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Use of anaesthetics in young children: Consensus statement of the European Society of Anaesthesiology, the European Society for Paediatric Anaesthesiology, the European Association of Cardiothoracic Anaesthesiology and the European Safe Tots Anaesthesia Research Initiative

Hansen, Tom G.

European Journal of Anaesthesiology: June 2017 - Volume 34 - Issue 6 - p 327–328
doi: 10.1097/EJA.0000000000000629
Editorial

From the Department of Clinical Research – Anaesthesiology, University of Southern Denmark, Odense, Denmark

Correspondence to Tom G. Hansen, MD, co-Chair of European Safe Tots Anaesthesia Research Initiative, Department of Clinical Research – Anaesthesiology, University of Southern Denmark, Odense, Denmark E-mail: tomghansen@dadlnet.dk

Experimental studies have shown that general anaesthetics may cause a variety of morphological changes in the developing immature brain of laboratory animals.1 In addition, there is some evidence that long-term and prolonged exposure may be worse than short-term exposure in some animal species.2,3 However, the relevance of these findings in human beings is currently unknown,4,5 and studies have shown controversial results.6–8 Although a number of investigations in humans have demonstrated an association between surgical and anaesthetic exposure and negative neurodevelopmental outcome,9–11 several others have been unable to find such an association or only in a minor subset of exposed children with or without extensive individual neurocognitive testing.12–18 It remains, therefore, very difficult to identify whether any negative neurodevelopmental effects are because of the anaesthetic drugs, the conduct of anaesthesia, surgical trauma or the underlying clinical conditions.3–19

Importantly, however, two prospective human studies, with the most robust designs, indicate that short-term single exposure of 60 min or less to surgery and anaesthesia is not associated with measurable long-term neurodevelopmental problems.12,16

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Food and Drug Administration statement

On the 14th of December 2016, the Food and Drug Administration (FDA) issued a warning statement for the United States of America regarding the use of anaesthesia or sedation in young children (and pregnant women).20 This statement highlights potential risk of anaesthetic procedures that last longer than 3 h or multiple procedures required in children less than 3 years of age. The evidence to support such warning is currently insufficient and incomplete. Therefore, this FDA warning is not shared by the European Societies listed below.

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The European Society of Anaesthesiology/European Society for Paediatric Anaesthesiology/European Association of Cardiothoracic Anaesthesiology/European Safe Tots Anaesthesia Research Initiative consensus statement

No child or pregnant woman should ever undergo any medical procedure that is not necessary. Similarly, young children (and pregnant women) should not undergo surgery and general anaesthesia for trivial reasons. However, delaying or avoiding surgery may result in a significant and real risk of a variety of adverse outcomes. If an invasive procedure is necessary, adequate anaesthesia/analgesia are mandatory. Indeed, there is good evidence that inadequate anaesthesia and analgesia may result in significant and serious complications.21,22 There is currently no evidence to support the suggestion that a change from established techniques for prolonged or repeated procedures would have any impact on long-term outcomes including neurocognition and development in young children.

Furthermore, the implied ‘safe’ cut-off points of age 3 years or duration of procedure of 3 h quoted in the FDA warning statement are not currently supported by evidence derived from human studies.

Given the uncertainty in this domain, it is reasonable to discuss all aspects of perioperative safety with patients, parents and families. However, discussion of hypothetical risks based primarily on animal research not confirmed in human studies may create anxiety.

Established well tolerated anaesthetic techniques delivered by trained and experienced staff in a paediatric environment supported by the necessary clinical organisation are essential factors for the delivery of well tolerated anaesthesia and sedation in children.23

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Conclusion

There is currently no compelling evidence to change anaesthetic practice, but anaesthesiologists should provide adequate information on the risks of avoiding a necessary intervention/anaesthesia procedure as well as on the potential risks associated with anaesthetic procedures. The European Societies listed above participate in international collaborations and support the principles of well tolerated conduct of anaesthesia in children and pregnant women. Information for parents and information for anaesthetists will be updated as and when new issues arise.

