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JAMA Oct 2021Death rattle, defined as noisy breathing caused by the presence of mucus in the respiratory tract, is relatively common among dying patients. Although clinical... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Death rattle, defined as noisy breathing caused by the presence of mucus in the respiratory tract, is relatively common among dying patients. Although clinical guidelines recommend anticholinergic drugs to reduce the death rattle after nonpharmacological measures fail, evidence regarding their efficacy is lacking. Given that anticholinergics only decrease mucus production, it is unknown whether prophylactic application may be more appropriate.
OBJECTIVE
To determine whether administration of prophylactic scopolamine butylbromide reduces the death rattle.
DESIGN, SETTING, AND PARTICIPANTS
A multicenter, randomized, double-blind, placebo-controlled trial was performed in 6 hospices in the Netherlands. Patients with a life expectancy of 3 or more days who were admitted to the participating hospices were asked to give advance informed consent from April 10, 2017, through December 31, 2019. When the dying phase was recognized, patients fulfilling the eligibility criteria were randomized. Of the 229 patients who provided advance informed consent, 162 were ultimately randomized. The date of final follow-up was January 31, 2020.
INTERVENTIONS
Administration of subcutaneous scopolamine butylbromide, 20 mg four times a day (n = 79), or placebo (n = 78).
MAIN OUTCOMES AND MEASURES
The primary outcome was the occurrence of a grade 2 or higher death rattle as defined by Back (range, 0-3; 0, no rattle; 3, rattle audible standing in the door opening) measured at 2 consecutive time points with a 4-hour interval. Secondary outcomes included the time between recognizing the dying phase and the onset of a death rattle and anticholinergic adverse events.
RESULTS
Among 162 patients who were randomized, 157 patients (97%; median age, 76 years [IQR, 66-84 years]; 56% women) were included in the primary analyses. A death rattle occurred in 10 patients (13%) in the scopolamine group compared with 21 patients (27%) in the placebo group (difference, 14%; 95% CI, 2%-27%, P = .02). Regarding secondary outcomes, an analysis of the time to death rattle yielded a subdistribution hazard ratio (HR) of 0.44 (95% CI, 0.20-0.92; P = .03; cumulative incidence at 48 hours: 8% in the scopolamine group vs 17% in the placebo group). In the scopolamine vs placebo groups, restlessness occurred in 22 of 79 patients (28%) vs 18 of 78 (23%), dry mouth in 8 of 79 (10%) vs 12 of 78 (15%), and urinary retention in 6 of 26 (23%) vs 3 of 18 (17%), respectively.
CONCLUSIONS AND RELEVANCE
Among patients near the end of life, prophylactic subcutaneous scopolamine butylbromide, compared with placebo, significantly reduced the occurrence of the death rattle.
TRIAL REGISTRATION
trialregister.nl Identifier: NTR6264.
Topics: Aged; Aged, 80 and over; Butylscopolammonium Bromide; Cholinergic Antagonists; Confidence Intervals; Death; Double-Blind Method; Drug Administration Schedule; Female; Hospice Care; Humans; Incidence; Informed Consent; Injections, Subcutaneous; Life Expectancy; Male; Middle Aged; Netherlands; Placebos; Proportional Hazards Models; Respiratory Sounds; Treatment Outcome
PubMed: 34609452
DOI: 10.1001/jama.2021.14785 -
JA Clinical Reports Apr 2020There have been only few reports on butylscopolamine-induced anaphylaxis despite its global usage as an anticholinergic agent for approximately 70 years. We present a...
BACKGROUND
There have been only few reports on butylscopolamine-induced anaphylaxis despite its global usage as an anticholinergic agent for approximately 70 years. We present a case of anaphylaxis caused by butylscopolamine.
CASE PRESENTATION
A 63-year-old woman underwent gastrointestinal endoscopic examination. She developed facial cyanosis and hypoxia after intravenous administration of butylscopolamine 10 mg, and her blood pressure was unmeasurable. Her hemodynamic condition recovered after a total of 0.6 mg adrenaline and bolus administration of 100 mg hydrocortisone. One hour after the onset of hypotension, both plasma histamine and serum tryptase were remarkably elevated to 271.7 nmol/L and 174 μg/L, respectively. Skin tests performed 47 days after anaphylaxis showed a positive result only for butylscopolamine among the exposed agents, which was confirmed by basophil activation tests using CD203c and CD63 as markers.
CONCLUSION
Butylscopolamine has the potential to cause severe anaphylaxis; hence, identification of the causative agent is important to prevent recurrence of anaphylaxis.
PubMed: 32270308
DOI: 10.1186/s40981-020-00331-w -
PloS One 2022First-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...
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.
Topics: Pregnancy; Female; Humans; Butylscopolammonium Bromide; Oxytocin; Bromides; Labor, Obstetric; Delivery, Obstetric; Randomized Controlled Trials as Topic
PubMed: 36327275
DOI: 10.1371/journal.pone.0276613 -
BMC Emergency Medicine Sep 2023BACKGROUND: Treatment of acute pain is an essential element of pre-hospital care for injured and critically ill patients. Clinical studies indicate the need for...
