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Marcin B, Katarzyna SA, Ivan K. The role of beta-adrenoreceptors in postoperative ileus in rats. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:4851-4857. [PMID: 38157026 PMCID: PMC11166813 DOI: 10.1007/s00210-023-02918-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 12/20/2023] [Indexed: 01/03/2024]
Abstract
The aim of the research was to evaluate the influence of antagonists of specific beta-adrenergic receptor subtypes on bowel motility following abdominal surgery in rat model of postoperative ileus. Bowel motility was measured by the intestinal transit of Evans blue introduced via orogastric tube after surgical procedures of skin incision, laparotomy and laparotomy with gut manipulation. Male rats were given individual adrenergic receptor subtypes antagonists intraperitoneally, and the influence of administered agents on intestinal transit of Evans blue was then evaluated. No statistically significant differences in the length of intestine in tested rats were observed. Propranolol administered prior to surgical procedure has shown protective effect on Evans blue migration in rats undergoing laparotomy and gut manipulation. Intestinal dye transit for propranolol doses of 10, 30 and 45 mg/kg was 18.00 ± 1.88c m, 23.75 ± 1.71 cm and 22.5 ± 2.43 cm, respectively, and for last two doses, statistically significant increase of dye passage was noted, compared to Evans blue transit of 11.00 ± 2.43 cm in the control group. No acceleration of dye migration was seen following administration of beta1-, beta2- and beta3-selective adrenergic receptor antagonist metoprolol, ICI 118.551 and SR58894A, respectively. Our research confirmed that propranolol at high doses, as seen by other researchers, improved bowel motility in early phase of postoperative ileus. That slight acceleration of intestinal dye transit after surgery with gut manipulation is rather connected with membrane-stabilizing action, than the receptor blocking effect, as this effect was not observed after the application of selective antagonists of respective subtypes of beta-adrenergic receptor.
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Affiliation(s)
- Bitel Marcin
- Department of Pharmacology, Faculty of Medicine, Medical University of Gdańsk, Dębowa Str. 23, 80-204, Gdańsk, Poland
| | | | - Kocić Ivan
- Department of Pharmacology, Faculty of Medicine, Medical University of Gdańsk, Dębowa Str. 23, 80-204, Gdańsk, Poland.
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Li M, Xu F, Liu M, Li Y, Zheng J, Zhu Y, Lin L, Chen J. Effects and Mechanisms of Transcutaneous Electrical Acustimulation on Postoperative Recovery After Elective Cesarean Section. Neuromodulation 2020; 23:838-846. [DOI: 10.1111/ner.13178] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 04/09/2020] [Accepted: 04/27/2020] [Indexed: 12/28/2022]
Affiliation(s)
- Miaomiao Li
- Division of Gastroenterology the First Affiliated Hospital of Nanjing Medical University Nanjing China
- Division of Gastroenterology the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University Huaian China
| | - Feng Xu
- Division of Gastroenterology Yinzhou Hospital Affiliated to Medical School of Ningbo University Ningbo China
| | - Minjie Liu
- Division of Obstetrics Yinzhou Hospital Affiliated to Medical School of Ningbo University Ningbo China
| | - Yinfang Li
- Division of Obstetrics Yinzhou Hospital Affiliated to Medical School of Ningbo University Ningbo China
| | - Jingfei Zheng
- Division of Obstetrics Yinzhou Hospital Affiliated to Medical School of Ningbo University Ningbo China
| | - Ying Zhu
- Division of Gastroenterology the First Affiliated Hospital of Nanjing Medical University Nanjing China
- Division of Gastroenterology Northern Jiangsu People's Hospital Yangzhou China
| | - Lin Lin
- Division of Gastroenterology the First Affiliated Hospital of Nanjing Medical University Nanjing China
| | - Jiande Chen
- Division of Gastroenterology and Hepatology Johns Hopkins University School of Medicine Baltimore MD USA
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Okada M, Itoh K, Kitakoji H, Imai K. Mechanism of Electroacupuncture on Postoperative Ileus Induced by Surgical Stress in Rats. Med Acupunct 2019; 31:109-115. [PMID: 31031877 DOI: 10.1089/acu.2018.1322] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Objectives: Acupuncture has been used for treating gastrointestinal (GI) disorders such as postoperative nausea and vomiting. Electroacupuncture (EA) accelerates GI transit following surgery and ameliorates postoperative ileus (POI) to restore colonic transit (CT); however, the mechanisms of this EA-induced restoration remain unclear. The aims of this study were to show CT following surgery and the effects of EA at ST 36 on POI induced by surgical stress (SS) in 45 conscious, male Sprague-Dawley rats. Materials and Methods: An operation was performed in each rat, setting a cannula into the cecum to connect the proximal colon to inject markers. On the day after surgery, 20 metal radiopaque markers were administered to the proximal colon of each rat. These markers were visible throughout the GI tract on soft X-ray immediately after administration and up to 240 minutes afterward. The rats were divided into 5 groups with 9 rats in each group: (1) SS; (2) 5 days post surgery (POST-5D); (3) SS + phentolamine; (4) EA alone; and (5) EA + atropine. The EA was performed at ST 36 for 20 minutes at a frequency of 10 Hz and agents were administered in the appropriate groups before markers were administered and measurements were taken. Measurements were performed the day after surgery except in the POST 5-D group. CT was calculated by the geometric center on the images showing the CT for each rat. Results: CT after surgery was delayed significantly and phentolamine accelerated CT. EA restored CT following surgery and atropine abolished the effect of EA on CT. Conclusions: The current study demonstrated that surgery induced a delay in CT through the sympathetic pathway via α-adrenoreceptors; CT was restored by EA. These results suggest that EA can be used to treat POI through mediation of the autonomic nervous system.
