Surg Endosc (2015) 29:2266–2269 DOI 10.1007/s00464-014-3939-2
and Other Interventional Techniques
Otilonium bromide as spasmolytic during endoscopic retrograde cholangiopancreatography ¨ mer Karahan • Barıs¸ Sevinc¸ • Ahmet Okus¸ O Serden Ay • Nergis Aksoy
•
Received: 18 May 2014 / Accepted: 7 October 2014 / Published online: 1 November 2014 Ó Springer Science+Business Media New York 2014
Abstract Background Endoscopic retrograde cholangiopancreatography (ERCP) is commonly used in both the diagnosis and the treatment of biliary and pancreatic disorders. The aim of this study is to evaluate the effects of OB usage during ERCP on duodenal motility, the tolerability of the procedure (by patients) and the difficulty of the procedure (by the endoscopist). Method The study was conducted in Konya Training and Research Hospital General Surgery Endoscopy Unit in randomized prospective pattern. The patients were divided into the two groups as spasmolytic and control groups. The procedure was performed under topical anesthesia and sedation. Results There were 100 cases included into the study (50 cases in each group). The mean duodenal motility score was found to be 1.9 ± 0.5 in the study group and 3 ± 0.6 in the control group. In the study group, the tolerability of the procedure score by the endoscopist was moderate in 16 % and well/very well in 78 % of the cases. On the other hand, in the control group, the scores were poor in 21 %, moderate in 71 %, and well/very well in 24 % of the cases. In terms of patient satisfaction, in study group 42 % of the
RCT registration ID: AEARCTR-0000429 (registration date: 04.07.2014). The full trial can be found at: http://www. socialscienceregistry.org/trials/429. ¨ . Karahan B. Sevinc¸ (&) S. Ay N. Aksoy O Department of General Surgery, Konya Training and Research Hospital, Meram Yeniyol, Meram, Konya, Turkey e-mail: [email protected] A. Okus¸ General Surgery, Mevlana University Medical School, Konya, Turkey
123
cases reported the procedure as moderate and 58 % reported as well/very well. However, in the control group 16 % of the cases reported the procedure as poor, 58 % moderate, and 26 % as well/very well. Conclusion Otilonium bromide is a safe agent with low side effects. It can be used before the ERCP procedure to decrease the duodenal motility. It eases the procedure, moreover, it increases the patients’ satisfaction. Keywords ERCP Otilonium bromide Duodenal motility Patient satisfaction Endoscopic retrograde cholangiopancreatography (ERCP) is commonly used both in the diagnosis and the treatment of biliary and pancreatic disorders. During the procedure duodenal motility has a great importance as it makes difficult to catheterizate the papilla and other manipulations. Otilonium Bromide (OB) is such a muscarinic agonist and calcium channel blocker that it ensures smooth muscle relaxation. It has a very limited side effect profile so a safe agent [1, 2]. It has been commonly used as a spasmolytic in irritable bowel syndrome. There are several studies showing OB as decreasing the complaints and having positive effects on the patients’ comfort [3, 4]. Although it relaxing effect on intestinal smooth muscles is known, there has been no study about the use of the agent during ERCP procedure so far.
Material and method After the getting approval from The Ethical Committee of The Ministry of Health of Turkey, the study was conducted in Konya Training and Research Hospital General Surgery Endoscopy Unit. The written informed consent was taken
Surg Endosc (2015) 29:2266–2269
2267
from all the patients. The study was a randomized controlled trial and the procedures were performed by a single experienced endoscopist.
Table 1 Demographic data
Patients
ASA score
The patients above 18 years of age who accepted to be involved in the study and having no known allergy to the agent were included in the study. Emergent cases, cases with low mental status and the pregnant women were excluded from the study. All the patients were informed about the design of the study and a written consent was taken from each of them. Another resident divided the patients into two groups as spasmolytic (study) and control group consecutively. The patients in study group, 2 (2 9 40 mg otilonium bromide) were given two tablets of OB orally with a little water 2 h before the procedure, No drugs were given to control group. The ERCP procedures were performed under routine topical anesthesia and sedation. For the sedation 0.1 mg/kg midazolam (Dormicum amp, Roche) administered intravenously. As the endoscopist did not know the groups, during the procedure IV hyoscine-n-butylbromide (Buscopan amp, Zentiva) was administered according to the endoscopist’ wish. The additional drug uses were recorded. During the procedure another resident scored the duodenal motility from 1 to 5 according to the following scale: 1: 2: 3: 4: 5:
no contraction. less than five contractions in a minute. 5–10 contractions/min. 11–15 contractions/min. continued contractions.
