Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Anesthesiology
Published in: BMC Anesthesiology 1/2023

Open Access 01-12-2023 | Premedication | Research

Median effective dose of esketamine for intranasal premedication in children with congenital heart disease

Authors: Jiajia Huang, Daoqing Liu, Jie Bai, Hongbin Gu

Published in: BMC Anesthesiology | Issue 1/2023

Login to get access

Abstract

Background

Esketamine is commonly used as a premedication for its sedation effect. However, the proper dosage for intranasal use in children with congenital heart disease (CHD) has not been determined. This study aimed to estimate the median effective dose (ED50) of esketamine for intranasal premedication in children with CHD.

Methods

Thirty-four children with CHD who needed premedication in March 2021 were enrolled. Intranasal esketamine was initiated at a dose of 1 mg/kg. Based on the outcome of sedation in the previous patient, the dose for the subsequent patient was either increased or reduced by 0.1 mg/kg, which was adjusted between each child. Successful sedation was defined as a Ramsay Sedation Scale score ≥ 3 and Parental Separation Anxiety Scale score ≤ 2. The required ED50 of esketamine was calculated using the modified sequential method. Non-invasive blood pressure, heart rate, saturation of peripheral oxygen, sedation onset time, and adverse reactions were recorded at 5 min intervals after drug administration.

Results

The 34 children enrolled had a mean age of 22.5 ± 16.4 (4–54) months and a mean weight of 11.2 ± 3.6 (5.5–20.5) kg; American Society of Anesthesiologists classification I–III. The ED50 of intranasal S(+)-ketamine (esketamine) required for preoperative sedation in pediatric patients with CHD was 0.7 (95% confidence interval: 0.54–0.86) mg/kg, and the mean sedation onset time was 16.39 ± 7.24 min. No serious adverse events, such as respiratory distress, nausea, and vomiting were observed.

Conclusions

The ED50 of intranasal esketamine was 0.7 mg/kg, which was safe and effective for preoperative sedation in pediatric patients with CHD.

