TECHNIQUES AND PROCEDURES Somatostatin and Its Analogs in the Short Bowel
Syndrome GAIL H. ROSEN, PHARMD Support Services, Department of Pharmacy Services, University of Maryland Medical System, University of
Nutrition
Maryland School of Pharmacy, and University of Maryland School of Medicine, Baltimore
in patients with metastatic carcinoid and vasoactive intestinal peptide-secreting tumors. This article will discuss the physiological effects of somatostatin and octreotide and will summarize the published clinical experience with the management of the short gut syndrome with octreotide.
ABSTRACT: The use of somatostatin to manage diarrhea associated with the short gut syndrome is impractical because of its need to be given by continuous infusion and a rebound effect on stool output with cessation of therapy. Octreotide has been used more successfully to control stool and electrolyte losses in patients with shortened gastrointestinal tracts. In published series and studies, all subjects appear to decrease stool losses, but clinical benefit for longterm use is not achieved for all patients. In the patients who do respond, the need for parenteral nutrition and intravenous hydration has been decreased or eliminated. The optimal dose is unclear, but many patients respond to 50-μg injections twice daily. Several investigations noted no additional beneficial effects with escalating dosages. Adverse effects include impairment of fat absorption, which may offset the therapeutic benefits of octreotide. The patients with the greatest response appear to have the least fat malabsorption. Other adverse effects noted when using octreotide for control of the short gut syndrome include pain associated with subcutaneous injection and abdominal complaints. Other potential concerns include the effect on gallstone formation in this high-risk population and intestinal
PHYSIOLOGICAL EFFECTS OF SOMATOSTATIN
Somatostatin is widely distributed anatomically and has a multiplicity of physiological effects. The highest concentration of somatostatin is found in the pancreas and gastrointestinal tract.2 Administration of somatostatin suppresses the secretion of numerous gastrointestinal hormones including gastrin, enteroglu-
gastric inhibitory peptide, motilin, secretin, peptide, glucagon, insulin, and pancreatic polypeptide. In normal subjects, the administration of somatostatin prolongs intestinal transit time. Somatostatin decreases gastrointestinal blood flow and absorption of macronutrients, including fat cagon,
vasoactive intestinal
adaptation.
and
carbohydrate.’
In studies of normal human subsomatostatin did not affect small bowel net water or electrolyte transport.4 In treating the diarrhea associated with the carcinoid syndrome or vipomas, somatostatin enhances water and sodium chloride absorption, presumably because of the inhibitory effect of somatostatin on secretagogue release.5
jects, Somatostatin and its synthetic analog, octreotide, have many potential uses in gastrointestinal diseased1 Somatostatin is unavailable commercially in the United States, but octreotide has been recently approved by the Food and Drug Administration. Octreotide’s labeled indications are for control of symptoms
DEVELOPMENT AND EFFECTS OF OCTREOTIDE
Somatostatin has a very short half-life of 2 to 3 minutes and therefore must be administered by continuous intravenous infusion. Also, presumably because of the short half-life, the cessation of the administration of somatostatin has been associated with rebound hypersecretion of growth hormone and other substances.’ Octreotide was developed by manipulating the somatostatin molecule to impede its degrada-
Address for reprints: Gail H. Rosen, PharmD, Department of Pharmacy Services, University of Maryland Medical System, 22 S. Greene Street. Street, Baltimore. Baltimore, MD 21201
81
Downloaded from ncp.sagepub.com at The University of Iowa Libraries on June 4, 2015
82
tion and prolong its half-life. The elimination half-life of octreotide is 90 minutes, allowing intermittent administration every 8 or 12 hours.6 Octreotide has similar pharmacological effects as somatostatin while being a more potent and longer-acting inhibitor of several hormones, including growth hormone, glucagon, and
insulin.’
