 23(2): 145-151.

References

[1] Stratmann G.Review article: neurotoxicity of anesthetic drugs in the developing brain[J]. Anesth Analg, 2011,113(5): 1170-1179.
[2] Lin EP, Lee JR, Lee CS, et al.Do anesthetics harm the developing human brain? an integrative analysis of animal and human studies[J]. Neurotoxicol Teratol, 2017, 60: 117-128.
[3] Wilder RT, Flick RP, Sprung J, et al.Early exposure to anesthesia and learning disabilities in a population-based birth cohort[J]. Anesthesiology, 2009, 110(4): 796-804.
[4] Ing C, DiMaggio C, Whitehouse A, et al. Long-term differences in language and cognitive function after childhood exposure to anesthesia[J]. Pediatrics, 2012,130(3): e476-e485.
[5] Kalkman CJ, Peelen L, Moons KG, et al.Behavior and development in children and age at the time of first anesthetic exposure[J]. Anesthesiology, 2009, 110(4): 805-812.
[6] Gesell developmental diagnosis scale[S]. Beijing: Beijing Mental Development Cooperative Group, 1985.
[7] 中华口腔医学会唇腭裂专业委员会. 唇腭裂序列治疗指南[J]. 中华口腔医学杂志, 2024, 59(3):221-229.
Society of Cleft Lip and Palate,Chinese Stomatological Association. Guideline for cleft lip and palate team approach management[J]. Chinese Journal of Stomatology, 2024, 59(3): 221-229.
[8] Walters JL, Paule MG.Review of preclinical studies on pediatric general anesthesia-induced developmental neurotoxicity[J]. Neurotoxicol Teratol, 2017, 60: 2-23.
[9] FDA drug safety communication: FDA review results in new warnings about using general 445 anesthetics and sedation drugs in young children and pregnant women[EB/OL].(2016-12-14)[2024-10-029].https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-review-results-new-warnings-about-using-general-anesthetics-and.
[10] Rugolph U, Antkowiak B.Molecular and neuronal substrates for general anaesthetics[J]. Nat Rev Neurosci, 2004, 5(9): 709-720.
[11] Disma N, O'Leary JD, Loepke AW, et al. Anesthesia and the developing brain: a way forward for laboratory and clinical research[J]. Paediatr Anaesth, 2018, 28(9):758-763.
[12] Neag MA, Mitre AO, Catinean A, et al.An overview on the mechanisms of neuroprotection and neurotoxicity of isoflurane and sevoflurane in experimental studies[J].Brain Res Bull, 2020, 165: 281-289.
[13] Ing C, Warner DO, Sun LS, et al.Anesthesia and developing brains: unanswered questions and proposed paths forward[J]. Anesthesiology, 2022, 136(3): 500-512.
[14] Edwards DA, Shah HP, Cao WG, et al.Bumetanide alleviates epileptogenic and neurotoxic effects of sevoflurane in neonatal rat brain[J]. Anesthesiology, 2010, 112(3): 567-575.
[15] Zeng F, Zhou M, Li Q, et al.Sevoflurane promotes neuronal ferroptosis via upregulation of PLIN4 to modulate the hippo signaling pathway[J]. Neurotoxicology, 2024, 105: 1-9.
[16] Zhou P, Zhang C, Huang G, et al.The effect of sevoflurane anesthesia for dental procedure on neurocognition in children: a prospective, equivalence, controlled trial[J]. BMC Pediatr, 2021, 21(1): 177-187.
[17] Davidson AJ, Disma N, de Graaff JC, et al. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia ininfancy (GAS): an international multicentre, randomised controlled trial[J]. Lancet, 2016, 387(10015): 239-350.
[18] McCann ME, de Graaff JC, Dorris L.et al. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia ininfancy (GAS): an international, multicentre, randomised, controlled equivalence trial[J]. Lancet, 2019, 393(10172): 664-677.
[19] She YJ, Xu HP, Gao Y, et al.Calpain-TRPC6 signaling pathway contributes to propofol-induced developmental neurotoxicity in rats[J]. Neurotoxicology, 2023, 95: 56-65.
[20] Briner A, Nikonenko I, De Roo M, et al.Developmental stage-dependent persistent impact of propofol anesthesia on dendritic spines in the rat medial prefrontal cortex[J]. Anesthesiology, 2011, 115(2): 282-293.
[21] Pearn ML, Hu Y, Niesman IR, et al.Propofol neurotoxicity is mediated by p75 neurotrophin receptor activation[J]. Anesthesiology, 2012, 116(2): 352-361.
[22] Creeley C, Dikranian K, Dissen G, et al.Propofol-induced apoptosis of neurones and oligodendrocytes in fetal and neonatal rhesus macaque brain[J]. Br J Anaesth. 2013, 110(Suppl 1): i29-i38.
[23] Morray JP, Bhananker SM.Recent findings from the pediatric perioperative cardiac arrest (POCA) registry[J]. ASA Newsl, 2005, 69: 10-12.
[24] Tagawa T, Sakuraba S, Kimura K, et al.Sevoflurane in combination with propofol, not thiopental, induces a more robust neuroapoptosis than sevoflurane alone in the neonatal mouse brain[J]. J Anesth, 2014, 28(6): 815-820.
[25] Davidson AJ, Huang GH, Rebmann CS, et al.Performance of entropy and bispectral index as measures of anaesthesia effect in children of different ages[J]. Br J Anaesth, 2005, 95(5): 674-679.
[26] Tokuwaka J, Satsumae T, Mizutani T, et al.Therelationship between age and minimum alveolar concentration of sevoflurane formaintaining bispectral index below 50 in children[J]. Anaesthesia, 2015, 70(3): 318-322.
[27] De Jong RH, Eger El.MAC expanded: AD50 and AD95 values of common inhalation anesthetics in man[J]. Anesthesiology, 1975, 42(4): 384-389.