Subsequently, there have been further studies with a retrospective propensity-matched case-control study from India comparing pre-endoscopy drink of NAC and SIM vs. standard fasting alone, showing better mucosal visibility with NAC + SIM at all endoscopically important landmarks except for distal duodenum [15]. An analysis of the literature shows that a majority of the studies stem from Asian centers. In this background, a recent European randomized trial from Belgium compared SIM against placebo (control solution). The study reported remarkably higher odds of adequate gastric mucosal visualization with SIM (OR, 73.6 [9.4–576.6]). However, median procedure time and patient satisfaction were similar [5]. The current study by Nabi et al. stems from these heterogeneities in literature and provides a one-of-a-kind four-arm randomized trial with SIM, NAC, SIM + NAC and water, respectively [7].

The key strengths of the trial are its large sample size (n = 800), double-blind randomization and use of an objective mucosal visibility score. The crux of the results indicates that SIM alone or in combination with NAC offers the two best modalities for improving mucosal visibility. However, more importantly for clinicians, all modalities perform similarly when it comes to translation to lesion detection rates. While the essence of the results is similar to what previous systematic reviews and recent studies indicate, the lack of differences in lesion detection remains a significant difference compared to the recent meta-analysis by Li et al., wherein the combination of SIM + NAC was superior for lesion detection [6]. The same fact brings into question whether only better mucosal visualization is a determinant metric or its translation to lesion detection rate gives a more outcome-oriented index. In this context, the current study was neither designed nor powered for superiority based on lesion-detection rates and this remains a key limitation. Another interesting data that stems out of the current trial is the lack of differences between SIM vs. SIM + NAC in mucosal visibility if EGD was carried out within 10-20 minutes of medication administration. This has important implications in endoscopy planning and the use of these agents, especially in centers with large volumes.

Certain concerns, however, remain with SIM, as it is water insoluble and may pose a challenge in endoscope cleaning, although there is scarce evidence of the impact of simethicone on endoscope re-processing effectiveness [8]. The amount of SIM dosage and method of admixing also need standardization in future studies to ensure uniformity in recommendations.

In conclusion, based upon the results of the current study of Nabi et al. as well as other evidence, as outlined above, it is possible to deduce that the use of MCTs such as SIM and NAC, with the key driver being SIM, allows for better mucosal visualization at EGD. However, the jury remains out on whether the lesion detection rate, which technically is a more important objective metric, is improved with the addition of MCTs. Also, the additional costs in using such drugs in the absence of better lesions detection rates would temper our enthusiasm in routine use of these agents.