Effects of Electroacupuncture on Opioid-Induced Constipation in Patients With Cancer: Study Protocol for a Multicenter Randomized Controlled Trial.

Background: Opioid-induced constipation (OIC) is one of the most prevalent adverse events associated with cancer patients who receive opioid analgesics for moderate to severe pain. Acupuncture may be an effective treatment for OIC. We designed this trial to assess the efficacy and safety of electroacupuncture for OIC in cancer patients. Methods: This is a multicenter, sham-controlled, parallel-group, subject- and assessor-blinded randomized trial. A total of 100 cancer patients with OIC will be randomly assigned to either the electroacupuncture group or the sham electroacupuncture group at a ratio of 1:1. Patients in each group will receive a total of 24-session treatment over 8 weeks, three sessions a week and 30 min each session. Thereafter, patients will be followed up for another 8 weeks. The primary outcome will be the proportion of responders, defined as a patient who has ≥3 spontaneous bowel movements (SBMs)/wk and ≥ increase of 1 SBM from baseline simultaneously for at least 6 out of 8 weeks of the treatment period. The secondary outcomes will include the mean weekly SBMs and complete spontaneous bowel movements, the mean Bristol Stool Form Scale score for stool consistency, the mean score for straining of SBM, the total and subscale scores of Patient Assessment of Constipation-Symptom questionnaires, and the total and subscale scores of Patient Assessment of Constipation-Quality of Life questionnaire. Patients' global assessment of treatment effectiveness, patients' expectation toward the effectiveness of acupuncture and safety of acupuncture will also be assessed. All efficacy analyses will be performed in the intention-to-treat population. Discussion: To improve the adherence to intervention protocols, the majority of the participants will be recruited from an inpatient setting. The results will help to determine the clinical effects and safety of electroacupuncture for the treatment of OIC among patients with cancer. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03797586, registered on 4 January 2019, https://clinicaltrials.gov/ct2/show/NCT03797586.

The efficacy of acupressure in managing opioid-induced constipation in patients with cancer: A single-blind randomized controlled trial.

PURPOSE: Opioid-induced constipation is one of the heath problems with a negative impact on the quality of life. This randomized-controlled trial aimed to investigate the effects of acupressure therapy on the management of opioid-induced constipation in patients with cancer. METHODS: The trial was conducted on 140 cancer patients, who were assigned to the acupressure (n = 70) and the control groups (n = 70). In addition to routine care, patients in the acupressure group received 8-min acupressure from the Zhongwan (CV12), Guanyuan (CV4), and Tianshu (ST25) acupoints once a day for 4 weeks. The outcomes included Defecation Diary (DD), Visual Analog Scale Questionnaire (VASQ), and Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL). RESULTS: We found a statistically significant difference between the acupressure and control groups in terms of stool consistency (2.22 ± 0.49 vs 1.80 ± 0.55) (p = 0.001), straining (1.98 ± 0.71 vs 2.91 ± 0.37) (p = 0.001), incomplete evacuation (0.37 ± 0.29 vs 0.61 ± 0.43) (p = 0.001), stool amount (0.93 ± 0.14 vs 0.95 ± 0.20) (p = 0.001), and the number of defecations (0.70 ± 0.22 vs 0.46 ± 0.29), (p = 0.001) measured at the fifth week. Besides, with the exception of stool amount, the DD scores obtained by the acupressure group significantly increased in the fifth week. Inter-group comparison of the pre-test and post-test scores showed that acupressure group obtained statistically significantly lower scores from the PAC-QOL (p = 0.0001). CONCLUSIONS: Findings of this trial suggested that a 4-week acupressure was an effective way to improve the quality of life and to reduce both the subjective and the objective constipation symptoms in patients with opioid-induced constipations. CLINICAL TRIAL NUMBER: NCT04876508.

Acupuncture Relieves Opioid-Induced Constipation in Clinical Cancer Therapy - A Meta-Analysis and Systematic Review.

Cancer pain is a common problem in clinical cancer therapy. Opioid analgesia is one of the most effective drugs for pain relief with satisfying performance besides the side effect of opioid-induced constipation (OIC). Acupuncture, as a Chinese traditional non-invasive intervention, has been applied to clinical cancer pain management and functional constipation therapy. However, only a few studies have adopted this treatment for OIC patients. Due to limited numbers of investigated subjects and variability of application methods, including treatment apparatus, acupoints, durations, and sessions, the interpretation of acupuncture's therapy effects from single-site randomized clinical trials (RCT) is limited. Therefore, we conducted a meta-analysis by collecting published data from Pubmed, Embase, Cochrane library, and Web of Science. Five RCTs focusing on the application of acupuncture with or without medication in OIC patients were included. An overall remission rate of 86.8% in the acupuncture-treated group was achieved, higher than the control group (78.9%; RR, 1.10, 95% CI [1.03, 1.18]). The symptom scores, reporting on defecation frequency, defecation straining, abdominal pain, defection time, and stool property, in acupuncture groups were lower than control groups with a standardized mean difference (SMD) of -2.21 [-4.15, -0.27]. The quality of life (QOL) for patients in the acupuncture treated group increased compared to the control group with reduced PAC-QOL scores (SMD, -1.02 [-1.78, -0.26]). Referring to the effects from pure acupuncture treatment (SMD, -0.43 [-0.83, -0.03]), the co-intervention of acupuncture and drugs (SMD, -1.77 [-2.51, -1.02]) improved the life quality of patients more remarkably (P < 0.05). Overall, our data confirmed the therapeutic effects of acupuncture in the treatment of OIC. The co-intervention of acupuncture with drugs improves the outcomes of OIC patients better than a single strategy. Combined therapy with both medicine and acupuncture has insightful potential for future clinical cancer patient management on constipation problems.

