Colonic mucosal abnormalities associated with oral sodium phosphate solution

0016-5107/96/4305-046355.00 + 0 GASTROINTESTINAL ENDOSCOPY Copyright © 1996 by the American Society for Gastrointestinal Endoscopy

Colonic mucosal abnormalities associated with oral sodium phosphate solution Felice R. Zwas, MD, Nicholas W. Cirillo, DO, Hashem B. EI-Serag, MD, Richard N. Eisen, MD Greenwich, Connecticut, and North Wilkesboro, North Carolina

Background: Oral sodium phosphate (NAP) is increasingly used as a colonic cleansing agent for colonoscopy. It has been shown to be efficacious, well-tolerated, and safe. Mucosal abnormalities associated with NaP have recently been described. We carried out this controlled study to assess whether bowel cleansing preparations commonly used in colonoscopy are associated with colonic mucosal changes that may mimic inflammatory bowel disease (IBD). Method: All patients undergoing colonoscopy from January 1994 to June 1994 were considered for the study. Patients with history or symptoms suggestive of IBD were excluded. Patients were randomized to receive polyethylene glycol-based lavage (PEG-ELS) or NaP solution as their bowel cleansing preparation. Two gastroenterologists performing the colonoscopies were blinded to the type of preparation. Any mucosal abnormalities were noted and photographic documentation and biopsy specimens were taken. Results: Ninety-seven patients were studied, 44 receiving PEG-ELS and 53 receiving NaP. Both groups were similar with regard to sex, age, and indication for colonoscopy. Fourteen patients were found to have nonspecific aphthoidlike erosions similar in appearance to Crohn's disease. These lesions, however, were not friable and biopsy results were not compatible with IBD. This mucosal abnormality was found in 13 patients who received NaP (24.5%) and only 1 patient who received PEG-ELS (2.3%). Conclusion: Nonspecific aphthoid-like mucosal lesions occur frequently in patients who received NaP for colonoscopy preparation. These lesions are endoscopically similar to those seen in Crohn's disease. Because of the potential for misinterpretation of these lesions, we do not recommend the use of NaP as a colonic cleansing preparation for patients with chronic diarrhea or in whom the diagnosis of IBD is suspected (Gastrointest Endosc 1996;43:463-6.)

Colonoscopy is a commonly used procedure for establishing the diagnosis and subsequent follow-up of inflammatory bowel disease (IBD).lAdequate bowel preparation is essential for proper visualization of the mucosa. Orthograde peroral colonic cleansing has become popular since the introduction of polyethylene glycol-electrolyte lavage solution (PEG-ELS). 2, 3 Oral Received May 5, 1995. For revision July 14, 1995. Accepted October 17, 1995. From the Greenwich Hospital, Yale University, Greenwich, Connecticut, and the Wilkes Regional Medical Center, North Wilkesboro, North Carolina. Reprint requests: Felice Zwas, MD, 2~ Dearfield Dr., Greenwich, CT 06831. 37/1/70046

VOLUME 43, NO. 5, 1996

sodium phosphate (NAP) is a strong osmotic laxative that is increasingly used as a colonic cleansing agent for colonoscopy.4-6 N a P has been shown to be efficacious, well-tolerated, and safe. Fleet enemas have long been observed to cause a colitis-like appearance, 7 and recently two reports have described NaP-induced mucosal lesions, s, 9 We encountered aphthoid-like lesions after use of N a P preparations in two patients undergoing colonoscopy for evaluation of chronic diarrhea. In both instances, we were surprised to find "aphthous ulcers," although neither patient had clinical features consistent with Crohn's disease. This prompted us to re-examine these patients with a different preparation (PEG-ELS) 1 week later. Surprisingly, these lesions GASTROINTESTINAL ENDOSCOPY 463

Table 1. Characteristic of the patients involved in the study PEG-ELS

NaP

Number (n) 44 53 Age (y) 36-85 (mean 57.2) 30-78(mean 59.6) Men 20 27 Women 24 26 Indication for colonoscopy Polyps surveillance 27 23 Guaiac positive 14 26 Constipation 3 4 cedure. They were to drink one 8-ounce glass every 15 minutes until completion. NaP was administered in two doses (each dose 1.5 ounces in 10 ounces of clear liquid), at 2 PM the day prior to colouoscopy and 3 hours prior to procedure. Two experienced board certified gastroenterologists performing the colonoscopies were blinded to the type of preparation. Pentax or Olympus videocolonoscopes were used for all cases (Pentax Precision Instrument Corp., Orangeburg, N.Y. and Olympus America Inc., Melville, N.Y.). Colonoscopes were cleaned using sodium dodecylbenzene sulfonate (Manu-Klenz). All mucosa] abnormalities seen on advancement of the colonoscope were noted and any aphthoid-like lesion was photographically documented and reviewed by both endoscopists. Biopsies were done on areas of mucosal abnormalities and all biopsy specimens were reviewed by a single pathologist who was blinded to the patient's name and type of bowel preparation.

