The hemodynamic effect of an intravenous antispasmodic on propofol requirements during colonoscopy: A randomized clinical trial.

PURPOSE: Hemodynamic status during induction of anesthesia may modify the amount of propofol needed to induce loss of consciousness (LOC). This study was aimed to evaluate the effect of antispasmodic-induced tachycardia on the concentration of propofol at the effect-site for inducing LOC when deep sedation was executed for colonoscopy. METHODS: One hundred and sixteen adult patients were randomly assigned to receive either 20 mg of the antispasmodic Buscopan intravenously (Buscopan group; n = 58) or normal saline (control group; n = 58) for colonoscopy. After administration of Buscopan, the antispasmodic or normal saline, propofol was given by means of target-controlled infusion to induce LOC. We recorded patient characteristics, hemodynamic profiles, effect-site propofol concentration upon LOC, total propofol dosage for colonoscopy, and colonoscopy outcomes. RESULTS: There were no significant differences in the characteristics between the two groups. Although the patients receiving Buscopan had a higher heart rate than those of the control group (101 ± 15 beats/minute vs. 77 ± 13 beats/minute; p < 0.001), we found no significant difference between two groups in the effect-site propofol concentration for inducing LOC (3.9 ± 0.6 µg/mL vs. 3.8 ± 0.6 µg/mL; p = 0.261) nor total propofol dosage required for colonoscopy (3.2 ± 1.4 mg/kg vs. 3.1 ± 1.1 mg/kg; p = 0.698). Both groups had comparable colonoscopy outcomes, including percentage of patients completing the procedure and total procedure time. CONCLUSION: The hemodynamic responses to intravenous Buscopan neither affected the effect-site propofol concentration needed to induce LOC, nor the total propofol dosage required for colonoscopy in this study. There is no need to modify the dosage of propofol in patients subject to Buscopan premedication in colonoscopy.

Peppermint oil solution is useful as an antispasmodic drug for esophagogastroduodenoscopy, especially for elderly patients.

BACKGROUND: Although hyoscine butyl bromide (HB) and glucagon (GL) are often used as antispasmodic drugs during esophagogastroduodenoscopy (EGD), these agents may cause adverse effects. Recently, it was reported that peppermint oil solution (PO) was very effective and had few side effects. AIM: We clarified the efficacy and usefulness of PO as an antispasmodic during upper endoscopy, especially for elderly patients. METHODS: This study was a non-randomized prospective study. The antispasmodic score (1-5, where 5 represents no spasm) was defined according to the degree of spasms of the antrum and difficulty of biopsy. We compared the antispasmodic scores between non-elderly patients (younger than 70) and elderly patients (70 years old or older) according to the antispasmodic agent. RESULTS: A total of 8,269 (Group PO: HB: GL: NO (no antispasmodic) = 1,893: 6,063: 157: 156) EGD procedures were performed. There was no significant difference in the antispasmodic score between Group PO (mean score ± standard deviation: 4.025 ± 0.925) and Group HB (4.063 ± 0.887). Among the non-elderly patients, those in Group PO (n = 599, 3.923 ± 0.935) had a worse antispasmodic score than those in Group HB (n = 4,583, 4.062 ± 0.876, P < 0.001). However, among the elderly patients, those in Group PO (n = 1,294, 4.073 ± 0.917) had similar scores to those in Group HB (n = 1,480, 4.064 ± 0.921, P = 0.83), and significantly better scores than those in Group GL (n = 69, 3.797 ± 0.933, P < 0.05). CONCLUSION: Peppermint oil was useful as an antispasmodic during EGD, especially for elderly patients.

Muscarinic receptor subtype-3 gene ablation and scopolamine butylbromide treatment attenuate small intestinal neoplasia in Apcmin/+ mice.

