Patient in Mayfield Head Pins Requiring Prone Bronchoscopy for Mucus Plug Obstruction: A Case Report.

Mucus plug obstruction is a common complication in prone patients associated with loss of ventilation and hemodynamic instability. This case presents a 62-year-old female with chronic bronchitis who underwent posterior cervical fusion for a type III dens fracture with extension into the pars articularis and pedicles. Glycopyrrolate was administered to assist with fiberoptic intubation. After successful intubation, bronchoscopy revealed copious endotracheal secretions requiring preoperative therapeutic removal. Despite extensive removal of thick endotracheal secretions preoperatively, obstructive mucus plugging developed intraoperatively with complete loss of end-tidal carbon dioxide (ETCO2) while the patient was in Mayfield head pins. With limited airway access, suctioning and prone flexible bronchoscopy were performed, successfully restoring ETCO2. This experience underscores the need for heightened awareness and preparedness for mucus plug obstruction in chronic bronchitis patients undergoing prone cervical spine surgeries.

Interoceptive Signals Bias Decision Making in Rhesus Macaques.

Several influential theories have proposed that interoceptive signals, sent from the body to the brain, contribute to neural processes that coordinate complex behaviors. Using pharmacological agents that do not cross the blood-brain barrier, we altered interoceptive states and evaluated their effect on decision-making in rhesus monkeys. We used glycopyrrolate, a non-specific muscarinic (parasympathetic) antagonist, and isoproterenol, a beta-1/2 (sympathetic) agonist, to create a sympathetic-dominated physiological state indexed by increased heart rate. Rhesus monkeys were trained on two variants of an approach-avoidance conflict task, where they chose between enduring mildly aversive stimuli in exchange for a steady flow of rewards, or cancelling the aversive stimuli, forgoing the rewards. The delay to interrupt the aversive stimuli and the reward were used as a measure of the cost-benefit estimation that drove the monkeys' decisions. Both drugs altered approach-avoidance decisions, substantially reducing the delay to interrupt the aversive stimuli. To determine whether this autonomic state lowered tolerance to aversive stimuli or reduced the subjective value of the reward, we tested the effects of glycopyrrolate on a food preference task. Food preference was unaltered, suggesting that the sympathetic dominated state selectively reduces tolerance for aversive stimuli without altering reward-seeking behaviors. As these drugs have no direct effect on brain physiology, interoceptive afferents are the most likely mechanism by which decision making was biased toward avoidance.

Efficacy and Safety of Glycopyrrolate in the Management of Organophosphate and Carbamate Poisoning: A Systematic Review.

OBJECTIVE: There is a lack of evidence on the effectiveness of antidotes in the management of organophosphate and carbamate (OPC) poisoning. We aimed to review the efficacy and safety of glycopyrrolate in the management of OPC poisoning. METHODOLOGY: Databases such as PubMed, Scopus, Embase, and Cochrane Library were extensively searched from inception to November 2022 and updated till October 2023. Interventional, observational, and descriptive studies assessing the efficacy and safety of glycopyrrolate administered in any dose, route, and duration for the management of OPC poisoning published in the English language were considered for this review. The treatment with any other regimen that did not include glycopyrrolate was regarded as the comparator. The survival, intensive care unit (ICU) days and ventilatory outcomes were considered efficacy outcomes, and adverse effects were considered safety outcomes. Suitable quality assessment tools were used to assess the risk of bias in the included studies. Two independent reviewers were involved in the study selection, data extraction, and quality assessment and any discrepancies were resolved through mutual discussion or consultation with a third reviewer. RESULTS: A total of 9 studies (2 RCTs, 4 cohorts, 1 case series, and 2 case reports) out of 591 nonduplicate records were considered for this review. Overall, the RCTs were observed to have a moderate quality, and observational studies and descriptive studies were found to have good quality. All the included studies used atropine administration as a standard treatment option along with glycopyrrolate. The OPC patients treated with glycopyrrolate had a fewer hospitalization days with comparable recovery and ventilatory outcomes than those that had not been treated with glycopyrrolate. The occurrence of adverse events and complications was lower in the glycopyrrolate group than in the control group. CONCLUSION: Currently, there is a lack of comparative studies to recommend the use of glycopyrrolate in OPC poisoning, and further interventional studies are required to make an evidencebased recommendation on this topic.

