Retention of extended release nifedipine capsules in a patient with enteric stricture causing recurrent small bowel obstruction.

Abstract: Medication bezoars from extended release medication have been reported in the literature. This has become an increasing phenomenon with the popularity of extended release formulations, which aim to increase therapeutic compliance. We report on a patient who experienced recurrent bouts of small bowel obstruction, necessitating surgical exploration.

Key Words: medication bezoar, bowel obstruction

Case Report

A 74-year-old man presented with a history of small bowel (terminal ileum) resection approximately two years prior for intussusception, treated laparoscopically at an outside institution. A year later, he experienced intermittent episodic obstructive symptoms with abdominal cramping pain, nausea, and vomiting. He was admitted to the hospital three times over the previous year for similar complaints. During each occasion, symptoms were managed conservatively and resolved. A small bowel follow-through revealed obstruction of the small bowel secondary to retention of plastic medication capsules. He had terminated the medication nine months before the current presentation. However, episodic obstructive symptoms recurred, and he subsequently sought treatment at our institution. His past medical history included intussusception near the terminal ileum treated with laparoscopic resection with benign pathology. He also had a mild degree of iron deficiency anemia, hypothyroidism, and hypertension. At admission, the patient was on metoprolol, Vasotec, verapamil, and Synthroid.

On physical examination, his vital signs were stable. Abdomen was benign and mildly distended. There was no guarding or rebound. His laboratory workup was within normal limits except for the mild anemia (hemoglobin/hematocrit 11.9/38.2). A further workup with upper and lower endoscopies revealed mild antritis and duodenitis, with a grade 1 esophageal varices and diverticulosis with an internal hemorrhoid. The small bowel follow through showed multiple, smooth discoid-filling defects measuring 10 mm in diameter, accumulating at three different places of relative stenosis or bends along the small bowel (Fig. 1). They were approximately lo-cated at the proximal jejunum, mid jejunum, and the ileum.

The patient subsequently underwent an exploratory laparotomy. Upon entering the abdomen, we found a moderate degree of adhesion. Segments of small bowel were found to be thickened and inflamed. The mesentery along these segments was also remarkably thickened with creeping fat beyond the mesenteric border of the bowel. Medication capsules were palpated through the small bowel wall with a bean bag-type consistency. There was an area of severe stricture near the previous anastomotic site (Fig. 2). There were two other areas of moderate stenosis proximal to the previous anastomosis. About 80 cm of small bowel encompassing the strictures was resected and an ileo-ileo side-to-side functional end-to-endanastomosis was performed. The patient subsequently recovered without complication and was discharged home on postoperative day 6 after tolerating a regular diet and having normal bowel function.

[FIGURE 1 OMITTED]

The pathology revealed multiple mucosal diaphragm-like bands adjacent to the stricture of the previous anastomosis, showing mucosal ulceration, mixed inflammatory cell infiltrate, disruption of the muscularis mucosa with smooth muscle proliferation, and fibrosis. A total of 64 intraluminal plastic capsules measuring 1.2 cm in diameter and 0.5 cm in thickness were retrieved (Fig. 3).

Discussion

Bezoars are persistent concretions of foreign matter found within the stomach of humans. The word is thought to be of Persian origin. (1) There are four main categories of bezoars. Among the wide variety of materials which form bezoars, plant and vegetable matter (phytobezoar), hair (trichobezoar), and orange pith or parsimmon (disopyrobezoar) are the more common ones. Pharmacobezoars, consisting of medications, are uncommon. (2) Presenting symptoms are similar to other bezoars: weight loss, nausea, vomiting, and early satiety. Intermittent or complete obstruction accounts for all these symptoms. If left untreated, medication bezoars can cause ulceration and hemorrhage as well as excessive release of active agents and may give rise to overdose symptoms. (3,4,5)

[FIGURE 2 OMITTED]