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Affiliation(s)
- Misaki Okada
- Department of Acupuncture and Moxibustion, Meiji University of Integrative Medicine, Kyoto, Japan
| | - Kazunori Itoh
- Department of Acupuncture and Moxibustion, Meiji University of Integrative Medicine, Kyoto, Japan
| | - Hiroshi Kitakoji
- Department of Acupuncture and Moxibustion, Takarazuka University of Medical and Health Care, Hyogo, Japan
| | - Kenji Imai
- Department of Acupuncture and Moxibustion, Faculty of Health Science, Teikyo Heisei University, Tokyo, Japan
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Wan Q, Ding W, Cui X, Zeng X. CONSORT-epidural dexmedetomidine improves gastrointestinal motility after laparoscopic colonic resection compared with morphine. Medicine (Baltimore) 2018; 97:e11218. [PMID: 29924051 PMCID: PMC6024965 DOI: 10.1097/md.0000000000011218] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND We have previously shown that epidural dexmedetomidine, when used as an adjunct to levobupivacaine for control of postoperative pain after open colonic resection, improves recovery of gastrointestinal motility compared with morphine. METHODS Sixty patients undergoing laparoscopic colonic resection were enrolled and allocated randomly to treatment with dexmedetomidine (group D) or morphine (group M). Group D received an epidural loading dose of dexmedetomidine (5 mL, 0.5 μg/kg), followed by continuous epidural administration of dexmedetomidine (80 μg) in 0.125% levobupivacaine (240 mL) at a rate of 5 mL/h for 2 days. Group M received an epidural loading dose of morphine (5 mL, 0.03 mg/kg) followed by continuous epidural administration of morphine (4.5 mg) in 0.125% levobupivacaine (240 mL) at a rate of 5 mL/h for 2 days. Verbal rating score (VRS) of pain, postoperative analgesic requirements, side effects related to analgesia, and time to postoperative first flatus (FFL) and first feces (FFE) were recorded. RESULTS VRS and postoperative analgesic requirements were not significantly different between the treatment groups. In contrast, FFL and FFE were significant delayed in group M compared with group D (P < .05). Patients in group M also had a significantly higher incidence of nausea, vomiting, and pruritus (P < .05). No neurological deficits were observed in either group. CONCLUSIONS Compared with morphine, epidural dexmedetomidine is a better adjunct to levobupivacaine for control of postoperative pain after laparoscopic colonic resection.
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Zádori ZS, Gyires K. In Vivo Measurement of Intragastric Pressure with a Rubber Balloon in the Anesthetized Rat. ACTA ACUST UNITED AC 2018; 57:21.12.1-6.17.11. [DOI: 10.1002/0471140856.tx2112s57] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Zoltán S. Zádori
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University Budapest Hungary
| | - Klára Gyires
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University Budapest Hungary
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Zeng XZ, Lu ZF, Lv XQ, Guo YP, Cui XG. Epidural Co-Administration of Dexmedetomidine and Levobupivacaine Improves the Gastrointestinal Motility Function after Colonic Resection in Comparison to Co-Administration of Morphine and Levobupivacaine. PLoS One 2016; 11:e0146215. [PMID: 26751791 PMCID: PMC4709108 DOI: 10.1371/journal.pone.0146215] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 12/14/2015] [Indexed: 01/10/2023] Open
Abstract
UNLABELLED Gastrointestinal motility may be impaired after intestinal surgery. Epidural morphine is effective in controlling postoperative pain, but can further reduce gastrointestinal motility. Here, we aimed to investigate the effects of epidural dexmedetomidine on gastrointestinal motility in patients undergoing colonic resection. Seventy-four patients undergoing colonic resection were enrolled in this clinical trial and allocated randomly to treatment with dexmedetomidine (D group) or morphine (M group). The D group received a loading dose epidural administration of 3 ml dexmedetomidine (0.5 μg kg(-1)) and then a continuous epidural administration of 80 μg dexmedetomidine in 150 ml levobupivacaine (0.125%) at 3 ml h(-1) for two days. The M group received a loading dose epidural administration of 3 ml morphine (0.03 mg kg(-1)) and then a continuous epidural administration of 4.5 mg morphine in 150 ml levobupivacaine at 3 ml h(-1) for two days. Verbal rating score (VRS), postoperative analgesic requirements, side effects related to analgesia, the time to postoperative first flatus (FFL) and first feces (FFE) were recorded. VRS and postoperative analgesic requirements were not significantly different between treatment groups. In contrast, the time to FFL and time to FFE were significant longer in M group in comparison to D group (P < 0.05). Moreover, patients in M group had a significantly higher incidence of nausea, vomiting, and pruritus (P < 0.05). No patients showed neurologic deficits in either group. In comparison to morphine, epidural dexmedetomidine is safe and beneficial for the recovery of gastrointestinal motility after colonic resection when used as an adjunct with levobupivacaine for postoperative pain control. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR-TRC-14004644.
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Affiliation(s)
- Xian-Zhang Zeng
- Department of Anesthesiology, Second Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, Heilongjiang, China
| | - Zhi-Fang Lu
- Department of Anesthesiology, Second Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, Heilongjiang, China
| | - Xiang-Qi Lv
- Department of Anesthesiology, Second Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, Heilongjiang, China
| | - Yue-Ping Guo
- Department of Anesthesiology, Second Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, Heilongjiang, China
| | - Xiao-Guang Cui
- Department of Anesthesiology, Second Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, Heilongjiang, China
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Wang L, Mogami S, Yakabi S, Karasawa H, Yamada C, Yakabi K, Hattori T, Taché Y. Patterns of Brain Activation and Meal Reduction Induced by Abdominal Surgery in Mice and Modulation by Rikkunshito. PLoS One 2015; 10:e0139325. [PMID: 26421719 PMCID: PMC4589401 DOI: 10.1371/journal.pone.0139325] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Accepted: 09/11/2015] [Indexed: 12/15/2022] Open
Abstract
Abdominal surgery inhibits food intake and induces c-Fos expression in the hypothalamic and medullary nuclei in rats. Rikkunshito (RKT), a Kampo medicine improves anorexia. We assessed the alterations in meal microstructure and c-Fos expression in brain nuclei induced by abdominal surgery and the modulation by RKT in mice. RKT or vehicle was gavaged daily for 1 week. On day 8 mice had no access to food for 6–7 h and were treated twice with RKT or vehicle. Abdominal surgery (laparotomy-cecum palpation) was performed 1–2 h before the dark phase. The food intake and meal structures were monitored using an automated monitoring system for mice. Brain sections were processed for c-Fos immunoreactivity (ir) 2-h after abdominal surgery. Abdominal surgery significantly reduced bouts, meal frequency, size and duration, and time spent on meals, and increased inter-meal interval and satiety ratio resulting in 92–86% suppression of food intake at 2–24 h post-surgery compared with control group (no surgery). RKT significantly increased bouts, meal duration and the cumulative 12-h food intake by 11%. Abdominal surgery increased c-Fos in the prelimbic, cingulate and insular cortexes, and autonomic nuclei, such as the bed nucleus of the stria terminalis, central amygdala, hypothalamic supraoptic (SON), paraventricular and arcuate nuclei, Edinger-Westphal nucleus (E-W), lateral periaqueduct gray (PAG), lateral parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius (NTS). RKT induced a small increase in c-Fos-ir neurons in the SON and E-W of control mice, and in mice with surgery there was an increase in the lateral PAG and a decrease in the NTS. These findings indicate that abdominal surgery inhibits food intake by increasing both satiation (meal duration) and satiety (meal interval) and activates brain circuits involved in pain, feeding behavior and stress that may underlie the alterations of meal pattern and food intake inhibition. RKT improves food consumption post-surgically that may involve modulation of pain pathway.
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Affiliation(s)
- Lixin Wang
- CURE/Digestive Diseases Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, University of California at Los Angeles, and VA Greater Los Angeles Health Care System, Los Angeles, California, United States of America
- * E-mail:
| | - Sachiko Mogami
- Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan
| | - Seiichi Yakabi
- CURE/Digestive Diseases Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, University of California at Los Angeles, and VA Greater Los Angeles Health Care System, Los Angeles, California, United States of America
| | - Hiroshi Karasawa
- CURE/Digestive Diseases Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, University of California at Los Angeles, and VA Greater Los Angeles Health Care System, Los Angeles, California, United States of America
| | - Chihiro Yamada
- Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan
| | - Koji Yakabi
- Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Tomohisa Hattori
- Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan
| | - Yvette Taché
- CURE/Digestive Diseases Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, University of California at Los Angeles, and VA Greater Los Angeles Health Care System, Los Angeles, California, United States of America
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8
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Holmes GM, Swartz EM, McLean MS. Fabrication and implantation of miniature dual-element strain gages for measuring in vivo gastrointestinal contractions in rodents. J Vis Exp 2014:51739. [PMID: 25285858 DOI: 10.3791/51739] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Gastrointestinal dysfunction remains a major cause of morbidity and mortality. Indeed, gastrointestinal (GI) motility in health and disease remains an area of productive research with over 1,400 published animal studies in just the last 5 years. Numerous techniques have been developed for quantifying smooth muscle activity of the stomach, small intestine, and colon. In vitro and ex vivo techniques offer powerful tools for mechanistic studies of GI function, but outside the context of the integrated systems inherent to an intact organism. Typically, measuring in vivo smooth muscle contractions of the stomach has involved an anesthetized preparation coupled with the introduction of a surgically placed pressure sensor, a static pressure load such as a mildly inflated balloon or by distending the stomach with fluid under barostatically-controlled feedback. Yet many of these approaches present unique disadvantages regarding both the interpretation of results as well as applicability for in vivo use in conscious experimental animal models. The use of dual element strain gages that have been affixed to the serosal surface of the GI tract has offered numerous experimental advantages, which may continue to outweigh the disadvantages. Since these gages are not commercially available, this video presentation provides a detailed, step-by-step guide to the fabrication of the current design of these gages. The strain gage described in this protocol is a design for recording gastric motility in rats. This design has been modified for recording smooth muscle activity along the entire GI tract and requires only subtle variation in the overall fabrication. Representative data from the entire GI tract are included as well as discussion of analysis methods, data interpretation and presentation.
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Affiliation(s)
- Gregory M Holmes
- Department of Neural and Behavioral Sciences, Penn State University College of Medicine;
| | - Emily M Swartz
- Department of Neural and Behavioral Sciences, Penn State University College of Medicine
| | - Margaret S McLean
- Department of Neural and Behavioral Sciences, Penn State University College of Medicine
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Raju DP, Hakendorf P, Costa M, Wattchow DA. Efficacy and safety of low-dose celecoxib in reducing post-operative paralytic ileus after major abdominal surgery. ANZ J Surg 2013; 85:946-50. [PMID: 26780018 DOI: 10.1111/ans.12475] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/15/2013] [Indexed: 01/15/2023]
Abstract
BACKGROUND A number of interventions have been used to decrease the incidence of post-operative paralytic ileus. A secondary outcome of a randomized controlled study showed that COX-2 inhibitors decreased the incidence of paralytic ileus. We sought to study a large cohort of patients undergoing major abdominal operations who were treated with a COX-2 inhibitor. METHODS This is a retrospective review of prospectively collected data. All eligible patients were given a COX-2 inhibitor--celecoxib 100 mg--twice daily starting on the day of surgery until the seventh day post-operatively or discharge, whichever was earlier. The rate of paralytic ileus was calculated and compared with historical data. Secondary outcome measures were the effect of using COX-2 inhibitors on renal function, electrolytes and haemoglobin, morbidity and leak rates. RESULTS Two hundred and fifty-two patients were treated with celecoxib; the control arm consisted of 67 historical patients. Of the 252 patients, we had complete data for 235 patients and ileus in 17 patients (7.23%) compared with 13.4% in the control group (P = 0.05). Subgroup analysis showed ileus in 5.45% of colectomy patients and 6.36% of patients who have had a colectomy and high anterior resection. There was no detriment of measured blood tests. There were leaks in two treated patients, both of whom did not require a laparotomy. CONCLUSIONS The use of low-dose COX-2 inhibitor over a short period of time decreases the paralytic ileus rates and does not cause any significant morbidity.
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Affiliation(s)
- Devinder P Raju
- Department of Colorectal Surgery, Flinders Medical Center, Adelaide, South Australia, Australia
| | - Paul Hakendorf
- Department of Clinical Epidemiology, Flinders Medical Center, Adelaide, South Australia, Australia
| | - Marcello Costa
- Department of Human Physiology, Flinders University, Adelaide, South Australia, Australia
| | - David A Wattchow
- Department of Colorectal Surgery, Flinders Medical Center, Flinders Private Hospital, Flinders University, Adelaide, South Australia, Australia
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10
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Atrial stretch delays gastric emptying of liquids in awake rats. Life Sci 2013; 92:569-75. [PMID: 23352973 DOI: 10.1016/j.lfs.2013.01.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2012] [Revised: 11/16/2012] [Accepted: 01/10/2013] [Indexed: 12/19/2022]
Abstract
AIMS We previously reported that mechanical atrial stretch (AS) by balloon distention increased gastric tonus in anesthetized rats. The present study evaluated the effect of AS on the gastric emptying of a liquid test meal in awake rats and its underlying neural mechanisms. MAIN METHODS Anesthetized male rats received a balloon catheter into the right atrium and a gastrostomy cannula. The next day, mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), and cardiac output (CO) were continuously monitored. After the first 20min of monitoring (basal interval), the balloon was either distended or not (control) with 30, 50, or 70μl saline for 5min. Fifteen minutes later, the rats received the test meal (glucose solution with phenol red), and fractional gastric dye retention was determined 10, 20, or 30min later. KEY FINDINGS Heart rate and CVP values were transiently increased by 50 or 70μl AS but not 30μl AS, whereas gastric emptying was slower after 30, 50, or 70μl AS than after sham distention. Subdiaphragmatic vagotomy or splanchnicotomy+celiac ganglionectomy and capsaicin, ondansetron, hexamethonium, L-NAME, and glibenclamide treatment prevented the AS-induced delay in gastric emptying, whereas atropine and guanethidine treatment failed to prevent it. SIGNIFICANCE Atrial stretch inhibited the gastric emptying of liquid via non-adrenergic and non-cholinergic pathways that activate nitric oxide-K(+)ATP channels.
