Influence of General Anesthesia on the Dynamic Changes in Brain Damage Markers During and After Craniosynostosis Operations in Infancy

NCT05911139 | Enrolling By Invitation

• 2 other identifiers: EK2/2022/24051/0564/23
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Craniosynostosis; Anesthesia

Keywords

anesthesia; children; neurotoxicity; neuron specific enolase; S100B protein; neurofilament light chain

Outcome Measures

Primary Outcomes (3)

• Blood biomarker level of neuron-specific enolase (NSE)

  Three determinations of the level of NSE- 1, Immediately after the introduction of general anesthesia; 2, immediately after the end of anesthesia; 3, 48 hours after anesthesia

  48 hours

• Blood biomarker level of protein S100

  Three determinations of the level of protein S100- 1, Immediately after the introduction of general anesthesia; 2, immediately after the end of anesthesia; 3, 48 hours after anesthesia

  48 hours

• Blood biomarker level of neurofilament light chain (NfL)

  Three determinations of the level of NfL, Immediately after the introduction of general anesthesia; 2, immediately after the end of anesthesia; 3, 48 hours after anesthesia

  48 hours

Secondary Outcomes (1)

• child's psychomotor development (PMV)

  36 months

Other Outcomes (6)

• other parameters- age

  1 hours

• other parameters- weight

  1 hour

• other parameters- sex

  1 hour

Study Arms (1)

pediatric patients

Patients indicated for surgical treatment of single-layer craniosynostosis will be selected for the study, anticipated 15 patients per calendar year

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Prospective recruitment of patients indicated for surgical treatment of single-stage craniosynostoses at NUCHD Bratislava. 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).

You may qualify if:

• The child's parents will sign an informed consent to be included in the study.

You may not qualify if:

• Patients with comorbidities, syndromic craniosynostosis will be excluded from the study.

Sponsors & Collaborators

• Comenius University: lead

Study Sites (1)

Department of paediatric anaesthesiology and intensive medicine

Bratislava, 83340, Slovakia

Location

Related Publications (8)

• McGuigan S, Evered L, Scott DA, Silbert B, Zetterberg H, Blennow K. Comparing the effect of xenon and sevoflurane anesthesia on postoperative neural injury biomarkers: a randomized controlled trial. Med Gas Res. 2022 Jan-Mar;12(1):10-17. doi: 10.4103/2045-9912.324591.

  PMID: 34472497 BACKGROUND

• Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, Barro C, Kappos L, Comabella M, Fazekas F, Petzold A, Blennow K, Zetterberg H, Kuhle J. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018 Oct;14(10):577-589. doi: 10.1038/s41582-018-0058-z.

  PMID: 30171200 BACKGROUND

• Stojanovic Stipic S, Carev M, Bajic Z, Supe Domic D, Roje Z, Jukic A, Stipic T. Increase of plasma S100B and neuron-specific enolase in children following adenotonsillectomy: a prospective clinical trial. Eur Arch Otorhinolaryngol. 2017 Oct;274(10):3781-3788. doi: 10.1007/s00405-017-4698-1. Epub 2017 Aug 7.

  PMID: 28785895 BACKGROUND

• Flick RP, Katusic SK, Colligan RC, Wilder RT, Voigt RG, Olson MD, Sprung J, Weaver AL, Schroeder DR, Warner DO. Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. Pediatrics. 2011 Nov;128(5):e1053-61. doi: 10.1542/peds.2011-0351. Epub 2011 Oct 3.

  PMID: 21969289 BACKGROUND

• Bong CL, Allen JC, Kim JT. The effects of exposure to general anesthesia in infancy on academic performance at age 12. Anesth Analg. 2013 Dec;117(6):1419-28. doi: 10.1213/ANE.0b013e318299a7c2.

  PMID: 24132012 BACKGROUND

• Brambrink AM, Evers AS, Avidan MS, Farber NB, Smith DJ, Zhang X, Dissen GA, Creeley CE, Olney JW. Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology. 2010 Apr;112(4):834-41. doi: 10.1097/ALN.0b013e3181d049cd.

  PMID: 20234312 BACKGROUND

• Liu F, Patterson TA, Sadovova N, Zhang X, Liu S, Zou X, Hanig JP, Paule MG, Slikker W Jr, Wang C. Ketamine-induced neuronal damage and altered N-methyl-D-aspartate receptor function in rat primary forebrain culture. Toxicol Sci. 2013 Feb;131(2):548-57. doi: 10.1093/toxsci/kfs296. Epub 2012 Oct 11.

  PMID: 23065140 BACKGROUND

• Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler J, Dikranian K, Tenkova TI, Stefovska V, Turski L, Olney JW. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science. 1999 Jan 1;283(5398):70-4. doi: 10.1126/science.283.5398.70.

  PMID: 9872743 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood sampling - before anesthesia, at the end of anesthesia and 48 hours after the end of anesthesia - determination of S100B protein level

MeSH Terms

Conditions

Craniosynostoses; Neurotoxicity Syndromes; Charcot-Marie-Tooth disease, Type 1F

Condition Hierarchy (Ancestors)

Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nervous System Diseases; Poisoning; Chemically-Induced Disorders

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 36 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2023
• First Posted: June 20, 2023
• Study Start: October 1, 2022
• Primary Completion: September 30, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 23, 2023

Record last verified: 2023-06

Locations

SL (1)