|Year : 2017 | Volume
| Issue : 6 | Page : 631-635
Improvement of Quality of Nonanesthetic Colonoscopy by Preoperative Administration of Pinaverium Bromide
Xiao-Lin Wang1, Jian-Ning Zhou2, Li Ren3, Xiao-Li Pan2, Hong-Yu Ren2, Jun Liu2
1 Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, China
2 Division of Gastroenterology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
3 Division of Pharmacy, Zaoyang First People's Hospital, Zaoyang, Hubei 441200, China
|Date of Submission||20-Oct-2016|
|Date of Web Publication||6-Mar-2017|
Division of Gastroenterology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022
Source of Support: None, Conflict of Interest: None
Background: Nonanesthetic colonoscopy is popular in clinical practice in China. However, intestinal spasms often result in a prolonged examination time, increased operating difficulties, decreased polyp detection rate, and failure to complete the procedure clinically. Therefore, exploring alternative approaches that can reduce the pain in patients during colonoscopy is of utmost importance, and finding the optimal preoperative administration to improve the quality of nonanesthetic colonoscopy is also necessary. This study aimed to investigate the effects of the prophylactic administration of pinaverium bromide before colonoscopy and the effects of pinaverium bromide alone at different time points or combined with scopolamine butylbromide.
Methods: A randomized controlled trial was performed on a cohort of 1000 patients who underwent colonoscopy in outpatient clinic of Wuhan Union Hospital. The patients were randomly assigned to the following groups: Group A, given oral pinaverium bromide (100 mg, three times a day) one day before examination combined with intramuscular injection of scopolamine butylbromide (20 mg) 10 min before colonoscopy; Group B0, given pinaverium bromide alone on the day of colonoscopy (100 mg, three times a day); Group B1, given pinaverium bromide alone (100 mg, three times a day) one day before colonoscopy; Group B2, given pinaverium bromide alone (100 mg, three times a day) two days before colonoscopy; and Group C, given scopolamine butylbromide alone (20 mg) before colonoscopy. The successful rate of colonoscopy, procedure time, degree of abdominal pain, and polyp detection rate were recorded and compared among all groups.
Results: The successful rate of colonoscopy in Group B1(82.0%) and Group B2(83.0%) was significantly higher than that in Group B0(62.0%, all P < 0.01). The time to reach the ileocecal region in Group B1and Group B2were lower than those in Group B0(all P < 0.05). However, no significant differences were observed in polyp detection rate between Group B1(24.0%) or Group B2(26.0%), and Group B0(22.4%, all P > 0.05). Furthermore, there were no significant differences in the various parameters examined between Group B1and Group B2(P > 0.05). The successful rate of colonoscopy in Group A (92.0%) was significantly higher than that in Group B1(82.0%) and Group C (80.0%; both P < 0.05). Moreover, the time for the colonoscope to reach the ileocecal region in Group A were markedly shorter as compared to those in Group B1 and Group C (P < 0.05). The polyp detection rate in Group A was 32.0%, significantly higher than that in Group B1(24.0%, P < 0.05) and Group C (24.2%, P < 0.05).
Conclusion: Administration of pinaverium bromide alone one day before examination was beneficial to relieve symptoms of abdominal pain during nonanesthetic colonoscopy. In addition, therapeutic effects were improved when pinaverium bromide administration was combined with intramuscular injection of scopolamine butylbromide. Therefore, the combined use of pinaverium bromide with scopolamine butylbromide might have great application value to improve the quality of nonanesthetic colonoscopy in the preoperative preparation.
Keywords: Abdominal Pain; Pinaverium Bromide; Routine Colonoscopy
|How to cite this article:|
Wang XL, Zhou JN, Ren L, Pan XL, Ren HY, Liu J. Improvement of Quality of Nonanesthetic Colonoscopy by Preoperative Administration of Pinaverium Bromide. Chin Med J 2017;130:631-5
|How to cite this URL:|
Wang XL, Zhou JN, Ren L, Pan XL, Ren HY, Liu J. Improvement of Quality of Nonanesthetic Colonoscopy by Preoperative Administration of Pinaverium Bromide. Chin Med J [serial online] 2017 [cited 2017 Sep 21];130:631-5. Available from: http://www.cmj.org/text.asp?2017/130/6/631/201597
Xiao-Lin Wang and Jian-Ning Zhou contributed equally to this work.