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Huang YM, Yang CCH, Lai CJ, Kuo TBJ. The influence of autonomic interventions on the sleep-wake-related changes in gastric myoelectrical activity in rats. Neurogastroenterol Motil 2011; 23:560-e208. [PMID: 21342364 DOI: 10.1111/j.1365-2982.2011.01687.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Significant changes in autonomic activity occur at sleep-wake transitions and constitute an ideal setting for investigating the modulatory role of the autonomic nervous system on gastric myoelectrical activity (GMA). METHODS Using continuous power spectral analysis of electroencephalogram, electromyogram, and electrogastromyogram (EGMG) data from freely moving rats that had undergone chemical sympathetomy and/or truncal vagotomy, sleep-wake-related fluctuations in GMA were compared among the intervention groups. KEY RESULTS The pattern and extent of fluctuations in EGMG power across the sleep-wake states was blunted most significantly in rats undergoing both chemical sympathectomy and truncal vagotomy. The effect of these interventions also varied with respect to the transition between different sleep-wake states. The most prominent influences were observed between active waking and quiet sleep and between paradoxical sleep and quiet sleep. CONCLUSIONS & INFERENCES The sleep-wake-related fluctuations in EGMG power are a result of joint contributions from both sympathetic and vagal innervation. Vagotomy mainly resulted in a reduction in EGMG power, while the role of sympathetic innervation was unveiled by vagotomy and this was reflected most obviously in the extent of the fluctuations in EGMG power.
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Affiliation(s)
- Y M Huang
- Department of Surgery, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
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12
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Gourcerol G, Adelson DW, Million M, Wang L, Taché Y. Modulation of gastric motility by brain-gut peptides using a novel non-invasive miniaturized pressure transducer method in anesthetized rodents. Peptides 2011; 32:737-46. [PMID: 21262308 PMCID: PMC3060955 DOI: 10.1016/j.peptides.2011.01.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2010] [Revised: 01/11/2011] [Accepted: 01/11/2011] [Indexed: 01/18/2023]
Abstract
Acute in vivo measurements are often the initial, most practicable approach used to investigate the effects of novel compounds or genetic manipulations on the regulation of gastric motility. Such acute methods typically involve either surgical implantation of devices or require intragastric perfusion of solutions, which can substantially alter gastric activity and may require extended periods of time to allow stabilization or recovery of the preparation. We validated a simple, non-invasive novel method to measure acutely gastric contractility, using a solid-state catheter pressure transducer inserted orally into the gastric corpus, in fasted, anesthetized rats or mice. The area under the curve of the phasic component (pAUC) of intragastric pressure (IGP) was obtained from continuous manometric recordings of basal activity and in responses to central or peripheral activation of cholinergic pathways, or to abdominal surgery. In rats, intravenous ghrelin or intracisternal injection of the thyrotropin-releasing hormone agonist, RX-77368, significantly increased pAUC while coeliotomy and cacal palpation induced a rapid onset inhibition of phasic activity lasting for the 1-h recording period. In mice, RX-77368 injected into the lateral brain ventricle induced high-amplitude contractions, and carbachol injected intraperitoneally increased pAUC significantly, while coeliotomy and cecal palpation inhibited baseline contractile activity. In wild-type mice, cold exposure (15 min) increased gastric phasic activity and tone, while there was no gastric response in corticotropin releasing factor (CRF)-overexpressing mice, a model of chronic stress. Thus, the novel solid-state manometric approach provides a simple, reliable means for acute pharmacological studies of gastric motility effects in rodents. Using this method we established in mice that the gastric motility response to central vagal activation is impaired under chronic expression of CRF.
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Affiliation(s)
- Guillaume Gourcerol
- CURE/Digestive Diseases Research Center, and Center for Neurobiology of Stress, Department of Medicine, Division of Digestive Diseases, University of California, Los Angeles, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA
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13
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Leslie JB, Viscusi ER, Pergolizzi JV, Panchal SJ. Anesthetic Routines: The Anesthesiologist's Role in GI Recovery and Postoperative Ileus. Adv Prev Med 2010; 2011:976904. [PMID: 21991449 PMCID: PMC3168940 DOI: 10.4061/2011/976904] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2010] [Accepted: 11/13/2010] [Indexed: 12/22/2022] Open
Abstract
All patients undergoing bowel resection experience postoperative ileus, a transient cessation of bowel motility that prevents effective transit of intestinal contents or tolerance of oral intake, to varying degrees. An anesthesiologist plays a critical role, not only in the initiation of surgical anesthesia, but also with the selection and transition to effective postoperative analgesia regimens. Attempts to reduce the duration of postoperative ileus have prompted the study of various preoperative, perioperative, and postoperative regimens to facilitate gastrointestinal recovery. These include modifiable variables such as epidural anesthesia and analgesia, opioid-sparing anesthesia and analgesia, fluid restriction, colloid versus crystalloid combinations, prokinetic drugs, and use of the new peripherally acting mu-opioid receptor (PAM-OR) antagonists. Review and appropriate adaptation of these multiple modifiable interventions by anesthesiologists and their surgical colleagues will facilitate implementation of a best-practice management routine for bowel resection procedures that will benefit the patient and the healthcare system.
