Influence of General Anesthesia on the Dynamic Changes in Brain Damage Markers During and After Craniosynostosis Operations in Infancy
Influence of General Anesthesia on the Dynamic Changes in Brain Damage Markers During and After Craniosynostosis Operations in Infancy
The issue of anesthetics neurotoxicity is one of the most discussed topics in pediatric anesthesiology, thus it opens the question of the safety of commonly used anesthetics in the pediatric patient. Preclinical studies have shown that anesthetics can have a toxic effect on the maturing brain of pups and cause cognitive impairment. In human medicine, the influence of anesthetics is studied by monitoring the psychomotor development of children who have undergone surgery under general anesthesia. Some work deals with laboratory evidence of brain damage due to general anesthesia, but none of the work deals with the observation of markers of brain damage in infants. The aim of this work is to examine the dynamics of changes in the concentrations of selected markers of brain damage in craniosynostosis operations under general anesthesia in infants in order to optimize perioperative management and the correct timing of surgery.
More than twenty years ago, experimental work found that anesthetics can be toxic to the maturing brain of animal pups and cause cognitive impairment (Ikonomidou, 1999). The presented evidence suggested that the action of commonly used anesthetics triggers biochemical and morphological changes in immature neurons, which ultimately lead to their extinction (Creeley, 2013; Liu, 2012; Brambrink, 2010). Recent clinical studies have shown that general anesthesia can also have a negative effect on a child's cognitive functions (DiMaggio, 2017; Bong, 2013; Naumann, 2012; Flick, 2011). In another published study, it was found that the effect of general anesthesia in younger children leads to a more significant increase in markers of brain damage, neuron-specific enolase (NSE) and S100B protein (S100B), compared to older children (Stojanovic Stipic, 2017). It has also been shown, that the level of neurofilament light chain (NfL), a biomarker of axonal damage found in wide variety of neurological disorders (Khalil, 2018), is increased in adult patient's blood after anesthesia (Evered, 2018). Knowing the dynamics of brain damage markers can help optimize perioperative management and consideration of postponing the consider postponing surgery until later in childhood.
The aim of the submitted project is:
To determine the dynamic changes in the concentration of selected markers of brain damage (NSE, S100B and NfL) during inhalation anesthesia in infants.
To determine the dynamic changes in the concentration of these markers depending on:
A) age of the child B) duration of general anesthesia C) type of operation (open cranioplasty versus endoscopic cranioplasty)
Assessment of psychomotor development in the preoperative and postoperative period with an interval of 1 year after the operation and in the 36th month of the child's life.
Analysis of the relationship between changes in psychomotor development and changes in the concentration of brain damage markers.
Publication and implementation of the results into clinical practice.
Main benefit:
Optimization of surgical treatment of craniosynostosis with regard to minimizing the neurotoxic effect of anesthesia.
Secondary benefits:
Determining the dynamics of changes in the values of selected markers of brain damage under general anesthesia in craniosynostosis operations. Monitoring the relationship of selected parameters (length of anesthesia, patient age, weight, sex, type of surgical correction (endoscopic vs open), type of craniosynostosis, blood loss + correction and side reactions to changes in brain damage markers (NSE, S100B and NfL)).
Despite the fact that the investigators do not yet have clear results of the study, or a clear consensus of professional societies, the investigators assume that general anesthesia, especially repeated or long-term, can affect the maturing central nervous system of the child. The assumption is that due to the vulnerability of the brain, the increase in markers will be higher in the younger age of the child (endoscopic cranioplasty). European anesthesia societies do not share the FDA's full view. They mainly disagree with the insufficiently substantiated determination of the age limit of 3 years and the duration of general anesthesia of more than 3 hours as a risk factor increasing the incidence of neurotoxic damage. To date, no work has been published to monitor markers of brain damage in infants under general anesthesia.
To help in the future specify the optimal perioperative management, the method of anesthesia and the appropriate timing of the surgical procedure in order to consider postponing it to a later age of the child and at the same time to avoid unnecessary postponement of surgical procedures.
Description of the work plan:
Patient recruitment, preoperative preparation
Surgical performance under general anesthesia and perioperative marker collection
Postoperative follow-up
In the second and third stages /t.j. in the second and third year of the project/
Preoperative examinations will be coordinated by a participating neurosurgeon and anesthesiologist. Surgical intervention and perioperative examinations will be coordinated by the participating neurosurgeon.
Type of surgery. The study will use two surgical techniques: endoscopic cranioplasty and open cranioplasty.
Postoperative follow-up.
Postoperative examinations will be coordinated by a participating neurosurgeon. Evaluation and publication of results.
Social and other benefits and commercial use of project outputs. The social benefits of the project result from its scientific and medical outputs. The investigators do not yet have definitive results from clinical trials or a clear consensus of professional anesthesiology societies regarding the possible neurotoxicity of anesthetics, but the investigators nevertheless assume that general anesthesia, especially long-term anesthesia, has a negative effect on a child's developing brain. A large number of procedures cannot be postponed, but it is really necessary to pay great attention to a thorough indication of the operation or examination under general anesthesia and analgesia. When indicating anesthesia, it is necessary to keep in mind the fundamental, still debated discrepancy between the degree of neurotoxicity of general anesthetics and the possible consequences of insufficient or no analgesia and anesthesia. Although recent studies suggest that a single general anesthesia (lasting less than 3 hours) is unlikely to affect a child's behavior or learning, it is really important not to underestimate the issue of neurotoxicity and to consider whether all imaging and surgical procedures under general anesthesia or analgesia it is really necessary to realize it by the age of three. Before each anesthesia, the investigators should evaluate the benefits of anesthesia against the potential risks, especially if the procedures are longer than 3 hours or repeated procedures in children under three years of age. The aim of this project is to monitor the dynamics of changes in brain damage markers in infants during surgical procedures, when general anesthesia lasts on average longer than 3 hours. This is the first project that does not only deal with the observation of psychomotor development of children under the influence of long-term general anesthesia. Several aspects of this project have not yet been published and there is a high presumption of obtaining original results.
Inclusion Criteria:
Patients indicated for surgical treatment of single-layer craniosynostosis will be selected for the study. Surgical treatment will be performed according to conventional indications (endoscopic correction in patients under 6 months of age, open correction in patients older than 6 months) under general anesthesia. ASA 1 - 2. The signing of informed consent to inclusion in the study is also a condition. In the preoperative period, the investigators will assess the achieved developmental level of the child using the Bayley scale (Bayley - III).
Exclusion Criteria: