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Risk of esketamine anesthesia on the emergence delirium in preschool children after minor surgery: a prospective observational clinical study

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Abstract

Emergence delirium (ED) is a common mental complication during recovery from anesthesia. However, studies on the effects of esketamine, an intravenous anesthetic for pediatrics, on ED are still lacking. This study aimed to investigate the effects of a single-dose of esketamine during anesthesia induction on ED after minor surgery in preschool children. A total of 230 children (aged 2–7 years) completed the study. The exposed group (0.46 mg kg−1: average dose of esketamine) was associated with an increased incidence of ED and a higher maximum Pediatric Anesthesia Emergence Delirium score than the non-exposed group. The length of post-anesthesia care unit stay was longer in the exposed group than the non-exposed group. In contrast, extubation time, face, legs, activity, cry, and consolability (FLACC) scores, and the proportions of rescue analgesics were comparable between the two groups. Furthermore, five factors, including preoperative anxiety scores, sevoflurane and propofol compared with sevoflurane alone for anesthesia maintenance, dezocine for postoperative analgesia, FLACC scores, and esketamine exposure, were associated with ED. In conclusion, a near-anesthetic single-dose of esketamine for anesthesia induction may increase the incidence of ED in preschool children after minor surgery. The use of esketamine in preschool children for minor surgery should be noticed during clinical practice.

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All data generated or analyzed during this study were included in the published article. Further inquiries about the datasets can be directed to the corresponding author on reasonable request.

References

  1. Evered L, Silbert B, Knopman DS, Scott DA, DeKosky ST, Rasmussen LS, Oh ES, Crosby G, Berger M, Eckenhoff RG, Nomenclature Consensus Working G (2018) Recommendations for the nomenclature of cognitive change associated with Anaesthesia and surgery-2018. Br J Anaesth 121(5):1005–1012. https://doi.org/10.1016/j.bja.2017.11.087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Urits I, Peck J, Giacomazzi S, Patel R, Wolf J, Mathew D, Schwartz R, Kassem H, Urman RD, Kaye AD, Viswanath O (2020) Emergence delirium in perioperative pediatric care: a review of current evidence and new directions. Adv Ther 37 (5):1897–1909. https://doi.org/10.1007/s12325-020-01317-x

  3. Dahmani S, Delivet H, Hilly J (2014) Emergence delirium in children: an update. Curr Opin Anaesthesiol 27(3):309–315. https://doi.org/10.1097/ACO.0000000000000076

    Article  CAS  PubMed  Google Scholar 

  4. Martini DR (2005) Commentary: the diagnosis of delirium in pediatric patients. J Am Acad Child Adolesc Psychiatry 44(4):395–398. https://doi.org/10.1097/01.chi.0000153716.52154.cf

    Article  PubMed  Google Scholar 

  5. Mason KP (2017) Paediatric emergence delirium: a comprehensive review and interpretation of the literature. Br J Anaesth 118(3):335–343. https://doi.org/10.1093/bja/aew477

    Article  CAS  PubMed  Google Scholar 

  6. Dahmani S, Stany I, Brasher C, Lejeune C, Bruneau B, Wood C, Nivoche Y, Constant I, Murat I (2010) Pharmacological prevention of sevoflurane- and desflurane-related emergence agitation in children: a meta-analysis of published studies. Br J Anaesth 104(2):216–223. https://doi.org/10.1093/bja/aep376

    Article  CAS  PubMed  Google Scholar 

  7. Kain ZN, Caldwell-Andrews AA, Maranets I, McClain B, Gaal D, Mayes LC, Feng R, Zhang H (2004) Preoperative anxiety and emergence delirium and postoperative maladaptive behaviors. Anesth Analg 99(6):1648–1654. https://doi.org/10.1213/01.ANE.0000136471.36680.97

    Article  PubMed  Google Scholar 

  8. White PF, Schuttler J, Shafer A, Stanski DR, Horai Y, Trevor AJ (1985) Comparative pharmacology of the ketamine isomers. Studies in volunteers. Br J Anaesth 57(2):197–203. https://doi.org/10.1093/bja/57.2.197