M3 subtype muscarinic receptors (CHRM3) are over-expressed in colon cancer. In this study, we used Apc(min/+) mice to identify the role of Chrm3 expression in a genetic model of intestinal neoplasia, explored the role of Chrm3 in intestinal mucosal development and determined the translational potential of inhibiting muscarinic receptor activation. We generated Chrm3-deficient Apc(min/+) mice and compared intestinal morphology and tumor number in 12-week-old Apc(min/+)Chrm3(-/-) and Apc(min/+)Chrm3(+/+) control mice. Compared with Apc(min/+)Chrm3(+/+) mice, Apc(min/+)Chrm3(-/-) mice showed a 70 and 81% reduction in tumor number and volume, respectively (P < 0.01). In adenomas, ß-catenin nuclear staining was reduced in Apc(min/+)Chrm3(-/-) compared with Apc(min/+)Chrm3(+/+) mice (P < 0.02). Whereas Apc gene mutation increased the number of crypt and Paneth cells and decreased villus goblet cells, these changes were absent in Apc(min/+)Chrm3(-/-) mice. To determine whether pharmacological inhibition of muscarinic receptor activation attenuates intestinal neoplasia, we treated 6-week-old Apc(min/+) mice with scopolamine butylbromide, a non-subtype-selective muscarinic receptor antagonist. After 8 weeks of continuous treatment, scopolamine butylbromide-treated mice showed a 22% reduction in tumor number (P = 0.027) and a 36% reduction in tumor volume (P = 0.004) as compared with control mice. Compared with Chrm3 gene ablation, the muscarinic antagonist was less efficacious, most probably due to shorter duration of treatment and incomplete blockade of muscarinic receptors. Overall, these findings indicate that interplay of Chrm3 and ß-catenin signaling is important for intestinal mucosal differentiation and neoplasia and provide a proof-of-concept that pharmacological inhibition of muscarinic receptor activation can attenuate intestinal neoplasia in vivo.

Effect of hyoscine butylbromide (HBB) on the uterine corpus: quantitative assessment with T2-weighted (T2W) MRI in healthy volunteers.

PURPOSE: To investigate effects of hyoscine butylbromide (HBB) on the appearance of three zonal anatomy of the uterine corpus on T2-weighted images (T2WI). MATERIALS AND METHODS: Sagittal T2WI of the pelvis were acquired before and after intramuscular administration of HBB with interval of 10 minutes in 22 healthy volunteers. By drawing polygonal regions of interest (ROIs), the uterine corpus was delineated into outer myometrium (OM), junctional zone (JZ), and endometrium (EM) in 20 subjects. Areas (mm(2)) and relative signal intensity (rSI) of each layer were compared between pre-HBB and post-HBB administration images by using paired t-tests. Histogram analysis was conducted for the uterine layers and changes were visualized. RESULTS: Areas of OM were significantly increased (P = 0.014) and mean rSI of JZ and OM were significantly increased (P = 0.007 and 0.001, respectively) after administration of HBB. Histogram showed an increase in the number of pixels with higher rSI in the OM, which was considered to be caused by an increase in interstitial fluid and vascular dilatation. EM did not show significant changes. CONCLUSION: Layer-wise ROI analyses demonstrated changes in the area and rSI in T2WI of the uterus after HBB administration. Histogram analysis contributed to the investigation of signal changes.

Effect of butylscopolamine on image quality in MRI of the prostate.

AIM: To evaluate the impact of butylscopolamine on the quality of magnetic resonance imaging (MRI) images of the prostate. MATERIAL AND METHODS: Eighty-two MRI examinations of the prostate were retrospectively analysed. MRI was performed with a combined endorectal/body phased-array coil including proton density-weighted (PD) sequence, T1-weighted turbo spin-echo (TSE)-sequence, and T2-weighted TSE-sequences. Forty milligrams of butylscopolamine was administered intramuscularly in 31 patients (im-group) and intravenously in 30 patients (iv-group). Twenty-one patients did not receive premedication with butylscopolamine (ø-group). Overall image quality, delineation of the bowel wall, and visualization of the prostate, neurovascular bundle, and pelvic lymph nodes were evaluated qualitatively using a five-point scale (from 1=excellent to 5=non-diagnostic/structure not discernible). Motion artefacts within the endorectal coil were quantified by baseline adjusted signal intensities inside the endorectal coil area. RESULTS: Delineation of the bowel wall using the PD-sequence was significantly improved after both intramuscular and intravenous butylscopolamine administration (ø-group: 3.6+/-0.7; im-group: 2.9+/-0.7; iv-group: 2.9+/-0.7; p=0.001). However, there were no significant differences in motion artefacts measured within the endorectal coil (ø-group: 1.18+/-0.14; im-group: 1.15+/-0.11; iv-group: 1.12+/-0.06; p=0.39). There were also no significant differences in qualitative assessment of visualization of the prostate, neurovascular bundle, pelvic lymph nodes, and of overall image quality between the study groups. CONCLUSION: : In conclusion, butylscopolamine had only a small effect on image quality and is not mandatory for MRI of the prostate.

