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ED50 and ED95 of propofol combined with different doses of esketamine for children undergoing upper gastrointestinal
Xiao-Su Zheng1, Yang Shen1, Yan-Yan Yang1
1Department of Anaesthesiology, Shanghai Children's Medical Centre, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Insights
Adding esketamine to propofol during pediatric endoscopy significantly reduces the required propofol dose. While higher esketamine doses lower propofol needs and hemodynamic effects, they increase adverse events like vomiting and visual disturbances.
Area of Science:
- Pediatric Anesthesiology
- Pharmacology
- Gastroenterology
Background:
- Propofol and esketamine are common anesthetics for pediatric procedures.
- Coadministration may reduce drug doses and adverse events.
- Optimal dosing strategies for combined use in children are not well-defined.
Purpose of the Study:
- To determine the median effective dose (ED50) of propofol when coadministered with varying doses of esketamine in children undergoing upper gastrointestinal endoscopy.
- To evaluate the impact of esketamine on propofol dosage requirements and safety profiles.
Main Methods:
- A four-arm randomized controlled trial involving 92 pediatric patients.
- Patients received esketamine at 0, 0.25, 0.5, or 1 mg/kg.
- Propofol dosage was determined using the Dixon and Massey up-and-down method.
Main Results:
- The ED50 of propofol was significantly lower with higher esketamine doses (0.5 and 1 mg/kg) compared to lower doses (0 and 0.25 mg/kg).
- Total propofol doses were significantly reduced in the 0.5 and 1 mg/kg esketamine groups.
- The 1 mg/kg esketamine group experienced a higher incidence of vomiting and visual disturbances.
Conclusions:
- Coadministering esketamine (0.5-1 mg/kg) with propofol significantly reduces propofol dosage and associated hemodynamic changes in pediatric endoscopy.
- Higher esketamine doses decrease propofol requirements but increase the risk of adverse effects like vomiting and visual disturbances.
What Is Known And Objective:
Propofol and esketamine are routine anaesthetics used in sedation or general anaesthesia for paediatric procedures. Coadministration could reduce the dose of either propofol or esketamine required and lower the incidence of drug-related adverse events. We designed a four-arm randomized controlled trial in children undergoing diagnostic upper gastrointestinal endoscopy to investigate the dose of propofol with different doses of esketamine inducing appropriate depth of anaesthesia in 50% patients (median effective dose, ED50 ).
Methods:
After getting the approval of the research ethics committee and informed consent, 92 paediatric patients planning for upper gastrointestinal endoscopy were divided into four groups randomly: esketamine 0, 0.25, 0.5 and 1 mg/kg groups (n = 23/group). Propofol doses followed the Dixon and Massey up-and-down method with different starting and interval doses between groups. During the first attempt of endoscope insertion, if patients' reactions prevented the insertion, it would be considered as a failure. The awakening time, total propofol doses, as well as the perioperative and post-procedure adverse events were evaluated and recorded for each patient.
Results And Discussion:
The ED50 (median, 95% confidence interval) of propofol was significantly greater in esketamine 0 and 0.25 mg/kg groups in comparison with the esketamine 0.5 and 1 mg/kg groups (4.1 [3.3-4.9]; 3.1 [2.5-3.8] mg/kg vs. 1.8 [1.1-2.4]; 0.8 [0.2-1.3] mg/kg, respectively, p < .05). The total doses of propofol in esketamine 0.5 and 1 mg/kg groups were statistically lower than these in esketamine 0 and 0.25 mg/kg group (p < .01). The mean blood pressure was lower in the esketamine 0 mg/kg group than that in 1 mg/kg group after administration and during the procedure (p < .01). The esketamine 1 mg/kg group showed a higher incidence of vomiting and visual disturbances than the other three groups (p < .001).
What Is New And Conclusion:
In children who accomplished diagnostic paediatric upper gastrointestinal endoscopy under deep sedation/anaesthesia, the total dosage of propofol needed was reduced significantly in esketamine 0.5 and 1 mg/kg groups with a corresponding reduce in propofol-related hemodynamic changes. However, a higher incidence of esketamine-related adverse effects was found in esketamine 1 mg/kg group.
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