MECHANISMS OF DIARRHEA IN THE SHORT GUT SYNDROME
Several mechanisms have been proposed to cause the diarrhea associated with the short gut syndrome. An increase in gut hormones, especially gastrin, has been observed.’ The physical loss of intestinal surface area may decrease the absorption of nutrients. The presence of malabsorbed nutrients may produce an osmotic stimulus and promote diarrhea. Increased transit times through the shortened gut may be responsible for part of the large fecal outputs. A disturbance in intestinal transport may be in part a result of a secretory process because patients with a short gut syndrome persistently have large volumes of stool output in the fasting state. Finally, the underlying disease itself, such as Crohn’s disease or radiation enteropathy, may impair the gut’s ability to function.’ Pharmacological manipulation of the short gut syndrome with histamine receptor antagonists, loperamide and other antidiarrheal agents, cholestyramine, and nutrition support with enteral products has sustained many patients with the short gut syndrome without the use of supplemental intravenous fluids, intravenous electrolytes, or parenteral nutrition.9 Some patients, despite traditional management, continue to require intravenous support for the maintenance of nutritional, electrolyte, and fluid status. Both somatostatin and octreotide have been used to manage these patients. SOMATOSTATIN AND THE SHORT GUT SYNDROME
One
of the use of somatostatin to manage stool outputs of four patients with short bowel syndromes as a result of multiple surgical resections for Crohn’s disease.1o Somatostatin infusions of 4 Agl min for 24 hours decreased stool weight in all four patients without affecting fecal fat output. When the infusion was discontinued, however, the patients experienced a rebound increase in stools of greater weights than baseline. The need to infuse this agent continuously limits its utility.
study reports
OCTREOTIDE AND THE SHORT GUT SYNDROME
Table 1 outlines the case reports and studies with octreotide to control the short gut syndrome. The mechanism of action of octreotide in this setting is unclear. Ladefoged et al expressed that the increases
in net absorption of sodium and water were due to a reduction in the secretion of digestive juices.&dquo; Cooper et al noted a reduction in salt and water excretion as well as a slowing of gastrointestinal transit time.12 Although no effect on gastric emptying was noted, mouth-to-stoma transit time and small bowel transit times were significantly lengthened. Cooper et al postulated that the effect on transit time was a secondary effect due to octreotide’s effect on fluid transport. Octreotide administration resulted in greater increases in transit time when compared with administration of oral or intramuscular codeine, loperamide, and soy polysaccharide in four patients.&dquo; PRACTICAL ROLE OF OCTREOTIDE
Although most of the results of investigations with octreotide to manage the short gut syndrome report a decrease in stool output, the effects have not been sufficient in all patients to eliminate the need for parenteral nutrition or intravenous hydration therapy. In the study of Ladefoged et al, four patients continued to administer octreotide long term.ll All patients needed to continue intravenous saline but were able to decrease the volume to 1 L/d. In the series of Cooper et al, two of the five patients continued octreotide long term. Both of these patients were able to discontinue intravenous hydration therapy.&dquo; Nightingale et al reported decreased fecal outputs in all patients studied, but only one patient chose to continue treatment at home.14 A case report of a 5-year-old child with a short bowel describes good long-term tolerance with the administration of octreotide, allowing a total transition from parenteral to enteral nutrition.l5 Two of six patients administered octreotide at home for more than 2 years in the randomized, crossover trial of Shaffer et a1.16 Table 1 summarizes the response to octreotide and long-term use in the case report by Williams et al17 and the series by Rosenberg and Brown&dquo; and Gilsdorf et al.19 DOSAGE OF OCTREOTIDE
The optimal dose of octreotide in the short gut is not established, but many studies report a lack of additional desired effects with escalating the dose. Ladefoged et al showed equivalent effects with a 600-j.tg/d dose by continuous infusion as compared with 50 Ag twice a day by subcutaneous injection.ll Cooper et al reported that there was no increase in clinical effects observed when the dose was increased from 50 Ag twice daily to three times a day.l2 Similarly, Nightingale et al found that there was no additional benefit when the dose of octreotide was increased from 50 Ag twice daily to 100 Ag thrice daily. 14
syndrome
ADVERSE EFFECTS
Cooper et al noted that fat excretion was increased with the administration of octreotide. 12 This effect on
Downloaded from ncp.sagepub.com at The University of Iowa Libraries on June 4, 2015
Table 1. Octreotide
use
for the short bowel
syndrome*
*
Oct, octreotide; IV, intravenous; TPN, total parenteral nutrition; BID, twice daily; TID, thrice daily; SQ, subcutaneous; IM, intramuscular; Q12H, every 12 hours; GI, gastrointestinal. 83 Downloaded from ncp.sagepub.com at The University of Iowa Libraries on June 4, 2015