| Introduction|| |
Currently, improving the detection rate of colorectal polyps is imperative for the prevention of the high incidence of colorectal cancer. Colonoscopy is the most direct and effective procedure for diagnosing a variety of colorectal diseases. Nonanesthetic colonoscopy is popular in clinical practice in China. However, the intestinal spasms often result in a prolonged examination time, increased operating difficulties, decreased polyp detection rate, and failure to complete the procedure clinically. Previous studies have shown that colonoscopic examination could not be completed in 2.4% patients because of pain associated with the procedure. In addition, re-examination was refused in 20.7% of patients due to a high fear factor. Therefore, exploring alternative approaches that can reduce the pain in patients during colonoscopy is of utmost importance, and finding the optimal preoperative administration to improve the quality of nonanesthetic colonoscopy is also necessary. In this randomized controlled trial, we investigated the effects of the prophylactic administration of pinaverium bromide before colonoscopy and the effects of pinaverium bromide alone at different time points or combined with scopolamine butylbromide on the successful rate of colonoscopy, procedure time, abdominal pain, and polyp detection rate, in order to provide insights in the application of pinaverium bromide during nonanesthetic colonoscopy in China.
| Methods|| |
This randomized controlled trial was performed on a total of 1000 patients, who visited the outpatient clinic of Wuhan Union Hospital from August 2015 to June 2016 for a routine colonoscopy, and patients were randomly assigned in a controlled fashion into five groups (n = 200 in each group): Group A, given oral pinaverium bromide (100 mg, three times a day) one day before examination combined with intramuscular injection of scopolamine butylbromide (20 mg) 10 min before colonoscopy; Group B0, given pinaverium bromide alone on the day of colonoscopy (100 mg, three times a day); Group B1, given pinaverium bromide alone (100 mg, three times a day) one day before colonoscopy; Group B2, given pinaverium bubromide alone (100 mg, three times a day) two days before colonoscopy; and Group C, intramuscularly given scopolamine butylbromide alone (20 mg) before colonoscopy. Pinaverium bromide alone at different time points or combined with other medication were randomly assigned according to the random number table. The individuals in each group were randomly assigned to different treatment groups. Patients with the following conditions were excluded from this study: Colon surgery, an incomplete intestinal obstruction or evidence of previous severe intestinal stenosis, severe cardiopulmonary disease, pregnancy, and administration of antispasmodic or anticholinergic medications within one month before the procedure. Colonoscopy was performed by an experienced gastroenterologist who was also responsible for evaluating the examination duration, the degree of abdominal pain, and polyp detection, which were recorded by the assistants. This study was approved by the Ethics Committee of Wuhan Union Hospital, and all patients provided written informed consent.
Drugs and equipment
The drugs and equipment in this study were as follows: pinaverium bromide, 50 mg/tablet (Abbott, USA); polyethylene glycol electrolyte powder composed of 64 g polyethylene glycol 4000, 5.7 g anhydrous sodium sulfate, 1.68 g sodium bicarbonate, 1.46 g sodium chloride, and 0.75 g potassium chloride; 30 ml simethicone emulsion (1 ml emulsion containing 40 mg simethicone); scopolamine butylbromide, 20 mg/ampoule and an Olympus CF-Q260AI colonoscope (Japan).
Administration of polyethylene glycol electrolyte
Only clear liquid food was allowed one day before the procedure, and fasting began at 8 p.m. Two packets of polyethylene glycol electrolyte were dissolved in 2000 ml warm water and consumed within 2 h. At 4 am on the day of the procedure, another two packets of polyethylene glycol electrolyte were dissolved in 2000 ml warm water and consumed within 2 h. At 6 a.m. on the day of the procedure, 30 ml simethicone was taken orally.
Administration of pinaverium bromide
Patients in Group B0 were orally administered with 100 mg pinaverium bromide (50 mg/tablet) 2 h before the examination; those in Group B1 were given 100 mg pinaverium bromide (three times a day) with meals one day before examination and another 100 mg was given 2 h before the examination, and those in Group B2 were given 100 mg pinaverium bromide (three times a day) with meals two days before examination and another 100 mg was given 2 h before examination.
Administration of scopolamine butylbromide
Scopolamine butylbromide 20 mg dissolved in 1 ml of 0.9% saline was intramuscularly injected 10 min before examination.
Abdominal pain scores
The degree of abdominal pain experienced by the individuals during colonoscopy was recorded by the physicians and assistants and scored as follows: Grade I, no abdominal pain with successful examination; Grade II, slight abdominal pain with successful examination; Grade III, moderate but tolerable abdominal pain with successful examination; and Grade IV, severe abdominal pain with un-completed procedure and unsuccessful examination.
