Evaluation of the risk factors for the failure of a single prophylactic dose of anticholinergic drugs for irinotecan-induced cholinergic symptoms.

OBJECTIVE: Irinotecan (IRI) is an anticancer drug that is frequently used to treat colorectal, gastric, and pancreatic cancers. Its side effects include cholinergic symptoms, such as diarrhea, abdominal pain, nausea, and hyperhidrosis. Anticholinergic medicines are frequently used for treatment or prophylaxis; however, the risk factors for the failure of a single prophylactic anticholinergic administration remain unclear. Moreover, an appropriate anticholinergic drug for prophylaxis remains unknown. Thus, we aimed to identify the risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs for IRI-induced cholinergic symptoms and to evaluate the usefulness of multiple prophylactic doses of anticholinergic drugs. MATERIALS AND METHODS: Patients who underwent IRI treatment for colorectal, gastric, or pancreatic cancer and received prophylactic anticholinergic drugs for IRI-induced cholinergic symptoms (n = 135) were retrospectively evaluated. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for failure of a single prophylactic dose of anticholinergic drugs. We also evaluated the efficacy of multiple prophylactic anticholinergic drug administration. RESULTS: Based on univariate and multivariate analyses, colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were identified as risk factors for failure of a single prophylactic dose of anticholinergic drugs. The efficacy of multiple prophylactic doses was confirmed to be 95% of the patients who had a single prophylactic failure due to temporary effect but symptom appearance after a certain period of time (wearing-off). CONCLUSION: We determined that colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs, and that multiple prophylactic doses for wearing-off can be a promising method.

The effect of intravenous hyoscine butylbromide on slow progress in labor (BUSCLAB): A double-blind randomized placebo-controlled trial.

BACKGROUND: Prolonged labor is a common condition associated with maternal and perinatal complications. The standard treatment with oxytocin for augmentation of labor increases the risk of adverse outcomes. Hyoscine butylbromide is a spasmolytic drug with few side effects shown to shorten labor when used in a general population of laboring women. However, research on its effect on preventing prolonged labor is lacking. We aimed to assess the effect of hyoscine butylbromide on the duration of labor in nulliparous women showing early signs of slow labor. METHODS AND FINDINGS: In this double-blind randomized placebo-controlled trial, we included 249 nulliparous women at term with 1 fetus in cephalic presentation and spontaneous start of labor, showing early signs of prolonged labor by crossing the alert line of the World Health Organization (WHO) partograph. The trial was conducted at Oslo University Hospital in Norway from May 2019 to December 2021. One hundred and twenty-five participants were randomized to receive 1 ml hyoscine butylbromide (Buscopan) (20 mg/ml), while 124 received 1 ml sodium chloride intravenously. Randomization was computer-generated, with allocation concealment by opaque sequentially numbered sealed envelopes. The primary outcome was duration of labor from administration of the investigational medicinal product (IMP) to vaginal delivery, which was analyzed by Weibull regression to estimate the cause-specific hazard ratio (HR) of vaginal delivery between the 2 treatment groups, with associated 95% confidence interval (CI). A wide range of secondary maternal and perinatal outcomes were also evaluated. Time-to-event outcomes were analyzed by Weibull regression, whereas continuous and dichotomous outcomes were analyzed by median regression and logistic regression, respectively. All main analyses were based on the modified intention-to-treat (ITT) set of eligible women with signed informed consent receiving either of the 2 treatments. The follow-up period lasted during the postpartum hospital stay. All personnel, participants, and researchers were blinded to the treatment allocation. Median (mean) labor duration from IMP administration to vaginal delivery was 401 (440.8) min in the hyoscine butylbromide group versus 432.5 (453.6) min in the placebo group. We found no statistically significant association between IMP and duration of labor from IMP administration to vaginal delivery: cause-specific HR of 1.00 (95% CI [0.77, 1.29]; p = 0.993). Among 255 randomized women having received 1 dose of IMP, 169 women (66.3%) reported a mild adverse event: 75.2% in the hyoscine butylbromide group and 57.1% in the placebo group (Pearson's chi-square test: p = 0.002). More than half of eligible women were not included in the study because they did not wish to participate or were not included upon admission. The participants might have represented a selected group of women reducing the external validity of the study. CONCLUSIONS: One intravenous dose of 20 mg hyoscine butylbromide was not found to be superior to placebo in preventing slow labor progress in a population of first-time mothers at risk of prolonged labor. Further research is warranted to answer whether increased and/or repeated doses of hyoscine butylbromide might have an effect on duration of labor. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03961165) EudraCT (2018-002338-19).