At the end of the procedure, the endoscopist scored the patients’ tolerability procedure as poor, moderate, well or very well. After the procedure another resident asked the patients’ satisfaction as poor, moderate, well or very well. The coworkers who take the informed consent, randomized the patients into groups, scored the motility and made the analysis were independent from each other and did not know the groups. The statistical analysis was made by IBM SPSS Statistics 20.0 software. In the analysis Chi-square and student T tests were used where appropriate and the statistical significance was accepted as 0.05.
Study group (n: 50)
Control group (n: 50)
p
Age
61.8 ± 20.5
66 ± 15.2
[0.05
Gender (M/F)
33/17
30/20
[0.05
1.5 ± 0.6
1.7 ± 0.6
[0.05
ASA American Society of Anesthesiologists
47 female and 53 male and the mean age of the cases was 63.9 ± 18. There were no difference in between the groups in terms of age, gender, and ASA (American Society of Anesthesiologists) scores. The demographics of the patients were given in Table 1. Moreover, there was no difference between the cases in terms of the primary disorders. The main indication for ERCP was common bile duct stone (88 % in spasmolytic and 84 % in control group). In 98 % of procedures, endoscopic sphincterotomy was performed. Biliary stents were placed in two (4 %) cases in spasmolytic group and four (8 %) cases in control group (p [ 0.05). In none of the cases included in the study, no anatomical variations were encountered. The mean duodenal motility score was found to be 1.9 ± 0.5 in the study group and 3 ± 0.6 in the control group. The difference was statistically significant (p \ 0.001). In the study group, the tolerability of the procedure score by the endoscopist was moderate in 16 % and well/ very well in 78 % of the cases. On the other hand, in the control group, the scores were poor in 21 %, moderate in 71 %, and well/very well in 24 % of the cases. The difference was found to be significant (p \ 0.001) (Fig. 1). In terms of patient satisfaction, in study group 42 % of the cases reported the procedure as moderate and 58 % reported as well/very well. However, in the control group 16 % of the cases reported the procedure as poor, 58 % moderate, and 26 % as well/very well. The patient satisfaction rates were significantly higher in the study group (p \ 0.001) (Fig. 2).
Findings There were 100 cases included into the study (50 cases in each group) in between April and August 2013. There were
Fig. 1 The tolerability of the procedure was scored by the endoscopist. p \ 0.05 (Chi-square test). The procedure was better tolerated in the study group than in control group
123
2268
Surg Endosc (2015) 29:2266–2269
Fig. 2 Comparison of the groups in terms of patient satisfaction. p \ 0.05 (Chi-square test). The patient satisfaction was found to be better in study group
Table 2 Comparison of the patients with only otilonium bromide and only Buscopan in terms of duodenal motility and pulse Otilonium bromide (n: 42) Duodenal motility Pulse/min
1.9 ± 0.6 83.8 ± 13.4
Buscopan (n: 39)
p*
3 ± 0.5
\0.001
99.1 ± 14
\0.001
* Student T test
cases with only OB shows that oral OB can be used as an alternative spasmolytic agent. Spasmolytic agents are widely used during ERCP for the inhibition of the motility and to ease the catheterization of the papilla. For this purpose, agents like glucagon and buscopan are widely used [5–7]. OB is a spasmolytic with minimal systemic distribution and even higher doses are well tolerated [8]. However, widely used Buscopan has some anticholinergic side effects like tachycardia, dry mouth, accommodation disorders, and urinary retention. Therefore, it should be used carefully in cases with co-morbidities like bronchial asthma, thyrotoxicosis, and heart failure [9–11]. The half life of Buscopan is 10 min and it needs additional doses. Moreover, oral use of OB is another advantage. Although its spasmolytic effect is well known, there is only one study about the use of OB in endoscopic procedures [12]. The only study about the use of OB during gastrointestinal system endoscopy (n = 63; 49 upper, 14 lower). In literature, there is no study about the usage of OB during ERCP. This study showed the significant inhibition of the duodenal motility by oral OB use. Inhibition of the duodenal motility positively affects procedure for the endoscopist. Moreover, the higher patient satisfaction rate in the study group can be explained by the decrease in duodenal contractions. There are some limitations in our study. We did not use placebo in the control group and the evaluation of the tolerability and patient satisfaction were subjective. However, with the adequate population and as being randomized prospective, the study has valuable results.