84 Table 1-cont.
fecal fat may offset the beneficial effects of octreotide in managing the short gut syndrome in some patients. In the study by Cooper et al, the two patients who were successfully controlled with octreotide had the least fat malabsorption.12 One study reported a patient who developed an intestinal obstruction during therapy that may have been contributed to by the octreotide.ll Complaints of pain associated with the subcutaneous injection prompted Gilsdorf et al to promote the coadministration of octreotide in parenteral nutrient admixtures; however, the stability and compatibility of the coadmixture have not been demon-
strated.19 POTENTIAL CONCERNS
regarding the use of octreotide in patients with the short gut syndrome is the formation of gallstones. Gallstones have developed in patients on long-term octreotide. 20,21 Cholelithiasis has been reported to occur in as many as one third of patients with the short gut syndrome and may be further promoted by long-term parenteral nutrition.22 The question of whether the addition of octreotide therapy in this patient population further increases the risk of gallstone formation has not been answered. Another concern in using octreotide after massive gut resections is the effect on intestinal adaptation. Endogenous secretions of gut peptides, such as enteroglucagon, secretin, cholecystokinin, and gastrin, appear to be important stimuli for adaptation.23 Ohlbaum et al performed an ileal biopsy in their pediatric patient during octreotide administration and observed slightly atrophied intestinal villi despite the adminisOne
concern
tration of enteral
feedings.15
and
a
rebound effect
REFERENCES 1. Grosman I, Simon D. Potential gastrointestinal uses of somatostatin and its synthetic analogue octreotide. Am J Gastroenterol 1990;85:1061-72. 2. O’Donnell LJ, Farthing MJ. Therapeutic potential of a long acting somatostatin analogue in gastrointestinal diseases. Gut
1989;30:1165-72. 3. Katz MD, Erstad BL. Octreotide, a new somatostatin analogue. Clin Pharm 1989;8:255-73. 4. Krejs GJ, Browne R, Raskin P. Effect of intravenous somatostatin on jejunal absorption of glucose, amino acids, water and
6.
The use of somatostatin to manage diarrhea associated with the short gut syndrome is impractical because of its need to be given by continuous infusion
stool output with cessation of
adverse effects noted when octreotide is used for control of the short gut syndrome include pain associated with subcutaneous injection and abdominal complaints. Potential concerns include the effect on gallstone formation in this high-risk population and intestinal adaptation.
electrolytes. Gastroenterology 1980;78:346-9. MI, Bai JC, Santangelo WC, et al. Effect of somatostatin analog on water and electrolyte transport and transit time in human small bowel. Dig Dis Sci 1987;32:1092-6. Rosenberg JM. Octreotide: A synthetic analog of somatostatin. Drug Intell Clin Pharm 1988;22:748-54. Murphy JP, King DR, Dubois A. Treatment of gastric hypersecretion with cimetidine in the short-bowel syndrome. N Engl J
5. Dueon
CONCLUSION
on
therapy. Octreotide has been used more successfully to control stool and electrolyte losses in patients with shortened gastrointestinal tracts. In published series and studies, all subjects appear to have decreased stool losses, but clinical benefit for long-term use is not achieved for all patients. In the patients who do respond, the need for parenteral nutrition and intravenous hydration has been decreased or eliminated. The optimal dose is unclear, but many patients respond to 50-j.tg injections twice daily. Several investigations noted no additional beneficial effects with escalating dosages. Adverse effects include impairment of fat absorption, which may offset the therapeutic benefits of octreotide. The patients with the greatest response appear to have the least fat malabsorption. Other
7.
Med 1979;300:80-1.
Downloaded from ncp.sagepub.com at The University of Iowa Libraries on June 4, 2015
85 8. Weser E. Nutritional aspects of
malabsorption.
Am J Med
1979;67:1014-20. 9.
Jeejeebhoy KN. Therapy
of the
short-gut syndrome. Lancet
1983;1:1427-9. Gorelick FS, Sherwin RS, et al. Somatostatin decreases diarrhea in patients with the short-bowel syndrome. J Clin Gastroenterol 1982;4:521-4. 11. Ladefoged K, Christensen KC, Hegnhoj J, et al. Effect of a long acting somatostatin analogue SMS 201-995 on jejunostomy effluents in patients with severe short bowel syndrome. Gut 10.
Dharmsathaphorn K,
12.
Cooper JC, Williams NS, King RF, et al. Effects of a longacting somatostatin analogue in patients with severe ileostomy diarrhoea. Br J Surg 1986;73:128-31. Rodrigues CA, Lennard-Jones JE, Thompson DG, et al. The effects of octreotide, soy polysaccharide, codeine and loperamide on nutrient, fluid and electrolyte absorption in the shortbowel syndrome. Aliment Pharmacol Ther 1989;3:159-69. Nightingale JM, Walker ER, Burnham WR, et al. Does a somatostatin analogue (Octreotide) reduce the need for parenteral fluids in patients with a short bowel? Gut 1988;29:A1434-
1989;30:943-9.