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.
Topics: Adult; Humans; Ketamine; Analgesics, Non-Narcotic; Dipyrone; Acetaminophen; Nalbuphine; Pirinitramide; Butylscopolammonium Bromide; Physician Executives; Analgesics; Analgesics, Opioid; Fentanyl; Germany; Acute Pain; Morphine Derivatives
PubMed: 37710177
DOI: 10.1186/s12873-023-00878-8 -
Journal of Pain and Symptom Management May 2022A need exists for studies investigating symptom relief at the end of life. Randomised controlled trials (RCTs) are the gold standard for demonstrating efficacy of... (Review)
Review
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.
Topics: Butylscopolammonium Bromide; Death; Hospice Care; Hospitalization; Humans; Informed Consent; Multicenter Studies as Topic; Randomized Controlled Trials as Topic
PubMed: 34954069
DOI: 10.1016/j.jpainsymman.2021.12.018 -
BMC Pregnancy and Childbirth May 2020The objective of this systematic review and meta-analysis was to assess the effectiveness of hyoscine n-butylbromide in labor progress. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The objective of this systematic review and meta-analysis was to assess the effectiveness of hyoscine n-butylbromide in labor progress.
METHODS
The databases including PubMed, the Cochrane Library, Science-Direct, Scopus and Web of Science were searched for studies published up to December 2019. Articles that published as randomized controlled trials (RCTs), and full-text articles published in English or other languages were included and participants were primi or multigravida women who were in active phase of labor. The intervention included HBB compared to placebo (normal saline) that was used during active phase of labor. Pooled estimates were measured using the fixed or random effect model, while the overall effect was reported in a mean difference (MD). All data were analyzed using Review Manager 5.3.
RESULTS
Twenty studies involving 3108 women were included in meta-analysis. Based on subgroup analysis by parity, use of HBB significantly reduced the duration of the first stage of labor in primigravida women (MD = - 57.73; 95% CI: [- 61.48, - 53.60]) and in multigravida women (MD = - 90.74; 95% CI: [- 97.24, - 84.24]). Administering HBB could reduce the second stages of labor in primigravidas and multigravidas about 6 min and 4 min respectively. Also, HBB reduced the duration of the third stage of labor in multigravidas about 3 min. APGAR score at one and 5 min after birth was not affected. The main maternal adverse effect was tachycardia and dry mouth. Labor duration in studies in which the participants were primi-and multigravida was not presented based on separate parities except for four papers, and the route of HBB administration was not the same across all studies.
CONCLUSIONS
Although, the effect of HBB was minimal when multigravidas and primigravidas women were considered together, the HBB was clinically effective in primigravida and multigravida women for shortening the first and the second stages of labor. Also, HBB could reduce the length of the third stage of labor in multigravidas.
Topics: Adult; Apgar Score; Butylscopolammonium Bromide; Cholinergic Antagonists; Female; Gravidity; Humans; Labor Stage, First; Labor, Obstetric; Muscarinic Antagonists; Parity; Pregnancy; Scopolamine; Young Adult
PubMed: 32404072
DOI: 10.1186/s12884-020-2832-3 -
Journal of Nuclear Medicine : Official... May 2022This article reports the preliminary results of a phase II clinical trial investigating the use of the estrogen receptor (ER)-targeting PET tracer...
This article reports the preliminary results of a phase II clinical trial investigating the use of the estrogen receptor (ER)-targeting PET tracer 4-fluoro-11β-methoxy-16α-F-fluoroestradiol (F-4FMFES) and F-FDG PET in endometrial cancers. In parallel, noninvasive interventions were attempted to slow progression of F-4FMFES metabolites in the intestines to reduce abdominal background uptake. In an ongoing study, 25 patients who received prior pathologic confirmation of an ER-positive endometrial cancer or endometrial intraepithelial neoplasia agreed to participate in the ongoing clinical trial. Patients were scheduled for F-FDG and F-4FMFES PET/CT imaging in random order and within 2 wk. Patients were administered either 4 mg of loperamide orally before F-4FMFES tracer injection or repeated intravenous injection of 20 mg of hyoscine -butylbromide during F-4FMFES PET/CT. Regions of interest covering the whole abdomen and excluding the liver, bladder, and uterus were drawn for the F-4FMFES PET images, and an SUV threshold of more than 4 was applied. The volume of the resulting region was compared between the different interventions to estimate the extent of the intestinal background uptake. Repeated injection of hyoscine -butylbromide substantially reduced the intestinal background volume, whereas loperamide had a significant but moderate effect. F-4FMFES tumor SUV ranged from 3.0 to 14.4 (9.4 ± 3.2), whereas F-FDG SUV ranged from 0 to 22.0 (7.5 ± 5.1). Tumor-to-background ratio was significantly higher for F-4FMFES (16.4 ± 5.4) than for F-FDG (7.4 ± 4.6). Significant differences were observed between grade 1 and higher-grade tumors concerning F-4FMFES uptake and contrast, F-FDG uptake, and the F-FDG/F-4FMFES uptake ratio. It is possible to improve F-4FMFES abdominal background using hyoscine -butylbromide. Both F-FDG and F-4FMFES PET are suitable for detection of ER-positive endometrial cancers, although F-4FMFES yielded a better tumor contrast than did F-FDG.
