Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1016/j.bjane.2022.09.003
Brazilian Journal of Anesthesiology
Original Investigation

Comparison between oral midazolam versus oral ketamine plus midazolam as preanesthetic medication in autism spectrum disorder: double-blind randomized clinical trial

Heber de Moraes Penna, Andreia Portela Martins Paiva, Antônio José Marques Romano, Rodrigo Leal Alves, Paulo do Nascimento Junior, Norma Sueli Pinheiro Módolo

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Abstract

Background
Conventional dental care is often impossible in patients with Autism Spectrum Disorder (ASD). Non-collaborative behaviors, sometimes associated with aggressiveness, are usual justifications for premedication in this population. Thereby, this research focuses on the effects of oral midazolam versus oral ketamine plus midazolam as preanesthetic medication in ASD.

Methods
The sample included 64 persons with ASD, aged 2˗59 years, scheduled for dental care under general anesthesia. The primary objective of this study was to compare degrees of sedation between two parallel, double-blinded, equally proportional groups randomized to receive oral midazolam (0.5 mg.kg−1, maximum 15 mg) or oral midazolam (0.5 mg.kg−1) associated with oral S(+)-ketamine (3 mg.kg−1, maximum 300 mg). The secondary outcomes were the need of physical stabilization to obtain intravenous line, awakening time, and occurrence of adverse events.

Results
According to the dichotomous analysis of sedation level (Ramsay score 1 and 2 versus Ramsay ≥ 3), oral association of S(+)-ketamine and midazolam improved sedation, with increased probability of Ramsay ≥ 3, Relative Risk (RR) = 3.2 (95% Confidence Interval [95% CI] = 1.32 to 7.76) compared to midazolam alone. Combined treatment also made it easier to obtain venous access without physical stabilization, RR = 2.05 (95% CI = 1.14 to 3.68). There were no differences between groups regarding awakening time and the occurrence of adverse events.

Conclusion
The association of oral S(+)-ketamine with midazolam provides better preanesthetic sedation rates than midazolam alone and facilitates intravenous line access in patients with autism.

Keywords

Autism;  Autism spectrum disorder;  Dental care;  Ketamine;  Midazolam;  Preanesthetic medication

References

1 MJ Maenner, KA Shaw, J Baio, et al. Prevalence of autism spectrum disorder among children aged 8 years – Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2016 MMWR Surveillance Summaries, 69 (2020), pp. 1-12

2 H Rodgers, J McCluney Prevalence of autism (including Asperger's syndrome) in school age children in Northern Ireland 2021. [Internet] Prevalence of autism (including Asperger's syndrome) in school age children in Northern Ireland 2021 (2021), pp. 1-25 Available from https://www.health-ni.gov.uk/sites/default/files/publications/health/asd-children-ni-2021.pdf

3 American Psychiatric Association. American Psychiatric Association. DSM-5 Task Force (5th ed.), Diagnostic and statistical manual of mental disorders: DSM-5, 1 (2013), pp. 1-991

4 K Ouchi, K Sugiyama Required propofol dose for anesthesia and time to emerge are affected by the use of antiepileptics: prospective cohort study BMC Anesthesiology, 15 (2015), p. 34

5 MA Manso, C Guittet, F Vandenhende, L Granier Efficacy of oral midazolam for minimal and moderate sedation in pediatric patients: A systematic review Pediatric Anesthesia, 29 (2019), pp. 1094-1106

6 J Sado-Filho, KA Viana, P Corrêa-Faria, LR Costa, PS Costa Randomized clinical trial on the efficacy of intranasal or oral ketamine-midazolam combinations compared to oral midazolam for outpatient pediatric sedation PLOS ONE, 14 (2019) e0213074-e0213074

7 N Poonai, K Canton, S Ali, et al. Intranasal ketamine for procedural sedation and analgesia in children: A systematic review PLOS ONE, 12 (2017), Article e0173253

8 C Chen, X Cheng, L Lin, F Fu Preanesthetic nebulized ketamine vs preanesthetic oral ketamine for sedation and postoperative pain management in children for elective surgery Medicine, 100 (2021) e24605-e24605

9 N Taghizadeh, A Davidson, K Williams, D Story Autism spectrum disorder (ASD) and its perioperative management Pediatric Anesthesia, 25 (2015), pp. 1076-1084

10 N Taghizadeh, G Heard, A Davidson, K Williams, D Story The experiences of children with autism spectrum disorder, their caregivers and health care providers during day procedure: A mixed methods study Paediatric Anaesthesia, 29 (2019), pp. 927-937