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Affiliation(s)
- John B Leslie
- Department of Anesthesiology, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259-5404, USA
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14
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Wattchow DA, De Fontgalland D, Bampton PA, Leach PL, McLaughlin K, Costa M. Clinical trial: the impact of cyclooxygenase inhibitors on gastrointestinal recovery after major surgery - a randomized double blind controlled trial of celecoxib or diclofenac vs. placebo. Aliment Pharmacol Ther 2009; 30:987-98. [PMID: 19694636 DOI: 10.1111/j.1365-2036.2009.04126.x] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Ileus occurs after abdominal surgery and may be severe. Inhibition of prostaglandin release reduces post-operative ileus in a rat model. AIM To determine whether prostaglandin inhibition by cyclooxygenase inhibitors, celecoxib or diclofenac, could enhance gastrointestinal recovery and reduce post-operative ileus in humans. METHODS Two hundred and ten patients undergoing elective major abdominal surgery were randomized to receive twice daily placebo (n = 67), celecoxib (100 mg, n = 74) or diclofenac (50 mg, n = 69), preoperatively and continuing for up to 7 days. Primary outcomes were hallmarks of gut recovery. Secondary outcomes were paralytic ileus, pain and complications. RESULTS There was no clinically significant difference between the groups for restoration of bowel function. There was a significant reduction in paralytic ileus in the celecoxib-treated group (n = 1, 1%) compared with diclofenac (n = 7, 10%) and placebo (n = 9, 13%); P = 0.025, RR 0.20, CI 0.01-0.77. Pain scores, analgesia, transfusion requirements and adverse event rates were similar between study groups. CONCLUSIONS Perioperative low dose celecoxib, but not diclofenac, markedly reduced the development of paralytic ileus following major abdominal surgery, but did not accelerate early recovery of bowel function. This was independent of narcotic use and had no increase in post-operative complications.
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Affiliation(s)
- D A Wattchow
- Departments of Surgery, Flinders Medical Centre, Bedford Park, SA, Australia.
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Holmes GM, Tong M, Travagli RA. Effects of brain stem cholecystokinin-8s on gastric tone and esophageal-gastric reflex. Am J Physiol Gastrointest Liver Physiol 2009; 296:G621-31. [PMID: 19136379 PMCID: PMC2660178 DOI: 10.1152/ajpgi.90567.2008] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The actions of cholecystokinin (CCK) on gastrointestinal functions occur mainly via paracrine effects on peripheral sensory vagal fibers, which engage vago-vagal brain stem circuits to convey effector responses back to the gastrointestinal tract. Recent evidence suggests, however, that CCK also affects brain stem structures directly. Many electrophysiological studies, including our own, have shown that brain stem vagal circuits are excited by sulfated CCK (CCK-8s) directly, and we have further demonstrated that CCK-8s induces a remarkable degree of plasticity in GABAergic brain stem synapses. In the present study, we used fasted, anesthetized Sprague-Dawley rats to investigate the effects of brain stem administration of CCK-8s on gastric tone before and after activation of the esophageal-gastric reflex. CCK-8s microinjected in the dorsal vagal complex (DVC) or applied on the floor of the fourth ventricle induced an immediate and transient decrease in gastric tone. Upon recovery of gastric tone to baseline values, the gastric relaxation induced by esophageal distension was attenuated or even reversed. The effects of CCK-8s were antagonized by vagotomy or fourth ventricular, but not intravenous, administration of the CCK-A antagonist lorglumide, suggesting a central, not peripheral, site of action. The gastric relaxation induced by DVC microinjection of CCK-8s was unaffected by pretreatment with systemic bethanecol but was completely blocked by NG-nitro-L-arginine methyl ester, suggesting a nitrergic mechanism of action. These data suggest that 1) brain stem application of CCK-8s induces a vagally mediated gastric relaxation; 2) the CCK-8s-induced gastric relaxation is mediated via activation of nonadrenergic, noncholinergic pathways; and 3) CCK-8s reverses the esophageal-gastric reflex transiently.
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Affiliation(s)
- Gregory M. Holmes
- Department of Neuroscience, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana
| | - Melissa Tong
- Department of Neuroscience, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana
| | - R. Alberto Travagli
- Department of Neuroscience, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana
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Abstract
Gastric reflexes are mediated mainly by vago-vagal reflex circuits in the caudal medulla. Despite the fact that brainstem vago-vagal circuitry remains intact after spinal cord injury (SCI), patients with SCI at the cervical level most often present gastric stasis with an increased risk of reflux and aspiration of gastric contents. Using a miniature strain gauge sutured to the gastric surface; we tested gastric motility and reflexive gastric relaxation following oesophageal distension (oesophageal-gastric relaxation reflex) in animals 3 days after a severe spinal contusion at either the third or ninth thoracic spinal segment (acute T3- or T9 SCI, respectively). Both basal gastric motility and the oesophageal-gastric relaxation reflex were significantly diminished in animals with T3 SCI. Conversely, both basal gastric motility and the oesophageal-gastric relaxation reflex were not significantly reduced in T9 SCI animals compared to controls. The reduced gastric motility and oesophageal-gastric reflex in T3 SCI rats was not ameliorated by celiac sympathectomy. Our results show that gastric stasis following acute SCI is independent of altered spinal sympathetic input to the stomach caudal to the lesion. Our data suggest that SCI may alter the sensitivity of vagal reflex function, perhaps by interrupting ascending spinosolitary input to brainstem vagal nuclei.