Topics: Butylscopolammonium Bromide; Endometrial Neoplasms; Estradiol; Female; Fluorodeoxyglucose F18; Humans; Loperamide; Positron Emission Tomography Computed Tomography; Receptors, Estrogen
PubMed: 34413142
DOI: 10.2967/jnumed.121.262617 -
International Journal of Legal Medicine Jul 2021Scopolamine is an alkaloid which acts as competitive antagonists to acetylcholine at central and peripheral muscarinic receptors. We report the case of a 41-year-old...
Scopolamine is an alkaloid which acts as competitive antagonists to acetylcholine at central and peripheral muscarinic receptors. We report the case of a 41-year-old male convict with a 27-year history of cannabis abuse who suddenly died in the bed of his cell after having smoked buscopan® tablets. Since both abuse of substances and recent physical assaults had been reported, we opted for a comprehensive approach (post-mortem computed tomography CT (PMCT), full forensic autopsy, and toxicology testing) to determine which was the cause of the death. Virtopsy found significant cerebral edema and lungs edema that were confirmed at the autopsy and at the histopathological examination. Scopolamine was detected in peripheral blood at the toxic concentration of 14 ng/mL in blood and at 263 ng/mL in urine, and scopolamine butyl bromide at 17 ng/mL in blood and 90 ng/mL in urine. Quetiapine, mirtazapine, lorazepam, diazepam, and metabolites and valproate were also detected (at therapeutic concentrations). Inmates, especially when they have a history of drug abuse, are at risk to use any substance they can find for recreational purposes. In prisons, active surveillance on the management and assumption of prescribed drugs could avoid fatal acute intoxication.
Topics: Adult; Autopsy; Butylscopolammonium Bromide; Edema; Fatal Outcome; Forensic Toxicology; Humans; Male; Prisoners; Scopolamine; Substance Abuse Detection
PubMed: 33890166
DOI: 10.1007/s00414-021-02583-2 -
Scientific Reports Jun 2022Hyoscine-N-butylbromide (HBB) is the most used antiperistaltic agent during esophagogastroduodenoscopy (EGD). However, almost half of the elderly have a contraindication... (Randomized Controlled Trial)
Randomized Controlled Trial
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).
Topics: Aged; Antidiarrheals; Butylscopolammonium Bromide; Contraindications; Double-Blind Method; Endoscopy, Digestive System; Humans; Hydrocarbons, Brominated; Menthol; Prospective Studies; Scopolamine
PubMed: 35729250
DOI: 10.1038/s41598-022-14693-x -
World Journal of Urology Jul 2021To investigate whether placebo is non-inferior to continuous infusion of butylscopolamine in patients with renal colic. (Randomized Controlled Trial)
Randomized Controlled Trial
The BUSCOPAN study: a randomized-controlled non-inferiority trial of a continuous butylscopolamine infusion versus placebo in patients with a renal colic not responding to oral non-steroidal anti-inflammatory drugs.
PURPOSE
To investigate whether placebo is non-inferior to continuous infusion of butylscopolamine in patients with renal colic.
METHODS
We conducted a placebo-controlled, multicenter, double-blind randomized clinical trial (RCT) including 128 patients with renal colic (confirmed by ultrasound or CT-scan). Patients were randomized to receive either continuous IV butylscopolamine 100 mg/24 h or placebo (saline). Primary outcome is the amount of opioid escape medication used, measured in doses administered. Secondary outcomes are pain measured on a Numeric Rating Scale (NRS), side effects, and time of drug administration. Non-inferiority was assessed using linear regression with robust standard errors, with non-inferiority limit set at 0.5 units of escape medication.
RESULTS
Median number of doses of escape medication was one in both groups. The number of extra doses in the placebo group compared with the butylscopolamine group was 0.05, with a 95% robust confidence interval (CI) of 0.38-0.47. Upper limit of the CI remained below the non-inferiority limit of 0.5 (p = 0.04). No differences in secondary endpoints were seen between the groups.
CONCLUSION
Placebo is non-inferior to continuous IV butylscopolamine for pain relief in patients with renal colic. Based on this study and previous evidence, there is no role for continuous butylscopolamine IV in the treatment of renal colic. Trial NL7819.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Butylscopolammonium Bromide; Double-Blind Method; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Muscarinic Antagonists; Renal Colic; Treatment Failure
PubMed: 32949255
DOI: 10.1007/s00345-020-03460-0