11 W Funk, W Jakob, T Riedl, K Taeger Oral preanaesthetic medication for children: double-blind randomized study of a combination of midazolam and ketamine vs midazolam or ketamine alone British Journal of Anaesthesia, 84 (2000), pp. 335-340

12 MAE Ramsay, TM Savege, BRJ Simpson, R Goodwin Controlled sedation with Alphaxalone-Alphadolone BMJ, 2 (1974), pp. 656-659

13 R Core Team R: A language and environment for statistical computing [Internet] R: A language and environment for statistical computing (2018) Available from https://www.r-project.org/

14 M de Onis Development of a WHO growth reference for school-aged children and adolescents Bull World Health Organ, 85 (2007), pp. 660-667

15 Organization WH. Child growth standards /Standards / Body mass index-for-age (BMI-for-age) [Internet]. 2006. Available from: https://www.who.int/tools/child-growth-standards.

16 World Health Organization. Obesity and overweight [Internet]. 2021. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.

17 MA Peltoniemi, TI Saari, NM Hagelberg, K Laine, KJ Kurkinen, PJ Neuvonen, et al. Rifampicin has a profound effect on the pharmacokinetics of oral S-ketamine and less on intravenous S-ketamine Basic Clin Pharmacol Toxicol, 111 (2012), pp. 325-332

18 S Fanta, M Kinnunen, JT Backman, E Kalso Population pharmacokinetics of S-ketamine and norketamine in healthy volunteers after intravenous and oral dosing Euro J Clin Pharmacol, 71 (2015), pp. 441-447

19 B Arnold, A Elliott, D Laohamroonvorapongse, J Hanna, D Norvell, J Koh Autistic children and anesthesia: is their perioperative experience different? Pediatric Anesthesia, 25 (2015), pp. 1103-1110

20 S Lukmanji, SA Manji, S Kadhim, et al. The co-occurrence of epilepsy and autism: A systematic review Epilepsy Behavior, 98 (2019), pp. 238-248

21 Saúde Ministério da Pesquisa nacional de saúde: 2019: percepção do estado de saúde, estilos de vida, doenças crônicas e saúde bucal: Brasil e grandes regiões/IBGE Coordenação de Trabalho e Rendimento (2020) [Internet]Available from https://biblioteca.ibge.gov.br/visualizacao/livros/liv101764.pdf

22 Z Zheng, L Zhang, S Li, F Zhao, Y Wang, L Huang, et al. Association among obesity, overweight and autism spectrum disorder: a systematic review and meta-analysis Scientific Reports, 7 (2017), p. 11697

23 R Houghton, RC Ong, F Bolognani Psychiatric comorbidities and use of psychotropic medications in people with autism spectrum disorder in the United States Autism Research, 10 (12) (2017), pp. 2037-2047

24 JS Swartz, KE Amos, M Brindas, LG, Ruth Girling, M Graham Benefits of an individualized perioperative plan for children with autism spectrum disorder Pediatric Anesthesia, 27 (2017), pp. 856-862

25 SA Sheta, M AlSarheed Oral midazolam premedication for children undergoing general anaesthesia for dental care Inter J Pediatrics (2009), pp. 1-7 2009

26 WD Hedrich, HE Hassan, H Wang Insights into CYP2B6-mediated drug–drug interactions Acta Pharmaceutica Sinica B, 6 (2016), pp. 413-425

27 UM Zanger, K Klein Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance Frontiers in Genetics, 4 (2013)

28 PF Wang, A Neiner, ED Kharasch Stereoselective ketamine metabolism by genetic variants of cytochrome P450 CYP2B6 and cytochrome P450 oxidoreductase Anesthesiology, 129 (2018), pp. 756-768

29 IS Grant, WS Nimmo, JA Clements Pharmacokinetics and analgesic effects of I.M. and oral ketamine Br J Anaesth, 53 (1981), pp. 805-810

30 G Mion, T Villevieille Ketamine pharmacology: An update (Pharmacodynamics and molecular aspects, recent findings) CNS Neuro Therap, 19 (2013), pp. 370-380

31 B Trabold, A Rzepecki, K Sauer, J Hobbhahn A comparison of two different doses of ketamine with midazolam and midazolam alone as oral preanaesthetic medication on recovery after sevoflurane anaesthesia in children Pediatric Anesthesia, 12 (2002), pp. 690-693

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