Effectiveness and safety of prehospital analgesia including nalbuphine and paracetamol by paramedics: an observational study.

BACKGROUND: The aim of this study was to examine the effectiveness and safety of prehospital analgesia with nalbuphine and/or paracetamol by paramedics. METHODS: In this retrospective trial, following the implementation of a standard-operating-procedure for pain requiring treatment as defined as a score ≥4 on the 0-10 Numeric Rating Scale for pain, all emergency operations in the district of Gütersloh between January 1, 2020, and June 30, 2022, with analgesic administration by paramedics in patients ≥18 years were included in the study. Analgesic agents employed by the paramedics included nalbuphine and/or paracetamol, butylscopolamine for abdominal colic, and esketamine in case of failure of the other analgesics. The primary endpoint was the patients' rating of their pain on the Numeric Rating Scale at the end of the operation. Additional covariates included sex, cause of pain, analgesics used, Numeric Rating Scale at beginning and analgesic-associated complications (reduced level of consciousness, hypotension, desaturation, a- or bradypnea). RESULTS: A total of 1931 emergency operations (female: N.=1039 [53.8%]) with pain requiring treatment (non-traumatic cause: N.=1106 [57.3%]; initial Numeric Rating Scale: 8.0±1.4). Analgesics applied were nalbuphine + paracetamol (50.6%), paracetamol (38.7%), butylscopolamine (13.4%), nalbuphine (7.7%), and esketamine (4.9%). Mean pain reduction was 4.3±2.3 (nalbuphine + paracetamol: 5.0±2.1; nalbuphine: 4.7±2.3) and paracetamol: 3.3±2.2, respectively. Factors influencing a change in the Numeric Rating Scale were trauma (regression-coefficient: -0.308, 95% CI: -0.496 - -0.119, P=0.0014 vs. non-trauma; nalbuphine [yes vs. no]: regression-coefficient 0.684, 95% CI 0.0774-1.291, P=0.03; nalbuphine + paracetamol: regression-coefficient 0.763, 95% CI 0.227-1.299, P=0.005). At the end of the operation, 49.7% had a Numeric Rating Scale <4, 34.3% had a Numeric Rating Scale 4-5, and 16.0% had a Numeric Rating Scale ≥6. Factors influencing a Numeric Rating Scale <4 at end of use were trauma vs. non-trauma: odds ratio 0.788, 95% CI 0.649-0.957, P=0.02. The Numeric Rating Scale at beginning reported: odds ratios 0.754, 95% CI 0.700-0.812, P<0.0001. Analgesic-associated complications were not observed. CONCLUSIONS: Prehospital analgesia by paramedics with nalbuphine as monotherapy or in combination with paracetamol allows for sufficient analgesia without the occurrence of complications.

Application of analgesics in emergency services in Germany: a survey of the medical directors.

