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Treatment of Acute Colonic Pseudo-Obstruction With Tegaserod
CASE REPORT
Treatment of Acute Colonic Pseudo-Obstruction With Tegaserod Ruben Ramirez, MD, Marc J. Zuckerman, MD, Reza A. Hejazi, MD and Sita Chokhavatia, MD
Abstract: Acute colonic pseudo-obstruction is characterized by symptoms, signs and radiologic appearance of large bowel obstruction in the absence of a true mechanical obstruction. Several pharmacologic treatments have been proposed. We present a case of a patient with Guillain-Barre´ syndrome complicated by acute colonic pseudo-obstruction, who had a clinical response to tegaserod, a partial 5-hydroxytryptamine type-4 agonist. 5-Hydroxytryptamine type 4 agonists may be an option in the treatment of acute colonic pseudo-obstruction. Key Indexing Terms: Acute colonic pseudo-obstruction; Tegaserod; Ogilivie syndrome. [Am J Med Sci 2010;339(6):575–576.]
CASE REPORT Acute colonic pseudo-obstruction is characterized by symptoms, signs and radiologic appearance of large bowel obstruction in the absence of a true mechanical obstruction.1 The pathophysiology is not well understood. A proposed theory involves transient impairment of the sacral parasympathetic nerves causing atony of the distal large bowel, resulting in functional obstruction. Several pharmacologic treatments such as neostigmine have been proposed.2 We present a case of a patient with Guillain-Barre´ syndrome complicated by acute colonic pseudo-obstruction, in whom neostigmine was thought to be contraindicated. A 57-year-old man with Guillain-Barre´ syndrome and progressive ascending muscular weakness was hospitalized for significant autonomic dysfunction and pronounced muscular weakness. He developed diffuse abdominal pain and distention, and had been unable to pass gas or feces for 5 days while in the hospital. He had not been taking any narcotic or any medication that might slow gut motility, and he did not have a history of constipation. The physical examination was significant for abdominal distention, hyperactive bowel sounds, diffuse abdominal tenderness and no impacted stool in the rectum. Laboratory data including complete blood count, electrolytes, renal function, magnesium and phosphate were normal. An abdominal computed tomography showed dilated colon, with cecal maximum diameter of 8.3 cm, without associated abnormality of the bowel wall or small bowel dilation, all consistent with acute colonic pseudo-obstruction (Ogilvie syndrome). Successful endoscopic colonic decompression was performed the next day and supportive measures continued, including nasogastric (NG) suction and maintaining electrolyte balance. The patient developed recurrent distention within 24 hours. Neostigmine was thought to be contraindicated because
From the Division of Gastroenterology (RR, MJZ, RAH), Texas Tech University Health Sciences Center; El Paso, Texas; and Division of Gastroenterology (SC), Mount Sinai School of Medicine, New York, New York. Submitted December 17, 2009; accepted in revised form February 12, 2010. Correspondence: Marc J. Zuckerman, MD, Division of Gastroenterology, Texas Tech University Health Sciences Center, 4800 Alberta Avenue, El Paso, TX 79905 (E-mail: [email protected]).
of autonomic dysfunction and he failed to respond to erythromycin. Tegaserod (6 mg) was then given every 12 hours via NG tube and within 14 hours the patient started passing gas and had a spontaneous bowel movement. Abdominal pain and distention resolved, confirmed by an abdominal film. The patient continued to receive tegaserod until discharge, 7 days later with no recurrence of obstructive symptoms.
