Role of somatostatin-14 and its analogues in the management of gastrointestinal fistulae: clinical data

Abstract

Somatostatin-14 and its analogue octreotide both exert inhibitory effects on gastrointestinal secretions and may therefore be beneficial in the treatment of gastrointestinal fistulae. There are no studies that have compared these two drugs directly and hence this paper aims to review studies that are available for each drug. There are only six controlled studies that have examined the effects of somatostatin-14 and octreotide on fistula output reduction, three for each drug. All studies compared conservative therapy and the drug in combination with conservative therapy. Of the somatostatin-14 studies, two showed a significant effect on output (p<0.05) and the other demonstrated an output reduction on day 1 that was twice that in the control group (NS). Of the octreotide studies, one showed a significant effect (p<0.01) and the other two showed no effect of the drug on output. No study with either drug has demonstrated an increase in the number of patients that have achieved closure. However, a positive effect on the time to achieve closure has been found. Of the five controlled studies with somatostatin-14, all showed a significant reduction in time to closure. Of the two controlled studies with octreotide, one showed a significant reduction (p=0.002) and the other showed no difference. Due to the limited number of trials, a definitive evaluation of the efficacies of somatostatin-14 and octreotide in the treatment of gastrointestinal fistulae is not possible. However, currently available information seems to suggest a considerable benefit of somatostatin-14 when administered in association with standard conservative treatment, but this needs to be confirmed in a large prospective controlled study.

Figure 1 The goals of treatment for patients with gastrointestinal fistulae.

Figure 2 Volume and protein concentration of pancreatic secretions following octreotide (100 µg three times daily) administration.¹⁶ Reproduced with permission from Jenkins et al.¹⁶

Figure 3 Effect of octreotide on exocrine pancreatic secretions diminishes after several days.¹⁸ Basal, baseline pancreatic secretion, collection period 30 minutes; stimulated, pancreatic secretion during continuous infusion of secretin (1 U/kg body weight) and ceruletide (80 ng/kg body weight), collection period 60 minutes. *p<0.05 versus day 0.

Figure 4 Time to achieve fistula output reductions of 50%, 75%, and 100% in patients treated with total parenteral nutrition (TPN), alone or in combination with somatostatin-14.²³ Reproduced from Torres and colleagues.²³

Figure 5 Effect of octreotide on fistula output in a crossover study. Patients received either: placebo (broken line) then octreotide (solid line) or octreotide (solid line) then placebo (broken line). After four days all patients received octreotide (solid line) until closure of the fistula or operation.²⁷

Figure 6 Fistula output in patients administered either octreotide or placebo.²⁴

Figure 7 Effects of total parenteral nutrition (TPN) alone or in combination with glucagon, calcitonin, or somatostatin-14 on reduction in fistula output.¹²

Figure 8 Effects of somatostatin-14 and octreotide on first day fistula output. *p<0.05, ***p<0.001.

Figure 9 Effect of somatostatin-14 on the rate of fistula closure over 30 days of treatment, in patients receiving total parenteral nutrition (TPN).³⁷ p=0.0006. Source: Isenmann et al.³⁷

Figure 10 Effects of total parenteral nutrition (TPN) alone or in combination with glucagon, calcitonin, or somatostatin-14 on cicatrisation time.¹² p<0.001.

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Figure 11 Percentage and time of closure of fistulae treated with four different treatment schedules: somatostatin-14+total parenteral nutrition (TPN), calcitonin+TPN, glucagon+TPN, and TPN alone.¹² Reprinted with permission from J Am Coll Surg 1986;163:428–32.

Figure 12 Time to closure in the trial of Spiliotis and colleagues.³⁹