Influence of N-butylscopolamine on SUV in FDG PET of the bowel.

OBJECTIVES: Peristalsis can lead to confusing FDG PET bowel uptake artefacts and potential for recording inaccurate mean standardised uptake value (SUV) measurements in PET-CT scans. Accordingly, we investigate the influence of different SUV normalisations on FDG PET uptake of the bowel and assess which one(s) have least dependence on body size factors in patients with and without the introduction of the anti-peristalsis agent N-butylscopolamine (Buscopan). METHODS: This study consisted of 92 prospective oncology patients, each having a whole body (18)F-FDG PET scan. Correlations were investigated between height, weight, glucose, body mass index (bmi), lean body mass (lbm) and body surface area (bsa) with maximum and mean SUV recorded for bowel normalised to weight (SUV(w)), lbm (SUV(lbm)), bsa (SUV(bsa)) and blood glucose corrected versions (SUV(wg), SUV(lbmg), SUV(bsag)). RESULTS: Standardised uptake value normalisations were significantly different between control and Buscopan groups with less variability experienced within individual SUV normalisations by the administration of Buscopan. Mean SUV normalisations accounted for 80% of correlations in the control group and 100% in the Buscopan group. Further, >86% of all correlations across both groups were dominated by mean SUV normalisations of which, about 69% were accounted for by SUV(bsa) and SUV(bsag). CONCLUSIONS: We recommend avoiding mean SUV(bsa) and individual glucose normalisations especially, mean SUV(bsag) as these dominated albeit relatively weak correlations with body size factors in control and Buscopan groups. Mean and maximum SUV(w) and SUV(lbm) were shown to be independent of any body size parameters investigated in both groups and therefore considered suitable for monitoring FDG PET uptake in the normal bowel for our patient cohort.

Hyoscine butylbromide potently blocks human nicotinic acetylcholine receptors in SH-SY5Y cells.

Hyoscine butylbromide (HBB; tradenames: Buscopan/Buscapina is an antispasmodic drug for the treatment of abdominal pain associated with gastrointestinal cramping. As a hyoscine derivative, this compound competitively inhibits muscarinic acetylcholine (ACh) receptors on smooth muscle cells in the gastrointestinal tract. Preliminary investigations suggested that it might also inhibit nicotinic ACh receptors. This study investigated the effect of HBB on nicotinic ACh receptor-mediated membrane currents in SH-SY5Y cells. ACh and nicotine application-induced comparable membrane currents with EC(50) values of 25.9+/-0.6 and 40.1+/-0.4microM, respectively. When coapplied with 100microM ACh, HBB concentration-dependently suppressed currents with an IC(50) value of 0.19+/-0.04microM, and was approximately seven-times more potent than the ganglionic blocker, hexamethonium (IC(50)=1.3+/-0.3microM). Increasing the agonist concentration to 5mM did not affect the amount of block by HBB, which suggests a non-competitive mode of action. These functional in vitro data demonstrate for the first time that HBB blocks neuronal nicotinic ACh receptors in the same concentration range as it inhibits muscarinic ACh receptors. If one hypothesizes that HBB might also affect nicotinic receptors in autonomic neurons in vivo (e. g. in the enteric nervous system), this effect could contribute to its spasmolytic activity.

