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

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.

Esketamine Exposure Impairs Cardiac Development and Function in Zebrafish Larvae

“…Specifically, after exposure to esketamine, there was no significant difference in the effect of 1.10 mg/L zebrafish embryo groups on heart rate, while a significant decrease was observed in the 100 mg/L group. The observed differences can be ascribed to the varying cardiovascular characteristics of embryos and adults, as well as to the impact of drug dosage on cardiovascular responses [ 28 ]. The significant decrease in SV and CO seen in the 100 mg/L concentration group may be explained by esketamine’s primary direct inhibitory effect on the heart at high doses, which is probably caused by inhibited calcium ion transport, sympathetic nerve blockade, or depletion of presynaptic catecholamine stores [ 29 ].…”

Intranasale Schmerzmittel in der Notfallmedizin – Was ist die Evidenz? Teil 2 Esketamin

“…B. in den Indikationen Einleitung der Anästhesie und Sedierung bei zahnärztlichen Eingriffen mit Initialdosen von 0,5-2 mg/kg durchgeführt. Diese Dosen sollten nach Effekt titriert werden [17,18,19,20,21,22].…”