13.
14.
5. 15. Ohlbaum P, Galperine RI, Demarquez JL, et al. Use of a longacting somatostatin analogue (SMS 201-995) in controlling a significant ileal output in a 5-year-old child. J Pediatr Gastroen-
terol Nutr 1987;6:466-70. 16. Shaffer JI, O’Hankahan I, Kowniken S, et al. Does somatostatin analogue (SMS 201-995) reduce high output stoma effluent? A controlled trial. Gut 1988;29:A1432-3. 17. Williams NS, Cooper JC, King RF, et al. Use of a long acting somatostatin analogue in controlling life threatening ileostomy diarrhoea. Br Med J 1984;20:1025-8. 18. Rosenberg L, Brown RA. Sandostatin in the management of nonendocrine gastrointestinal and pancreatic disorders: a preliminary study. Can J Surg 1991;34:223-9. 19. Gilsdorf RB, Gilles P, Gigliotti LM. Somatostatin effect on gastrointestinal losses in patients with short bowel syndrome. A.S.P.E.N. 13th Clinical Congress Abstracts. 1989:478. 20. Buscail L, Tauber JP, Escourrou J, et al. Gallstone formation and occurrence of cholesterol monohydrate crystals in gallbladder bile of patients with longterm sandostatin treatment. Gas21.
22.
troenterology 1989;96:A580. Plockinger U, Dienemann D, Quabe HJK. Gastrointestinal side-effects of octreotide during long term treatment of acromegaly. J Clin Endocrinol Metab 1990;71:1658-62. Roslyn JJ, Pitt HA, Mann LL, et al. Gallbladder disease in patients on long-term parenteral nutrition. Gastroenterology 1983;84:148-54.
23. Bristol JB, Williamson RC, Chir M. Nutrition, intestinal adaptation. JPEN 1988;12:299-309.
Downloaded from ncp.sagepub.com at The University of Iowa Libraries on June 4, 2015
operations, and
Syndrome GAIL H. ROSEN, PHARMD Support Services, Department of Pharmacy Services, University of Maryland Medical System, University of
Nutrition
Maryland School of Pharmacy, and University of Maryland School of Medicine, Baltimore
in patients with metastatic carcinoid and vasoactive intestinal peptide-secreting tumors. This article will discuss the physiological effects of somatostatin and octreotide and will summarize the published clinical experience with the management of the short gut syndrome with octreotide.
ABSTRACT: The use of somatostatin to manage diarrhea associated with the short gut syndrome is impractical because of its need to be given by continuous infusion and a rebound effect on stool output with cessation of therapy. Octreotide has been used more successfully to control stool and electrolyte losses in patients with shortened gastrointestinal tracts. In published series and studies, all subjects appear to decrease stool losses, but clinical benefit for longterm use is not achieved for all patients. In the patients who do respond, the need for parenteral nutrition and intravenous hydration has been decreased or eliminated. The optimal dose is unclear, but many patients respond to 50-μg injections twice daily. Several investigations noted no additional beneficial effects with escalating dosages. Adverse effects include impairment of fat absorption, which may offset the therapeutic benefits of octreotide. The patients with the greatest response appear to have the least fat malabsorption. Other adverse effects noted when using octreotide for control of the short gut syndrome include pain associated with subcutaneous injection and abdominal complaints. Other potential concerns include the effect on gallstone formation in this high-risk population and intestinal
PHYSIOLOGICAL EFFECTS OF SOMATOSTATIN
Somatostatin is widely distributed anatomically and has a multiplicity of physiological effects. The highest concentration of somatostatin is found in the pancreas and gastrointestinal tract.2 Administration of somatostatin suppresses the secretion of numerous gastrointestinal hormones including gastrin, enteroglu-
gastric inhibitory peptide, motilin, secretin, peptide, glucagon, insulin, and pancreatic polypeptide. In normal subjects, the administration of somatostatin prolongs intestinal transit time. Somatostatin decreases gastrointestinal blood flow and absorption of macronutrients, including fat cagon,
vasoactive intestinal
adaptation.
and
carbohydrate.’
