Reversibility of gastric mucosal lesions induced by sodium phosphate tablets and characterized by probe-based confocal laser endomicroscopy

Abstract

Background and study aims: Adequate bowel preparation is key for the optimal quality of colonoscopy. The sodium phosphate laxatives used for preparation may induce gastric injuries. However, in vivo studies monitoring the effects of sodium phosphate on the gastric mucosa are currently lacking. We aimed to characterize the effects of sodium phosphate tablets (Colokit®; Mayoly Spindler, Chatou, France) on the gastric mucosa in a large-animal model.

Methods: Fourteen anesthetized pigs were used for this study. Fundic mucosal sites were analyzed at 1.5, 24, and 72 hours after the endoscopically guided application of sodium phosphate tablets (NaPT) and placebo tablets (PlaT) and were compared with unexposed sites. Different mucosal parameters were assessed with white light endoscopy, probe-based confocal laser endomicroscopy (pCLE), histology, and ex vivo permeability measurements.

Results: At 90 minutes after the application of NaPT, significant increases in epithelial irregularity and crypt pit intensity were observed with pCLE. These microscopic lesions persisted at 24 hours but were resolved at 72 hours. In addition, white light endoscopy revealed local exanthema in 57 % of the animals at 1.5 hours after NaPT application. Such lesions were observed in 22 % of the pigs at 24 hours and disappeared at 72 hours after application. After 1.5 hours, PlaT induced a slight but significant increase in epithelial irregularity, as well as architectural scores that were significantly lower than the ones induced by NaPT and that disappeared after 72 hours.

Conclusions: The direct and prolonged gastric application of NaPT in pigs can induce acute superficial macroscopic and microscopic injuries that are reversible within 72 hours.

Fig. 1

Study design. In study 1 (n = 5), analysis was performed on sodium phosphate tablet (NaPT) sites at 1.5 hours after the application of NaPT tablets and on unexposed mucosa, referred to as control (CTRL) sites. In studies 2 and 3 (n = 9), analysis was performed on NaPT, PLaT, and CTRL sites at 1.5, 24, and 72 hours after the application of NaPT and placebo tablets (PLaT). At each considered time point (0, 1.5, 24, and 72 hours), the endoscopic aspect was reported, and probe-based confocal laser endomicroscopy (pCLE) was carried out for 1 minute at each site.

Fig. 2

Endoscopic views. a The drug tablets – that is, the sodium phosphate tablet (thin arrow) and the placebo tablet (thick arrow) – a few minutes after endoscopic placement on the fundic mucosa of pigs. b The same sites at 24 hours. The endoscopic clip was initially positioned between the two tablets to allow re-identification of the sites after complete dissolution of the tablets.

Fig. 3

Short-term effects of sodium phosphate tablets (NaPT) 1.5 hours after application onto the fundic mucosa of pigs, assessed with probe-based confocal laser endomicroscopy (studies 2 and 3) and graded. a Semiquantitative lesion score of surface epithelium architecture. b Semiquantitative lesion score of crypts architecture. c Variations of fluorescein intensity in the crypt lumen [(H1.5 – H0) × 100 /H0]. d Variations of intercryptic intensity. Wilcoxon signed-rank test: * P ≤ 0.05, *** P < 0.0001; Mann – Whitney test: ^# P < 0.0025. PlaT, placebo tablet; Ct, control; AU, arbitrary units.

Fig. 4

Observations made in pigs with probe-based confocal laser endomicroscopy at the sodium phosphate tablet site. a Normal appearance immediately before tablet application. b, c Severe epithelial irregularity and architectural disorganization at 1.5 and 24 hours, respectively. d Partial healing of these mucosal alterations at 72 hours.

Fig. 5

Time course of endomicroscopic aspects at 1.5, 24, and 72 hours after the application of sodium phosphate tablets (NaPT) or placebo tablets (PlaT) in pigs. Control (Ct): unexposed mucosal area. a Semiquantitative lesion score of surface epithelium architecture. b Semiquantitative lesion score of crypts architecture. c Variations of fluorescein intensity in the crypt lumen [(H1.5 – H0) × 100 /H0]. d Variations of intercryptic intensity. Wilcoxon signed-rank test: * P  ≤ 0.05 vs. value at H0. Mann – Whitney test: ^# P  < 0.05 vs. value of Ct at identical time and ^‡ P  < 0.05 vs. value of PlaT at identical time. AU, arbitrary units.