    Article  CAS  PubMed  Google Scholar 

  9. Himmelseher S, Pfenninger E (1998) The clinical use of S-(+)-ketamine—a determination of its place. Anasthesiol Intensivmed Notfallmed Schmerzther 33(12):764–770. https://doi.org/10.1055/s-2007-994851

    Article  CAS  PubMed  Google Scholar 

  10. Wang J, Huang J, Yang S, Cui C, Ye L, Wang SY, Yang GP, Pei Q (2019) Pharmacokinetics and safety of esketamine in Chinese patients undergoing painless gastroscopy in comparison with ketamine: a randomized, open-label clinical study. Drug Des Devel Ther 13:4135–4144. https://doi.org/10.2147/DDDT.S224553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bowdle TA, Radant AD, Cowley DS, Kharasch ED, Strassman RJ, Roy-Byrne PP (1998) Psychedelic effects of ketamine in healthy volunteers: relationship to steady-state plasma concentrations. Anesthesiology 88(1):82–88. https://doi.org/10.1097/00000542-199801000-00015

    Article  CAS  PubMed  Google Scholar 

  12. Pfenninger EG, Durieux ME, Himmelseher S (2002) Cognitive impairment after small-dose ketamine isomers in comparison to equianalgesic racemic ketamine in human volunteers. Anesthesiology 96(2):357–366. https://doi.org/10.1097/00000542-200202000-00022

    Article  CAS  PubMed  Google Scholar 

  13. Jeong WJ, Kim WY, Moon MG, Min DJ, Lee YS, Kim JH, Park YC (2012) The effect of ketamine on the separation anxiety and emergence agitation in children undergoing brief ophthalmic surgery under desflurane general anesthesia. Korean J Anesthesiol 63(3):203–208. https://doi.org/10.4097/kjae.2012.63.3.203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lee YS, Kim WY, Choi JH, Son JH, Kim JH, Park YC (2010) The effect of ketamine on the incidence of emergence agitation in children undergoing tonsillectomy and adenoidectomy under sevoflurane general anesthesia. Korean J Anesthesiol 58(5):440–445. https://doi.org/10.4097/kjae.2010.58.5.440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Schmitz A, Weiss M, Kellenberger C, O’Gorman Tuura R, Klaghofer R, Scheer I, Makki M, Sabandal C, Buehler PK (2018) Sedation for magnetic resonance imaging using propofol with or without ketamine at induction in pediatrics—a prospective randomized double-blinded study. Paediatr Anaesth 28(3):264–274. https://doi.org/10.1111/pan.13315

    Article  PubMed  Google Scholar 

  16. Abitagaoglu S, Koksal C, Alagoz S, Karip CS, Ari DE (2021) Effect of ketamine on emergence agitation following septoplasty: a randomized clinical trial. Braz J Anesthesiol 71(4):381–386. https://doi.org/10.1016/j.bjane.2020.12.027

    Article  PubMed  PubMed Central  Google Scholar 

  17. Ringblom J, Wahlin I, Proczkowska M (2018) A psychometric evaluation of the Pediatric Anesthesia Emergence Delirium scale. Paediatr Anaesth 28(4):332–337. https://doi.org/10.1111/pan.13348

    Article  PubMed  Google Scholar 

  18. Sikich N, Lerman J (2004) Development and psychometric evaluation of the pediatric anesthesia emergence delirium scale. Anesthesiology 100(5):1138–1145. https://doi.org/10.1097/00000542-200405000-00015

    Article  PubMed  Google Scholar 

  19. Hauber JA, Davis PJ, Bendel LP, Martyn SV, McCarthy DL, Evans MC, Cladis FP, Cunningham S, Lang RS, Campbell NF, Tuchman JB, Young MC (2015) Dexmedetomidine as a rapid bolus for treatment and prophylactic prevention of emergence agitation in anesthetized children. Anesth Analg 121(5):1308–1315. https://doi.org/10.1213/ANE.0000000000000931