Figure 1. Video endoscopic photographs of typical NaPinduced lesions. A, Multiple well-circumscribed aphthoid-like erosions with normal intervening mucosa. B, lesions with a surrounding red halo.

were completely gone. Biopsy specimens obtained during each procedure failed to reveal a n y evidence of Crohn's disease. We continued to sporadically encount e r these lesions in a s y m p t o m a t i c patients p r e p p e d with N a P who were u n d e r g o i n g colonoscopy for polyp surveillance. These observations p r o m p t e d us to c a r r y out a prospective, randomized, single-blind controlled s t u d y to assess w h e t h e r certain bowel cleansing preparations commonly used in colonoscopy are associated with colonic mucosal abnormalities t h a t m a y mimic IBD.

METHOD All patients undergoing colonoscopy from January 1994 to June 1994 were considered for the study. Patients with history or symptoms suggestive Of IBD or chronic diarrhea or with a history of renal, cardiac, or hepatic failure were excluded. All patients were randomized to receive PEG-ELS (Colyte) or NaP (Fleets Phosphasoda) as their bowel cleansing preparation. All patients were instructed to remain on a clear liquid diet for 24 hours prior to the procedure. Patients receiving PEG-ELS were instructed to begin drinking 1 gallon of the solution at 2 PM the day prior to the pro464 G A S T R O I N T E S T I N A L E N D O S C O P Y

RESULTS N i n e t y - s e v e n p a t i e n t s qualified for the study, 47 m e n a n d 50 women. Forty-four received P E G - E L S a n d 53 received NaP. Both groups were similar with r e g a r d to sex, age, and indication for colonoscopy. Characteristics of the p a t i e n t s undergoing colonoscopy are outlined in Table 1. F o u r t e e n p a t i e n t s were found to h a v e aphthoid-like erosions noted on adv a n c e m e n t of the colonoscope. T h e s e were small (1 to 3 ram), shallow lesions, f r e q u e n t l y s u r r o u n d e d with a reddish halo (Fig. 1). This mucosal a b n o r m a l i t y was found in 13 patients who received N a P (24.5%) and only 1 p a t i e n t who received P E G - E L S (2.3%). Using chi s q u a r e d test, the difference b e t w e e n the two groups was significant at a n a value of 0.05. These patients were comparable to the r e s t of the group with r e g a r d to age and sex. T e n p a t i e n t s u n d e r w e n t colonoscopy for polyps, 2 for constipation, a n d 2 for guaiacpositive stool. F o u r p a t i e n t s h a d these lesions scatt e r e d t h r o u g h o u t the colon a n d 10 p a t i e n t s h a d t h e m c o n c e n t r a t e d in the left colon. E i g h t of the 13 patients who received N a P h a d multiple lesions (>30) t h a t app e a r e d endoscopically indistinguishable from Crohn's disease; the r e m a i n i n g 5 h a d fewer scattered discrete small lesions (5 to 10). T h e r e were two small lesions seen in the P E G - E L S patient. All the biopsy specim e n s exhibited minimal to mild e d e m a and superficial fresh h e m o r r h a g e in the u p p e r portion of the l a m i n a VOLUME 43, NO. 5, 1996

Figure 2. Histologic micrographs of NaP-induced lesions. A, Architecturally normal mucosa with slight congestion and edema of the superficial lamina propria. (H&E stain, original magnification x200.) B, Similar mucosa with mild nonspecific inflammation, focal separation of the surface epithelium, and reactive epithelial changes (H&E stain, original magnification x200.) Note the absence of features of IBD in both.

propria, with variable degrees of denudation of the surface epithelium (Fig. 2). Two exhibited mild inflammation with an increase in lymphocytes, plasma cells, and scattered neutrophils in the lamina propria and mild reactive epithelial changes in the crypts. One specimen contained a small superficial erosion with fibrin and neutrophils located beneath the eroded surface. However, none of the biopsy specimens exhibited features typical of idiopathic IBD such as basal lymphoplasmacytosis, architectural crypt distortion, or significant cryptitis. DISCUSSION

Colonoscopy is an important tool for the diagnosis and follow-up of IBD. 1 Proper colonic preparation is essential for a good endoscopic study, as well as for the safety of the patient. The search is continuing for the "ideal" colonic preparation, aiming at better patient compliance, shorter colonic preparation time, and better colonic cleansing. Since its introduction in 1980, 2 PEG-ELS has been a popular method of orthoVOLUME 43, NO. 5, 1996

grade colonic preparation. 2, 3 However, 5% to 10% of patients find the taste disagreeable or the prescribed volume unacceptable. N a P is a highly osmotic cathartic that has emerged as a safe, well-tolerated, and efficacious preparation. 4-6 Although asymptomatic hyperphosphatemia is seen in up to 40% of patients receiving NaP, ~ serious hyperphosphatemia is rare and usually occurs in patients with renal failure 1° or with much higher doses of NaP. 11 Multiple trials in both outpatient and inpatient populations have shown oral N a P to be at least as effective as PEG-ELS and better tolerated. 4-6 Sodium phosphosoda enemas are well known to cause proctoscopic and histologic abnormalities of the lower colon and rectum 7 and are generally avoided as a sigmoidoscopy preparation in suspected patients with IBD. Gross mucosal changes include hyperemia, obliteration of the vascular pattern and, occasionally, friability. Biopsies reveal disruption of the surface epithelium on light microscopy. In an early study comparing the efficacy and patient compliance of N a P and GASTROINTESTINAL ENDOSCOPY

