1064 Gut 1994; 35: 1064-1069 Effect of octreotide on gastrointestinal pressure profiles in health and in functional and organic gastrointestinal disorders Gut: first published as 10.1136/gut.35.8.1064 on 1 August 1994. Downloaded from K Haruma, J A Wiste, M Camilleri Abstract study of the clinical efficacy of a long acting The somatostatin analogue, octreotide, somatostatin analogue, octreotide, in patients restores normal pressure profiles in dis- with progressive systemic sclerosis. Octreotide orders of upper gut motility. This study stimulated MMC-like activity (which will be aimed to evaluate the acute effects of referred to as an 'activity front' throughout this octreotide in five healthy subjects and in manuscript) in the small bowel, improved 50 consecutive patients with functional some symptoms, and reduced breath hydrogen (n=22) or organic (n=28) dysmotility. excretion after an oral glucose load, suggesting Antroduodenojejunal manometry was an effect on small bowel bacterial overgrowth.8 performed during three hours' fasting, It is not clear which subsets of patients with for two hours after a standard meal, and progressive systemic sclerosis respond to this 30 minutes after subcutaneous injection of medication, but these new and interesting 50 ,ug octreotide. Antral motility, before observations suggested that octreotide might and after octreotide, and characteristics restore normal motility in patients with upper of spontaneous migrating motor com- gastrointestinal motility disorders. plexes and octreotide induced activity To further address this hypothesis and to fronts were compared. Octreotide inhib- identify which subgroups of patients might ited antral motility and induced a small respond to octreotide treatment, we evaluated intestinal activity front followed by motor a consecutive series of 50 patients with quiescence in all healthy subjects and suspected upper gastrointestinal dysmotility patients. The duration and propagation referred to a single clinical motility laboratory. velocity of activity fronts were greater Our primary aims were to evaluate the effects than those of spontaneous migrating of octreotide on postprandial antral motility motor complexes. Thirty per cent of and to characterise the duration, amplitude, http://gut.bmj.com/ activity fronts began simultaneously at frequency of contractions, and propagation of different levels ofsmall bowel, and in 20%/ the activity front in these patients and in five a second, normally propagated activity healthy volunteers. Our secondary aim was to front developed within 30 minutes of determine from this pilot study whether any octreotide injection. Octreotide induces specific disease subgroups showed responses rapidly propagated, long activity fronts, that could provide the rationale for further even in patients with neuropathology, testing in future studies. on October 1, 2021 by guest. Protected copyright. and this may initially facilitate the intestinal propulsion of chyme. Propulsion may not occur, however, if Methods octreotide induces simultaneous activity fronts or ifthe activity front is followed by PATIENTS AND HEALTHY CONTROLS prolonged quiescence. Inhibition ofantral We studied 50 consecutive patients who were motility suggests that octreotide may not referred for a standard upper gastrointestinal be effective in gastroparesis. motility study and consented to participate. (Gut 1994; 35: 1064-1069) Patients were 15 to 67 years of age (mean: 37-7 years) and there were 37 women and 13 men. All women of childbearing potential had a neg- Upper gastrointestinal manometry is an ative plasma (,B-HCG) pregnancy test within established method for the identification of 24 hours of the motility study. Five healthy stomach and upper small bowel motility volunteers (age range: 30-44 years; mean age: Gastroenterology Research Unit, Mayo disorders.' Studies of pressure profiles in 34-6 years) were recruited by public advertise- Clinic and Mayo these regions correlate well with two broad ment. The research protocol was approved by Foundation, categories of motility disorders - neuropathies the Mayo Institutional Review Board. Rochester, MN 55905, USA and myopathies.2 Pharmacological studies K Haruma showing changes in these profiles in health and J A Wiste restoration of normal pressure profiles are UPPER GASTROINTESTINAL MANOMETRY M Camilleri usually a prerequisite for developing new This was performed using a multilumen (n=8 Correspondence to: treatments for these motility disorders. Thus, or 12) assembly with five or six ports placed Dr M Camilleri, Gastroenterology Research several studies have shown that exogenous fluoroscopically across the antroduodenal Unit, Mayo Clinic, 200 First somatostatin induces a migrating motor junction and three or six ports in the duode- Street SW, Rochester, MN 55905, USA. complex (MMC)-like activity front in num and jejunum. The method has been Accepted for publication experimental animals and in healthy human described fully elsewhere.9 Patients stopped 16 November 1993 volunteers.3-7 These observations led to a short taking any medication that might influence $ oni:vr Pt mo ty0 1065 the three-hour fasting period, we characterised the first complex. The velocity of propagation was considered fast when the MMC or activity front propagated through the duodenum and Gut: first published as 10.1136/gut.35.8.1064 on 1 August 1994. Downloaded from dd jejunum at a rate faster than 11 cm per minute, which is at the 95th centile for propagation velocities in healthy subjects.10 :N . YM-F' L ' The same parameters were documented for wi ;. ti,i ., <t & O^|.