Trial registration

: The trial was registered in the Chinese Clinical Trial Registry Network (ChiCTR2100044551) on 24/03/2021.
Literature
1.
Ahmed MI, Farrell MA, Parrish K, Karla A. Preoperative anxiety in children risk factors and non-pharmacological management. Middle East J Anaesthesiol. 2011;21(2):153–64.PubMed
2.
Jung MJ, Libaw JS, Ma K, Whitlock EL, Feiner JR, Sinskey JL. Pediatric distraction on induction of Anesthesia with virtual reality and perioperative anxiolysis: a Randomized Controlled Trial. Anesth Analg. 2021;132(3):798–806.CrossRefPubMedPubMedCentral
3.
Mason KP. Paediatric emergence delirium: a comprehensive review and interpretation of the literature. Br J Anaesth. 2017;118(3):335–43.CrossRefPubMed
4.
Li HP, Liu KP, Yao L. Dexmedetomidine in combination with ketamine for pediatric procedural sedation or premedication: a meta-analysis. Am J Emerg Med. 2021;50:442–8.CrossRefPubMed
5.
Lei H, Chao L, Miao T, Ya Jun L, Shen Ling L, Yan Ying P, et al. Incidence and risk factors of bradycardia in pediatric patients undergoing intranasal dexmedetomidine sedation. Acta Anaesthesiol Scand. 2020;64(4):464–71.CrossRefPubMed
6.
van Hoorn CE, Flint RB, Skowno J, Davies P, Engelhardt T, Lalwani K, et al. Off-label use of dexmedetomidine in paediatric anaesthesiology: an international survey of 791 (paediatric) anaesthesiologists. Eur J Clin Pharmacol. 2021;77(4):625–35.CrossRefPubMed
7.
Tervonen M, Pokka T, Kallio M, Peltoniemi O. Systematic review and meta-analysis found that intranasal dexmedetomidine was a safe and effective sedative drug during paediatric procedural sedation. Acta Paediatr. 2020;109(10):2008–16.CrossRefPubMed
8.
Salman S, Tang EKY, Cheung LC, Nguyen MN, Sommerfield D, Slevin L, et al. A novel, palatable paediatric oral formulation of Midazolam: pharmacokinetics, tolerability, efficacy and safety. Anaesthesia. 2018;73(12):1469–77.CrossRefPubMed
9.
Li M, Wang YT, Zhang MZ. Clinical observation of oral administration of Midazolam, ketamine and dexmedetomidine in children with tetralogy of Fallot. J Shanghai Jiaotong Univ. 2017;37(1):71–4.
10.
Weber F, Wulf H, el Saeidi G. Premedication with nasal s-ketamine and midazolam provides good conditions for induction of anesthesia in preschool children. Can J Anaesth. 2003;50(5):470–5.CrossRefPubMed
11.
Lu X, Tang L, Lan H, Li C, Lin H. 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. 2021;12:808930.CrossRefPubMed
12.
Pace NL, Stylianou MP. Advances in and limitations of up-and-down methodology: a précis of clinical use, study design, and dose estimation in anesthesia research. Anesthesiology. 2007;107(1):144–52.CrossRefPubMed
13.
Lee TS, Hou X. Vasoactive effects of ketamine on isolated rabbit pulmonary arteries. Chest. 1995;107(4):1152–5.CrossRefPubMed
14.
Oklü E, Bulutcu FS, Yalçin Y, Ozbek U, Cakali E, Bayindir O. Which anesthetic agent alters the hemodynamic status during pediatric catheterization? Comparison of propofol versus ketamine. J Cardiothorac Vasc Anesth. 2003;17(6):686–90.CrossRefPubMed
15.
Williams GD, Maan H, Ramamoorthy C, Kamra K, Bratton SL, Bair E, et al. Perioperative complications in children with pulmonary hypertension undergoing general anesthesia with ketamine. Paediatr Anaesth. 2010;20(1):28–37.CrossRefPubMed
16.
Williams GD, Philip BM, Chu LF, Boltz MG, Kamra K, Terwey H, et al. Ketamine does not increase pulmonary vascular resistance in children with pulmonary hypertension undergoing sevoflurane anesthesia and spontaneous ventilation. Anesth Analg. 2007;105(6):1578–84. table of contents.CrossRefPubMed
17.
Koinig H, Marhofer P. S(+)-ketamine in paediatric anaesthesia. Paediatr Anaesth. 2003;13(3):185–7.CrossRefPubMed
18.
Zheng XS, Shen Y, Yang YY, He P, Wang YT, Tao YY, et al. E.D. (50) and E.D. (95) of propofol combined with different doses of esketamine for children undergoing upper gastrointestinal endoscopy: a prospective dose-finding study using up-and-down sequential allocation method. J Clin Pharm Ther. 2022;47(7):1002–9.CrossRefPubMed
19.
Weber F, Wulf H, Gruber M, Biallas R. S-ketamine and s-norketamine plasma concentrations after nasal and i.v. administration in anesthetized children. Paediatr Anaesth. 2004;14(12):983–8.CrossRefPubMed
20.
Flint RB, Brouwer CNM, Kränzlin ASC, Lie AHL, Bos AP, Mathôt RAA. Pharmacokinetics of S-ketamine during prolonged sedation at the pediatric intensive care unit. Paediatr Anaesth. 2017;27(11):1098–107.CrossRefPubMed
21.
Marhofer P, Freitag H, Hochtl A, Greher M, Erlacher W, Semsroth M. S(+)-ketamine for rectal premedication in children. Anesth Analg. 2001;92(1):62–5.CrossRefPubMed
22.
Boddu SHS, Kumari S. A Short Review on the Intranasal Delivery of Diazepam for Treating Acute Repetitive Seizures.Pharmaceutics. 2020;12(12).
23.
Keller LA, Merkel O, Popp A. Intranasal drug delivery: opportunities and toxicologic challenges during drug development. Drug Deliv Transl Res. 2022;12(4):735–57.CrossRefPubMed
24.
Knoester PD, Jonker DM, Van Der Hoeven RT, Vermeij TA, Edelbroek PM, Brekelmans GJ, et al. Pharmacokinetics and pharmacodynamics of Midazolam administered as a concentrated intranasal spray. A study in healthy volunteers. Br J Clin Pharmacol. 2002;53(5):501–7.CrossRefPubMedPubMedCentral
25.
Bahetwar SK, Pandey RK, Saksena AK, Chandra G. A comparative evaluation of intranasal midazolam, ketamine and their combination for sedation of young uncooperative pediatric dental patients: a triple blind randomized crossover trial. J Clin Pediatr Dent. 2011;35(4):415–20.CrossRefPubMed
26.
Sheta SA, Al-Sarheed MA, Abdelhalim AA. Intranasal dexmedetomidine vs midazolam for premedication in children undergoing complete dental rehabilitation: a double-blinded randomized controlled trial. Paediatr Anaesth. 2014;24(2):181–9.CrossRefPubMed
Metadata
Title
Median effective dose of esketamine for intranasal premedication in children with congenital heart disease
Authors
Jiajia Huang
Daoqing Liu
Jie Bai
Hongbin Gu
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2023
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/s12871-023-02077-1

Other articles of this Issue 1/2023

BMC Anesthesiology 1/2023 Go to the issue

Research

Effects of preoperative oral enzyme-hydrolyzed rice flour solution on gastric emptying and insulin resistance in patients undergoing laparoscopic cholecystectomy: a prospective randomized controlled trial

Research

Predictors and nomogram of in-hospital mortality in sepsis-induced myocardial injury: a retrospective cohort study

Editorial

Enhanced recovery after surgery: comes out to the Sun

Research

The Minimum Effective Concentration (MEC95) of different volumes of ropivacaine for ultrasound-guided caudal epidural block: a dose-finding study

Research

A novel nomogram for predicting the prolonged length of stay in post-anesthesia care unit after elective operation

Research

Continuous nerve block versus thoracic epidural analgesia for post-operative pain of pectus excavatum repair: a systematic review and meta-analysis