Eur J Pediatr Surg 2018; 28(05): 400-405
DOI: 10.1055/s-0037-1603641
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Safeguarding Infant Brains: A Multidisciplinary Challenge—Results of a Survey, Update on Current Scientific Evidence, and Recommendations on How to Deal with Possible Anesthetic Drug Neurotoxicity

Frank Weber
1   Department of Anaesthesia, Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, The Netherlands
,
John Vlot
2   Department of Pediatric Surgery, Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, The Netherlands
,
Rene Wijnen
2   Department of Pediatric Surgery, Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

16 February 2017

25 April 2017

Publication Date:
08 June 2017 (online)

Abstract

Introduction Potential neurotoxicity of anesthetic drugs has been among the most intensively discussed issue in pediatric anesthesia for more than 10 years. It remains unclear how far this discussion has reached the European pediatric surgical community. Our aim was to investigate the thoughts of pediatric surgeons regarding this topic. In addition, we provide an update on the current scientific evidence regarding neurotoxicity together with recommendations for clinical practice.

Materials and Methods A web-based survey to assess the thoughts of practicing European pediatric surgeons regarding neurotoxicity and how it may have influenced their daily practice of pediatric surgery was launched via the European Pediatric Surgeons' Association Web site.

Results A total of 72 responses could be analyzed. A majority of the respondents were interested in the topic but felt a need to further explore it. Thirty-one respondents have changed their daily practice of pediatric surgery due to potential anesthetic drug toxicity. Eighteen respondents reported to be concerned about neurotoxicity, 29 held a neutral position, and 8 were not concerned. Twenty-seven respondents found it a shared responsibility of the surgeon and the anesthesiologist to deal with the neurotoxicity issue. The majority of respondents found a necessity for further research on anesthetic drug neurotoxicity, assigning the highest priority to prospective longitudinal human studies and the lowest to animal studies.

Conclusion The neurotoxicity question has reached the pediatric surgical community. Currently available scientific data do not support the theory of anesthetic drug-induced neurotoxicity in young children. Recent interdisciplinary clinical research focuses on neurodevelopmental outcome after surgery in neonates and infants. The European Safe Anesthesia For Every Tot initiative suggests focusing on proper conduct of anesthesia in children rather than on possible anesthetic drug neurotoxicity.