|..gs e. _ g ;.,* the activity fronts induced by octreotide. The , ., ,. - ;, ' i_'-3;; onset of activity fronts at different levels of 4 ..; <,l / ',;t 5 te1m} small intestine was indicated by the time point when that a .:L Sr.ve i= contractile 30 particular level showed : frequency of 10 per min or greater. When the onset of activity fronts at the three or six -I F tR .; S s } a recording sites in the small bowel were within sd l t f t;] ,. ; ;.L,. E Si 10 seconds of the first site they were deemed * | | .;.> 4 * r '1 i-. sit t 3t f 3wt5'911 to be simultaneous. All other fronts were characterised as retrograde or antegrade Figure 1: Experimental design relative to the site of onset of the octreotide induced activity front. Ten of the 50 patients gastrointestinal motility at least 48 hours showed two octreotide induced activity fronts. +.l 1 -.L i w - _ itsi Sbefore the study. Pressure profiles were The characteristics of these second fronts were recorded for three hours during fasting and for similarly analysed. two hours after a standardised meal. At the end of the latter period, all subjects were given a subcutaneous injection of 50 ,ug octreotide STATISTICAL ANALYSIS (Sandostatin, Sandoz Pharmaceutical Corp, Student's t test (two-tailed test) was used to East Hanover, NJ, USA), and the pressure compare spontaneous MMCs with octreotide profile was monitored over the next 30 minutes induced activity fronts in healthy subjects (Fig 1). A preliminary study in three separate and distal antral motility indices before and patients had shown that 100 ,ug octreotide after octreotide treatment in healthy controls invariably induced nausea, and that vomiting and patients. Parameters characterising occurred within five minutes of the injection in MMCs and first and second octreotide two patients. We had also observed that within induced activity fronts in the entire group of five minutes of the subcutaneous injection, a patients were compared by analysis of phase III-like activity front was induced in each variance, followed by Scheffe's F multigroup http://gut.bmj.com/ patient. In view of these preliminary findings, comparison test.11 Data were expressed as we elected to use a subcutaneous 50 jig dose in mean (SEM). the subsequent 50 patients. The previous data of Soudah et al8 also suggested that patients with progressive systemic sclerosis were about Results 10 times less sensitive to the effects of octreotide than healthy subjects, who typically QUALITATIVE EFFECTS OF OCTREOTIDE IN on October 1, 2021 by guest. Protected copyright. required 10 jig of subcutaneous octreotide to HEALTHY SUBJECTS induce phase III-like activity fronts. Manometry showed normal motility in all healthy subjects: all had one or more spontaneous MMC during the three hour ANALYSIS OF MANOMETRIC PROFILES fasting period. The onset of the spontaneous We quantitated the distal antral motility index MMCs was in the antrum in two subjects and for 30 minutes before and after the octreotide in the duodenum in three. Octreotide (50 ,ug) injection using the following formula9: induced activity fronts within five minutes (mean: 2-8 minutes; range: 1-0-4 1 minutes) Motility index=log, (E amplitudesxno of contractions+ 1) in all subjects. The activity front originated in the duodenum in all subjects. One volunteer Phase III of the fasting MMC was charac- had two activity fronts during the 30 minute terised in detail with measurement of mean period after octreotide. amplitude, frequency of contractions, site of of and duration onset, velocity propagation, TABLE I Characteristics ofspontaneous migrating motor of the complex at the level of the distal duo- complexes (MMC) and octreotide induced activityfronts in denum, or in the proximal jejunum for those five healthy volunteers (mean (SEM)) MMCs with onset beyond the angle of Treitz. Octreotide In patients with previous Roux-Y gastrectomy, Spontaneous induced characteristics of the MMC were measured MMC activity front in the Roux limb 10 cm beyond the gastro- Duration (min) 4-9 (1 5) 11-8 (2 7)t jejunostomy. The antral component of the Frequency of contractions (no/min) 11-6 (0 3) 11-4 (0 3) phase III complex was identified by the Mean amplitude of contractions occurrence of at least five distal antral contrac- (mm Hg) 29-1 (2-0) 24-1 (4-1) tions, followed by prolonged quiescence, Propagation velocity (cm/min) 7-6 (2 0) 22-4 (6 1)*t indicative of phase I activity, In each subject *p<0-05; tp = 0-05. tData on propagation excluded from with more than one spontaneous MMC during analysis in one patient who had simultaneous activity front.