In studies of normal human subsomatostatin did not affect small bowel net water or electrolyte transport.4 In treating the diarrhea associated with the carcinoid syndrome or vipomas, somatostatin enhances water and sodium chloride absorption, presumably because of the inhibitory effect of somatostatin on secretagogue release.5
jects, Somatostatin and its synthetic analog, octreotide, have many potential uses in gastrointestinal diseased1 Somatostatin is unavailable commercially in the United States, but octreotide has been recently approved by the Food and Drug Administration. Octreotide’s labeled indications are for control of symptoms
DEVELOPMENT AND EFFECTS OF OCTREOTIDE
Somatostatin has a very short half-life of 2 to 3 minutes and therefore must be administered by continuous intravenous infusion. Also, presumably because of the short half-life, the cessation of the administration of somatostatin has been associated with rebound hypersecretion of growth hormone and other substances.’ Octreotide was developed by manipulating the somatostatin molecule to impede its degrada-
Address for reprints: Gail H. Rosen, PharmD, Department of Pharmacy Services, University of Maryland Medical System, 22 S. Greene Street. Street, Baltimore. Baltimore, MD 21201
81
Downloaded from ncp.sagepub.com at The University of Iowa Libraries on June 4, 2015
82
tion and prolong its half-life. The elimination half-life of octreotide is 90 minutes, allowing intermittent administration every 8 or 12 hours.6 Octreotide has similar pharmacological effects as somatostatin while being a more potent and longer-acting inhibitor of several hormones, including growth hormone, glucagon, and
insulin.’
MECHANISMS OF DIARRHEA IN THE SHORT GUT SYNDROME
Several mechanisms have been proposed to cause the diarrhea associated with the short gut syndrome. An increase in gut hormones, especially gastrin, has been observed.’ The physical loss of intestinal surface area may decrease the absorption of nutrients. The presence of malabsorbed nutrients may produce an osmotic stimulus and promote diarrhea. Increased transit times through the shortened gut may be responsible for part of the large fecal outputs. A disturbance in intestinal transport may be in part a result of a secretory process because patients with a short gut syndrome persistently have large volumes of stool output in the fasting state. Finally, the underlying disease itself, such as Crohn’s disease or radiation enteropathy, may impair the gut’s ability to function.’ Pharmacological manipulation of the short gut syndrome with histamine receptor antagonists, loperamide and other antidiarrheal agents, cholestyramine, and nutrition support with enteral products has sustained many patients with the short gut syndrome without the use of supplemental intravenous fluids, intravenous electrolytes, or parenteral nutrition.9 Some patients, despite traditional management, continue to require intravenous support for the maintenance of nutritional, electrolyte, and fluid status. Both somatostatin and octreotide have been used to manage these patients. SOMATOSTATIN AND THE SHORT GUT SYNDROME
One
of the use of somatostatin to manage stool outputs of four patients with short bowel syndromes as a result of multiple surgical resections for Crohn’s disease.1o Somatostatin infusions of 4 Agl min for 24 hours decreased stool weight in all four patients without affecting fecal fat output. When the infusion was discontinued, however, the patients experienced a rebound increase in stools of greater weights than baseline. The need to infuse this agent continuously limits its utility.