Time to reach the ileocecal region
The time for the colonoscope to reach the ileocecal region was defined as <5 min, 5–10 min, and >10 min.
The number and sizes of polyps detected in different sections of the intestine were recorded, and biopsy samples were collected and sent for histopathological examination. The percentage of polyps detected in each group was calculated (number of patients detected with polyps/total number of patients × 100%), and the differences in detection rates between groups were statistically analyzed.
The data were statistically analyzed using SPSS statistical software version 20.0 (SPSS Inc., Chicago, IL, USA). Data were presented as mean ± standard deviation (SD) for quantitative variables or as percentages for qualitative variables. Data comparison was performed using the Chi-squaretest. A P< 0.05 was considered statistically significant.
| Results|| |
Group A included 108 males and 92 females with mean age of 47.5 ± 5.6 years; Group B0 consisted of 105 males and 95 females with mean age of 46.4 ± 6.3 years; Group B1 included 94 males and 106 females with mean age of 49.7 ± 4.8 years; Group B2 included 103 males and 97 females with mean age of 47.1 ± 7.5 years; and Group C included 94 males and 106 females with mean age of 45.3 ± 5.2 years. Among these five groups, no significant differences were observed in gender, age, body mass index, reasons for colonoscopy, and severity of the disease [Table 1].
|Table 1: Baseline clinical characteristics among five groups in this study|
Click here to view
Examination was considered successful when patients experienced Grades I and II abdominal pain. The successful rate in Groups A, B0, B1, B2, and C was 92.0% (184/200), 62.0% (124/200), 82.0% (164/200), 83.0% (166/200), and 80.0% (160/200), respectively. In Groups A, B1, and B2, the colonoscopy was not terminated early due to intolerable abdominal pain in all cases.
The successful rate in Groups B1 and B2 was significantly higher than that in Group B0(χ2 = 19.840, P < 0.001and χ2 = 22.120, P < 0.001). No significant difference in successful rate was observed between Groups B1 and B2(χ2 = 0.070, P = 0.448). The time for the colonoscope to reach the ileocecal region in Groups B1 and B2 was significantly shorter than that in Group B0(χ2 = 19.410, P < 0.001 and χ2 = 25.080, P < 0.001); however, no significant difference was found between Groups B1 and B2(χ2 = 0.69, P = 0.236). Furthermore, there were no significant differences in polyp detection rate among Groups B1(24.0%), B2(26.0%), and B0(22.4%) (B1 vs. B2: χ2 = 0.220, P = 0.057; B1 vs. B0: χ2 = 1.060, P = 0.152; B2 vs. B0: χ2 = 0.320, P = 0.314).
It was found that the successful rate in Group A was significantly higher than that in Group B1 and Group C (χ2 = 8.842, P = 0.002 and χ2 = 11.960, P< 0.001). In addition, the time for the colonoscope to reach the ileocecal region was significantly shorter in Group A than that in Group B1 and Group C (χ2 = 21.240, P = 0.030 and χ2 = 24.750, P = 0.028). Furthermore, the polyp detection rate was markedly higher in Group A (32.0%) than that in Group B1(24.0%; χ2 = 3.170, P = 0.027) and Group C (24.2%; χ2 = 4.470, P = 0.044). No adverse reactions occurred, except for the presence of dry mouth in two patients, each from Group A and Group C. The information of colonoscopy in these five groups is shown in [Table 2].
| Discussion|| |
Effective bowel preparation and strictly followed endoscopic procedures are vital to the success of colorectal cancer examination. Nonanesthetic colonoscopy involves intermittent air insufflation and constant rotation of the endoscope, which, due to the anatomical characteristics of the intestine, can easily stretch and pull the intestines to form loops. The stretch might induce intestinal spasms, especially when patients are under stress, which might lead to abdominal pain and other discomforts. In the most severe cases, patients might not be able to tolerate the pain and the examination needs to be terminated early. Therefore, gastroenterologists are constantly exploring alternative, effective, and safe approaches to reduce the discomfort and pain in patients during colonoscopic examination. In the past, intramuscular injections of anisodamine or diazepam were given before colonoscopy, but general anesthesia is more commonly used in recent years. Although these methods can partially reduce intestinal cramps and alleviate abdominal pain, they are also often accompanied with various adverse reactions such as dry mouth, dysuria, drowsiness, palpitations, and dizziness. In addition to the adverse effects of short-acting anesthetics on the respiratory and cardiovascular systems, the need for anesthesiologists and additional personnel during colonoscopy significantly increases the cost of surgery. Furthermore, if operation-induced intestinal looping occurs when the patient is under general anesthesia, the risk of intestinal injury increases whereas the overall safety factor decreases.