Effects of glycopyrrolate and atropine for oral secretions and perioperative hemodynamics in children undergoing tonsillectomy and adenoidectomy: a prospective, single-center, randomized, double-blind, controlled trial.

Introduction: Glycopyrrolate is commonly researched as a preoperative medication or in conjunction with cholinesterase inhibitors to counteract the lingering muscarinic effects of non-depolarizing muscarinic agents. However, studies have yielded inconsistent results regarding the superiority of glycopyrrolate over other anti-cholinergic drugs, such as atropine, particularly its effect on heart rate, blood pressure (BP), and glandular secretions. This study aimed to evaluate the differences in perioperative oral secretions, hemodynamics, and recovery quality with glycopyrrolate versus those with atropine before anesthesia induction in children undergoing tonsillectomy and adenoidectomy. Methods: In this prospective, single-center, randomized, double-blind, controlled trial, a total of 103 children were randomly assigned to group A (n = 51, glycopyrrolate 0.005 mg/kg) or B (n = 52, atropine 0.01 mg/kg). The follow-up anesthetic induction and maintenance protocols were the same in both groups. Vital signs, duration of surgery, extubation time, degree of wetness around the vocal cords during tracheal intubation, weight of oral secretions, and perioperative complications were recorded. Results: No significant differences were observed in the degree of wetness around the vocal cords during tracheal intubation, as well as in the weight of oral secretions, duration of surgery, or extubation time, between the two groups. The intraoperative and postoperative heart rates were lower in group A than in group B (110.18 ± 10.58 vs. 114.94 ± 11.14, p = 0.028; 96.96 ± 10.81 vs. 103.38 ± 10.09, p = 0.002). The differences observed in the intraoperative and preoperative heart rates were lower in group A than in group B (23.84 ± 9.62 vs. 29.65 ± 8.75, p = 0.002). The differences observed in the postoperative and preoperative heart rates were lower in group A than in group B (10.63 ± 9.97 vs. 18.09 ± 9.39, p = 0.000). Conclusion: Glycopyrrolate showed a smoother change in heart rate than atropine during and after tonsillectomy and adenoidectomy, with no effect on BP or recovery quality, and did not increase oral secretions. The findings indicate that glycopyrrolate can serve as an alternative to atropine to prevent secretions in anesthesia induction for tonsillectomy and adenoidectomy in children. Trial registration: This study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR2200063578; Date of Registration: 12/09/2022).

Use of sugammadex in prevention of post-operative urinary retention in minimally invasive hernia surgery.

PURPOSE: Post-operative urinary retention (POUR) is a known complication of hernia surgery. Minimally invasive inguinal hernia repair (IHR) is typically done under general anesthesia with neuromuscular blockade (NMB), which is commonly reversed with an anticholinesterase inhibitor paired with an anticholinergic agent. Sugammadex is a unique NMB reversal agent that does not have to be paired with an anticholinergic. We sought to explore the role of sugammadex in reducing the rate of POUR following these procedures. METHODS: Data were collected retrospectively at a single institution between February 2016 and October 2019. We identified and studied patients who underwent minimally invasive IHR and received either sugammadex or neostigmine/glycopyrrolate for NMB reversal. The primary endpoint was POUR requiring bladder catheterization. Secondary endpoints included post-operative and 30-day readmissions. RESULTS: 274 patients were included in this study (143 received neostigmine and glycopyrrolate, 131 sugammadex). The sugammadex patients were on average 5 years older than the neostigmine/ glycopyrrolate patients (63.2 vs 58.2, p = 0.003), and received less median intravenous fluids (IVF) (900 ml vs 1000 ml; p = 0.015). There was a significant difference in the rate of POUR between the sugammadex and neostigmine/glycopyrrolate patients (0.0% vs 8.4%, p ≤ 0.001). The difference remained significant after controlling for age and IVF. The odds of POUR for those who received neostigmine/glycopyrrolate were 25 × higher than the odds of those who received sugammadex. CONCLUSION: The results of this study reflect the protective role of sugammadex against POUR in minimally invasive IHR cases.

The effect of glycopyrrolate vs. atropine in combination with neostigmine on cardiovascular system for reversal of residual neuromuscular blockade in the elderly: a randomized controlled trial.