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Affiliation(s)
- M Tong
- Neurotrauma and Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA
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de Backer O, Blanckaert B, Leybaert L, Lefebvre RA. A novel method for the evaluation of intestinal transit and contractility in mice using fluorescence imaging and spatiotemporal motility mapping. Neurogastroenterol Motil 2008; 20:700-7. [PMID: 18248582 DOI: 10.1111/j.1365-2982.2007.01073.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
This study introduces a novel, simplified method for the evaluation of murine intestinal transit and contractility using fluorescence and video imaging. Intestinal transit was measured by evaluating the intestinal distribution of non-absorbable fluorescein-labelled dextran (70 kDa, FD70) along the gastrointestinal (GI) tract. After excision of the GI tract, two full-field images--one in normal illumination mode and another in fluorescent mode--were taken with a charge coupled device (CCD) camera and subsequently matched for calculation of fluorescence distribution along the GI tract. Immediately after, intestinal contractility was evaluated in different regions of the intact intestine by spatiotemporal motility mapping (i.e. video imaging). In control mice, the small intestine showed vigorous oscillatory contractions and FD70 was primarily distributed within the terminal ileum/caecum at 90 min postgavage. As validation step, the effect of intestinal manipulation (IM, surgical procedure) and two pharmacological agents--known to alter GI motility--was tested. At 24 h postoperatively, spontaneous contractile activity of the small intestine was nearly abolished in IM mice, leaving the small intestine distended and resulting in a significantly delayed intestinal transit. In accordance, spontaneous mechanical activity of circular muscle strips in standard organ baths was significantly reduced in IM mice compared to control mice. Administration of atropine (1-3 mg kg(-1), i.p.) suppressed spontaneous contractile activity along the entire intestinal tract and induced a dose-related delay in intestinal transit. In contrast, metoclopramide (3-10 mg kg(-1), i.p.) markedly increased contractile activity--however only in the upper GI tract--and accelerated intestinal transit in a dose-dependent manner.
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Affiliation(s)
- O de Backer
- Heymans Institute of Pharmacology, Faculty of Medicine, Ghent University, Ghent, Belgium
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18
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Appleyard CB, Cruz ML, Rivera E, Hernández GA, Flores I. Experimental endometriosis in the rat is correlated with colonic motor function alterations but not with bacterial load. Reprod Sci 2008; 14:815-24. [PMID: 18089600 DOI: 10.1177/1933719107309722] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Endometriosis commonly presents with symptoms that mimic chronic gastrointestinal disorders. The authors used the autotransplantion model of endometriosis in rats to investigate the possible underlying mechanisms. After the rats were killed, the presence of endometriotic vesicles, colonic inflammation, and white blood cell (WBC) numbers in the peritoneal fluid was determined. Sections of colon and of jejunum were collected for measurement of myeloperoxidase (MPO) activity and bacterial counts, and isometric recording in response to acetylcholine was measured in segments of longitudinal and circular smooth muscle. Experimental animals had significantly more colonic damage, MPO activity, and WBC numbers than controls did. There was no significant difference in the total bacterial load; however, experimental animals demonstrated an increased tension in the longitudinal muscle, which correlated with WBC numbers and colonic damage. In summary, this study presents evidence for a significant effect of peritoneal endometriosis on colonic function and integrity, which may help explain the gastrointestinal symptoms associated with this disease.
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Affiliation(s)
- Caroline B Appleyard
- Department of Physiology and Pharmacology, Ponce School of Medicine, Ponce, Puerto Rico.
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Fukuda H, Tsuchida D, Koda K, Miyazaki M, Pappas TN, Takahashi T. Inhibition of sympathetic pathways restores postoperative ileus in the upper and lower gastrointestinal tract. J Gastroenterol Hepatol 2007; 22:1293-9. [PMID: 17688668 DOI: 10.1111/j.1440-1746.2007.04915.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Postoperative ileus (POI) is a transient bowel dysmotility following abdominal surgery. The effects of adrenergic blocking agents and celiac ganglionectomy were studied in rats to investigate the possible involvement of the adrenergic pathway in whole gastrointestinal (GI) transit in the early and late phases of POI. METHODS After laparotomy, the terminal ileum was manipulated for 10 min. (51)Cr was administered into the stomach or colon immediately after surgery. In another group, (51)Cr was administered 24 h after surgery. Three hours after (51)Cr was administered, the rats were killed, and GI and colonic transit was calculated as a geometric center (GC). RESULTS Gastrointestinal transit was significantly delayed 3 h after intestinal manipulation, compared with GI transit in rats that had anesthesia only. Three hours after intestinal manipulation, guanethidine (5 mg/kg) and yohimbine (3 mg/kg) significantly improved delayed GI transit. Celiac ganglionectomy also significantly improved delayed GI transit. Twenty-seven hours after intestinal manipulation, guanethidine, yohimbine and celiac ganglionectomy improved delayed GI transit induced by intestinal manipulation. Colonic transit was delayed 3 h after intestinal manipulation, and delayed colonic transit was partially restored within 27 h of intestinal manipulation. Guanethidine, yohimbine and celiac ganglionectomy improved delayed colonic transit 3 h and 27 h after intestinal manipulation. CONCLUSIONS Adrenoceptors activated by intestinal manipulation impair the motility of the entire GI tract in both the early and the late phase of POI.