Some medications which have been reported to cause pharmacobezoars are aluminum hydroxide gel for treating hyperphosphatemia in renal failure, (6,7,8) enteric-coated aspirin, (9,10) sucralfate, (11) guar gum, (12) cholestyramine, (13) enteral feeding solution, (13) bulk laxative, (14) and nifedipine XL. (15)

Bezoars may form as a result of GI surgery, pathologic or iatrogenic narrowing of the GI anatomy, or slowed GI motility. Other risk factors include vagotomy, gastrectomy, gastric outlet obstruction, diabetes mellitus, drug therapy (narcotics, anticholinergic agents), and peripheral neuropathy. (16) The unique nifedipine gastrointestinal therapeutic system, (a "push-pull" osmotic pump) delivers nifedipine, a relatively insoluble drug, by a membrane-controlled, osmotically powered push-pull process. (17) The bilayer tablet contains active drug in the top layer (60-80% nifedipine) and an osmotic polymer-driving agent in the bottom layer (20-40% polyethylene oxide). The entire capsule is covered with a layer of indigestible, semi-permeable membrane with a single laser-drilled orifice on the drug side. The shell of the nifedipine XL is composed of cellulose acetate, and the polymer-driving agent within is polyethylene oxide. During the transit through the gastrointestinal tract, the driving agent expands at a constant rate as it becomes hydrated, places pressure on the nifedipine, and expels it from the capsule slowly. This system results in linear (zero order) release of nifedipine and a nearly steady-state of pharmacokinetics with continuous use. (17) The insoluble casing is intended to be excreted in the feces. The presence of multiple strictures of the small bowel with consequent impaired emptying, facilitated the formation of pharmacobezoars in this patient and manifested as recurrent episodes of small bowel obstruction. In fact, despite the effectiveness of this system of medication delivery, the manufacturer warns against using the drug in patients with preexisting severe gastrointestinal narrowing (pathologic or iatrogenic). (4,18)

[FIGURE 3 OMITTED]

Retention of nonbiodegradable tablets is a predictable problem when treating common conditions in older patients in whom strictures are likely to be prevalent (postoperative anatomy, adhesion, and anastomosis). There are also numerous situations where retention of nifedipine XL capsules gave rise to clinical confusion. It has been reported to mimic the appearance of colonic polyps (19) (pseudopolyposis medicamentosus); a false positive result on barium enema study, and cystic pneumatosis intestinalis, (20) where crepitus from palpation of the anterior abdominal wall originated not from pneumatosis but from palpation of numerous shells rubbing against each other ("colonic crunch"). (21)

Conclusion

The retention of the 64 shells of nifedipine XL in this patient can be explained by the physical (density, size, adhesiveness, hardness) and pharmacological properties of nifedipine (a direct relaxing effect on smooth muscle), multiple diaphragm-like bands along the small bowel, and previous small bowel surgery and anastomotic stricture. As gastrointestinal therapeutic system formulation becomes increasingly popular due to better compliance and pharmacokinetics among the elderly population, physicians should be aware of potential complications in high risk patients. A detailed history and physical examination may prevent pharmacobezoars in those with prior peptic ulcer disease, cancer, or other conditions which may potentially lead to narrowing of the gastrointestinal lumen.

References

1. Elgood C. A treatise on the bezoar stone: By the late Mahmud bin Masud the Imad-ul-din the physician of Ispahan. Ann Med Hist 1935;7:73-80.

2. Stack PE, Thomas E. Pharmacobezoar: An evolving new entity. Dig Dis 1995;13:356-364.

3. Bogacz K, Caldron P. Enetric-coated aspirin bezoar: elevation of serum salicylate level by barium study; case report and review of medical management. Am J Med 1987;83:783-786.

4. Prisant LM, Carr AA, Bottini PB, et al. Nifedipine GITS (gastrointestinal therapeutic system) bezoar. Arch Intern Med 1991;151:1868-1869.