ABSTRAC: BACKGROUND: Treatment of acute pain is an essential element of pre-hospital care for injured and critically ill patients. Clinical studies indicate the need for improvement in the prehospital analgesia. OBJECTIVE: The aim of this study is to assess the current situation in out of hospital pain management in Germany regarding the substances, indications, dosage and the delegation of the use of analgesics to emergency medical service (EMS) staff. MATERIAL AND METHODS: A standardized survey of the medical directors of the emergency services (MDES) in Germany was carried out using an online questionnaire. The anonymous results were evaluated using the statistical software SPSS (Chi-squared test, Mann-Whitney-U test). RESULTS: Seventy-seven MDES responsible for 989 rescue stations and 397 EMS- physician bases in 15 federal states took part in this survey. Morphine (98.7%), Fentanyl (85.7%), Piritramide (61%), Sufentanil (18.2%) and Nalbuphine (14,3%) are provided as opioid analgesics. The non-opioid analgesics (NOA) including Ketamine/Esketamine (98,7%), Metamizole (88.3%), Paracetamol (66,2%), Ibuprofen (24,7%) and COX-2-inhibitors (7,8%) are most commonly available. The antispasmodic Butylscopolamine is available (81,8%) to most rescue stations. Fentanyl is the most commonly provided opioid analgesic for treatment of a traumatic pain (70.1%) and back pain (46.8%), Morphine for visceral colic-like (33.8%) and non-colic pain (53.2%). In cases of acute coronary syndrome is Morphine (85.7%) the leading analgesic substance. Among the non-opioid analgesics is Ketamine/Esketamine (90.9%) most frequently provided to treat traumatic pain, Metamizole for visceral colic-like (70.1%) and non-colic (68.6%) as well as back pain (41.6%). Butylscopolamine is the second most frequently provided medication after Metamizole for "visceral colic-like pain" (55.8%). EMS staff (with or without a request for presence of the EMS physician on site) are permitted to use the following: Morphine (16.9%), Piritramide (13.0%) and Nalbuphine (10.4%), and of NOAs for (Es)Ketamine (74.1%), Paracetamol (53.3%) and Metamizole (35.1%). The dosages of the most important and commonly provided analgesic substances permitted to independent treatment by the paramedics are often below the recommended range for adults (RDE). The majority of medical directors (78.4%) of the emergency services consider the independent application of analgesics by paramedics sensible. The reason for the relatively rare authorization of opioids for use by paramedics is mainly due to legal (in)certainty (53.2%). CONCLUSION: Effective analgesics are available for EMS staff in Germany, the approach to improvement lies in the area of application. For this purpose, the adaptations of the legal framework as well as the creation of a guideline for prehospital analgesia are useful.

Ultrasonographic Assessment of Small Intestinal Motility Following Hyoscine Butylbromide Administration in Horses: A Pilot Study.

Horses commonly receive hyoscine butylbromide (HB) prior to hospital admission for colic. This could alter the appearance of the small intestine (SI) on ultrasound scan and affect clinical decision making. The aim of this study was to assess the impact of HB on ultrasonographically assessed SI motility and heart rate. Six horses hospitalised for medical colic with no significant abnormalities on baseline abdominal ultrasound examination were included. Ultrasound was performed in three locations (right inguinal, left inguinal and hepatoduodenal window) before and at 1, 5, 15, 30, 45, 60, 90, and 120 minutes after intravenous injection of 0.3 mg/kg HB. Three blinded reviewers assessed SI motility using a subjective grading scale from 1 to 4, one being normal motility and four being no motility. Moderate interindividual and interobserver variability was observed, but none of the included horses developed dilated turgid loops of SI. Hyoscine butylbromide did not significantly reduce SI motility grade in any location (P = .60 left inguinal, P = .16 right inguinal, P = .09 duodenum). Heart rate (mean ± SD) was 33 ± 3 prior to HB injection and peaked at 71.3 ± 9 one-minute postinjection. Heart rate was significantly increased until 45 minutes (48 ± 9) after HB administration (P = .04). The appearance of dilated turgid SI loops common with strangulating intestinal lesions did not appear to develop following HB administration. Hyoscine butylbromide administered shortly before abdominal ultrasound examination would not be expected to affect clinical decision making in horses without small intestinal disease.

LC-MS/MS approach for simultaneous assessment of hyoscine N-butyl bromide and ketoprofen in biological fluids and pharmaceuticals.

The mixture of hyoscine N-butyl bromide (HBB) and ketoprofen (KTP) is commonly used for the handling of abdominal spasms and pain relief. There are two challenges that restrict the simultaneous assessment of HBB and KTP in biological fluids and pharmaceuticals. The first issue is the difficulty of elution of HBB and the second one is the presence of KTP as a racemic mixture in all pharmaceutical formulations, which obscures its appearance as a single peak. An ultrasensitive and highly efficient liquid chromatography-mass/mass spectrometric (LC-MS/MS) method is designed and validated for the first concurrent assessment of HBB and KTP in spiked human serum and urine, and pharmaceutical formulations. The estimated linearity ranges for HBB and KTP were respectively, 0.5-500 and 0.05-500 ng/ml, with excellent correlation coefficients. Validation results showed that the value of relative standard deviations were <2% for HBB and KTP. The mean extraction recoveries for HBB and KTP were, respectively, 91.04 and 97.83% in Spasmofen® ampoules; 95.89 and 97.00% in spiked serum; and 97.31 and 95.63% in spiked urine. The presented innovative chromatographic approach was utilized for the measurement of trace amounts of coexisting pharmaceuticals in pharmacokinetics studies and routine therapeutic medication monitoring.

