Supplementary Material for: Effects of L-Menthol and Carbon Dioxide on the Adenoma Detection Rate during Colonoscopy: L-Menthol and Carbon Dioxide on Colonoscopy

<b><i>Background and Aims:</i></b> We examined the efficacy of the combined use of L-menthol spraying (L-mentholS) as an antispasmodic agent and carbon dioxide insufflation (CO<sub>2</sub>I) on the adenoma detection rate (ADR) in a prospective, single-center trial with a 2 × 2 factorial design. <b><i>Methods:</i></b> We randomly assigned 611 patients scheduled to undergo colonoscopy to 4 groups: (1) the L-mentholS + CO<sub>2</sub>I (<i>n</i> = 153), (2) L-mentholS + air insufflation (AI; <i>n</i> = 156), (3) CO<sub>2</sub>I (<i>n</i> = 153), and (4) AI (<i>n</i> = 149) groups. We used 20 mL of 0.8%-L-menthol solution for the L-mentholS. The primary outcome was the difference in the ADR, and the secondary outcomes were the differences in colonic peristalsis and abdominal pain. ­<b><i>Results:</i></b> The ADRs were not different among the groups: 1/2/3/4; 39.9%/43.6%/41.2%/51.0%. CO<sub>2</sub>I was associated with a significant decrease in the ADR (OR 0.57; 95% CI 0.35– 0.93) with a multiple logistic regression. The interaction between L-mentholS and CO<sub>2</sub>I was associated with a suppression of the decrease in the ADR. Both L-mentholS and CO<sub>2</sub>I were associated with a significant decrease in abdominal pain, and L-mentholS was associated with a significant improvement of peristalsis. <b><i>Conclusions:</i></b> The fact that CO<sub>2</sub>I was associated with significant decreases in the ADR was a problem. The combined use of L-mentholS and CO<sub>2</sub>I could help to suppress the decrease in the ADR.