5. Shepherd M. Bezoar formed by fragments of extended-release nifedipine tablets. Clin Pharm 1993;12:849-852.

6. Potyk D. Intestinal obstruction from impacted antacid tablets. N Eng J Med 1970;283:134-135.

7. Brettschneider L, Monafo W, Osborne DP. Intestinal obstruction due to antacid gels. Gestroenterology 1965;49:291-294.

8. Korenman MD, Stubbs MB, Fish JC. Intestinal obstruction from medication bezoars. JAMA 1978;240:54-55.

9. Harris FC. Pylori stenosis hold-up of enteric-coated aspirin tablets. Br J Surg 1973;60:979-981.

10. Sogge MR, Griffith JL, Sinar DR, Mayes GR. Lavage to remove enteric-coated aspirin and gastric outlet obstruction. Ann Intern Med 1977;87:721-722.

11. Algozzine GJ, Hill G, Scoggins WG, et al. Sucralfate bezoar. N Eng J Med 1983;309:1387.

12. Lewis JH, Esophageal and small bowel obstruction from guar gum-containing 'diet pills': Analysis of 26 cases reported in the Food and Drug Administration. Am J Gastroenterol 1992;87:1424-1428.

13. Cohen MI, Winslow PR, Boley SJ. Intestinal obstruction associated with cholestyramine therapy. N Eng J Med 1969;280:1285-1286.

14. Agha FP, Nostrant TT, Fiddian-Green RG. 'Giant colonic bezoar'; A medication bezoar due to psylliumseed husks. Am J gastroenterol 1984;79:319-321.

15. Stack PE, Patel NR, Young MF, et al. Pharmacobezoars: The irony of the antidote. First case of nifedipine XL bezoar. J Clin Gastroenterol 1994;19:264-271.

16. Calabuig R, Navarro S, Carrio I, et al. Gastric emptying and bezoars. Am J Surg 1989;157:287-290.

17. Chung M, Reitberg DP, Gaffney M, et al. Clinical pharmacokinetics of nifedipine gastrointestinal therapeutic system: A controlled release formulation of nifedipine. Am J Med 1987;83:10-14.

18. Gasperino JL. Procardia XL bezoar. Arch Intern Med 1992;152:880-881.

19. Raufman JP, Soldevila-Pico C. Pseudopolyposis medicamentosus. Gastrointest Endosc 1993;39:213-214.

20. Kwon HY, Scott RL, Mulloy JP. Small bowel Procardia XL tablet bezoar mimicking cystic pneumatosis intestinalis. Abdom Imaging 1996;21:142-144.

21. Melchreit R, McGowan G, Hyams JS. "Colonic crunch" sign in sunflower-seed bezoar. N Eng J Med 1984;310:1748-1749.

22. Greenstein DB, Wilcox CM, Frontin K, et al. Nifedipine (Procardia XL) as a cause of false positive results on barium study. Southern Med J 1994;87:808-810.

Birds sing after a storm; why shouldn't people feel as free to delight
in whatever sunlight remains to them?
--Rose Kennedy

Wing C. Yeen, MD, MBA, and Irwin H. Willis, MD, FACS

From the Department of General Surgery, Mount Sinai Medical Center of Greater Miami, Miami Beach, FL.

Reprint requests to Wing C. Yeen, MD, Mt. Sinai Medical Center, 4300 Alton Road, Suite 212A, Miami Beach, FL 33140. Email: [e-mail]

Accepted April 19, 2005.

RELATED ARTICLE: Key Points

* Pharmacobezoars is an increasing phenomenon with the popularity of extended release formulation of medication aiming to increase therapeutic compliance.

* Presenting symptoms due to intermittent or complete obstruction include weight loss, nausea, vomiting and early satiety.

* Bezoars may form as a result of GI surgery, pathologic or iatrogenic narrowing of the GI anatomy or slowed GI motility.

* Physicians should be aware of the potential complications in high risk patients.

* A detailed history and physical examination may prevent pharmacobezoars in those with prior peptic ulcer disease, cancer, or other conditions potentially leading to narrowing of the gastrointestinal lumen.