In the study group in 16 % of the cases there were in need of additional hyoscine-n-butylbromide use, whereas this rate was found to be 78 % in the control group. Additional spasmolytic need was significantly lower in study group (p \ 0.001). Intravenous Buscopan administration was under control of the endoscopist’ wish. In the sub-analysis, we had two groups of patients as only OB (n: 42) and only Buscopan (n: 39). In the group with only OB was administered, the mean duodenal motility score was found to statistically lower than only Buscopan group (Table 2). As the most frequent side effect of Buscopan is tachycardia, the mean pulses of the vases were compared and it was found to be statistically lower in OB group. In the study group, we did not meet any side effects of the drug. We met mild acute pancreatitis in one case in study group and in two cases in the control group. All the cases were administered to hospital and IV fluid and electrolyte treatment were administered. In all the cases, pancreatitis resolved in 24 h and the patients were discharged from the hospital.
¨ mer Karahan, Barıs¸ Sevinc¸, Ahmet Okus¸ , Serden Disclosures Drs O Ay and Nergis Aksoy have no conflicts of interest and financial ties to disclose.
Discussion
References
This study shows that oral otilonium bromide usage during ERCP significantly decreases the duodenal motility and eases the procedure. The lower duodenal motility score in
123
Conclusion Otilonium bromide is a safe drug with low side effects. It can be safely used during ERCP to inhibit the duodenal motility and to ease the catheterization of the papilla. It positively affects the procedure both for the endoscopist and the patient.
1. Evangelista S (1999) Otilonium bromide: a Selective spasmolytic for the gastrointestinal tract. J Int Med Res 27:207–222 2. Strege PR, Evangelista S, Lyford GL, Sarr MG, Farrugıa G (2004) Otilonium bromide inhibits calcium entry through L-type
Surg Endosc (2015) 29:2266–2269
3. 4.
5.
6.
7.
calcium channels in human intestinal smooth muscle. Neurogastroenterol Motil 16:167–173 Spinelli A (2007) Irritable bowel syndrome. Clin Drug Investig 27(1):15–33 Battaglia G, Morselli-Labate AM, Camarri E, Francavilla A, De Marco F, Mastropaolo G, Naccarato R (1998) Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study. Aliment Pharmacol Ther 12(10):1003–1010 Lynch CR, Khandekar S, Lynch SM et al (2007) Sublingual L-hyoscyamine for duodenal antimotility during ERCP: a prospective randomized doubleblinded study. Gastrointest Endosc 66:748–752 Hannigan BF, Axon AT, Avery S et al (1982) Buscopan or glucagon for endoscopic cannulation of ampulla of vater? J R Soc Med 75:21–22 Yamamoto N, Nakai Y, Sasahira N, Hirano K, Tsujino T, Isayama H, Komatsu Y, Tada M, Yoshida H, Kawabe T, Hiki N, Kaminishi M, Kurosaka H, Omata M (2006) Efficacy of peppermint oil as an
2269
8.
9. 10. 11.
12.