Role of intravenously administered hyoscine butyl bromide in retrograde terminal ileoscopy: a randomized, double-blinded, placebo-controlled trial.

AIM: To evaluated the role of hyoscine butyl bromide in facilitating retrograde ileoscopy. METHODS: Retrograde terminal ileoscopy was attempted in 200 consecutive patients undergoing colonoscopy. After intubation of the cecum and visualization of the ileocecal valve, butyl bromide injection or normal saline was given intravenously to the patients in a double blind random fashion. The pulse rate and oxygen saturation were measured continuously. After completion of the procedure, endoscopists were then asked to score the ease of intubation and the ease of visualization of the terminal ileum on a visual scale of 1 to 10. The patients were also asked to score the pain after receiving hyoscine butyl bromide injection on a score of 1 to 10. RESULTS: Terminal ileoscopy could be performed in 188 patients. The mean (SD) visual analogue score for the ease of intubation of the cecum was 7.4 (0.65) in the injection group and 5.9 (0.8) in the placebo group (P < 0.001). The mean (SD) length of ileum visualized in the injection group was 14.4 (3.3) cm and 10.4 (2.7) cm in the placebo group (P < 0.001). The mean (SD) visual analogue score for ease of visualization of the terminal ileum was 7.5 (0.69) in the injection group and 5.9 (0.7) in the placebo group (P < 0.001). The pain score experienced by the patients was 6.5 (0.7) in the injection group and 6.7 (0.69) in the placebo group (P < 0.008). Although the pulse rate increased significantly in patients receiving the drug, no statistically significant difference was noted in the oxygen saturation between the two groups either before or after administration of the drug. No complications were observed in either of the groups. CONCLUSION: Hyoscine butyl bromide injection is a useful adjunct in helping the intubation and visualization of terminal ileum during colonoscopy.

Concurrent duodenal manometric and impedance recording to evaluate the effects of hyoscine on motility and flow events, glucose absorption, and incretin release.

Upper gastrointestinal motor function and incretin hormone secretion are major determinants of postprandial glycemia and insulinemia. However, the impact of small intestinal flow events on glucose absorption and incretin release is poorly defined. Intraluminal impedance monitoring is a novel technique that allows flow events to be quantified. Eight healthy volunteers were studied twice, in random order. A catheter incorporating six pairs of electrodes at 3-cm intervals, and six corresponding manometry sideholes, was positioned in the duodenum. Hyoscine butylbromide (20 mg) or saline was given as an intravenous bolus, followed by a continuous intravenous infusion of either hyoscine (20 mg/h) or saline over 60 min. Concurrently, glucose and 3-O-methylglucose (3-OMG) were infused into the proximal duodenum (3 kcal/min), with frequent blood sampling to measure glucose, 3-OMG, insulin, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The frequency of duodenal pressure waves and propagated pressure wave sequences was reduced by hyoscine in the first 10 min (P<0.01 for both), but not after that time. In contrast, there were markedly fewer duodenal flow events throughout 60 min with hyoscine (P<0.005). Overall, blood glucose (P<0.01) and plasma 3-OMG concentrations (P<0.05) were lower during hyoscine than saline, whereas plasma insulin, GLP-1, and GIP concentrations were initially (t=20 min) lower during hyoscine (P<0.05). In conclusion, intraluminal impedance measurement may be more sensitive than manometry in demonstrating alterations in duodenal motor function. A reduction in the frequency of duodenal flow events is associated with a decreased rate of glucose absorption and incretin release in healthy subjects.

Effect of morphine and M-cholinoceptor blocking drugs on human sphincter of Oddi during choledochofiberscopy manometry.