    Article  CAS  PubMed  Google Scholar 

  20. Shi M, Miao S, Gu T, Wang D, Zhang H, Liu J (2019) Dexmedetomidine for the prevention of emergence delirium and postoperative behavioral changes in pediatric patients with sevoflurane anesthesia: a double-blind, randomized trial. Drug Des Devel Ther 13:897–905. https://doi.org/10.2147/DDDT.S196075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Crellin DJ, Harrison D, Santamaria N, Babl FE (2015) Systematic review of the Face, Legs, Activity, Cry and Consolability scale for assessing pain in infants and children: Is it reliable, valid, and feasible for use? Pain 156(11):2132–2151. https://doi.org/10.1097/j.pain.0000000000000305

    Article  PubMed  Google Scholar 

  22. Lu X, Tang L, Lan H, Li C, Lin H (2021) A comparison of intranasal dexmedetomidine, esketamine or a dexmedetomidine-esketamine combination for induction of anaesthesia in children: a randomized controlled double-blind trial. Front Pharmacol 12:808930. https://doi.org/10.3389/fphar.2021.808930

  23. Donahue PJ, Dineen PS (1992) Emergence delirium following oral ketamine. Anesthesiology 77(3):604–605. https://doi.org/10.1097/00000542-199209000-00036

    Article  CAS  PubMed  Google Scholar 

  24. Short B, Fong J, Galvez V, Shelker W, Loo CK (2018) Side-effects associated with ketamine use in depression: a systematic review. Lancet Psychiatry 5(1):65–78. https://doi.org/10.1016/S2215-0366(17)30272-9

    Article  PubMed  Google Scholar 

  25. Clements JA, Nimmo WS, Grant IS (1982) Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans. J Pharm Sci 71(5):539–542. https://doi.org/10.1002/jps.2600710516

    Article  CAS  PubMed  Google Scholar 

  26. Clements JA, Nimmo WS (1981) Pharmacokinetics and analgesic effect of ketamine in man. Br J Anaesth 53(1):27–30. https://doi.org/10.1093/bja/53.1.27

    Article  CAS  PubMed  Google Scholar 

  27. Zarate CA Jr, Brutsche N, Laje G, Luckenbaugh DA, Venkata SL, Ramamoorthy A, Moaddel R, Wainer IW (2012) Relationship of ketamine’s plasma metabolites with response, diagnosis, and side effects in major depression. Biol Psychiatry 72(4):331–338. https://doi.org/10.1016/j.biopsych.2012.03.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Idvall J, Ahlgren I, Aronsen KR, Stenberg P (1979) Ketamine infusions: pharmacokinetics and clinical effects. Br J Anaesth 51(12):1167–1173. https://doi.org/10.1093/bja/51.12.1167

    Article  CAS  PubMed  Google Scholar 

  29. Grant IS, Nimmo WS, McNicol LR, Clements JA (1983) Ketamine disposition in children and adults. Br J Anaesth 55(11):1107–1111. https://doi.org/10.1093/bja/55.11.1107

    Article  CAS  PubMed  Google Scholar 

  30. Little B, Chang T, Chucot L, Dill WA, Enrile LL, Glazko AJ, Jassani M, Kretchmer H, Sweet AY (1972) Study of ketamine as an obstetric anesthetic agent. Am J Obstet Gynecol 113(2):247–260. https://doi.org/10.1016/0002-9378(72)90774-0

    Article  CAS  PubMed  Google Scholar 

  31. Reich DL, Silvay G (1989) Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth 36(2):186–197. https://doi.org/10.1007/BF03011442

    Article  CAS  PubMed  Google Scholar 

  32. Bali A, Dang AK, Gonzalez DA, Kumar R, Asif S (2022) Clinical uses of ketamine in children: a narrative review. Cureus 14 (7):e27065. https://doi.org/10.7759/cureus.27065

  33. Mathisen LC, Skjelbred P, Skoglund LA, Oye I (1995) Effect of ketamine, an NMDA receptor inhibitor, in acute and chronic orofacial pain. Pain 61(2):215–220. https://doi.org/10.1016/0304-3959(94)00170-J

