scopic sedation is increasing, and several studies showed the safety of administering propofol by endoscopist.17,18 However, the indications of propofol for sedation in various countries still imply that it should be used only by anesthesiologists or by intensive-care specialists owing to the narrow therapeutic effect of propofol.19 Instead of propofol, other sedative drugs such as midazolam and meperidine are safe and useful for diagnostic and therapeutic endoscopy without assist of anesthetics or in- tensive-care specialists for supervision. Midazolam with meperi- dine is more frequently used wherever anesthesiologists are not available. However, midazolam with meperidine have a longer half-life than propofol and long procedure during ESD could be at high risk of accumulation of the drugs. Therefore, we performed a randomized prospective study to evaluate whether BIS monitoring during sedation induced by midazolam and meperidine could improve the satisfaction of the endoscopists and patients and reduce the dose of drugs. We also evaluated the efficacy of the BIS monitor in preventing adverse effects of sedation during ESD procedure. MATERIALS AND METHODS 1. Patients From September 2009 and January 2010, we prospectively enrolled 56 patients who were randomized to BIS group (n=28) or non-BIS group (n=28). ESD was performed for gastric adeno- mas, differentiated-type gastric cancers greater than 30 mm in diameter without ulceration and gastric cancers up to 30 mm with ulceration, or minute submucosal invasion. Patients were excluded if they were under 18 years of age, had an ASA clas- sification of 4 to 5, were pregnant, had a history of stroke or an allergy to sedative drugs. This protocol was approved by the Institutional Review Board at Samsung Medical Center. The sample size was calculated as the difference in the satis- faction score (0 to 10) of more than two points between the BIS group and non-BIS group. Assuming a standard deviation of patients satisfaction between the BIS group and non-BIS group as 1.87 and 3.03, respectively, each group required 28 patients (ά =0.05, power=80%). Sixty lesions in 56 patients were included. All of the study patients were randomly divided into one of two groups by the SPSS program (SPSS Inc., Chicago, IL, USA). The level of sedation in the BIS group was monitored using BIS, and the level of sedation in non-BIS group was monitored using MOAA/S. The ESD procedure was performed by one experienced thera- peutic endoscopist (Jae J. Kim). Blood pressure, heart rate, oxy- gen saturation, and the depth of sedation were checked using standard monitoring systems during procedure. All parameters were recorded every three minutes and the time of all events was recorded in two groups. The patients and endoscopist could not watch the BIS monitoring during the procedure. The assis- tant could not see the BIS score during ESD procedure in non- Kang KJ, et al: Efficacy of BIS during ESD 161 BIS group. The score for satisfaction was obtained from both the patients and endoscopist after the ESD and the scores for recall of pain during the procedure were recorded. The scores ranged from 0 to100 (the lowest score, 0, the highest score, 100), using the 100 mm visual analog scale. 2. Monitoring of alertness and sedation MOAA/S scores range from 1 to 5: unresponsive to shaking, 1; responsive to shaking only, 2; responsive to normal verbal com- mands, 3; lethargic but responsive to normal verbal commands, 4; responsive and alert, 5.20 The level of sedation with BIS scores was defined as follows: >85 (awake), 76 to 85 (moderate seda- tion), 66 to 75 (deep sedation), and 45 to 65 (general anesthesia). The target level of sedation in this study was moderate to deep sedation for the ESD. This level was achieved with a score of 2 or 3 on the MOAA/S and that for the BIS was 65 to 80. 3. Sedative dosage The initial intravenous dose of midazolam was 0.03 mg/kg in patients less than 60 years of age and 60 kg, 2 mg in patients less than 60 years of age and more than 60 kg, and 1 mg in patients more than 60 years old. The initial intravenous dose of meperidine was 25 mg in patients less than 60 kg, and 50 mg in patients less than 60 years old and more than 60 kg. If addi- tional doses were needed (MOAA/S score ≥4 or BIS score >80), midazolam (0.5 to 1 mg) or meperidine (25 mg) was added. 4. Statistical methods Baseline data from the patients in the two groups were com- pared by chi-square test or Fisher’s exact test for categorical variables. A Student’s t-test for normally distributed continu- ous variables and a Mann-Whitney test for non-normally dis- tributed continuous variables were used. For the analysis of a correlation between the BIS and MOAA scores, the correlation coefficient with repeated observations reported by Bland and Altman was used in non-BIS group. Before the analysis, the BIS was log-transformed to approximate a normal distribution. RESULTS 1. Patient characteristics Fifty-six patients were enrolled and 6 patients (2 patients in BIS group and 4 patients in non-BIS group) were dropped from the study because of paradoxical reactions during the proce- dure. There was no statistical difference in baseline characteris- tics of the patients between the two groups (Table 1). Although the tumor size of the lesions in non-BIS group was smaller than in BIS group (p=0.03), there was no statistical difference in the resected tumor size, procedure time, and curative resection rates between the two groups (Table 2).