DISCUSSION Management of acute colonic pseudo-obstruction includes general measures such as correction of electrolyte imbalances, treatment of underlying conditions, stopping any contributing agents, nothing by mouth, intravenous fluids and NG tube placement.2 Treatment options for acute colonic pseudo-obstruction have had variable outcomes and include medications (neostigmine and erythromycin), endoscopic decompression, percutaneous tube cecostomy and possibly surgical decompression. Intravenous neostigmine is the best-documented pharmacologic treatment.3 Although cisapride, a 5-hydroxytryptamine type 4 (5HT4) receptor agonist, has been used successfully in some patients,4,5 to our knowledge, this is the first case report of acute colonic pseudo-obstruction with a clinical response to treatment with tegaserod, a partial 5-HT4 receptor agonist. Tegaserod significantly accelerates gastric emptying, small bowel and colonic transit times, and was approved for use in chronic constipation and constipation—predominant irritable bowel syndrome.6 Side-Effects/Toxicity Our patient was treated before March 30, 2007, when Novartis suspended U.S. sales of tegaserod. There was concern about a possible link between the use of tegaserod and increased risk of ischemic adverse events.7 The literature then and now does not suggest a particular safety issue in the use of tegaserod in the setting of our patient. Although 5-HT4 receptor agonists all have prokinetic effects in the gut, they differ in many aspects (some of which are unrelated to the 5-HT4 receptor) that may influence the benefit/risk profile of agent.7 Prucalopride and other highly selective 5-HT4 receptor agonists under development may have improved efficacy and safety to treat patients with gastrointestinal motility disorders.7 5-HT4 receptor agonists may be a viable option in the treatment of acute colonic pseudo-obstruction. ACKNOWLEDGMENT The authors thank Dr. Richard McCallum and Georgina Grado. REFERENCES 1. Ogilvie H. Large-intestine colic due to sympathetic deprivation; a new clinical syndrome. Br Med J 1948;2:671–3.
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Ramirez et al
2. De Giorgio R, Knowles CH. Acute colonic pseudo-obstruction. Br J Surg 2009;96:229 –39.
5. Mazloum BW, Barnes JB, Lee M. Cisapride as a successful treatment for acute intestinal pseudo-obstruction. South Med J 1996;89:828 –30.
3. Ponec RJ, Saunders MD, Kimmey MB. Neostigmine for the treatment of acute colonic pseudo-obstruction. N Engl J Med 1999;341: 137– 41.
6. Degen L, Petrig C, Studer D, et al. Effect of tegaserod on gut transit in male and female subjects. Neurogastroenterol Motil 2005;17: 821– 6.
4. MacColl C, MacCannell KL, Baylis B, et al. Treatment of acute colonic pseudoobstruction (Ogilvie’s syndrome) with cisapride. Gastroenterology 1990;98:773– 6.
7. De Maeyer JH, Lefebvre RA, Schuurkes JA. 5-HT4 receptor agonists: similar but not the same. Neurogastroenterol Motil 2008; 20:99 –112.
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Treatment of Acute Colonic Pseudo-Obstruction With Tegaserod Ruben Ramirez, MD, Marc J. Zuckerman, MD, Reza A. Hejazi, MD and Sita Chokhavatia, MD
Abstract: Acute colonic pseudo-obstruction is characterized by symptoms, signs and radiologic appearance of large bowel obstruction in the absence of a true mechanical obstruction. Several pharmacologic treatments have been proposed. We present a case of a patient with Guillain-Barre´ syndrome complicated by acute colonic pseudo-obstruction, who had a clinical response to tegaserod, a partial 5-hydroxytryptamine type-4 agonist. 5-Hydroxytryptamine type 4 agonists may be an option in the treatment of acute colonic pseudo-obstruction. Key Indexing Terms: Acute colonic pseudo-obstruction; Tegaserod; Ogilivie syndrome. [Am J Med Sci 2010;339(6):575–576.]
CASE REPORT Acute colonic pseudo-obstruction is characterized by symptoms, signs and radiologic appearance of large bowel obstruction in the absence of a true mechanical obstruction.1 The pathophysiology is not well understood. A proposed theory involves transient impairment of the sacral parasympathetic nerves causing atony of the distal large bowel, resulting in functional obstruction. Several pharmacologic treatments such as neostigmine have been proposed.2 We present a case of a patient with Guillain-Barre´ syndrome complicated by acute colonic pseudo-obstruction, in whom neostigmine was thought to be contraindicated. A 57-year-old man with Guillain-Barre´ syndrome and progressive ascending muscular weakness was hospitalized for significant autonomic dysfunction and pronounced muscular weakness. He developed diffuse abdominal pain and distention, and had been unable to pass gas or feces for 5 days while in the hospital. He had not been taking any narcotic or any medication that might slow gut motility, and he did not have a history of constipation. The physical examination was significant for abdominal distention, hyperactive bowel sounds, diffuse abdominal tenderness and no impacted stool in the rectum. Laboratory data including complete blood count, electrolytes, renal function, magnesium and phosphate were normal. An abdominal computed tomography showed dilated colon, with cecal maximum diameter of 8.3 cm, without associated abnormality of the bowel wall or small bowel dilation, all consistent with acute colonic pseudo-obstruction (Ogilvie syndrome). Successful endoscopic colonic decompression was performed the next day and supportive measures continued, including nasogastric (NG) suction and maintaining electrolyte balance. The patient developed recurrent distention within 24 hours. Neostigmine was thought to be contraindicated because
From the Division of Gastroenterology (RR, MJZ, RAH), Texas Tech University Health Sciences Center; El Paso, Texas; and Division of Gastroenterology (SC), Mount Sinai School of Medicine, New York, New York. Submitted December 17, 2009; accepted in revised form February 12, 2010. Correspondence: Marc J. Zuckerman, MD, Division of Gastroenterology, Texas Tech University Health Sciences Center, 4800 Alberta Avenue, El Paso, TX 79905 (E-mail: [email protected]).