The effect of anti-spasmodic administration on the accuracy of magnetic resonance imaging staging of rectal cancer.

BACKGROUNDS: Magnetic resonance imaging is the primary method for local staging in rectal cancer patients. Administration of intravenous (IV) hyoscine butylbromide is thought to improve accuracy, but there are contraindications and potential adverse effects. The aim was to assess the efficacy of IV hyoscine butylbromide on the accuracy of MRI rectal cancer staging of T2 and T3 rectal cancers. METHODS: A retrospective cohort study was carried out on patients prospectively recorded on the Cabrini Monash colorectal neoplasia database. A total of 74 patients (53 males, 21 females) MRI pelvis and rectums with antispasmodics were performed at multiple centres in the pre-operative setting between 2010 and 2016. Each patient underwent total mesorectal excision of rectal cancer. The excision specimens were assessed and given a pathological TNM stage, which was considered the reference standard. RESULTS: There was no statistically significant impact on the overall accuracy of MRI rectal cancer staging between patient groups who received IV hyoscine butylbromide and groups who did not receive IV hyoscine butylbromide. The accuracy of T2 and T3 staged rectal cancers was more likely to be correct (compared with T1 cancers) with the administration of IV hyoscine butylbromide. Still, there was no improvement in the accuracy of N-staging. CONCLUSION: Given the potential side effects and adverse outcomes of IV anti-spasmodic agents, department protocols may need to be re-assessed regarding the prescription of these medications for MRI rectal cancer staging.

Cardiovascular effects of hyoscine butylbromide in patients under general anaesthesia.

BACKGROUND: Cardiovascular effects for drugs such as hyoscine butylbromide are poorly documented in the literature, unlike atropine, which is considered the antimuscarinic of choice in the presence of intraoperative bradycardia. AIM: The aim of the study was to describe the dose-related cardiovascular effect of hyoscine butylbromide in patients between 18 and 65 years of age, with low perioperative risk undergoing elective surgery under general anaesthesia on an outpatient basis or hospitalised at our institution between 1 January and 31 May 2019. METHODS: Descriptive, cross-sectional, retrospective study; 28 patients with low perioperative risk who underwent general anaesthesia were selected. Changes in heart rate and blood pressure were analysed during the first 6 minutes after the administration of hyoscine butylbromide. The data obtained was recorded in a Microsoft Excel database and analysed using the Excel analysis tool and IBM SPSS. RESULTS: The average dose of 0.15mg/kg of hyoscine butylbromide achieved an increase in heart rate and mean arterial pressure in 96% and 92.8%, respectively, in the first 6 minutes after the administration. Significant changes in heart rate and blood pressure were obtained during the first 6 minutes at doses between 0.05mg/kg and 0.15mg/kg. CONCLUSION: Hyoscine butylbromide generates positive effects on the heart rate and blood pressure of patients under general anaesthesia, representing a possible alternative in the management of intraoperative bradycardia.

Silver Nanoparticles Application as a Colorimetric Probe for the Spectrophotometric Determination of Hyoscine Butylbromide in Pharmaceutical Formulations.

BACKGROUND: Hyoscine butylbromide is used as an antispasmodic in treating peptic ulcers, gastritis, and various disorders of the gastrointestinal tract that are characterized by spasms. It has also found employment for the relief of spasmodic conditions of the bile duct and urinary tract and for the treatment of dysmenorrhea. OBJECTIVE: In this study, the application of silver nanoparticles (Ag NPs) as a colorimetric probe for the fast, selective, and simple determination of hyoscine butylbromide was described. METHODS: The proposed method was based on the Ag NPs aggregation induced by their interaction with the cited drug. This interaction produced a color change from yellow to colorless measured at 405 nm. RESULTS: The method linear concentration range was 0.10-50.0 µg/mL with a correlation equation (y = 0.0132 x + 0.3174), correlation coefficient of 0.9981, and quantification limits of 0.091 µg/mL. A thorough investigation was done to validate the method's analytical performance, and the findings were satisfactory. With great accuracy and precision, this approach was used to identify the medication in pharmaceutical tablet samples with recovery percentages ranging from 96.20 to 98.10%. CONCLUSIONS: Since there are no critical reaction conditions or solvent extraction involved in the described method, it is distinguished by its simplicity. The results were quite consistent with those attained using the approved standard method. HIGHLIGHTS: Simple, fast, and sensitive colorimetric probe developed for determination of hyoscine butylbromide in pharmaceutical formulations.