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Affiliation(s)
- Hiroyuki Fukuda
- Department of Surgery, Duke University Medical Center and VA Medical Center, Durham, North Carolina, USA
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Wolff BG, Weese JL, Ludwig KA, Delaney CP, Stamos MJ, Michelassi F, Du W, Techner L. Postoperative Ileus-Related Morbidity Profile in Patients Treated with Alvimopan after Bowel Resection. J Am Coll Surg 2007; 204:609-16. [PMID: 17382220 DOI: 10.1016/j.jamcollsurg.2007.01.041] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2006] [Revised: 01/02/2007] [Accepted: 01/17/2007] [Indexed: 01/15/2023]
Abstract
BACKGROUND Postoperative ileus (POI), an interruption of coordinated bowel motility after operation, is exacerbated by opioids used to manage pain. Alvimopan, a peripherally acting mu-opioid receptor antagonist, accelerated gastrointestinal (GI) recovery after bowel resection in randomized, double-blind, placebo-controlled, multicenter phase III POI trials. The effect of alvimopan on POI-related morbidity for patients who underwent bowel resection was evaluated in a post-hoc analysis. STUDY DESIGN Incidence of POI-related postoperative morbidity (postoperative nasogastric tube insertion or POI-related prolonged hospital stay or readmission) was analyzed in four North American trials for placebo or alvimopan 12 mg administered 30 minutes or more preoperatively and twice daily postoperatively until hospital discharge (7 or fewer postoperative days). GI-related adverse events and opioid consumption were summarized for each treatment. Estimations of odds ratios of alvimopan to placebo and number needed to treat (NNT) to prevent one patient from experiencing an event of POI-related morbidity were derived from the analysis. RESULTS Patients receiving alvimopan 12 mg were less likely to experience POI-related morbidity than patients receiving placebo (odds ratio = 0.44, p < 0.001). Fewer patients receiving alvimopan (alvimopan, 7.6%; placebo, 15.8%; NNT = 12) experienced POI-related morbidity. There was a lower incidence of postoperative nasogastric tube insertion, and other GI-related adverse events on postoperative days 3 to 6 in the alvimopan group than the placebo group. Opioid consumption was comparable between groups. CONCLUSIONS Alvimopan 12 mg was associated with reduced POI-related morbidity compared with placebo, without compromising opioid-based analgesia in patients undergoing bowel resection. Relatively low NNTs are clinically meaningful and reinforce the potential benefits of alvimopan for the patient and health care system.
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Affiliation(s)
- Bruce G Wolff
- Division of Colon and Rectal Surgery, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
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Zhou T, Wu XT, Zhou YJ, Huang X, Fan W, Li YC. Early removing gastrointestinal decompression and early oral feeding improve patients' rehabilitation after colorectostomy. World J Gastroenterol 2006; 12:2459-63. [PMID: 16688845 PMCID: PMC4088090 DOI: 10.3748/wjg.v12.i15.2459] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the feasibility, safety, and tolerance of early removing gastrointestinal decompression and early oral feeding in the patients undergoing surgery for colorectal carcinoma.
METHODS: Three hundred and sixteen patients submitted to operations associated with colorectostomy from January 2004 to September 2005 were randomized to two groups: In experimental group (n = 161), the nasogastric tube was removed after the operation from 12 to 24 h and was promised immediately oral feeding; In control group (n = 155), the nasogastric tube was maintained until the passage of flatus per rectum. Variables assessed included the time to first passage of flatus, the time to first passage of stool, the time elapsed postoperative stay, and postoperative complications such as anastomotic leakage, acute dilation of stomach, wound infection and dehiscense, fever, pulmonary infection and pharyngolaryngitis.
RESULTS: The median and average days to the first passage of flatus (3.0 ± 0.9 vs 3.6 ± 1.2, P < 0.001), the first passage of stool (4.1 ± 1.1 vs 4.8 ± 1.4 P < 0.001) and the length of postoperative stay (8.4 ± 3.4 vs 9.6 ± 5.0, P < 0.05) were shorter in the experimental group than in the control group. The postoperative complications such as anastomotic leakage (1.24% vs 2.58%), acute dilation of stomach (1.86% vs 0.06%) and wound complications (2.48% vs 1.94%) were similar in the groups, but fever (3.73% vs 9.68%, P < 0.05), pulmonary infection (0.62% vs 4.52%, P < 0.05) and pharyngolaryngitis (3.11% vs 23.23%, P < 0.001) were much more in the control group than in the experimental group.
CONCLUSION: The present study shows that application of gastrointestinal decompression after colorectostomy can not effectively reduce postoperative complications. On the contrary, it may increase the incidence rate of fever, pharyngolaryngitis and pulmonary infection. These strategies of early removing gastrointestinal decompression and early oral feeding in the patients undergoing colorectostomy are feasible and safe and associated with reduced postoperative discomfort and can accelerate the return of bowel function and improve rehabilitation.
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Affiliation(s)
- Tong Zhou
- Department of Gastrointestinal Surgery, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
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