OBJECTIVE: To evaluate the effects of morphine on the human sphincter of Oddi pressure and the antagonism of anticholinergic agents against morphine. METHODS: The action of these drugs on the sphincter of Oddi (SO) was evaluated by means of choledochofiberscopy manometry in 40 operated patients with T-tube. The patients were divided randomly into 4 groups: anisodamine, atropine, buscopan, and control. The following data were recorded: duodenal pressure (DP), basal pressure of the sphincter of Oddi (BPSO), contractive amplitude of the sphincter of Oddi (CASO), contractive frequency of the sphincter of Oddi (CFSO), contractive duration of the sphincter of Oddi (CDSO), and pressure of the common bile duct (PCBD). Both morphine and anticholinergic agents were given intramuscularly. RESULTS: After injection of 10 mg morphine, BPSO, CASO, CFSO, and PCBD increased significantly. After injection of 15 mg anisodamine or 0.75 mg atropine, CASO, BPSO declined obviously, and after injection of 20 mg buscopan, CASO, BPSO, CFSO declined obviously, but in anisodamine, atropine and buscopan groups, they differed insignificantly. CONCLUSIONS: The results illustrate that SO manometry via choledochofiberscopy is a new method for SO dynamic study. Morphine can increase DP, BPSO, CASO, PCBD, but anisodamine atropine and buscopan can antagonize the effect of morphine.

Optimizing colonic distention for multi-detector row CT colonography: effect of hyoscine butylbromide and rectal balloon catheter.

PURPOSE: To investigate the effects of hyoscine butylbromide and an inflatable rectal balloon catheter on luminal distention during computed tomographic (CT) colonography. MATERIALS AND METHODS: One hundred thirty-six subjects undergoing CT colonography were randomized to receive either 20 mg or 40 mg of hyoscine butylbromide or no spasmolytic. Subjects were also independently randomized to undergo CT colonography with an inflatable rectal balloon catheter or a standard thin rectal tube. Multi-detector row CT colonography was performed with patients in prone and supine positions, with colonic segmental distention assessed by a single observer with a four-point scale. A simple assessment of whether distention was adequate for clinical interpretation was also made, and the effect of hyoscine butylbromide and catheter use was examined by using multivariate ordered logistic regression. RESULTS: Administration of hyoscine butylbromide was associated with significantly improved cecal (P =.05), ascending (P =.001), and transverse (P <.001) colonic distention when patients were supine and improved ascending (P <.001) and descending (P <.001) colonic distention when patients were prone. Compared with control subjects, patients given a spasmolytic had odds of 6.49 for clinically adequate distention throughout all colonic segments (P =.001). There was no incremental advantage with use of a 40-mg dose. In contrast, rectal balloon catheter use was not significantly associated with improved distention. CONCLUSION: Hyoscine butylbromide improves colonic distention during CT colonography and should be routinely administered where it is available. Use of a thin rectal tube for insufflation is adequate.

Valor terapêutico da associaçäo de espasmolítico com analgésico contendo brometo de N-butilescopolamina com dipirona / Therapeutic value of the combination between an spasmolithic with an analgesic: scopolamine-N-butyl bromide and dipirone

A grande mioria das combinaçöes de fármacos säo irracionais e perigosas. Por outro lado, existem algumas associaçöes medicamentosas que apresentam bases farmacológicas racionais ao lado de uma adequada relaçäo benefício/risco. A associaçäo entre o brometo de N-butilescopolamina com a dipirona é aprovada pelas autoridades sanitárias em vários países apresentando claras indicações terapêuticas, No Brasil particularmente, essa combinaçäo foi aprovada há mais de trinta anos, estando mesmo padronizada em muitos hospitais, principalmente na emergência. A classe médica considera essa combinaçäo fixa como uma associação analgésica de primeira escolha, prática, de baixo custo e muito eficaz

Factors that affect the variability in heart rate during endoscopic retrograde cholangiopancreatography.

OBJECTIVE: To find out if drugs, position, and endoscopic manipulation during endoscopic retrograde cholangiopancreatography (ERCP) influence the changes in the variability of heart rate. DESIGN: Single-blind randomised trial. SUBJECTS: 10 volunteers given butyscopolamine, glucagon, or saline intravenously on three different study days, and 10 patients who had ERCP without butylscopolamine or glucagon. MAIN OUTCOME MEASURES: Holter tape analysis for ischaemia and changes in the variability of heart rate. RESULTS: 5 volunteers developed tachycardia after butylscopolamine, while 2 developed tachycardia after glucagon. During ERCP 9 patients developed tachycardia, and 2 developed myocardial ischaemia. Vagal tone decreased in the volunteers after butylscopolamine, but no changes were seen after glucagon or placebo, or in patients during ERCP. CONCLUSIONS: Butylscopolamine reduced vagal tone in volunteers. Patients who were having ERCP without butylscopolamine had a stable vagal tone. The previously observed reduced vagal tone during ERCP may therefore be primarily the result of giving butylscopolamine.

