2.1 Ethics approval and consent to participate
This study was approved by the Ethics Committee of the School of Dentistry, Aichi Gakuin University (approval number: 490). Clinical trial registration was performed at UMIN-CTR before the start of the study (approval number: 000026737). After providing an adequate explanation regarding the aims of the research to all subjects, we obtained written informed consent from all the patients.
2.2 Subjects
Overall, 39 ASA-PS 1–2 patients between 20 and 70 years of age who were scheduled to undergo general anesthesia at our hospital. Patients who did not give consent, who had neuromuscular diseases, or who had a BMI ≥25 were excluded from the study. Patients were randomly assigned to the following three groups: patients receiving RB the stock solution of 10 mg/ml (Group 1:13 patients), patients receiving the two-fold dilution of 5 mg/ml (Group 2:13patients), or patients receiving the three-fold dilution of 3.3 mg/ml (Group 3: 13patients). To dilute RB, 0.9% saline was used.
2.3 Methods of anesthesia
No premedication was used. After entering the operating room, the venous line was secured with a 20-G needle from the largest vein, excluding the cephalic vein, in the forearm. Furthermore, a TOF watchÒ was attached to the opposite arm. After induction of anesthesia with propofol at 1 to 2 mg/kg, it was visually confirmed that there was no residual propofol in the intravenous route, and RB at 0.6 mg/kg was administered in 10 seconds. The degree of vascular pain was evaluated based on the visual evaluation of escape behaviors from vascular pain. The time from RB administration until the maximum blocking of T1 by TOF stimulation was measured. In addition, the pH of the RB solution in Groups 1, 2, and 3 was measured using a pH meter (A&D AP-20).
2.4 Evaluation parameters
For the patient background, sex, age, height, and weight were evaluated. We also investigated the onset time of muscle relaxation using TOF and the escape behaviors from the vascular pain. The degree of vascular pain was evaluated using the scale devised by Shevchenko et al. as follows: grade 1= no response, grade 2= movement at the wrist only, grade 3 = withdrawal involving the arm only (elbow or shoulder), grade 4 = generalized response or withdrawal in more than one extremity. Pain of grade 2 or above was considered to indicate vascular pain1).
2.5 Statistical analysis
The minimum sample size (30 patients) was calculated from a preliminary study based on the onset time of muscle relaxation (effect size 0.5, a-error level 0.05, and power 0.8). Statistical analysis was performed for age, height, weight, and the onset time of muscle relaxation using one-way ANOVA and multiple comparison by Tukey’s method. The chi-square test using the m × n division table was employed to investigate the impact of sex. In addition, escape behaviors from vascular pain were tested by the Kruskal-Willis test, and p<0.05 was considered to indicate significance.