BACKGROUND: Glycopyrrolate-neostigmine (G/N) for reversing neuromuscular blockade (NMB) causes fewer changes in heart rate (HR) than atropine-neostigmine (A/N). This advantage may be especially beneficial for elderly patients. Therefore, this study aimed to compare the cardiovascular effects of G/N and A/N for the reversal of NMB in elderly patients. METHODS: Elderly patients aged 65-80 years who were scheduled for elective non-cardiac surgery under general anesthesia were randomly assigned to the glycopyrrolate group (group G) or the atropine group (group A). Following the last administration of muscle relaxants for more than 30 min, group G received 4 ug/kg glycopyrrolate and 20 ug/kg neostigmine, while group A received 10 ug/kg atropine and 20 ug/kg neostigmine. HR, mean arterial pressure (MAP), and ST segment in lead II (ST-II) were measured 1 min before administration and 1-15 min after administration. RESULTS: HR was significantly lower in group G compared to group A at 2-8 min after administration (P < 0.05). MAP was significantly lower in group G compared to group A at 1-4 min after administration (P < 0.05). ST-II was significantly depressed in group A compared to group G at 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, and 15 min after administration (P < 0.05). CONCLUSIONS: In comparison to A/N, G/N for reversing residual NMB in the elderly has a more stable HR, MAP, and ST-II within 15 min after administration.

Glycopyrrolate as an Adjunct in the Management of Anastomotic Leak Following Repair of Esophageal Atresia: A Clinicoradiological Perspective.

Context: Anastomotic leak after primary repair of esophageal atresia (EA) with tracheoesophageal fistula (TEF) is a well-known complication and can represent a challenging clinical scenario. Aims: The present study aimed to evaluate the role of glycopyrrolate as an adjunct in the treatment of anastomotic leak after primary repair of EA Vogt type 3b. Settings and Design: A retrospective study was carried out in our tertiary care teaching institute from January 2015 to December 2022. Materials and Methods: Neonates with EA with distal TEF with primary repair who had developed anastomotic leak, managed by the author(s), were studied. The study included patients with major, minor, and radiological leaks. Glycopyrrolate was administered in the dose of 4 µg/kg 8 hourly. The outcomes of the study were either resolution or progression of the leak. Results: There were 21 patients who were managed with glycopyrrolate in addition to the classical treatment of the anastomotic leak following repair of EA with distal TEF. The male: female ratio was 1:1.1. All the cases had anastomotic leaks with either clinically detectable in the chest tube (15) or radiological leak (6). The leaks were detected early in patients with major leak (mean = 3.2 ± 0.84 days) compared to minor leak (mean =4.9 ± 1.29 days). Radiological leaks were detected in all the neonates on postoperative day 7. In five patients with major leak, there was a negligible reduction in the amount of chest tube output, and were subjected to diversion procedures. There were a total of three deaths out of five in this group. In 10 patients with minor leak, there was complete resolution of anastomotic leak in eight patients (80%); there was one patient each with mortality and diversion procedure. The patients with a radiological leak (6) did not show any deterioration, and they were fed 1-5 days after the esophagogram. Conclusions: Glycopyrrolate may be an advantageous postoperative adjunct in the management of minor and radiological leak after tracheoesophageal repair.

Pharmacologic Management of Sialorrhea in Neonatal and Pediatric Patients.

Sialorrhea, defined as an excess flow of saliva or excessive secretions, is common in patients with cerebral palsy and other neurologic disorders and is associated with clinical complications such as increased risk of local skin reactions, infections, aspiration, pneumonia, and dehydration. Upon failure of non-pharmacologic measures, clinicians have several noninvasive pharmacologic options available to manage sialorrhea. This review of the literature provides detailed descriptions of medications used, efficacy, safety, and practical considerations for use of non-injectable pharmacologic agents. The literature search included published -human studies in the English language in PubMed and Google Scholar from 1997 to 2022. Relevant citations within articles were also screened. A total of 15 studies representing 719 pediatric patients were included. Glycopyrrolate, atropine, scopolamine, and trihexyphenidyl all have a potential role for sialorrhea management in children; however, glycopyrrolate remains the most studied option with 374 (n = 52.0%) of the 719 patients included in the systematic review receiving this medication. Overall, glycopyrrolate showed similar efficacy but higher tolerability than its comparators in 2 comparative studies and is often considered the first-line agent. Patient-specific (age, route of administration) and medication-specific (dosage formulation, medication strength) considerations must be weighed when initiating a new therapy or switching to another medication upon treatment failure. Owing to the high propensity of adverse events with all agents, clinicians should consider initiating doses at the lower end of the dosage range, as previous studies have noted a dose-dependent relationship.

Effect of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler combined with nasal high-flow nasal cannula on elderly patients with COPD and respiratory failure.

Objective: To explore the clinical effect of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) combined with high-flow nasal cannula (HFNC) in the treatment of elderly patients with chronic obstructive pulmonary disease (COPD) and respiratory failure. Methods: The clinical records of 94 elderly patients with COPD and respiratory failure who were treated in Yongkang First People's Hospital from February 2022 to January 2023 were retrospectively selected. Among them, 46 patients received HFNC alone (Control-group) and 48 patients received HFNC combined with BGF MDI (Study-group). The treatment effect, arterial blood gas status, pulmonary function, and acute physiology and chronic health evaluation (APACHE) II score before and after treatment were analyzed in both groups. Results: The total efficacy of treatment in the Study-group (95.8%) was higher than that in the Control-group (78.3%) (P<0.05). After treatment, the partial pressure of arterial carbon dioxide (PaCO2), residual volume, and APACHE II scores in the two groups decreased compared to those before treatment, with the Study-group lower overall. However, arterial oxygen saturation (SaO2), oxygen partial pressure (PaO2), the percentage of peak expiratory flow (PEF), and forced expiratory volume in one second (FEV1) as percent of predicted (%FEV1) were higher than before treatment, and higher in the Study-group (P<0.05). Conclusions: Compared with HFNC alone, BGF MDI combined with HFNC can effectively regulate the arterial blood gas status of elderly patients with COPD and respiratory failure, restore pulmonary function, and improve the overall treatment effect.

A Case of Pharmacologic Anisocoria in Systemic Glycopyrrolate Use from Presumed Local Ocular Inoculation.

Anisocoria is a common finding in ophthalmic clinical practice. History taking and examination is critical in appropriately diagnosing and managing anisocoria, as the differential can be extensive ranging from benign to life-threatening entities. This case discusses the presentation of a 22-year-old female with a history of myopia and hyperhidrosis who presented with pharmacologic anisocoria which was presumed to be from inadvertent topical exposure to conventional glycopyrrolate tablets. To our knowledge, pharmacologic mydriasis from exposure to residue from conventional glycopyrrolate tablets has not been reported in the English literature. This case highlights the importance of medication and contact lens handling with anticholinergic agents.

Post-operative urinary retention is impacted by neuromuscular block reversal agent choice: A retrospective cohort study in US hospital setting.

STUDY OBJECTIVE: Perioperative neuromuscular blocking agents are pharmacologically reversed to minimize complications associated with residual neuromuscular block. Neuromuscular block reversal with anticholinesterases (e.g., neostigmine) require coadministration of an anticholinergic agent (e.g., glycopyrrolate) to mitigate muscarinic activity; however, sugammadex, devoid of cholinergic activity, does not require anticholinergic coadministration. Single-institution studies have found decreased incidence of post-operative urinary retention associated with sugammadex reversal. This study used a multicenter database to better understand the association between neuromuscular block reversal technique and post-operative urinary retention. DESIGN: Retrospective cohort study utilizing large healthcare database. SETTING: Non-profit, non-governmental and community and teaching hospitals and health systems from rural and urban areas. PATIENTS: 61,898 matched adult inpatients and 95,500 matched adult outpatients. INTERVENTIONS: Neuromuscular block reversal with sugammadex or neostigmine plus glycopyrrolate. MEASUREMENTS: Incidence of post-operative urinary retention by neuromuscular block reversal agent and the independent association of neuromuscular block reversal technique and risk of post-operative urinary retention. MAIN RESULTS: The incidence of post-operative urinary retention was 2-fold greater among neostigmine with glycopyrrolate compared to sugammadex patients (5.0% vs 2.4% inpatients; 0.9% vs 0.4% outpatients; both p < 0.0001). Multivariable logistic regression identified reversal with neostigmine to be independently associated with greater risk of post-operative urinary retention (inpatients: odds ratio, 2.20; 95% confidence interval, 2.00 to 2.41; p < 0.001; outpatients: odds ratio, 2.57; 95% confidence interval, 2.13 to 3.10; p < 0.001). Post-operative urinary retention-related visits within 2 days following discharge were five-fold higher among those reversed with neostigmine than sugammadex among inpatients (0.05% vs. 0.01%, respectively; p = 0.018) and outpatients (0.5% vs. 0.1%; p < 0.0001). CONCLUSION: Though this study suggests that neuromuscular block reversal with neostigmine can increase post-operative urinary retention risk, additional studies are needed to fully understand the association.