Effect of N-butylscopolamine on intestinal uptake of fluorine-18-fluorodeoxyglucose in PET imaging of the abdomen.

AIM: Circumscribed or diffuse intestinal uptake of F-18-fluorodeoxyglucose (FDG) is a frequent finding in PET imaging of the abdomen often interfering with correct scan interpretation. The aim of the present study was to determine whether the antiperistaltic agent N-butylscopolamine reduces intestinal FDG-uptake. METHODS: Whole body scans from 40 patients with malignant lymphoma and no evidence for intraabdominal tumor involvement were analyzed (6 bed positions; scan start 60 min post injection of approximately 350 MBq FDG; emission time 9 min per position; no attenuation correction). Twenty patients received 20 mg N-butylscopolamine in combination with an intravenous injection of FDG (test group) and 20 patients received only FDG (control group). For analysis, the intensity of bowel loops and diffuse abdominal background were compared to normal liver on a 4 point scale (0 = lowest intensity, 3 = highest) by two experienced nuclear medicine physicians. Furthermore, focal intestinal uptake was evaluated quantitatively by a ROI technique and bowel to liver ratios (b/l) were calculated. RESULTS: Bowel loops had lower intensity and occupied less abdominal regions in the test group than in the control group (visual score 1 vs. 1.5, p = 0.01; abdominal regions 1 of 5 vs. 2.5 of 5, p = 0.04). The visual score for diffuse abdominal background was 0.5 in the test group and 1 in the control group (p = 0.04). Bowel uptake interfered with scan interpretation in 1 of 20 patients in the test group and 6 of 20 patients in the control group (p = 0.01). The b/l ratios were 1.5 +/- 0.7 in the test group and 2.3 +/- 1.4 in the control group (p = 0.08). CONCLUSION: Administration of N-butylscopolamine reduces intestinal uptake of FDG and may facilitate accurate interpretation of abdominal FDG-PET studies.

Antispasmodic action of propinox on the isolated human gallbladder: possible mechanism of action

Propinox is an antispasmodic drug frequently used in the treatment of disorders of the gastrointestinal tract, the uterus and the galbladder, but little is known about its relaxing activity in gallbladder tissue. The main objective of this study was to determine the antispasmodic activity of propinox, compared to other antispasmodics, in the gallblader and to assess its binding affinity to receptor sites which may be involved in its mechanism of action. Antispasmodic activity of propinox, (-) scopolamine-n-butyl bromide, atropine and verapamil was determined in human gallbladders to reduce the risk of interspecies variability. Inhibitory activities (ED50) of carbachol-induced contraction were: atropine 5.03x10(-8) M>propinox 1.25x10(-7) M> verapamil 6.63x10(-6)M> (-) scopolamine-n-butyl1 bromide 5.4x10(-5) M. pD'2 for propinox was 6.94, indicating non competitive inhibition of carbachol action. Radioligand binding studies were performed to determine if the antisplasmodic action of the drug involved binding to muscarinic receptors or calciumatagonist sites. The inhibition constant (Ki) of proponix for muscarinic receptors of guinea pig ileum smoth muscle, which contains a mixed M2-M3 receptor population, was 1.6x10(-6) M. Ki for brain muscarinic receptors (M1) was 1.0x10(-4) M, for cardiac receptors (M1) was 1.0x10(-4)M, for receptors (M2) 1.2x10(-6)M and from salivary gland receptors (M3) 1.5x10(-6)M. For binding to the dihidropiridine calcium antagonist binding sites, Ki were: 4.9x10(-5)M for propinox and 2.2x10(-7)M for verapamil. For the phenylakylamine binding sites Ki were: 5.0x10(-6)M for propinox and 3.5x10(-8)M for verapamil. For the benzothiacepine binding sites, Ki for propinox was 5.2x10(-6)M. The following may be concluded: 1- The antispasmodic activity of propinox in isolated human galbladder was was comparatively less potent than of atropine and more potent than those verapamil and (-) scopolamine-n-butyl bromide. 2- Propinox showed binding to muscarinic and calcium receptors that can be related to its antisplasmodic activity; suggesting that the drug is an antispasmodic with anticholinergic and musculotropic activity. 3.- The dual mechanism of action, anticholinergic and calcium-blocking, would induce synergism of pharmacodynamic effects and minimize adverse events of pure antimuscarinic drugs or calcium antagonists.