study reports
OCTREOTIDE AND THE SHORT GUT SYNDROME
Table 1 outlines the case reports and studies with octreotide to control the short gut syndrome. The mechanism of action of octreotide in this setting is unclear. Ladefoged et al expressed that the increases
in net absorption of sodium and water were due to a reduction in the secretion of digestive juices.&dquo; Cooper et al noted a reduction in salt and water excretion as well as a slowing of gastrointestinal transit time.12 Although no effect on gastric emptying was noted, mouth-to-stoma transit time and small bowel transit times were significantly lengthened. Cooper et al postulated that the effect on transit time was a secondary effect due to octreotide’s effect on fluid transport. Octreotide administration resulted in greater increases in transit time when compared with administration of oral or intramuscular codeine, loperamide, and soy polysaccharide in four patients.&dquo; PRACTICAL ROLE OF OCTREOTIDE
Although most of the results of investigations with octreotide to manage the short gut syndrome report a decrease in stool output, the effects have not been sufficient in all patients to eliminate the need for parenteral nutrition or intravenous hydration therapy. In the study of Ladefoged et al, four patients continued to administer octreotide long term.ll All patients needed to continue intravenous saline but were able to decrease the volume to 1 L/d. In the series of Cooper et al, two of the five patients continued octreotide long term. Both of these patients were able to discontinue intravenous hydration therapy.&dquo; Nightingale et al reported decreased fecal outputs in all patients studied, but only one patient chose to continue treatment at home.14 A case report of a 5-year-old child with a short bowel describes good long-term tolerance with the administration of octreotide, allowing a total transition from parenteral to enteral nutrition.l5 Two of six patients administered octreotide at home for more than 2 years in the randomized, crossover trial of Shaffer et a1.16 Table 1 summarizes the response to octreotide and long-term use in the case report by Williams et al17 and the series by Rosenberg and Brown&dquo; and Gilsdorf et al.19 DOSAGE OF OCTREOTIDE
The optimal dose of octreotide in the short gut is not established, but many studies report a lack of additional desired effects with escalating the dose. Ladefoged et al showed equivalent effects with a 600-j.tg/d dose by continuous infusion as compared with 50 Ag twice a day by subcutaneous injection.ll Cooper et al reported that there was no increase in clinical effects observed when the dose was increased from 50 Ag twice daily to three times a day.l2 Similarly, Nightingale et al found that there was no additional benefit when the dose of octreotide was increased from 50 Ag twice daily to 100 Ag thrice daily. 14
syndrome
ADVERSE EFFECTS
Cooper et al noted that fat excretion was increased with the administration of octreotide. 12 This effect on
Downloaded from ncp.sagepub.com at The University of Iowa Libraries on June 4, 2015
Table 1. Octreotide
use
for the short bowel
syndrome*
*
Oct, octreotide; IV, intravenous; TPN, total parenteral nutrition; BID, twice daily; TID, thrice daily; SQ, subcutaneous; IM, intramuscular; Q12H, every 12 hours; GI, gastrointestinal. 83 Downloaded from ncp.sagepub.com at The University of Iowa Libraries on June 4, 2015
84 Table 1-cont.
fecal fat may offset the beneficial effects of octreotide in managing the short gut syndrome in some patients. In the study by Cooper et al, the two patients who were successfully controlled with octreotide had the least fat malabsorption.12 One study reported a patient who developed an intestinal obstruction during therapy that may have been contributed to by the octreotide.ll Complaints of pain associated with the subcutaneous injection prompted Gilsdorf et al to promote the coadministration of octreotide in parenteral nutrient admixtures; however, the stability and compatibility of the coadmixture have not been demon-
strated.19 POTENTIAL CONCERNS
regarding the use of octreotide in patients with the short gut syndrome is the formation of gallstones. Gallstones have developed in patients on long-term octreotide. 20,21 Cholelithiasis has been reported to occur in as many as one third of patients with the short gut syndrome and may be further promoted by long-term parenteral nutrition.22 The question of whether the addition of octreotide therapy in this patient population further increases the risk of gallstone formation has not been answered. Another concern in using octreotide after massive gut resections is the effect on intestinal adaptation. Endogenous secretions of gut peptides, such as enteroglucagon, secretin, cholecystokinin, and gastrin, appear to be important stimuli for adaptation.23 Ohlbaum et al performed an ileal biopsy in their pediatric patient during octreotide administration and observed slightly atrophied intestinal villi despite the adminisOne
concern
tration of enteral
feedings.15
and
a
rebound effect
REFERENCES 1. Grosman I, Simon D. Potential gastrointestinal uses of somatostatin and its synthetic analogue octreotide. Am J Gastroenterol 1990;85:1061-72. 2. O’Donnell LJ, Farthing MJ. Therapeutic potential of a long acting somatostatin analogue in gastrointestinal diseases. Gut
1989;30:1165-72. 3. Katz MD, Erstad BL. Octreotide, a new somatostatin analogue. Clin Pharm 1989;8:255-73. 4. Krejs GJ, Browne R, Raskin P. Effect of intravenous somatostatin on jejunal absorption of glucose, amino acids, water and
6.