The effect of sugammadex on postoperative urinary retention post-laparoscopic and robotic hysterectomy with and without concomitant procedures.

INTRODUCTION AND HYPOTHESIS: This study was aimed at determining the effect of sugammadex versus a combination of glycopyrrolate and neostigmine (GN) for neuromuscular reversal blockage on transient postoperative urinary retention (TPOUR) in patients undergoing a laparoscopic and robot-assisted laparoscopic hysterectomy. METHODS: We conducted a retrospective cohort study in patients undergoing a laparoscopic or robotic hysterectomy between February 2017 and December 2021. Patients with and without concomitant procedures were included. Demographics and perioperative data were extracted from the patient's medical record. Before discharge, all patients were required to spontaneously void and have a post-void residual of less than 150 ml. RESULTS: We identified 500 patients and 485 were included in the final analysis. We had 319 subjects who received sugammadex and 166 GN combination. Both groups had overall similar demographics and perioperative characteristics. Most patients had a conventional laparoscopy procedure (391 [82.5%]) compared with robotic (83 [17.5%]). Patients who received GN were significantly more likely to be discharged home with an indwelling catheter (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.09-3.05). After adjusting for perioperative medications and sling implantation during the surgery a logistic regression model continued to demonstrate that patients who received GN had significantly higher odds of being discharged with a catheter (OR, 1.79; 95% CI, 1.03-3.12). CONCLUSIONS: Our findings suggest that sugammadex decreases the odds of TPOUR after laparoscopic hysterectomies with and without slings compared with the combination of GN. Additional prospective trials are required to confirm this finding.

Effect of glycopyrrolate on the postoperative urine output of patients following kidney transplantation: a retrospective observational study.

OBJECTIVES: To compare the urine output and estimated glomerular filtration rate (eGFR) of patients postoperatively administered sugammadex or glycopyrrolate 7 days following kidney transplantation (KT). METHODS: We retrospectively enrolled 134 consecutive patients who underwent KT under general anesthesia. Their urine output and eGFR were recorded every 24 hours between postoperative day (POD) 1 and 7. We used regression analysis to evaluate the relationship between the reversal agent administered and the outcomes of the participants. RESULTS: The urine output and eGFR of the participants did not differ between the two groups. Multivariate analysis showed that body mass index (BMI) (odds ratio (OR) 1.21; 95% confidence interval (CI) 1.05-1.40), diabetes mellitus (OR 3.14; 95% CI 1.07-9.16), neurovascular disease (OR 7.00; 95% CI 1.61-30.42), and the duration of surgery (OR 1.01; 95% CI 1.00-1.01) were associated with lower urine output on POD 7. In addition, only BMI (OR 1.25; 95% CI 1.09-1.42) was associated with low eGFR on POD 7. CONCLUSIONS: The urine output and eGFR of patients administered sugammadex or glycopyrrolate following KT did not differ 7 days later. Moreover, glycopyrrolate does not affect urine output or eGFR on POD 7, according to multivariate regression analysis.

Exacerbations and Real-World Outcomes After Single-Inhaler Triple Therapy of Budesonide/Glycopyrrolate/Formoterol Fumarate, Among Patients with COPD: Results from the EROS (US) Study.