 
  • References

  • 1 Food and Drug Administration. FDA review results in new warnings about using general anesthetics and sedation drugs in young children and pregnant women. Silver Spring, MD; December 14, 2016 . Available at: http://www.fda.gov/Drugs/DrugSafety/ucm532356.htm . Accessed February 10, 2017
  • 2 Disma N, Mondardini MC, Terrando N, Absalom AR, Bilotta F. A systematic review of methodology applied during preclinical anesthetic neurotoxicity studies: important issues and lessons relevant to the design of future clinical research. Paediatr Anaesth 2016; 26 (01) 6-36
  • 3 Sanders RD, Hassell J, Davidson AJ, Robertson NJ, Ma D. Impact of anaesthetics and surgery on neurodevelopment: an update. Br J Anaesth 2013; 110 (Suppl. 01) i53-i72
  • 4 Hansen TG, Engelhardt T, Weiss M. The relevance of anesthetic drug-induced neurotoxicity. JAMA Pediatr 2017; 171 (01) e163481
  • 5 Hansen TG. Anesthesia-related neurotoxicity and the developing animal brain is not a significant problem in children. Paediatr Anaesth 2015; 25 (01) 65-72
  • 6 Backeljauw B, Holland SK, Altaye M, Loepke AW. Cognition and brain structure following early childhood surgery with anesthesia. Pediatrics 2015; 136 (01) e1-e12
  • 7 Stratmann G, Lee J, Sall JW. , et al. Effect of general anesthesia in infancy on long-term recognition memory in humans and rats. Neuropsychopharmacology 2014; 39 (10) 2275-2287
  • 8 Weiss M, Vutskits L, Hansen TG, Engelhardt T. Safe Anesthesia For Every Tot - the SAFETOTS initiative. Curr Opin Anaesthesiol 2015; 28 (03) 302-307
  • 9 Servick K. Biomedical research. Researchers struggle to gauge risks of childhood anesthesia. Science 2014; 346 (6214): 1161-1162
  • 10 Miller TL, Park R, Sun LS. Report on the Fifth PANDA Symposium on “Anesthesia and Neurodevelopment in Children”. J Neurosurg Anesthesiol 2016; 28 (04) 350-355
  • 11 Giliberti P, Mondì V, Conforti A. , et al. Near infrared spectroscopy in newborns with surgical disease. J Matern Fetal Neonatal Med 2011; 24 (Suppl. 01) 56-58
  • 12 Pelizzo G, Bernardi L, Carlini V. , et al. Laparoscopy in children and its impact on brain oxygenation during routine inguinal hernia repair. J Minim Access Surg 2017; 13 (01) 51-56
  • 13 Survey Monkey. Available at: http://www.surveymonkey.com/ . Accessed February 10, 2017
  • 14 Weber F, Van Beek S, Scoones G. Potential neurotoxicity of anesthetic drugs in young children: who cares? A survey among European anesthetists. Minerva Anestesiol 2016; 82 (03) 294-300
  • 15 Snoek KG, Capolupo I, Braguglia A. , et al. Neurodevelopmental outcome in high-risk congenital diaphragmatic hernia patients: an appeal for international standardization. Neonatology 2016; 109 (01) 14-21
  • 16 IJsselstijn H, Gischler SJ, Toussaint L, Spoel M, Zijp MH, Tibboel D. Growth and development after oesophageal atresia surgery: need for long-term multidisciplinary follow-up. Paediatr Respir Rev 2016; 19: 34-38
  • 17 Walker K, Halliday R, Holland AJ, Karskens C, Badawi N. Early developmental outcome of infants with infantile hypertrophic pyloric stenosis. J Pediatr Surg 2010; 45 (12) 2369-2372
  • 18 Clancy B, Finlay BL, Darlington RB, Anand KJ. Extrapolating brain development from experimental species to humans. Neurotoxicology 2007; 28 (05) 931-937
  • 19 Flick RP, Nemergut ME, Christensen K, Hansen TG. Anesthetic-related neurotoxicity in the young and outcome measures: the devil is in the details. Anesthesiology 2014; 120 (06) 1303-1305
  • 20 de Heer IJ, Tiemeier H, Hoeks SE, Weber F. Intelligence quotient scores at the age of 6 years in children anaesthetised before the age of 5 years. Anaesthesia 2017; 72 (01) 57-62
  • 21 Glatz P, Sandin RH, Pedersen NL, Bonamy AK, Eriksson LI, Granath F. Association of anesthesia and surgery during childhood with long-term academic performance. JAMA Pediatr 2017; 171 (01) e163470
  • 22 Graham MR, Brownell M, Chateau DG, Dragan RD, Burchill C, Fransoo RR. Neurodevelopmental assessment in kindergarten in children exposed to general anesthesia before the age of 4 years: a retrospective matched cohort study. Anesthesiology 2016; 125 (04) 667-677
  • 23 Davidson AJ, Disma N, de Graaff JC. , et al; GAS consortium. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet 2016; 387 (10015): 239-250
  • 24 Sun LS, Li G, Miller TL. , et al. Association between a single general anesthesia exposure before age 36 months and neurocognitive outcomes in later childhood. JAMA 2016; 315 (21) 2312-2320
  • 25 Pinyavat T, Warner DO, Flick RP. , et al. Summary of the update session on clinical neurotoxicity studies. J Neurosurg Anesthesiol 2016; 28 (04) 356-360
  • 26 Thompson ME. Preventing neurotoxicity: don't forget high-dose narcotic anesthetic. Paediatr Anaesth 2014; 24 (10) 1110-1111
  • 27 Marhofer P, Keplinger M, Klug W, Metzelder ML. Awake caudals and epidurals should be used more frequently in neonates and infants. Paediatr Anaesth 2015; 25 (01) 93-99