Effects of General Anesthesia on Brain FC and Cognition in Children With Potential Neurological Damage

Study Overview
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Brief Summary
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Postoperative Cognitive Dysfunction(POCD)is a common postoperative complications, existing clinical research focused on the adult patients, ignoring that the developing human brain with underlying neurological impairments may be at higher risk for cognitive impairment, so we need a prospective study, observe this kind of special groups in the brain structure and function of before and after general anesthesia, To determine the susceptibility to neurotoxicity of general anesthesia drugs.

Detailed Description
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Cognitive disorder refers to the abnormal or hindering of people's cognition of learning, memory, thinking, spirit, emotion and psychology, etc. In severe cases, aphasia, agnosia and apraxia will occur. In general, any factors that cause functional and structural abnormalities of the cerebral cortex can lead to cognitive impairment, and surgical anesthesia is one of the factors. Postoperative Cognitive Dysfunction (POCD) broadly refers to the temporary deterioration of cognitive function related to surgery. The diagnosis requires preoperative (as baseline) and postoperative neuropsychological tests, and the degree of postoperative cognitive decline can be determined by comparing the results of preoperative and postoperative tests. Numerous studies have shown that elderly patients are at higher risk for POCD after surgery and anesthesia. Although the neurotoxic effects of narcotic drugs on young neuronal cells have also been extensively discussed in recent years, the current lack of studies on POCD in children is in sharp contrast to the large literature on POCD in adults. The potential impact of general anesthesia on POCD in these younger populations, especially preschool and school age children, is largely unknown due to insufficient clinical evidence. The effects of general anesthesia on cognitive function in children are complex and controversial. Although a considerable number of animal studies have shown a link between general anesthesia and short-term or long-term neurocognitive impairment in animals, extrapolation of the results to humans remains difficult. Children's central nervous system has not yet mature, general anesthetics on its neurotoxic effect is still not clear, the existing clinical research results differ: some studies have shown that experience a single brief general anesthesia on children and long-term neurological development has no obvious negative impact, some research said general anesthesia to impaired cognitive function in children, especially after the experience again and again, long time exposure to anesthesia. However, few clinical studies have investigated the effects of general anesthesia on cognitive function in children with underlying neurological impairment. Are the effects of general anesthesia drugs on brain function and brain network structure in this special population with neurofragility different from those in children without neurological damage risk? Whether general anesthesia can increase the risk of postoperative cognitive impairment or aggravate the existing cognitive dysfunction in this special population deserves further study. Obstructive sleep disordered breathing (SDB) in children is a spectrum of continuous nocturnal breathing disorders characterized by more than airway obstruction and varying degrees of abnormal gas exchange. The mildest of the SDB is Primary Snoring (PS), which is characterized by habitual snoring (often defined as snoring more than three times per week) but few respiratory events (<1 event/hour), decreased oxygen saturation, or slight awakening due to labored breathing; The most severe condition is Obstructive Sleep Apnea (OSA), which is characterized by recurrent episodes of complete or partial airway obstruction, resulting in decreased oxygen saturation at night and or sleep awakenings. Children with OSA often present with snoring, sleep structure disorder, frequent oxygen desaturation, daytime sleepiness, attention deficit disorder and other symptoms. Adenoid and tonsillar hypertrophy is considered to be the most common cause of SDB in children. A large number of studies have shown that SDB patients have decreased cognitive function and learning ability, including attention, executive function, language learning and memory function. In addition, it has been reported that SDB children have structural changes in different brain regions, especially the hippocampus and frontal cortex, in addition to cognitive impairment. Some scholars believe that SDB may be an independent risk factor for postoperative cognitive impairment. The human brain can be regarded as a network of interconnected structures and synchronized functions. With the change of the functional state of the brain, the brain network is in dynamic change. The use of neuroimaging techniques (such as functional nuclear magnetic resonance, functional near infrared spectroscopy, etc.) and electrophysiological techniques (such as electroencephalography) can reconstruct the human brain network, which is conducive to the further study of brain structure and function. Based on these techniques, a growing number of researchers have found resting-state or task-state brain network changes in children with neuropsychiatric disorders with different patterns of cognitive and behavioral disorders, such as autism, attention deficit hyperactivity disorder, and epilepsy. In addition to brain network changes occurring in pathological conditions, many drugs that directly act on the central nervous system can also cause brain network changes, and general anesthesia drugs are one of them. The brain network changes in adults and children under maintenance of general anesthesia, which may be a macroscopic reflection of the molecular mechanism of consciousness loss caused by general anesthesia. Previous studies have shown that the prefrontal and frontal functional connectivity of electroencephalogram in children under maintenance of general anesthesia increases, while the parieto-occipital functional connectivity decreases. Thus, cognitive impairment is often accompanied by the change of brain network, and general anesthesia on brain networks may also be affected, in view of some adult clinical study shows that preoperative neurocognitie dysfunction or potential risk of cognitive dysfunction in patients with postoperative cognitive function damage probability increases, we hypothesized that: Children with SDB who are still in brain development and have a high risk of neurological injury belong to the special population who are more susceptible to the neurotoxicity of general anesthesia drugs. It is hypothesized that the susceptibility to neurotoxicity of general anesthesia drugs in this population is due to the more obvious inhibitory effect of general anesthesia drugs on the existing brain network connectivity. In diseases and general anesthetics on brain network, under the double whammy of SDB in children with the normal development of children after general anesthesia operation may face a higher risk of POCD, need to be evaluate cognitive function before and after exposure to general anesthesia, in order to make clear the SDB patients with preoperative cognitive development situation and short-term changes in cognitive function after general anesthesia surgery, At the same time, the changes of brain network before and after anesthesia in children with SDB were observed, and whether the changes of brain network were correlated with the changes of cognitive function was analyzed, so as to try to explain the increased susceptibility to neurotoxicity of general anesthesia in children with neurological injury risk. Above all，POCD is a common postoperative complications, existing clinical research focused on the adult patients, ignoring that the developing human brain with underlying neurological impairments may be at higher risk for cognitive impairment, so we need a prospective study, observe this kind of special groups in the brain structure and function of before and after general anesthesia, To determine the susceptibility to neurotoxicity of general anesthesia drugs.