Pinaverium bromide is a highly selective L-type calcium channel blocker that regulates visceral hypersensitivity and abnormal intestinal movement by inhibiting calcium influx.,,, Pinaverium bromide not only promotes regular bowel movement and reduces colonic transit time but also partially relieves abdominal pain by lowering the pain threshold in patients through modulating visceral hypersensitivity. Pinaverium bromide has been used to alleviate the symptoms of irritable bowel syndrome and pains related to colon cramps. Its inhibitory effect on intestinal smooth muscle contraction primarily reduces ineffective and transient spastic contractions but does not affect the spontaneous contraction of the intestine. During colonoscopy, air is intermittently insufflated to dilate the intestine, which in turn causes pain in the patients. A previous study has shown that pinaverium bromide could inhibit the activities of reagents that induced colon contractility; however, it could also alleviate pain by reducing sigmoid pressure. Pinaverium bromide has no anticholinergic activity and has a very low systemic absorption rate, with only 10% of the oral dose going into blood circulation. Of the 10% present in the circulation, 95–98% is bound to plasma proteins and is excreted through the intestinal tract after being metabolized in the liver. Therefore, pinaverium bromide acts mainly on the gastrointestinal tract with high selectivity and has no adverse cardiovascular effects.
It has previously been reported that pinaverium bromide was a simple and effective reagent in preventing abdominal pain caused by intestinal cramps during colonoscopy. In the current study, we demonstrated that abdominal pain and discomfort were significantly reduced when patients were given pinaverium bromide 1–2 days before colonoscopy. In addition, significant sense of intestinal relaxation, ease of endoscope maneuver, and a shortened procedure time were observed during colonoscopy. However, the study also found that pinaverium bromide taken two days before examination had no additional beneficial effect over pinaverium bromide taken one day before colonoscopy. This indicated that the administration of pinaverium bromide alone one day before procedure was as effective as pinaverium bromide administered two days before colonoscopy. Pinaverium bromide could alleviate the symptoms of abdominal pain in routine colonoscopy.
Scopolamine butylbromide is a synthetic, peripheral cholinergic receptor blocker that ameliorates the hyperreactivity of cholinergic receptors in the preganglionic sympathetic neurons and reduces the overcontraction of visceral smooth muscles.,, In contrast, an M-cholinergic receptor blocker, anisodamine, can inhibit peripheral cholinergic activities but its therapeutic dose has no significant inhibitory effect on excessive smooth muscle spasm. Meanwhile, the highly water-soluble and nearly lipid-insoluble properties of scopolamine butylbromide prevent it from passing through the blood-brain barrier. It has no antagonistic effect on central M-cholinergic receptors and has very weak activities in the central nervous system, and therefore rarely causes dry mouth or other clinical adverse reactions. A study has shown that scopolamine butylbromide is safe and effective for endoscopic examination and treatment of the gastrointestinal system. The current study revealed that the combined use of pinaverium bromide and scopolamine butylbromide achieved significantly better results than pinaverium bromide or scopolamine butylbromide used alone.
This study had certain limitations that should be taken into consideration. This was only a single-blind trial. In addition, the sample size was a little small.
In summary, the study demonstrated that pinaverium bromide alone taken one day before colonoscopy can effectively alleviate abdominal pain, facilitate the completion of routine colonoscopy, and reduce the examination time. Preoperative administration of pinaverium bromide has improved the quality of nonanesthetic colonoscopy. Moreover, the combined use of pinaverium bromide one day before the colonoscopy and intramuscular injection of scopolamine butylbromide shortly before colonoscopy demonstrated even better therapeutic effects, with significantly enhanced polyp detection rate. In conclusion, the combination of pinaverium bromide and scopolamine butylbromide treatment is inexpensive and safe, does not show significant adverse effects and significantly improves patient compliance. Therefore, the combination of pinaverium bromide and scopolamine butylbromide might be a promising and novel approach in the preoperative administration to improve the quality of nonanesthetic colonoscopy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Simmons DT, Harewood GC, Baron TH, Petersen BT, Wang KK, Boyd-Enders F, et al.