Hyoscine butylbromide mode of action on bowel motility: From pharmacology to clinical practice.

BACKGROUND: Hyoscine butylbromide (HBB) has been available for use as an antispasmodic since 1951 and is indicated for the treatment of abdominal pain associated with cramps. A previous review in 2007 summarized the evidence on the mode of action of HBB in vitro and in vivo in both animal and human studies. However, since then, novel publications have appeared within the literature and also our knowledge of what represents normal motility in humans has evolved. PURPOSE: This review is the result of the collaboration between a basic scientist and clinicians with the aim of providing an updated overview of the mechanisms of action of HBB and its clinical efficacy to guide not only use in clinical practice, but also future research.

Effects of Anticholinergics on Death Rattle: A Systematic Review and Network Meta-Analysis.

Background: Anticholinergics have been used to treat death rattle (DR) in dying patients with palliative care. However, the effect of anticholinergics is still controversial. No quantitative summary of their effects is reported. Objective: This study aimed to systematically review and quantitatively synthesize the effect of anticholinergics on DR treatment and prophylaxis. Design: A systematic search was performed in the electronic databases (PubMed, Embase®, and Cumulative Index to Nursing and Allied Health Literature [CINAHL]) from inception to October 2021. Studies conducted to determine the effect of anticholinergics compared with other anticholinergics or placebo on noise reduction score in dying patients were included. A network meta-analysis was performed for DR treatment. The effect of anticholinergics at four hours was assessed. A pairwise meta-analysis was performed for DR prophylaxis. Results: A total of nine studies were included with 1103 patients. Six studies were randomized controlled trials, and three studies were cohort studies. Seven studies were conducted for DR treatment, while two studies were conducted for DR prophylaxis. For DR treatment, no statistically significant difference was observed between each anticholinergic (hyoscine hydrobromide, hyoscine butyl bromide, atropine, and glycopyrrolate) and placebo and among any anticholinergics. However, the surface under cumulative ranking curve indicated that hyoscine butyl bromide had the highest surface under the cumulative ranking curve (SUCRA) with 71.3%. For DR prophylaxis, the relative risk of DR occurrence for hyoscine butyl bromide was 0.23 (0.04, 1.18; I2 = 84.5%) compared with no treatment. Conclusion: This study showed no strong evidence of the regular use of anticholinergics for DR treatment. In addition, hyoscine butyl bromide appears to have a high potential for DR prophylaxis.

Study protocol for the BUSCopan in LABor (BUSCLAB) study: A randomized placebo-controlled trial investigating the effect of butylscopolamine bromide to prevent prolonged labor.

BACKGROUND: First-time mothers are prone to prolonged labor, defined as the crossing of partograph alert or action lines. Prolonged labor may occur among as many as one out of five women, and is associated with a range of adverse birth outcomes. Oxytocin is the standard treatment for prolonged labor, but has a narrow therapeutic window, several adverse effects and limited efficacy. Despite poor evidence, labor wards often use antispasmodic agents to treat prolonged labor. The antispasmodic drug butylscopolamine bromide (Buscopan®) may shorten duration of labor, but studies on prevention of prolonged labor are lacking. In this randomized double-blind placebo-controlled clinical trial, we aim to evaluate the effect of butylscopolamine bromide on duration of labor in first-time mothers showing first signs of slow labor progress by crossing the World Health Organization partograph alert line. METHODS AND ANALYSIS: The study is a single center study at Oslo University Hospital, Oslo, Norway. We will recruit 250 primiparous women with spontaneous labor start at term. Women are included in the first stage of labor if they show signs of slow labor progress, defined as the crossing of the partograph alert line with a cervical dilation between 3-9 cm. Participants are randomized 1:1 to either 20 mg intravenous butylscopolamine bromide or intravenous placebo (1 mL sodium chlorine 9 mg/mL). We considered a mean difference of 60 minutes in labor duration clinically relevant. The primary outcome is duration of labor from the provision of the investigational medicinal product to vaginal delivery. The secondary outcomes include change in labor pain, use of oxytocin augmentation, delivery mode, and maternal birth experience. The primary data for the statistical analysis will be the full analysis set and will occur on completion of the study as per the prespecified statistical analysis plan. The primary outcome will be analyzed using Weibull regression, and we will treat cesarean delivery as a censoring event.