antispasmodic during endoscopic retrograde cholangiopancreatography. J Gastroenterol Hepatol 21(9):1394–1398 Sutton JA, Kilminster SG, Mould GP (1997) The clinical pharmacology of single doses of otilonium bromide in healthy volunteers. Eur J Clin Pharmacol 52(5):365–369 Lazzaroni M, Porro GB (2001) Preparation, premedication, and surveilance. Endoscopy 33(2):103–108 Bell GD (2000) Preparation, premedication, and surveillance. Endoscopy 32(2):92–100 Marshall JB, Patel M, Mahajan RJ, Early DS, King PD, Banerjee B (1999) Benefit of intravenous antispsamodic (hyoscyamine sulfate) as premedication for colonoscopy. Gastrointest Endosc 49:720–726 Go´mez NA, Leo´n CJ, Gutie´rrez J (1997) Use of spasmolytic agent otilonium bromide (spasmomen) in digestive endoscopy: a prospective study in 63 patients. Acta Gastroenterol Latinoam 27(3):123–125
123
and Other Interventional Techniques
Otilonium bromide as spasmolytic during endoscopic retrograde cholangiopancreatography ¨ mer Karahan • Barıs¸ Sevinc¸ • Ahmet Okus¸ O Serden Ay • Nergis Aksoy
•
Received: 18 May 2014 / Accepted: 7 October 2014 / Published online: 1 November 2014 Ó Springer Science+Business Media New York 2014
Abstract Background Endoscopic retrograde cholangiopancreatography (ERCP) is commonly used in both the diagnosis and the treatment of biliary and pancreatic disorders. The aim of this study is to evaluate the effects of OB usage during ERCP on duodenal motility, the tolerability of the procedure (by patients) and the difficulty of the procedure (by the endoscopist). Method The study was conducted in Konya Training and Research Hospital General Surgery Endoscopy Unit in randomized prospective pattern. The patients were divided into the two groups as spasmolytic and control groups. The procedure was performed under topical anesthesia and sedation. Results There were 100 cases included into the study (50 cases in each group). The mean duodenal motility score was found to be 1.9 ± 0.5 in the study group and 3 ± 0.6 in the control group. In the study group, the tolerability of the procedure score by the endoscopist was moderate in 16 % and well/very well in 78 % of the cases. On the other hand, in the control group, the scores were poor in 21 %, moderate in 71 %, and well/very well in 24 % of the cases. In terms of patient satisfaction, in study group 42 % of the
RCT registration ID: AEARCTR-0000429 (registration date: 04.07.2014). The full trial can be found at: http://www. socialscienceregistry.org/trials/429. ¨ . Karahan B. Sevinc¸ (&) S. Ay N. Aksoy O Department of General Surgery, Konya Training and Research Hospital, Meram Yeniyol, Meram, Konya, Turkey e-mail: [email protected] A. Okus¸ General Surgery, Mevlana University Medical School, Konya, Turkey
123
cases reported the procedure as moderate and 58 % reported as well/very well. However, in the control group 16 % of the cases reported the procedure as poor, 58 % moderate, and 26 % as well/very well. Conclusion Otilonium bromide is a safe agent with low side effects. It can be used before the ERCP procedure to decrease the duodenal motility. It eases the procedure, moreover, it increases the patients’ satisfaction. Keywords ERCP Otilonium bromide Duodenal motility Patient satisfaction Endoscopic retrograde cholangiopancreatography (ERCP) is commonly used both in the diagnosis and the treatment of biliary and pancreatic disorders. During the procedure duodenal motility has a great importance as it makes difficult to catheterizate the papilla and other manipulations. Otilonium Bromide (OB) is such a muscarinic agonist and calcium channel blocker that it ensures smooth muscle relaxation. It has a very limited side effect profile so a safe agent [1, 2]. It has been commonly used as a spasmolytic in irritable bowel syndrome. There are several studies showing OB as decreasing the complaints and having positive effects on the patients’ comfort [3, 4]. Although it relaxing effect on intestinal smooth muscles is known, there has been no study about the use of the agent during ERCP procedure so far.
Material and method After the getting approval from The Ethical Committee of The Ministry of Health of Turkey, the study was conducted in Konya Training and Research Hospital General Surgery Endoscopy Unit. The written informed consent was taken
Surg Endosc (2015) 29:2266–2269
2267
from all the patients. The study was a randomized controlled trial and the procedures were performed by a single experienced endoscopist.
Table 1 Demographic data
Patients
ASA score
The patients above 18 years of age who accepted to be involved in the study and having no known allergy to the agent were included in the study. Emergent cases, cases with low mental status and the pregnant women were excluded from the study. All the patients were informed about the design of the study and a written consent was taken from each of them. Another resident divided the patients into two groups as spasmolytic (study) and control group consecutively. The patients in study group, 2 (2 9 40 mg otilonium bromide) were given two tablets of OB orally with a little water 2 h before the procedure, No drugs were given to control group. The ERCP procedures were performed under routine topical anesthesia and sedation. For the sedation 0.1 mg/kg midazolam (Dormicum amp, Roche) administered intravenously. As the endoscopist did not know the groups, during the procedure IV hyoscine-n-butylbromide (Buscopan amp, Zentiva) was administered according to the endoscopist’ wish. The additional drug uses were recorded. During the procedure another resident scored the duodenal motility from 1 to 5 according to the following scale: 1: 2: 3: 4: 5:
no contraction. less than five contractions in a minute. 5–10 contractions/min. 11–15 contractions/min. continued contractions.
