Effective Dosage of Midazolam to Erase the Memory of Vascular Pain During Propofol Administration
Intravenous sedation with propofol is often administered to anxious patients in dental practice. Pain on injection of propofol is a common adverse effect. This study aimed to determine the age-adjusted doses of midazolam required to erase memory of vascular pain of propofol administration and assess whether the Ramsay Sedation Scale (RSS) after the pretreatment of midazolam was useful to predict amnesia of the vascular pain of propofol administration. A total of 246 patients with dental phobia requiring dental treatment under intravenous sedation were included. Patients were classified according to their age: 30s, 40s, 50s, and 60s. Three minutes after administration of a predetermined dose of midazolam, propofol was infused continuously. After completion of the dental procedure, patients were interviewed about the memory of any pain or discomfort in the injection site or forearm. The dosage of midazolam was determined using the Dixon up-down method. The first patient was administered 0.03 mg/kg, and if memory of vascular pain remained, the dosage was increased by 0.01 mg/kg for the next patient, and then if the memory was erased, the dosage was decreased by 0.01 mg/kg. The effective dosage of midazolam in 95% of each age group for erasing the memory of propofol vascular pain (ED95) was determined using logistic analysis. The accuracy of RSS to predict the amnesia of injection pain was assessed by receiver operating characteristic (ROC) analysis. The ED95 of midazolam to erase the memory of propofol vascular pain was 0.061 mg/kg in patients in their 30s, 0.049 mg/kg in patients in their 40s, 0.033 mg/kg in patients in their 50s, and 0.033 mg/kg in patients in their 60s. The area under the ROC curve was 0.31. The ED95 of midazolam required to erase the memory of propofol vascular pain demonstrated a downward trend with age. On the other hand, it was impossible to predict the amnesia of propofol vascular pain using the RSS.
The flow diagram of this study.
The consecutive dose of midazolam according to the up-down method for patients in their 30s. The number of patients required to get the 15th crossover point (•→○ or ○→•) was 28. If memories of injection pain remained (•), the dosage was increased by 0.01 mg/kg for the next patient, and then if memories were erased (○), the dosage was decreased by 0.01 mg/kg.
The consecutive dose of midazolam according to the up-down method for patients in their 40s. The number of patients that was required to get the 15th crossover point (•→○ or ○→•) was 28. If memories of injection pain remained (•), the dosage was increased by 0.01 mg/kg for the next patient, and then if memories were erased (○), the dosage was decreased by 0.01 mg/kg.
The consecutive dose of midazolam according to the up-down method for patients in their 50s. The number of patients that was required to get the 15th crossover point (•→○ or ○→•) was 20. If memories of injection pain remained (•), the dosage was increased by 0.01 mg/kg for the next patient, and then if memories were erased (○), the dosage was decreased by 0.01 mg/kg.
The consecutive dose of midazolam according to the up-down method for patients in their 60s. The number of patients that was required to get the 15th crossover point (•→○ or ○→•) was 26. If memories of injection pain remained (•), the dosage was increased by 0.01 mg/kg for the next patient, and then if memories were erased (○), the dosage was decreased by 0.01 mg/kg.
Effective dosage of midazolam in 95% of each age group (ED95) required to erase the memory of injection pain calculated by logistic regression analysis. ED95 was 0.061 (95% CI, 0.047–0.304) mg/kg in patients in their 30s, 0.049 (95% CI, 0.038–0.163) mg/kg in patients in their 40s, 0.033 (95% CI, 0.028–0.067) mg/kg in patients in their 50s, and 0.033 (95% CI, 0.027–0.085) mg/kg in patients in their 60s. The left end of the graph indicates the lower end of 95% CI and the right end indicates the upper end of 95% CI. The amount of midazolam required to erase the memory of injection pain demonstrated a downward trend with age, although there were no significant differences among the 4 groups.
The receiver operating characteristic (ROC) curve produced by RSS. The area under the curve (AUC) was 0.31. It is indicated by the gray zone, which shows that RSS was not a reliable predictor of amnesia.
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