Antiperistaltic effect and safety of L-menthol for esophagogastroduodenoscopy in the elderly with contraindication to hyoscine-N-butylbromide.

Hyoscine-N-butylbromide (HBB) is the most used antiperistaltic agent during esophagogastroduodenoscopy (EGD). However, almost half of the elderly have a contraindication to HBB. We aimed to evaluate L-menthol's antiperistaltic effect and safety for EGD in the elderly with contraindication to HBB. This prospective, randomized, double-blind, placebo-controlled study screened 86 elderly patients (≥ 65 years old) scheduled to undergo EGD, and 52 of them with contraindication to HBB were enrolled. The participants were randomized to receive L-menthol (n = 26) or a placebo (n = 26), which was locally sprayed on the gastric antrum endoscopically. The proportion of patients with no or mild peristalsis after medication and at the end of EGD was significantly higher in the L-menthol group (76.9%) than in the placebo group (11.5%, p < 0.001). L-Menthol administration significantly reduced peristaltic grade, improved contraction parameters, and eased intragastric examination relative to the placebo (p < 0.001, respectively). Hemodynamic changes, adverse events, and discomfort levels of patients were similar between the two groups. L-Menthol is an effective and safe alternative antiperistaltic medication for EGD in elderly patients with contraindication to HBB. Further large, randomized trials are required to clarify whether L-menthol can lead to better detection yield in the elderly.Clinical trial registration: The study was registered at ClinicalTrials.gov (NCT04593836).

Bowel preparation in MRI for detection of endometriosis: Comparison of the effect of an enema, no additional medication and intravenous butylscopolamine on image quality.

PURPOSE: To compare the effect of three different patient preparation strategies for reducing bowel motion on image quality in pelvic MRI. METHODS: Retrospective study in which 95 consecutive patients undergoing pelvic MRI were subdivided based on preparation type for reduction of bowel motion: group 1 (N = 31) fasted 4 h and applied an enema (Bisacodyl 10 mg); group 2 (N = 32) received no medication; group 3 (N = 32) received intravenous butylscopolamine (Buscopan® 50 mg). Image quality was reviewed by visual assessment of delineation (3-point-scale) of pelvic structures: uterus, adnexa, bladder, rectum, sigmoid, uterosacral ligaments, round ligaments and small bowel. As secondary endpoint the presence of rectal wall edema was evaluated. Interobserver agreement was calculated, as well as relative diagnostic odds ratios (RDOR) for the protocols to provide an outcome in the best delineation category. RESULTS: Interobserver agreement proportions varied from 0.48 to 1.00. The rectum and sigmoid colon respectively have a 5.4 and 2.6 RDOR when butylscopolamine is applied compared to Bisacodyl (P = 0.051; P = 0.008), and a 4.2 and 5.7 times higher RDOR with Bisacodyl preparation compared to no medical preparation (P = 0.006; P < 0.01). Small bowel delineation was significantly better with butylscopolamine compared to Bisacodyl (P = 0.007). There was no significant difference in delineation of the other structures between protocols. There is a significant higher chance of observing rectal wall edema with Bisacodyl compared to the other protocols (both P < 0.001). CONCLUSIONS: Butylscopolamine provides better delineation of the small bowel and rectosigmoid compared to Bisacodyl, which in turn, provides better delineation of the rectosigmoid compared to no medication. Moreover, Bisacodyl causes rectal wall edema in the majority of cases.

Prophylactic scopolamine butylbromide reduced death rattle in patients in the dying phase.

SOURCE CITATION: van Esch HJ, van Zuylen L, Geijteman ECT, et al. Effect of prophylactic subcutaneous scopolamine butylbromide on death rattle in patients at the end of life: the SILENCE randomized clinical trial. JAMA. 2021;326:1268-76. 34609452.

Hyoscine butylbromide in pain reduction associated with ultrasound-guided manual vacuum aspiration: a randomized placebo-controlled trial.