Impact of endoscopist withdrawal speed on polyp yield: Implications for optimal colonoscopy withdrawal time. Aliment Pharmacol Ther 2006;24:965-71. doi: 10.1111/j.1365-2036.2006.03080.x.
Annese V, Daperno M, Rutter MD, Amiot A, Bossuyt P, East J, et al.
European evidence based consensus for endoscopy in inflammatory bowel disease. J Crohns Colitis 2013;7:982-1018. doi: 10.1016/j.crohns.2013.09.016.
Dai Y, Liu JX, Li JX, Xu YF. Effect of pinaverium bromide on stress-induced colonic smooth muscle contractility disorder in rats. World J Gastroenterol 2003;9:557-61. doi: 10.3748/WJG.v9.i3.557.
Golovanova ES, Kravtsova TI, Vysokova OL. Effects of dicetel on gastrointestinal motility and vegetative dysfunction in patients with duodenal ulcer. Klin Med (Mosk) 2003;81:31-5.
Boyer JC, Magous R, Christen MO, Balmes JL, Bali JP. Contraction of human colonic circular smooth muscle cells is inhibited by the calcium channel blocker pinaverium bromide. Cell Calcium 2001;29:429-38. doi: 10.1054/ceca.2001.0205.
Li J, Li P, Bai J, Lyu H, Li Y, Yang H, et al.
Discriminating potential of extraintestinal systemic manifestations and colonoscopic features in Chinese patients with intestinal Behçet's disease and Crohn's disease. Chin Med J 2015;128:233-8. doi: 10.4103/0366-6999.149213.
] [Full text]
Annaházi A, Róka R, Rosztóczy A, Wittmann T. Role of antispasmodics in the treatment of irritable bowel syndrome. World J Gastroenterol 2014;20:6031-43. doi: 10.3748/wjg.v20.i20.6031.
Froguel E, Chaussade S, Roche H, Fallet M, Couturier D, Guerre J. Effects of an intestinal smooth muscle calcium channel blocker (pinaverium bromide) on colonie transit time in humans. Neurogastroenterol Motil 2008;2:176-9. doi: 10.1111/j.1365-2982.1990.tb00021.x.
Passaretti S, Sorghi M, Colombo E, Mazzotti G, Tittobello A, Guslandi M. Motor effects of locally administered pinaverium bromide in the sigmoid tract of patients with irritable bowel syndrome. Int J Clin Pharmacol Ther Toxicol 1989;27:47-50.
Zheng L, Lai Y, Lu W, Li B, Fan H, Yan Z, et al.
Pinaverium reduces symptoms of irritable bowel syndrome in a multicenter, randomized, controlled trial. Clin Gastroenterol Hepatol 2015;13:1285-92.e1. doi: 10.1016/j.cgh.2015.01.015.
Gutzeit A, Binkert CA, Koh DM, Hergan K, von Weymarn C, Graf N, et al.
Evaluation of the anti-peristaltic effect of glucagon and hyoscine on the small bowel: Comparison of intravenous and intramuscular drug administration. Eur Radiol 2012;22:1186-94. doi: 10.1007/s00330-011-2366-1.
Rondonotti E, Zolk O, Amato A, Paggi S, Baccarin A, Spinzi G, et al.
The impact of hyoscine-N-butylbromide on adenoma detection during colonoscopy: Meta-analysis of randomized, controlled studies. Gastrointest Endosc 2014;80:1103-12.e2. doi: 10.1016/j.gie.2014.05.319.
Cao HL, Chen X, Du SC, Song WJ, Wang WQ, Xu MQ, et al.
Detection rate, distribution, clinical and pathological features of colorectal serrated polyps. Chin Med J 2016;129:2427-33. doi: 10.4103/0366-6999.191759.
] [Full text]
Suzuki I, Miyazaki Y, Uchino T, Kagawa Y. Comparison in dissolution behavior of ethical and over-the counter scopolamine butylbromide. Yakugaku Zasshi 2011;131:1645-51. doi: 10.1248/yakushi.131.1645.
Chaptini LA, Janec EM, Seltzer G, Peikin S, Elfant AB. Sublingual hyoscyamine spray as premedication for colonoscopy: A randomized double-blinded placebo-controlled trial. Am J Surg 2008;196:51-5. doi: 10.1016/j.amjsurg.2007.06.030.
[Table 1], [Table 2]