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Therapeutic value of octreotide for patients with severe dumping syndrome—a review of randomised controlled trials
  1. J Li-Ling,
  2. M Irving
  1. Department of Surgery, Medical School, University of Newcastle upon Tyne, UK
  1. Professor Sir Miles Irving, Freeman Hospital, High Heaton, Newcastle upon Tyne NE7 7DN, UKm.h.irving{at}ncl.ac.uk

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Approximately 10%–50% of patients develop some manifestations of the dumping syndrome after gastric surgery. Among them, 5%–10% have clinically significant symptoms, and 1%–2% are debilitated by them.1 Early dumping, typically starting 10–30 minutes after a meal, usually involves both vasomotor and gastrointestinal complaints such as sweating, palpitation, weakness and faintness, abdominal bloating, cramping, and profound diarrhoea. Late dumping, often occurring 2–3 hours postprandially, involves mainly vascular complaints characterised by perspiration, palpitation, mental confusion, and sometimes syncope. It is estimated that, among all affected patients, 75% have early dumping symptoms. The symptoms of early dumping probably result from rapid emptying of hyperosmolar chyme into the small bowel leading to a large fluid shift from the intravascular space into the intestinal lumen, with consequent rapid small bowel distension and an increase in both the amplitude and frequency of bowel contractions. Late dumping is a consequence of reactive hypoglycaemia resulting from an exaggerated insulin and glucagon-like peptide-1 release.2 The diagnosis of late dumping syndrome can be often confirmed through frequent blood sampling after a provocation test using 75 g of orally administrated glucose.

The management of the dumping syndrome can be achieved in most cases by dietary modification and adjustment of lifestyle, in particular reduction of carbohydrate intake. However, in approximately 3%–5% of patients, severe symptoms of dumping can continue despite dietary changes. This results in marked weight loss, fear of eating and outdoor activities, or even an inability to maintain full time employment. For the past decade it has been suggested that octreotide (Sandostatin SMS 210–995; Novartis Pharmaceuticals, East Hanover, NJ, USA), an analogue of somatostatin, can alleviate dumping by slowing gastric emptying, inhibiting insulin release, decreasing enteric peptide secretion, increasing intestinal absorption of water and sodium, slowing monosaccharide absorption, increasing gut transit time, and preventing haemodynamic changes. In particular, octreotide has been demonstrated to be effective in patients refractory to standard therapy.3 4

Method

We have performed a systematic search for published randomised controlled trials on the effectiveness of octreotide in alleviating the symptoms of the dumping syndrome. Electronic databases (till end of March 2000) including Medline, EMBASE, and PubMed were searched using keywords including “randomis(z)ed trial”, “dumping syndrome”, and “octreotide”. In addition, citations of relevant primary and review articles were examined.

Result

Seven randomised controlled trials (excluding one probably duplicated4) were identified.5-11 The seven trials recruited a total of 63 patients with severe symptoms of dumping. Octreotide (50 or 100 μg) was given 15–60 minutes before either a meal or a provocative dose of oral glucose (75–100 g). The following evidence of the effectiveness of octreotide for ameliorating dumping symptoms after the provocative glucose challenge were extracted from the seven trials and are summarised in table 1.

Table 1

Randomised controlled trials on the effectiveness of octreotide for alleviating dumping syndrome after gastric/pancreatoduodenal surgery

(1) Alleviating diarrhoea, abdominal pain, dizziness, and palpitation.

(2) Minimising changes in orthostatic pulse and blood pressure.

(3) Minimising influence on packed cell volume and plasma osmolarity.

(4) Preventing late hypoglycaemia by reducing peak insulin concentration and prolonging maximal plasma glucose concentration.

Compared with the control cases, octreotide pretreatment resulted in significant improvement in symptoms in nearly all patients. Decreased gain in pulse rates and stabilised blood pressure were particularly recorded in four trials.5 6 10 11 Six trials described prevention of hypoglycaemia/rise of plasma insulin concentrations.5 6 8-11 One trial specifically recorded the induction of fasting migrating myoelectric complexes motility pattern (characteristic of interdigestive motility) and reduction in the duration and vigour of fed motility obtained with octreotide.7 However, the beneficial effect of octreotide on packed cell volume appeared uncertain.5 6 9-11Furthermore, while two trials reported reduction of diarrhoea,5 8 three described development or worsening of this symptom.6 8 9

Discussion

A recent editorial in the British Journal of Surgery stressed the importance of systematic reviews in assessing the effectiveness of treatment.12 Systematic review aims to provide an unbiased summary of the evidence base to inform a clinical or policy question, to identify gaps in the research, and to improve the quality of new research. In the practice of “evidence based medicine”, systematic reviewing plays a crucial part by providing the key information.

Our identified studies, admittedly involving relatively small numbers of patients, have unanimously shown short term benefit as well as promising long term results, confirming octreotide as an effective treatment for dumping syndrome. Side effects of octreotide such as steatorrhoea or early morning diarrhoea associated with long term treatment were managed with pancreatic enzyme replacement or an extra dose of octreotide before bedtime.6 8 Notably, gallstone formation, as one of the most frequent side effects of octreotide therapy, was not observed among the identified trials. Based on their results, Geer et al suggested that, instead of gastrin or motilin, peptides such as pancreatic polypeptide, neurotensin, and glucagon may play a part in the development of dumping symptoms.8 Administration of octreotide 30 minutes before, or immediately after, a meal offers a practical and effective approach to the treatment of early and late dumping syndromes. We recommend that octreotide should be given for patients with severe or refractory dumping syndromes.

Acknowledgments

This review is supported by a grant to MI from the Leverhulme Trust.

References

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