Opioid-Induced Constipation and Acupuncture: A Case Discussion.

BACKGROUND: Use of acupuncture for treatment of functional constipation is well studied; however, studies examining use of acupuncture for opioid-induced constipation are limited. CASE DESCRIPTION: A 70-year-old woman with newly diagnosed multiple myeloma discovered after presentation to the emergency room with severe back pain. Pain management required use of opioids, escalating to effect. Hospital course was complicated by opioid-induced constipation causing abdominal pain, nausea, and ileus despite aggressive titration of stimulant and osmotic laxatives as well as administration of suppositories and enemas on multiple occasions. Prior to nasogastric tube placement for the ileus, the patient requested acupuncture treatment in attempt to relieve constipation. Shortly after acupuncture session, patient passed multiple stools with improvement in abdominal pain and nausea and avoidance of nasogastric tube. CONCLUSION: Acupuncture for opioid-induced constipation may provide symptom relief through use of nonpharmacologic interventions; however, further studies are needed to determine the optimal therapeutic approach.

What to Do and What Not to Do in the Management of Opioid-Induced Constipation: A Choosing Wisely Report.

INTRODUCTION: Despite the essential utility of opioids for the clinical management of pain, opioid-induced constipation (OIC) remains an important obstacle in clinical practice. In patients, OIC hinders treatment compliance and has negative effects on quality of life. From a clinician perspective, the diagnosis and management of OIC are hampered by the absence of a clear, universal diagnostic definition across disciplines and a lack of standardization in OIC treatment and assessment. METHODS: A multidisciplinary panel of physician experts who treat OIC was assembled to identify a list of ten corrective actions-five "things to do" and five "things not to do"-for the diagnosis and management of OIC, utilizing the Choosing Wisely methodology. RESULTS: The final list of corrective actions to improve the diagnosis and clinical management of OIC emphasized a need for: (i) better physician and patient education regarding OIC; (ii) systematic use of diagnostically validated approaches to OIC diagnosis and assessment (i.e., Rome IV criteria and Bristol Stool Scale, respectively) across various medical contexts; and (iii) awareness about appropriate, evidence-based treatments for OIC including available peripheral mu-opioid receptor antagonists (PAMORAs). CONCLUSIONS: Physicians who prescribe long-term opioids should be forthcoming with patients about the possibility of OIC and be adequately versed in the most recent guideline recommendations for its management.

Mechanism of Xiahuang Granules in treating opioid-induced constipation based on network pharmacology / 中草药

Objective: To explore the potential mechanism of Xiahuang Granules in the treatment of opioid-induced constipation. Methods: Various medicinal ingredients and targets information of Xiahuang Granules were found in TCMSP database. In Genecards database, "opiod constipation", "opioid-induced bowel dysfunction" and "opioid-induced constipation" were used as keywords to search for targets related to opioid-induced constipation, and the active targets mapping of Xiahuang Granules were selected as the research targets. The common targets were imported into the STRING database to build the targets interaction network diagram, and Cytoscape 3.3.0 software was used for visual processing to screen out the core targets. The OmicsBean analysis platform and STRING database were used to conduct GO function enrichment and KEGG pathway enrichment analysis on the targets. Results: A total of 55 chemical constituents, 158 candidate target genes, 86 common targets after mapping Venny, 49 corresponding chemical components, 12 core targets and 19 main chemical components of Xiahuang Granules were obtained by screening. GO functional enrichment analysis showed 4 150 biological process items, involving chemical stimulus cell reactions, chemical reactions, biological quality control and other processes; A total of 302 cell composition items, involving voxel projection, extracellular space, and whole membrane processes; A total of 459 molecules function items, involving processes such as protein binding, molecular transduction activity, and enzyme binding were obtained. KEGG enrichment analysis revealed 149 signaling pathways related to the effect of Xiahuang Granules, involving the AGE-RAGE signaling pathway in diabetic complications and tumor necrosis factor signaling pathway, etc. The network of "medicinal herb-component-target-pathway" of Xiahuang Granules was established. Conclusion: The main chemical components of Xiahuang Granules including naringenin, nobiletin, aloe emodin, rhein may regulate endocrine resistance and tumor necrosis factor signaling pathways by acting on key proteins such as TNF, MAPK3, IL-6, VEGFA, and PTGS2, thus play a role in laxative, antispasmodic, and promoting gastrointestinal motility, which provides theoretical basis for Xiahuang Granules to treat opioid-induced constipation and is consistent with the preliminary verification results of Xiahuang granules.