At the end of the procedure, the endoscopist scored the patients’ tolerability procedure as poor, moderate, well or very well. After the procedure another resident asked the patients’ satisfaction as poor, moderate, well or very well. The coworkers who take the informed consent, randomized the patients into groups, scored the motility and made the analysis were independent from each other and did not know the groups. The statistical analysis was made by IBM SPSS Statistics 20.0 software. In the analysis Chi-square and student T tests were used where appropriate and the statistical significance was accepted as 0.05.
Study group (n: 50)
Control group (n: 50)
p
Age
61.8 ± 20.5
66 ± 15.2
[0.05
Gender (M/F)
33/17
30/20
[0.05
1.5 ± 0.6
1.7 ± 0.6
[0.05
ASA American Society of Anesthesiologists
47 female and 53 male and the mean age of the cases was 63.9 ± 18. There were no difference in between the groups in terms of age, gender, and ASA (American Society of Anesthesiologists) scores. The demographics of the patients were given in Table 1. Moreover, there was no difference between the cases in terms of the primary disorders. The main indication for ERCP was common bile duct stone (88 % in spasmolytic and 84 % in control group). In 98 % of procedures, endoscopic sphincterotomy was performed. Biliary stents were placed in two (4 %) cases in spasmolytic group and four (8 %) cases in control group (p [ 0.05). In none of the cases included in the study, no anatomical variations were encountered. The mean duodenal motility score was found to be 1.9 ± 0.5 in the study group and 3 ± 0.6 in the control group. The difference was statistically significant (p \ 0.001). In the study group, the tolerability of the procedure score by the endoscopist was moderate in 16 % and well/ very well in 78 % of the cases. On the other hand, in the control group, the scores were poor in 21 %, moderate in 71 %, and well/very well in 24 % of the cases. The difference was found to be significant (p \ 0.001) (Fig. 1). In terms of patient satisfaction, in study group 42 % of the cases reported the procedure as moderate and 58 % reported as well/very well. However, in the control group 16 % of the cases reported the procedure as poor, 58 % moderate, and 26 % as well/very well. The patient satisfaction rates were significantly higher in the study group (p \ 0.001) (Fig. 2).
Findings There were 100 cases included into the study (50 cases in each group) in between April and August 2013. There were
Fig. 1 The tolerability of the procedure was scored by the endoscopist. p \ 0.05 (Chi-square test). The procedure was better tolerated in the study group than in control group
123
2268
Surg Endosc (2015) 29:2266–2269
Fig. 2 Comparison of the groups in terms of patient satisfaction. p \ 0.05 (Chi-square test). The patient satisfaction was found to be better in study group
Table 2 Comparison of the patients with only otilonium bromide and only Buscopan in terms of duodenal motility and pulse Otilonium bromide (n: 42) Duodenal motility Pulse/min
1.9 ± 0.6 83.8 ± 13.4
Buscopan (n: 39)
p*
3 ± 0.5
\0.001
99.1 ± 14
\0.001
* Student T test
cases with only OB shows that oral OB can be used as an alternative spasmolytic agent. Spasmolytic agents are widely used during ERCP for the inhibition of the motility and to ease the catheterization of the papilla. For this purpose, agents like glucagon and buscopan are widely used [5–7]. OB is a spasmolytic with minimal systemic distribution and even higher doses are well tolerated [8]. However, widely used Buscopan has some anticholinergic side effects like tachycardia, dry mouth, accommodation disorders, and urinary retention. Therefore, it should be used carefully in cases with co-morbidities like bronchial asthma, thyrotoxicosis, and heart failure [9–11]. The half life of Buscopan is 10 min and it needs additional doses. Moreover, oral use of OB is another advantage. Although its spasmolytic effect is well known, there is only one study about the use of OB in endoscopic procedures [12]. The only study about the use of OB during gastrointestinal system endoscopy (n = 63; 49 upper, 14 lower). In literature, there is no study about the usage of OB during ERCP. This study showed the significant inhibition of the duodenal motility by oral OB use. Inhibition of the duodenal motility positively affects procedure for the endoscopist. Moreover, the higher patient satisfaction rate in the study group can be explained by the decrease in duodenal contractions. There are some limitations in our study. We did not use placebo in the control group and the evaluation of the tolerability and patient satisfaction were subjective. However, with the adequate population and as being randomized prospective, the study has valuable results.