    Article  CAS  PubMed  Google Scholar 

  34. Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN, Georgiou P, Pereira EFR, Albuquerque EX, Thomas CJ, Zarate CA Jr, Gould TD (2018) Ketamine and ketamine metabolite pharmacology: insights into therapeutic mechanisms. Pharmacol Rev 70(3):621–660. https://doi.org/10.1124/pr.117.015198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. McIntyre RS, Rosenblat JD, Nemeroff CB, Sanacora G, Murrough JW, Berk M, Brietzke E, Dodd S, Gorwood P, Ho R, Iosifescu DV, Lopez Jaramillo C, Kasper S, Kratiuk K, Lee JG, Lee Y, Lui LMW, Mansur RB, Papakostas GI, Subramaniapillai M, Thase M, Vieta E, Young AH, Zarate CA Jr, Stahl S (2021) Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: an international expert opinion on the available evidence and implementation. Am J Psychiatry 178(5):383–399. https://doi.org/10.1176/appi.ajp.2020.20081251

    Article  PubMed  PubMed Central  Google Scholar 

  36. Nishimura M, Sato K, Okada T, Yoshiya I, Schloss P, Shimada S, Tohyama M (1998) Ketamine inhibits monoamine transporters expressed in human embryonic kidney 293 cells. Anesthesiology 88(3):768–774. https://doi.org/10.1097/00000542-199803000-00029

    Article  CAS  PubMed  Google Scholar 

  37. Ebert TJ, Muzi M (1993) Sympathetic hyperactivity during desflurane anesthesia in healthy volunteers. A comparison with isoflurane. Anesthesiology 79(3):444–453. https://doi.org/10.1097/00000542-199309000-00006

    Article  CAS  PubMed  Google Scholar 

  38. Singh JB, Fedgchin M, Daly E, Xi L, Melman C, De Bruecker G, Tadic A, Sienaert P, Wiegand F, Manji H, Drevets WC, Van Nueten L (2016) Intravenous esketamine in adult treatment-resistant depression: a double-blind, double-randomization, placebo-controlled study. Biol Psychiatry 80(6):424–431. https://doi.org/10.1016/j.biopsych.2015.10.018

    Article  CAS  PubMed  Google Scholar 

  39. Wang X, Lin C, Lan L, Liu J (2021) Perioperative intravenous S-ketamine for acute postoperative pain in adults: a systematic review and meta-analysis. J Clin Anesth 68:110071. https://doi.org/10.1016/j.jclinane.2020.110071

  40. Ng KT, Sarode D, Lai YS, Teoh WY, Wang CY (2019) The effect of ketamine on emergence agitation in children: a systematic review and meta-analysis. Paediatr Anaesth 29(12):1163–1172. https://doi.org/10.1111/pan.13752

    Article  PubMed  Google Scholar 

  41. Moore AD, Anghelescu DL (2017) Emergence delirium in pediatric anesthesia. Paediatr Drugs 19(1):11–20. https://doi.org/10.1007/s40272-016-0201-5

    Article  PubMed  Google Scholar 

  42. An LJ, Zhang Y, Su Z, Zhang XL, Liu HL, Zhang ZJ, Hu JL, Li ST (2017) A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil. BMC Anesthesiol 17(1):154. https://doi.org/10.1186/s12871-017-0446-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Xia Y, Sun Y, Liu J (2021) Effects of dezocine on PAED scale and Ramsay sedation scores in patients undergoing NUSS procedure. Am J Transl Res 13(5):5468–5475

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Ye RR, Jiang S, Xu X, Lu Y, Wang YJ, Liu JG (2022) Dezocine as a potent analgesic: overview of its pharmacological characterization. Acta Pharmacol Sin 43(7):1646–1657. https://doi.org/10.1038/s41401-021-00790-6

    Article  CAS  PubMed  Google Scholar 

  45. Uezono S, Goto T, Terui K, Ichinose F, Ishguro Y, Nakata Y, Morita S (2000) Emergence agitation after sevoflurane versus propofol in pediatric patients. Anesth Analg 91(3):563–566. https://doi.org/10.1097/00000539-200009000-00012