Purpose: Triple therapy to prevent exacerbations from chronic obstructive pulmonary disease (COPD) is associated with improved health compared to single and dual-agent therapy in some populations. This study assessed the benefits of prompt administration of budesonide/glycopyrrolate/formoterol fumarate (BGF) following a COPD exacerbation. Patients and methods: EROS was a retrospective analysis of people with COPD using the MORE2 Registry®. Inclusion required ≥1 severe, ≥2 moderate, or ≥1 moderate exacerbation while on other maintenance treatment. Within 12 months following the index exacerbation, ≥1 pharmacy claim for BGF was required. Primary outcomes were the rate of COPD exacerbations and healthcare costs for those that received BGF promptly (within 30 days of index exacerbation) versus delayed (31-180 days) and very delayed (181-365 days). The effect of each 30-day delay in initiation of BGF was estimated using a multivariable negative binomial regression model. Results: 2409 patients were identified: 434 prompt, 1187 delayed, and 788 very delayed. The rate (95% CI) of total exacerbations post-index increased as time to BGF initiation increased: prompt 1.52 (1.39-1.66); delayed 2.00 (1.92-2.09); and very delayed 2.30 (2.20-2.40). Adjusting for patient characteristics, each 30-day delay in receiving BGF was associated with a 5% increase in the average number of subsequent exacerbations (rate ratio, 95% CI: 1.05, 1.01-1.08; p<0.05). Prompt initiation of BGF was also associated with lower post-index annualized COPD-related costs ($5002 for prompt vs $7639 and $8724 for the delayed and very delayed groups, respectively). Conclusion: Following a COPD exacerbation, promptly initiating BGF was associated with a reduction in subsequent exacerbations and reduced healthcare utilization and costs.

Glycopyrrolate-induced polyuria: An unexpected side effect.

Polyuria is urine output exceeding 3 L/d in adults, primarily due to solute and water diuresis. In a hospital setting, mannitol and diuretics commonly lead to polyuria. We have found an interesting association of polyuria with glycopyrrolate; to the best of our knowledge, no case is reported in the literature. Here, we are describing a case of Guillain-Barre Syndrome, which developed polyuria during the hospital stay, which was secondary to glycopyrrolate.

Relative bioavailability of budesonide/glycopyrrolate/formoterol fumarate triple therapy delivered using next generation propellants with low global warming potential.

INTRODUCTION: The climate crisis poses an immediate threat to human health and well-being, demanding urgent adaptions across sectors, including healthcare. The development of pressurized metered dose inhalers (MDIs) with greater sensitivity to the climate emergency using novel propellants with lower global warming potentials (GWPs), but comparable pharmacokinetic (PK) parameters to currently marketed MDIs, is a vital step toward reducing the impact of healthcare for respiratory disorders on climate change. This study evaluated the relative bioavailabilities of the individual components of a fixed-dose combination of budesonide/glycopyrrolate/formoterol fumarate (BGF) 160/9/4.8 µg per actuation between three different propellant formulations. METHODS: Healthy male participants (aged 18-60 years) were randomized into a single-blind, three-period, single-dose, single-center, crossover study (NCT04600505). The PK and safety and tolerability profiles of BGF MDI formulated with two novel propellants with low GWP (hydrofluoroolefin-1234ze [HFO]; hydrofluorocarbon-152a [HFC]) were compared with BGF MDI formulated with the propellant used in the currently marketed reference product (hydrofluoroalkane-134a [HFA]). The study included a screening period, three treatment periods (with 3- to 7-day washout periods between each dose), and a follow-up. The primary PK parameters assessed were maximum observed plasma concentration (Cmax), area under the plasma concentration curve (AUC) from time zero extrapolated to infinity (AUCinf), and AUC from time zero to the time of the last quantifiable analyte concentration (AUClast). The study was not powered to statistically demonstrate bioequivalence. RESULTS: Forty-seven participants completed the study, and 24 participants were evaluable for PK assessments. Systemic exposure, based on geometric mean ratios (90% confidence interval), to each BGF component from the test propellants delivered in a standard MDI was comparable with the reference propellant for AUClast (HFO vs. HFA: budesonide, 107.30 [94.53, 121.90]; glycopyrrolate, 106.10 [86.18, 130.60]; formoterol, 98.13 [86.44, 111.40]; HFC vs. HFA: budesonide, 98.80 [84.59, 115.40]; glycopyrrolate, 99.71 [80.84, 123.00]; formoterol, 107.00 [88.82, 128.90]); AUCinf (where evaluable) and Cmax followed the same trend. There were no serious adverse events or adverse events leading to treatment discontinuation. No new safety signals were observed. CONCLUSIONS: Systemic BGF component exposure was similar for both test propellants (HFO and HFC) compared with the HFA reference propellant, with an acceptable safety profile in the studied population. Therefore, both novel low GWP propellants show strong potential as candidates for development of MDIs with greater sensitivity to the climate crisis, a vital step toward ameliorating the detrimental impact of healthcare on the environment. Further investigation in larger studies is warranted.