The efficacy of abdominal massage in managing opioid-induced constipation.

PURPOSE: This study was conducted to determine the effects of abdominal massage in managing opioid-induced constipation. METHODS: Designed as a randomized controlled trial, this study was conducted between February 2017 and January 2018 with the participation of 204 patients who had complaints of opioid-induced constipation. The experimental and control group, each of which included 102 patients, were randomised using a previously prepared randomization checklist. Patients in the experimental group were given a 15-min video-guided abdominal massage training by the researcher, and the patients in this group were asked to perform abdominal massage for 4 weeks, twice a day, 30 min after breakfast and dinner. In the control group, the standard approach of the clinic was applied. A patient data form, the Defecation Diary, Visual Analogue Scale, and Patient Assessment of Constipation Quality of Life Questionnaire were used to the study. RESULTS: The data from the study showed that abdominal massage decreased the severity of constipation, the feeling of incomplete bowel emptying, the severity of straining, the severity of anal pain, and bloating (p < 0.05), provided better stool consistency (p < 0.05) and increased the number of defecations as well as quality of life scores (p < 0.05). CONCLUSION: The abdominal massage application increased the number of defecations by 13% and was an effective approach for managing opioid-induced constipation symptoms.

Food pyramid for subjects with chronic pain: foods and dietary constituents as anti-inflammatory and antioxidant agents.

Emerging literature suggests that diet constituents may play a modulatory role in chronic pain (CP) through management of inflammation/oxidative stress, resulting in attenuation of pain. We performed a narrative review to evaluate the existing evidence regarding the optimum diet for the management of CP, and we built a food pyramid on this topic. The present review also describes the activities of various natural compounds contained in foods (i.e. phenolic compounds in extra-virgin olive oil (EVO)) listed on our pyramid, which have comparable effects to drug management therapy. This review included 172 eligible studies. The pyramid shows that carbohydrates with low glycaemic index should be consumed every day (three portions), together with fruits and vegetables (five portions), yogurt (125 ml), red wine (125 ml) and EVO; weekly: legumes and fish (four portions); white meat, eggs and fresh cheese (two portions); red or processed meats (once per week); sweets can be consumed occasionally. The food amounts are estimates based on nutritional and practical considerations. At the top of the pyramid there is a pennant: it means that CP subjects may need a specific customised supplementation (vitamin B12, vitamin D, n-3 fatty acids, fibre). The food pyramid proposal will serve to guide dietary intake with to the intent of alleviating pain in CP patients. Moreover, a targeted diet can also help to solve problems related to the drugs used to combat CP, i.e. constipation. However, this paper would be an early hypothetical proposal due to the limitations of the studies.

The Efficacy and Safety of Transcutaneous Acupoint Interferential Current Stimulation for Cancer Pain Patients With Opioid-Induced Constipation: A Prospective Randomized Controlled Study.

INTRODUCTION: Opioid-induced constipation (OIC) is a principal complication secondary to analgesic therapy for cancer pain patients who suffer moderate to severe pain. In this study, we observe the efficacy and safety of transcutaneous acupoint interferential current (IFC) stimulation in those patients with OIC. METHODS: A total of 198 patients were randomly allocated to the IFC group and control group in a 1:1 ratio. Finally, 98 patients in the IFC group received 14 sessions administered over 2 weeks, whereas 100 patients in the control group took lactulose orally during the same period. Observation items were documented at management stage and at follow-up stage according to Cleveland Constipation Scales (CCS), pain Numeric Rating Scales (NRS) and Patient Assessment of Constipation Quality of Life (PAC-QoL). RESULTS: The total curative effects of the IFC group and the control group were indistinguishable (76.5% vs 70.0%, P = .299). Regarding CCS and PAC-QoL scores, no significant difference was observed between the 2 groups during the management time and at the follow-up stage of week 3 ( P > .05, respectively), but groups were distinguished at the follow-up stage of week 4 ( P < .001 and P = .031, respectively). The pain NRS decreased significantly at management stage week 2 and follow-up stage week 3 and week 4 ( P = .013, P = .041, P = .011, respectively). CONCLUSIONS: Transcutaneous acupoint IFC therapy over acupoints of Tianshu (ST25) and Zhongwan (RN12) may improve constipation and quality of life in cancer patients receiving opiates; further studies are worthwhile.