of autonomic dysfunction and he failed to respond to erythromycin. Tegaserod (6 mg) was then given every 12 hours via NG tube and within 14 hours the patient started passing gas and had a spontaneous bowel movement. Abdominal pain and distention resolved, confirmed by an abdominal film. The patient continued to receive tegaserod until discharge, 7 days later with no recurrence of obstructive symptoms.
DISCUSSION Management of acute colonic pseudo-obstruction includes general measures such as correction of electrolyte imbalances, treatment of underlying conditions, stopping any contributing agents, nothing by mouth, intravenous fluids and NG tube placement.2 Treatment options for acute colonic pseudo-obstruction have had variable outcomes and include medications (neostigmine and erythromycin), endoscopic decompression, percutaneous tube cecostomy and possibly surgical decompression. Intravenous neostigmine is the best-documented pharmacologic treatment.3 Although cisapride, a 5-hydroxytryptamine type 4 (5HT4) receptor agonist, has been used successfully in some patients,4,5 to our knowledge, this is the first case report of acute colonic pseudo-obstruction with a clinical response to treatment with tegaserod, a partial 5-HT4 receptor agonist. Tegaserod significantly accelerates gastric emptying, small bowel and colonic transit times, and was approved for use in chronic constipation and constipation—predominant irritable bowel syndrome.6 Side-Effects/Toxicity Our patient was treated before March 30, 2007, when Novartis suspended U.S. sales of tegaserod. There was concern about a possible link between the use of tegaserod and increased risk of ischemic adverse events.7 The literature then and now does not suggest a particular safety issue in the use of tegaserod in the setting of our patient. Although 5-HT4 receptor agonists all have prokinetic effects in the gut, they differ in many aspects (some of which are unrelated to the 5-HT4 receptor) that may influence the benefit/risk profile of agent.7 Prucalopride and other highly selective 5-HT4 receptor agonists under development may have improved efficacy and safety to treat patients with gastrointestinal motility disorders.7 5-HT4 receptor agonists may be a viable option in the treatment of acute colonic pseudo-obstruction. ACKNOWLEDGMENT The authors thank Dr. Richard McCallum and Georgina Grado. REFERENCES 1. Ogilvie H. Large-intestine colic due to sympathetic deprivation; a new clinical syndrome. Br Med J 1948;2:671–3.
The American Journal of the Medical Sciences • Volume 339, Number 6, June 2010
575
Ramirez et al
2. De Giorgio R, Knowles CH. Acute colonic pseudo-obstruction. Br J Surg 2009;96:229 –39.
5. Mazloum BW, Barnes JB, Lee M. Cisapride as a successful treatment for acute intestinal pseudo-obstruction. South Med J 1996;89:828 –30.
3. Ponec RJ, Saunders MD, Kimmey MB. Neostigmine for the treatment of acute colonic pseudo-obstruction. N Engl J Med 1999;341: 137– 41.
6. Degen L, Petrig C, Studer D, et al. Effect of tegaserod on gut transit in male and female subjects. Neurogastroenterol Motil 2005;17: 821– 6.
4. MacColl C, MacCannell KL, Baylis B, et al. Treatment of acute colonic pseudoobstruction (Ogilvie’s syndrome) with cisapride. Gastroenterology 1990;98:773– 6.
7. De Maeyer JH, Lefebvre RA, Schuurkes JA. 5-HT4 receptor agonists: similar but not the same. Neurogastroenterol Motil 2008; 20:99 –112.
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