    Article  CAS  PubMed  Google Scholar 

  46. Chu Q, Zhu K, Bai Y, Shang H, Zhang D, Zhao M, Zheng P, Jin X (2021) A single low dose of dexmedetomidine efficiently attenuates esketamine-induced overactive behaviors and neuronal hyperactivities in mice. Front Hum Neurosci 15:735569. https://doi.org/10.3389/fnhum.2021.735569

  47. Chu Q, Mao M, Bai Y, Sun L, Zhang D, Zheng P, Jin X (2022) Midazolam attenuates esketamine-induced overactive behaviors in mice before the sedation, but not during the recovery. Front Vet Sci 9:829747. https://doi.org/10.3389/fvets.2022.829747

  48. Fang XZ, Gao J, Ge YL, Zhou LJ, Zhang Y (2016) Network meta-analysis on the efficacy of dexmedetomidine, midazolam, ketamine, propofol, and fentanyl for the prevention of sevoflurane-related emergence agitation in children. Am J Ther 23(4):e1032–e1042. https://doi.org/10.1097/MJT.0000000000000321

    Article  PubMed  Google Scholar 

  49. Zhang J, Ma L, Wan X, Shan J, Qu Y, Hashimoto K (2021) (R)-Ketamine attenuates LPS-induced endotoxin-derived delirium through inhibition of neuroinflammation. Psychopharmacology (Berl) 238(10):2743–2753. https://doi.org/10.1007/s00213-021-05889-6

    Article  CAS  PubMed  Google Scholar 

  50. Wei Y, Chang L, Hashimoto K (2022) Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor. Mol Psychiatry 27(1):559–573. https://doi.org/10.1038/s41380-021-01121-1

    Article  CAS  PubMed  Google Scholar 

  51. Zhang JC, Yao W, Hashimoto K (2022) Arketamine, a new rapid-acting antidepressant: a historical review and future directions. Neuropharmacology 218:109219. https://doi.org/10.1016/j.neuropharm.2022.109219

  52. Hashimoto K (2023) Arketamine for cognitive impairment in psychiatric disorders. Eur Arch Psychiatry Clin Neurosci 14:1–13. https://doi.org/10.1007/s00406-023-01570-5

    Article  Google Scholar 

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Acknowledgements

The authors would like to acknowledge all of the staff who assisted this study.

Funding

This work was supported by the grants from the National Natural Science Foundation of China (Nos. 82171189, 82001157, 81971020).

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  1. Sai Chen and Jin-Jin Yang have contributed equally to the article.

Authors and Affiliations

  1. Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China

    Sai Chen, Jin-Jin Yang, Yue Zhang, Lei Lei, Di Qiu, Hui-Min Lv, Zhen-Tao Sun & Jian-Jun Yang

  2. Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan

    Kenji Hashimoto

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Correspondence to Kenji Hashimoto or Jian-Jun Yang.

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Conflict of interest

Dr. Hashimoto is the inventor of filed patent applications on “The use of R-Ketamine in the treatment of psychiatric diseases”, “(S)-norketamine and salt thereof as pharmaceutical”, “R-Ketamine and derivative thereof as prophylactic or therapeutic agent for neurodegeneration disease or recognition function disorder”, “Preventive or therapeutic agent and pharmaceutical composition for inflammatory diseases or bone diseases”, and “R-Ketamine and its derivatives as a preventive or therapeutic agent for a neurodevelopmental disorder” by the Chiba University. Dr. Hashimoto has also received speakers’ honoraria, consultant fee, or research support from Abbott, Boehringer-Ingelheim, Daiichi-Sankyo, Meiji Seika Pharma, Seikagaku Corporation, Dainippon-Sumitomo, Taisho, Otsuka, Murakami Farm and Perception Neuroscience. The other authors have no competing interests.

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Chen, S., Yang, JJ., Zhang, Y. et al. Risk of esketamine anesthesia on the emergence delirium in preschool children after minor surgery: a prospective observational clinical study. Eur Arch Psychiatry Clin Neurosci (2023). https://doi.org/10.1007/s00406-023-01611-z

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