Comparing N-acetylcysteine with sodium thiosulfate for relieving symptoms caused by Lugol’s iodine chromoendoscopy: a randomized, double-blind trial

Background and Aims Lugol's iodine chromoendoscopy is an important method to detect esophageal squamous cell carcinoma. Sodium thiosulfate solution (STS) has been used to neutralize iodine after Lugol's chromoendoscopy; however, it is not available in many medical centers. The aim of the current study was to assess the efficacy of N-acetylcysteine solution (NAC) for relieving symptoms caused by Lugol's iodine chromoendoscopy. Methods Patients were randomized to receive either STS or NAC after spraying Lugol's iodine solution on the esophagus. The neutralizing effects for residual iodine in the esophagus and gastric mucous pool were observed. The primary endpoint was the intensity of retrosternal pain and/or heartburn measured by a visual analog scale (VAS) score 30 minutes after chromoendoscopy. Secondary endpoints were the rate of patients with any adverse symptom, rate of moderate to severe retrosternal discomfort occurring, and heart rate variability between time points before and after chromoendoscopy. Results The neutralization rates for residual iodine between the NAC and STS groups were not significantly different (P > .999). The difference of median VAS scores between the NAC and STS groups 30 minutes after chromoendoscopy was .0 (P = .719; 95% confidence interval, .0-.0), and the 95% confidence interval higher limit was .0, which was less than our prespecified margin of .5, concluding an noninferiority of NAC with regard to STS. There was no significant difference between the 2 groups regarding the rate of patients with any adverse symptom, rate of moderate to severe retrosternal discomfort, or heart rate variability at 5 minutes or 30 minutes after chromoendoscopy. Conclusion As a very easily accessible reagent in clinical circumstances, NAC can also alleviate mucosal irritation symptoms induced by Lugol's chromoendoscopy at similar efficacy as STS and can be routinely recommended. (Clinical trial registration number: NCT04764643.) Lugol's iodine chromoendoscopy is an important method to detect esophageal squamous cell carcinoma. Sodium thiosulfate solution (STS) has been used to neutralize iodine after Lugol's chromoendoscopy; however, it is not available in many medical centers. The aim of the current study was to assess the efficacy of N-acetylcysteine solution (NAC) for relieving symptoms caused by Lugol's iodine chromoendoscopy. Patients were randomized to receive either STS or NAC after spraying Lugol's iodine solution on the esophagus. The neutralizing effects for residual iodine in the esophagus and gastric mucous pool were observed. The primary endpoint was the intensity of retrosternal pain and/or heartburn measured by a visual analog scale (VAS) score 30 minutes after chromoendoscopy. Secondary endpoints were the rate of patients with any adverse symptom, rate of moderate to severe retrosternal discomfort occurring, and heart rate variability between time points before and after chromoendoscopy. The neutralization rates for residual iodine between the NAC and STS groups were not significantly different (P > .999). The difference of median VAS scores between the NAC and STS groups 30 minutes after chromoendoscopy was .0 (P = .719; 95% confidence interval, .0-.0), and the 95% confidence interval higher limit was .0, which was less than our prespecified margin of .5, concluding an noninferiority of NAC with regard to STS. There was no significant difference between the 2 groups regarding the rate of patients with any adverse symptom, rate of moderate to severe retrosternal discomfort, or heart rate variability at 5 minutes or 30 minutes after chromoendoscopy. As a very easily accessible reagent in clinical circumstances, NAC can also alleviate mucosal irritation symptoms induced by Lugol's chromoendoscopy at similar efficacy as STS and can be routinely recommended. (Clinical trial registration number: NCT04764643.)