Mortality risk reduction with budesonide/glycopyrrolate/formoterol fumarate versus fluticasone furoate/umeclidinium/vilanterol in COPD: a matching-adjusted indirect comparison based on ETHOS and IMPACT.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. While two approved fixed-dose inhaled corticosteroid/long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) triple therapies reduce all-cause mortality (ACM) versus dual LAMA/LABA therapy in patients with COPD, head-to-head studies have not compared the effects of these therapies on ACM. We compared ACM in adults with moderate-to-very severe COPD receiving budesonide/glycopyrrolate/formoterol fumarate (BGF) in ETHOS versus fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in IMPACT using a matching-adjusted indirect comparison (MAIC). METHODS: A systematic literature review identified two studies (ETHOS [NCT02465567]; IMPACT [NCT02164513]) of ≥52 weeks reporting ACM as an efficacy endpoint in patients receiving triple therapy. As ETHOS and IMPACT lack a common comparator, an unanchored MAIC compared ACM between licensed doses of BGF (320/18/9.6 µg) from ETHOS and FF/UMEC/VI (100/62.5/25 µg) from IMPACT in patients with moderate-to-very severe COPD. Using on- and off-treatment data from the final retrieved datasets of the intention-to-treat populations, BGF data were adjusted according to aggregate FF/UMEC/VI data using 11 baseline covariates; a supplementary unadjusted indirect treatment comparison was also conducted. P-values for these post-hoc analyses are not adjusted for Type I error. RESULTS: ACM over 52 weeks was statistically significantly reduced by 39% for BGF versus FF/UMEC/VI in the MAIC (hazard ratio [HR] [95% CI]: 0.61 [0.38, 0.95], p = 0.030) and unadjusted analysis (HR [95% CI]: 0.61 [0.41, 0.92], p = 0.019). CONCLUSION: In this MAIC, which adjusted for population heterogeneity between ETHOS and IMPACT, ACM was significantly reduced with BGF versus FF/UMEC/VI in patients with moderate-to-very severe COPD.

Chronic obstructive pulmonary disease (known as COPD) is a leading cause of death worldwide, being responsible for over 3 million deaths in 2019. People living with COPD are more likely to die. Importantly, a sudden worsening of COPD symptoms (known as an exacerbation) is associated with a higher chance of death from heart-related and breathing-related problems. Therefore, reducing risk of death is an important treatment goal for COPD. Of the three medications approved for treating COPD that combine three drugs in a single-inhaler device, there are two­referred to generically as budesonide/glycopyrrolate/formoterol fumarate (BGF) and fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI)­that can reduce the risk of death in people living with COPD compared with treatments that combine two drugs. However, no studies have directly compared the risk of death in people living with COPD treated with these medicines. We compared the risk of death in people living with moderate-to-very severe COPD who received either BGF during a clinical trial called ETHOS or FF/UMEC/VI during a clinical trial called IMPACT. To make this comparison, we used a method called "matching-adjusted indirect comparison", which used specific features (such as sex, breathing difficulty, and whether they were current smokers) to match patients from the two studies to ensure similar groups were examined. Our analysis showed a 39% decrease in the chance of death in patients who received BGF compared with patients who received FF/UMEC/VI. This finding may be important for doctors to improve patient health and reduce the risk of death in people living with COPD.

The Physical Compatibility of Glycopyrrolate and Rocuronium.

OBJECTIVE: Scientific evidence has rarely, if at all, been reported in the literature demonstrating analytical confirmation of the physical compatibility and stability of glycopyrrolate and rocuronium combined. The purpose of this experiment was to determine if glycopyrrolate and rocuronium are physically compatible. METHODS: Glycopyrrolate and rocuronium were combined in various containers, observed over a 60-minute period, and compared against positive and negative controls. Measured metrics included color change, precipitate formation, Tyndall beam test, turbidity, and pH. Statistical analyses were used to assess significance of data trends. RESULTS: The combination of glycopyrrolate and rocuronium did not result in any color change, precipitate formation, a positive Tyndall beam test, or a significantly positive turbidity and did not result in any significant change in pH, regardless of container. CONCLUSION: Per the protocol used in this study, glycopyrrolate and rocuronium were determined to be physically compatible.