In the study group in 16 % of the cases there were in need of additional hyoscine-n-butylbromide use, whereas this rate was found to be 78 % in the control group. Additional spasmolytic need was significantly lower in study group (p \ 0.001). Intravenous Buscopan administration was under control of the endoscopist’ wish. In the sub-analysis, we had two groups of patients as only OB (n: 42) and only Buscopan (n: 39). In the group with only OB was administered, the mean duodenal motility score was found to statistically lower than only Buscopan group (Table 2). As the most frequent side effect of Buscopan is tachycardia, the mean pulses of the vases were compared and it was found to be statistically lower in OB group. In the study group, we did not meet any side effects of the drug. We met mild acute pancreatitis in one case in study group and in two cases in the control group. All the cases were administered to hospital and IV fluid and electrolyte treatment were administered. In all the cases, pancreatitis resolved in 24 h and the patients were discharged from the hospital.
¨ mer Karahan, Barıs¸ Sevinc¸, Ahmet Okus¸ , Serden Disclosures Drs O Ay and Nergis Aksoy have no conflicts of interest and financial ties to disclose.
Discussion
References
This study shows that oral otilonium bromide usage during ERCP significantly decreases the duodenal motility and eases the procedure. The lower duodenal motility score in
123
Conclusion Otilonium bromide is a safe drug with low side effects. It can be safely used during ERCP to inhibit the duodenal motility and to ease the catheterization of the papilla. It positively affects the procedure both for the endoscopist and the patient.
1. Evangelista S (1999) Otilonium bromide: a Selective spasmolytic for the gastrointestinal tract. J Int Med Res 27:207–222 2. Strege PR, Evangelista S, Lyford GL, Sarr MG, Farrugıa G (2004) Otilonium bromide inhibits calcium entry through L-type
Surg Endosc (2015) 29:2266–2269
3. 4.
5.
6.
7.
calcium channels in human intestinal smooth muscle. Neurogastroenterol Motil 16:167–173 Spinelli A (2007) Irritable bowel syndrome. Clin Drug Investig 27(1):15–33 Battaglia G, Morselli-Labate AM, Camarri E, Francavilla A, De Marco F, Mastropaolo G, Naccarato R (1998) Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study. Aliment Pharmacol Ther 12(10):1003–1010 Lynch CR, Khandekar S, Lynch SM et al (2007) Sublingual L-hyoscyamine for duodenal antimotility during ERCP: a prospective randomized doubleblinded study. Gastrointest Endosc 66:748–752 Hannigan BF, Axon AT, Avery S et al (1982) Buscopan or glucagon for endoscopic cannulation of ampulla of vater? J R Soc Med 75:21–22 Yamamoto N, Nakai Y, Sasahira N, Hirano K, Tsujino T, Isayama H, Komatsu Y, Tada M, Yoshida H, Kawabe T, Hiki N, Kaminishi M, Kurosaka H, Omata M (2006) Efficacy of peppermint oil as an
2269
8.
9. 10. 11.
12.
antispasmodic during endoscopic retrograde cholangiopancreatography. J Gastroenterol Hepatol 21(9):1394–1398 Sutton JA, Kilminster SG, Mould GP (1997) The clinical pharmacology of single doses of otilonium bromide in healthy volunteers. Eur J Clin Pharmacol 52(5):365–369 Lazzaroni M, Porro GB (2001) Preparation, premedication, and surveilance. Endoscopy 33(2):103–108 Bell GD (2000) Preparation, premedication, and surveillance. Endoscopy 32(2):92–100 Marshall JB, Patel M, Mahajan RJ, Early DS, King PD, Banerjee B (1999) Benefit of intravenous antispsamodic (hyoscyamine sulfate) as premedication for colonoscopy. Gastrointest Endosc 49:720–726 Go´mez NA, Leo´n CJ, Gutie´rrez J (1997) Use of spasmolytic agent otilonium bromide (spasmomen) in digestive endoscopy: a prospective study in 63 patients. Acta Gastroenterol Latinoam 27(3):123–125
123