Characterization of antimuscarinic effect of cimetropium bromide in guinea pig ileum.

Pharmacological characteristics of cimetropium bromide (cimetropium), a muscarinic receptor antagonist, were studied in longitudinal muscle preparations with myenteric plexus of guinea-pig ileum. Cimetropium was shown to have more potent antimuscarinic effect than butylscopolamine in inhibition of contraction of the preparations. Interestingly, when the inhibitory effects of cimetropium were compared in respect of relative potency to atropine between its effects on electrical field stimulation or nicotine-, and exogenous ACh-induced contraction, it has a more potent effect on the former contraction than that on the latter one. In the superfusion experiments of the preparation which had been preloaded with labelled choline, cimetropium decreased the labelled ACh release induced by electrical field stimulation under the muscarinic autoinhibition blocked-condition. From these findings, two pharmacologically characteristic effects of cimetropium in addition to post-synaptic muscarinic receptor antagonism were suggested: one is a weak effect on muscarinic autoreceptors in comparison to atropine and the other is an inhibitory effect on the ACh release.

The effects of the pharmacological manipulation of postoperative intestinal motility on colonic anastomoses. An experimental study in a rat model.

INTRODUCTION: The aim of the study was to determine the effects of pharmacological manipulation of postoperative intestinal motility on the resistance of colonic anastomoses. MATERIALS AND METHODS: Seventy-one Sprague-Dawley rats were divided into three groups: Group 1 (n = 20; colonic anastomosis+1 cc of saline solution subcutaneously, daily); Group 2 (n = 29; colonic anastomosis+1.2 mg/100 g body weight metoclopramide in 1 cc subcutaneously, daily); and Group 3 (n = 22; colonic anastomosis+2 mg/100 g body weight hyoscine N-butyl-bromide in 1 cc subcutaneously, daily). Surviving rats (20 in each group) were sacrificed 4 days after surgery and adhesions were evaluated. Each segment containing an anastomosis was removed and the bursting pressure was determined. RESULTS: The cause of death during the early postoperative period was dehiscence in 8 cases (7 in Group 2 and 1 in Group 3). General adhesion scores in Group 2 were higher than in Group 3 (P = 0.003). The score for adhesions to the anastomosis in Group 1 was higher than in Group 2, but no statistically significant difference was found. Bursting-pressure was significantly lower in Group 2 than in other groups (P = 0.001). In all cases leakage of dye was observed at the anastomosis. CONCLUSION: The use of metoclopramide (a gastrointestinal prokinetic agent) during the early postoperative period was associated with an increase in dehiscence in colonic anastomosis and, when animals survived, there was a significant decrease in anastomotic resistance. Hyoscine (an inhibitor of gastrointestinal motility) did not improve the healing of anastomoses.

Continuous subcutaneous infusion of hyoscine butylbromide reduces secretions in patients with gastrointestinal obstruction.

We describe the use of hyoscine butylbromide as a subcutaneous infusion in 3 patients with inoperable malignant bowel obstruction. An objective reduction of drainage from the gastrointestinal tract was observed with the hyoscine butylbromide infusion (60-120 mg/day). We suggest that this effect can be useful in the palliative treatment of vomiting in inoperable bowel obstruction.