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Acknowledgements relating to this article

Assistance with the Editorial: none.

Financial support and sponsorship: none.

Conflict of interest: none.

Comment from the Editor: this Editorial was checked and accepted by the editors but was not sent for external peer review. TGH is an Associate Editor of the European Journal of Anaesthesiology.

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References

1. Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 2003; 23:876–882.
2. Vutskits L, Xie Z. Lasting impact of general anaesthesia on the brain: mechanisms and relevance. Nat Rev Neurosci 2016; 18:705–717.
3. Zou X, Patterson TA, Divine RL, et al. Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain. Int J Dev Neurosci 2009; 27:727–731.
4. Todd MM. Anesthetic neurotoxicity: the collision between laboratory neuroscience and clinical medicine. Anesthesiology 2004; 101:227–230.
5. Andropoulos DB, Greene MF. Anesthesia and developing brains – implications of the FDA warning. N Engl J Med 2017; 376:905–907.
6. Hansen TG. Anesthesia-related neurotoxicity and the developing animal brain is not a significant problem in children. Paediatr Anaesth 2015; 25:65–72.
7. Rappaport BA, Suresh S, Hertz S, et al. Anesthetic neurotoxicity – clinical implications of animal models. N Engl J Med 2015; 372:796–797.
8. Psaty BM, Platt R, Altman RB. Neurotoxicity of generic anesthesia agents in infants and children: an orphan research question in search of a sponsor. JAMA 2015; 313:1515–1516.
9. Ing C, DiMaggio C, Whitehouse A, et al. Long-term differences in language and cognitive function after childhood exposure to anesthesia. Pediatrics 2012; 130:e476–e485.
10. Wilder RT, Flick RP, Sprung J, et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology 2009; 110:796–804.
11. Ing CH, DiMaggio CJ, Malacova E, et al. Comparative analysis of outcome measures used in examining neurodevelopmental effects of early childhood anesthesia exposure. Anesthesiology 2014; 120:1319–3214.
12. 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; 315:2312–2320.
13. Hansen TG, Pedersen JK, Henneberg SW, et al. Academic performance in adolescence after inguinal hernia repair in infancy: a nation-wide cohort study. Anesthesiology 2011; 114:1076–1085.
14. Hansen TG, Pedersen JK, Henneberg SW, et al. Educational outcome in adolescence following pyloric stenosis repair before 3 months of age: a nation-wide cohort study. Paediatr Anaesth 2013; 23:883–890.
15. Glatz P, Sandin RH, Pedersen NL, et al. Academic performance after anesthesia and surgery during childhood – a large scale nation-wide study. JAMA Pediatr 2017; 171:e163470.
16. Davidson AJ, Disma N, de Graaff JC, et al. 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; 387:239–250.
17. O’Leary JD, Janus M, Duku E, et al. A population-based study evaluating the association between surgery in early life and child development at primary school entry. Anesthesiology 2016; 125:272–279.
18. Graham MR, Brownell M, Chateau DG, et al. Neurodevelopmental assessment in kindergarten in children exposed to general anesthesia before the age of 4 years. A retrospective study. Anesthesiology 2016; 125:667–677.
19. Weiss M, Hansen TG, Engelhardt T. Ensuring safe anaesthesia for neonates, infants and young children: what really matters. Arch Dis Child 2016; 101:650–652.
20. FDA Drug Safety Communication. 2016 www.fda.gov/Drugs/DrugSafety/ucm532356.htm.
21. Anand KJS, Hickey PR. Halothane-morphine compared with high dose sufentanil for anesthesia and postop analgesia in neonatal cardiac surgery. N Engl J Med 1992; 326:1–9.
22. Anand KJS. Revisiting a dilemma: repetitive pain vs. opioid exposure? Acta Paediatr 2016; 105:736–737.
23. Weiss M, Vutskits L, Hansen TG, et al. Safe anesthesia for every Tot – the SAFETOTS initiative. Curr Opin Anaesthesiol 2015; 28:302–376.
© 2017 European Society of Anaesthesiology