The use of somatostatin to manage diarrhea associated with the short gut syndrome is impractical because of its need to be given by continuous infusion
stool output with cessation of
adverse effects noted when octreotide is used for control of the short gut syndrome include pain associated with subcutaneous injection and abdominal complaints. Potential concerns include the effect on gallstone formation in this high-risk population and intestinal adaptation.
electrolytes. Gastroenterology 1980;78:346-9. MI, Bai JC, Santangelo WC, et al. Effect of somatostatin analog on water and electrolyte transport and transit time in human small bowel. Dig Dis Sci 1987;32:1092-6. Rosenberg JM. Octreotide: A synthetic analog of somatostatin. Drug Intell Clin Pharm 1988;22:748-54. Murphy JP, King DR, Dubois A. Treatment of gastric hypersecretion with cimetidine in the short-bowel syndrome. N Engl J
5. Dueon
CONCLUSION
on
therapy. Octreotide has been used more successfully to control stool and electrolyte losses in patients with shortened gastrointestinal tracts. In published series and studies, all subjects appear to have decreased stool losses, but clinical benefit for long-term use is not achieved for all patients. In the patients who do respond, the need for parenteral nutrition and intravenous hydration has been decreased or eliminated. The optimal dose is unclear, but many patients respond to 50-j.tg injections twice daily. Several investigations noted no additional beneficial effects with escalating dosages. Adverse effects include impairment of fat absorption, which may offset the therapeutic benefits of octreotide. The patients with the greatest response appear to have the least fat malabsorption. Other
7.
Med 1979;300:80-1.
Downloaded from ncp.sagepub.com at The University of Iowa Libraries on June 4, 2015
85 8. Weser E. Nutritional aspects of
malabsorption.
Am J Med
1979;67:1014-20. 9.
Jeejeebhoy KN. Therapy
of the
short-gut syndrome. Lancet
1983;1:1427-9. Gorelick FS, Sherwin RS, et al. Somatostatin decreases diarrhea in patients with the short-bowel syndrome. J Clin Gastroenterol 1982;4:521-4. 11. Ladefoged K, Christensen KC, Hegnhoj J, et al. Effect of a long acting somatostatin analogue SMS 201-995 on jejunostomy effluents in patients with severe short bowel syndrome. Gut 10.
Dharmsathaphorn K,
12.
Cooper JC, Williams NS, King RF, et al. Effects of a longacting somatostatin analogue in patients with severe ileostomy diarrhoea. Br J Surg 1986;73:128-31. Rodrigues CA, Lennard-Jones JE, Thompson DG, et al. The effects of octreotide, soy polysaccharide, codeine and loperamide on nutrient, fluid and electrolyte absorption in the shortbowel syndrome. Aliment Pharmacol Ther 1989;3:159-69. Nightingale JM, Walker ER, Burnham WR, et al. Does a somatostatin analogue (Octreotide) reduce the need for parenteral fluids in patients with a short bowel? Gut 1988;29:A1434-
1989;30:943-9.
13.
14.
5. 15. Ohlbaum P, Galperine RI, Demarquez JL, et al. Use of a longacting somatostatin analogue (SMS 201-995) in controlling a significant ileal output in a 5-year-old child. J Pediatr Gastroen-
terol Nutr 1987;6:466-70. 16. Shaffer JI, O’Hankahan I, Kowniken S, et al. Does somatostatin analogue (SMS 201-995) reduce high output stoma effluent? A controlled trial. Gut 1988;29:A1432-3. 17. Williams NS, Cooper JC, King RF, et al. Use of a long acting somatostatin analogue in controlling life threatening ileostomy diarrhoea. Br Med J 1984;20:1025-8. 18. Rosenberg L, Brown RA. Sandostatin in the management of nonendocrine gastrointestinal and pancreatic disorders: a preliminary study. Can J Surg 1991;34:223-9. 19. Gilsdorf RB, Gilles P, Gigliotti LM. Somatostatin effect on gastrointestinal losses in patients with short bowel syndrome. A.S.P.E.N. 13th Clinical Congress Abstracts. 1989:478. 20. Buscail L, Tauber JP, Escourrou J, et al. Gallstone formation and occurrence of cholesterol monohydrate crystals in gallbladder bile of patients with longterm sandostatin treatment. Gas21.
22.
troenterology 1989;96:A580. Plockinger U, Dienemann D, Quabe HJK. Gastrointestinal side-effects of octreotide during long term treatment of acromegaly. J Clin Endocrinol Metab 1990;71:1658-62. Roslyn JJ, Pitt HA, Mann LL, et al. Gallbladder disease in patients on long-term parenteral nutrition. Gastroenterology 1983;84:148-54.
23. Bristol JB, Williamson RC, Chir M. Nutrition, intestinal adaptation. JPEN 1988;12:299-309.
Downloaded from ncp.sagepub.com at The University of Iowa Libraries on June 4, 2015
operations, and