465

PEG-ELS, random colonic biopsies were performed and revealed no histologic changes in either group. No comment was made regarding the gross appearance of the colonic mucosa. 4 A larger follow-up study of 113 patients, randomized to receive NaP, PEG-ELS, or lemon flavored castor oil, confirmed the efficacy and safety of NaP. The appearance of the colonic mucosa was, again, not described. 6 In this randomized single-blind controlled study, all patients with chronic diarrhea or history or symptoms suggestive of IBD were excluded. The endoscopic instruments were cleaned with sodium dodecylbenzene sulfonate (Manu-Klenz), a cleansing solution not reported to cause colonic mucosal abnormalities. Mucosal lesions were considered to be significant only if seen during advancement of the colonoscope to avoid misinterpretation with traumatic lesions. The histopathology of these mucosal abnormalities were similar to those described with Fleet phosphosoda enemas. Thus, we consider the lesions, seen in nearly 25% of patients receiving NaP and only a single patient on PEGELS (2.3%), to be a direct result of NaP preparation. A report recently described aphthoid erosions after colonic cleansing with NaP. 9 Subsequent authors suggested these lesions were the "red ring sign" of lymphoid hyperplasia and unrelated to the colonic preparation used. 12, 13 In our study, biopsies of the lesion did not show lymphoid aggregates or evidence of true aphthoid erosions. Thus, we do not believe these mucosal abnormalities represent true aphthoid erosions or lymphoid hyperplasia. In addition, we found these lesions almost exclusively in patients receiving NaP. The significance of these lesions lies in their potential misinterpretation as real aphthoid erosions of Crohn's disease. In this study, we demonstrated that NaP induces aphthoid-like lesions similar to those seen in Crohn's disease. Although these lesions can be ignored in pa-

4(}6

GASTROINTESTINAL ENDOSCOPY

tients undergoing surveillance colonoscopy, in patients with chronic diarrhea or in whom the diagnosis of IBD is suspected, it becomes increasingly difficult to decide which lesions are pathologic or artifactual. We, therefore, do not recommend the use of N a P as a bowel cleansing preparation in any patient with chronic diarrhea or a suspicion of IBD. REFERENCES 1. Haber GB. Role of endoscopy in inflammatory bowel disease. Dig Dis Sci 1987;12:16S-26S. 2. Davis GR, Santa Aria CA, Morawski SG, Fordtran JS. Development of a lavage solution associated with minimal water and electrolyte absorption or secretion. Gastroenterology 1980;78: 991-5. 3. Beck DE, Hartford FJ, DiPalma JA, Brady CE. Bowel cleansing with polyethylene glycol electrolyte lavage solution. South Med J 1985;78:1414-6. 4. Vanner SJ, MacDonald PH, Paterson WG, et al. A randomized prospective trial comparing oral sodium phosphate with standard polyethylene glycol based lavage solution (Golytely) in the preparation of patients for colonoscopy. Am J Gastroenterol 1990;85:422-7. 5. Cohen SM, Wexner SD, Binderow SR, et al. Prospective, randomized, endoscopic-blinded trial comparing colonoscopybowel cleansing methods. Dis Colon Rectum 1994;37:689-96. 6. Kolts BE, Lyles WE, Achem SR. A comparison of the effectiveness and patient tolerance of oral sodium phosphate, castor oil, and standard electrolyte lavage for colonoscopy preparation. Am J Gastroenterol 1993;88:1218-23. 7. Meisel JL, Bergman D, Graney D, et al. Human rectal mucosa: proctoscopic and morphological changes caused by laxatives. Gastroenterology 1977;72:1274-9. 8. E1-Serag HB, Zwas F, Cirillo N. Colonic mucosal abnormalities associated with bowel preparations [Abstract]. Gastrointest Endosc 1995;41:319. 9. Hixson LJ. Colorectal ulcers associated with sodium phosphate catharsis. Gastrointest Endosc 1995;42:101-2. 10. Zisper RD, Bischel MD, Abrams DE. Hypocalcemic tetany due to sodium phosphate ingestion in acute renal failure. Nephron 1975;14:378-81. 11. McConnell TH. Fatal hypocalcemia from phosphate absorption from laxative preparation. JAMA 1971;216:147-8. 12. Faigel DO, Furth EE, Bachwich DR. Aphthoid lesions of the rectum [Letter]. Gastrointest Endosc 1996;43:528. 13. Stark ME' W°lfe JT' Red ring sign vs' aphth°us ulcers °fc°l°nic mucosa? [Letter] Gastrointest Endosc 1996;43:529.

VOLUME 43, NO. 5, 1996