Official Title
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Effects of General Anesthesia on Brain Functional Connectivity and Cognition in Children With Potential Neurological Damage

Conditions
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Postoperative Cognitive Dysfunction

Intervention / Treatment
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* Drug: General anesthetic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 4 to 10 years old, both sexes; Apgar score ≥8 at birth; ASA (American Society of Anesthesiologists Physical Condition Rating) ⅰ-ⅲ; to be treated with SDB under general anesthesia; His legal guardian has signed the informed consent - Exclusion Criteria: Age < 4 years old; or age >10 years old; suffering from serious heart, lung and brain diseases; History of dystocia or perinatal cerebral ischemia and hypoxia; Gestational age at birth ≤32 weeks; Confirmed or suspected neurological retardation or hearing and vision abnormalities; suffering from malignant tumor; had received general anesthesia or deep sedation before enrollment

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 10 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group SDB<br>Children were divided into two groups according to whether they had SDB, group SDB: experimental group (SDB children), group control: control group (typical development children) | Drug: General anesthetic<br>* Monitoring the changes of brain functional connectivity and assess cognition in two groups after general anesthesia<br>|
| Group control<br>Children were divided into two groups according to whether they had SDB, group SDB: experimental group (SDB children), group control: control group (typical development children) | Drug: General anesthetic<br>* Monitoring the changes of brain functional connectivity and assess cognition in two groups after general anesthesia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the scores of Wechsler intelligence scale | The scores of Wechsler intelligence scale before operation and 1 day after operation were compared between the two groups. | The 1 day before surgery；24 hours after surgery | 
| The incidence of POCD | The incidence of POCD was calculated by Z-score method | up to 24 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| comparison of functional connectivity | The changes of brain functional connectivity were compared between the two groups under two states of consciousness (awake and anesthesia) | up to 5 minutes | 
| Correlation between fNIRS brain function connectivity and cognitive function changes | The correlation between cognitive function changes and brain functional connectivity, age and anesthesia time were evaluated | one day before surgery and 24 hours after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric anesthesia, POCD, fNIRS, functional connectivity