RESEARCH QUESTION: What is the effect of adding an anti-spasmodic drug to an existing ultrasound-guided manual vacuum aspiration (USG-MVA) protocol to alleviate immediate post-procedure abdominal cramping pain in women treated for early pregnancy loss? DESIGN: Double-blind, placebo-controlled, randomized controlled trial conducted between February 2018 and January 2020. Participants were assigned to receive a 1-ml intravenous injection containing 20-mg hyoscine butylbromide (HBB) (n=55) or saline (n =56) as a control immediately before USG-MVA. Primary outcome was reduced abdominal pain after adding a 20-mg dose of HBB to the current pain control regimen. Secondary outcomes were vaginal pain, complications and side-effects, women's pre- and post-procedure psychological state, physiological stress (saliva alpha-amylase) and procedure pain control satisfaction. Two-way mixed ANOVA was used to evaluate the main effects and interactions. RESULTS: VAS abdominal pain scores in the HBB group were 16% lower immediately after and 21% lower 2 h after surgery (not statistically significant). Two-way ANOVA indicated that time (F[1108] = 83.41, P < 0.001) was the only significant main effect for reduced abdominal pain after the procedure and vaginal pain score (F[1108] = 180.1, P < 0.0001) but not drug received. No adverse events were reported. No significant difference was found for psychological state, physiological stress and procedure pain control satisfaction between the two groups. CONCLUSIONS: Anti-spasmodic drugs can help to reduce abdominal cramping pain associated with USG-MVA; HBB produced an insignificant decrease in abdominal pain score. Further studies with longer acting or larger doses of anti-spasmodic drugs are warranted.

Reflections on Including Patients in a Randomized Placebo-Controlled Multicentre Trial in the Dying Phase - the SILENCE Study.

A need exists for studies investigating symptom relief at the end of life. Randomised controlled trials (RCTs) are the gold standard for demonstrating efficacy of medication, but they are difficult to perform at the end of life due to barriers such as the vulnerability of patients, and gatekeeping by healthcare professionals. We analyzed and reflected on recruitment, participation, and strategies used in an RCT at the end of life. The SILENCE study, performed in six inpatient hospice facilities, was a placebo-controlled trial to study the effect of ScopolamIne butyLbromidE giveN prophylactiCally for dEath rattle in dying patients. We addressed patients' vulnerability by using an advance consent procedure, and potential gatekeeping by extensive training of health care professionals and the appointment of hospice doctors as daily responsible researchers. In almost three years, 1097 patients were admitted of whom 626 were eligible at first assessment. Of these, 119 (19%) dropped out because of physical deterioration before they could be informed about the study (44) or sign informed consent (75). Twenty-five (4%) patients were not asked to participate. In 24 cases (4%), relatives advised against the patient participating. Overall, 229 patients (37%) gave informed consent to participate. The vulnerability of patients was the most important barrier in this medication study at the end of life. Gatekeeping by HCPs and relatives occurred in a small number of patients. The robust design and applied strategies to facilitate patient recruitment in this study resulted in a successful study with sufficient participants.

Administration of rectal cytotec versus rectal buscopan before hysteroscopy.

INTRODUCTION: Our objective was to compare the effect of rectal misoprostol (Cytotec) versus rectal hyoscine-n-butyl bromide (Buscopan) on patients undergoing hysteroscopy. We hypothesised that HBB may have a role in cervical priming. MATERIAL AND METHODS: This trial was conducted at Bezmialem Vakif University Hospital. Women of reproductive age between 18-50 years who were scheduled for operative hysteroscopy indicated by type 1 submucous myoma or endometrial polyps were recruited for the study. Ninety patients were divided randomly into three groups. Group 1 received placebo treatment. Group 2 received rectal 200 mcg misoprostol and Group 3 received rectal 20 mg hyoscine-n-butyl bromide two hours before the procedure. Procedures were performed using a bipolar 26 F (9 mm) continuous-flow rigid resectoscope with a 30° lens. The outcome measures included cervical dilation width and time, ease of cervical dilation, procedure time and operative complications. Postoperative self-rated pain was assessed one hour after the procedure. RESULTS: Thirteen patients (43. 3%) in the placebo treatment group, 11 patients (36.7%) in the misoprostol group and four patients (13.3%) in the hyoscine-n-butyl bromide group needed analgesics postoperatively (p = .02). The mean duration of cervical dilation time was longest in Group 1 and shortest in Group 3, however this difference did not reach statistical significance (p=.11). There was no difference with regard to other studied parameters. SUMMARY: HBB reduced the need for pain medication compared to placebo. Larger studies are needed to further investigate the role of HBB in facilitating pre-operative cervical priming.