Use of short-acting beta agonists in the treatment of asthma across five European countries

Commentary on: Janson C, Menzies-Gow A, Nan C, et al. SABINA: an overview of short-acting β2-agonist use in asthma in European countries. Adv Ther. 2020;37:1124–35.

Three cases of difficulty in achieving definitive loss of consciousness with remimazolam

Background Remimazolam is a novel, ultra-short-acting benzodiazepine used for general anesthesia. Because remimazolam is an emerging drug, the tolerance to remimazolam in benzodiazepine-taking patients has been unclear. Also, the efficacy of remimazolam in different races is not fully elucidated so far. Case presentation Here we experienced three cases in which high dose of remimazolam was needed for attempting to achieve appropriate anesthetic depth. Two of the three cases were of preoperatively benzodiazepine-taking patients. The other was a case of a Chinese patient. In all three cases, conversion to general anesthesia with propofol was necessitated. Conclusions When signs of inadequate sedative effect of remimazolam are observed in patients of benzodiazepine users or of different races, conversion to another sedative agent such as propofol should be considered.

Impact of intraoperative methadone use on postoperative opioid requirements after cardiac surgery

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Inadequate pain control after cardiac surgery increases postoperative morbidity. Increasing evidence suggests that perioperative intravenous (IV) methadone results in improved analgesia. This study evaluated the effect of intraoperative IV methadone on postoperative opioid requirements and surgical recovery. Methods A retrospective review of patients undergoing coronary artery bypass graft (CABG), valvular surgery or both between April 2017 and August 2018 was conducted. Patients were separated into a usual care cohort of those who received short-acting opioids (ie, IV fentanyl, hydromorphone, or morphine) alone or a methadone cohort of those who received IV methadone plus short-acting opioids. Opioid requirements were assessed within the first 24 hours of surgery (postoperative day [POD] 0) and 25 to 48 hours after surgery (POD 1) as oral morphine milligram equivalents (MME). Postoperative pain scores, adjunctive analgesia, time to extubation, use of noninvasive respiratory support (continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP]), and intensive care unit (ICU) and hospital length of stay (LOS) were also evaluated. Results A total of 117 patients were evaluated (methadone cohort, n = 52; usual care cohort, n = 65). Median cumulative intraoperative opioid consumption was less in the methadone cohort (150 MME vs 314.1 MME; P < 0.0001). The methadone cohort required 44% fewer MME than the usual care cohort on POD 0 (median MME, 15.8 vs 36; P = 0.025), with low and not significantly different opioid use in both cohorts on POD 1 (15.5 MME vs 7.5 MME; P = 0.47). Weight-based methadone dosing ranged from 0.1 to 0.4 mg/kg (mean, 0.22 mg/kg). There were no significant differences in pain scores, time to extubation, use of CPAP or BiPAP, or ICU and hospital LOS. Conclusion Intraoperative IV methadone in cardiac surgery patients was safe and significantly reduced intraoperative and postoperative opioid requirements on POD 0.

Cost-utility of as-needed ICS-formoterol versus to maintenance ICS in mild to moderate persistent asthma

Background Recent asthma guidelines, such as the Global Initiative for Asthma (GINA), recommend in adult patients as-needed inhaled corticosteroids (ICS)-formoterol as an alternative to maintenance ICS in mild to moderate persistent asthma. The introduction of these recommendations concerns whether using as-needed budesonide-formoterol would be more cost-effective than to maintenance ICS. This study aimed to evaluate the cost-effectiveness of as-needed combination low-dose budesonide-formoterol compared to short-acting β2-agonist (SABA) reliever therapy in patients with mild asthma. Methods A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with mild asthma in Colombia. Total costs and QALYs of low-dose budesonide-formoterol compared to short-acting β2-agonist (SABA) were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000. Results The model suggests a potential gain of 0.37 QALYs and per patient per year on as-needed ICS-formoterol and a reduction in the discounted cost per person-year, of as-needed ICS-formoterol to maintenance ICS, of US$40. This position of dominance of as-needed ICS-formoterol negates the need to calculate an incremental cost-effectiveness ratio. In the deterministic and probabilistic sensitivity analysis, our base‐case results were robust to variations in all assumptions and parameters. Conclusion Low-dose budesonide-formoterol as a reliever was cost-effective when added to usual care in patients with mild asthma. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Economic consequences of the overuse of short-acting beta-adrenergic agonists (SABA) in the treatment of asthma in Spain

Objective: To determine the relationship between short-acting beta-adrenergic agonist (SABA) overuse and healthcare resource use and costs in asthma patients in routine clinical practice. Methods: A longitudinal retrospective study in Spanish primary and specialized care using the BIG-PAC® Medical Records Database was conducted. Asthma patients ≥12 years of age who attended ≥ 2 consultations during 2017 and had 1-year follow-up data available were included. Main outcomes were demographics, comorbidities, medication, clinical and healthcare resource use and costs. The relationship between SABA overuseand healthcare costs, and between asthma severity and healthcare costs was determined. Results: This SABA use IN Asthma (SABINA) study included 39,555 patients, mean (standard deviation, SD) age 49.8 (20.7) years; 64.2% were female. Charlson comorbidity index was 0.7 (1.0). SABA overuse (≥ 3 canisters/year) was 28.7% (95% CI: 27.7–29.7), with an overall mean number of 3.3 (3.6) canisters/year. Overall, 5.1% of patients were prescribed ≥12 canisters/year. SABA overuse was correlated with healthcare costs (ρ = 0.621; p < 0.001).The adjusted mean annual cost/patient, according to the Global Initiative for Asthma (GINA 2019) classification of asthma severity, was €2,231, €2,345, €2,735, €3,473, and €4,243,for GINA steps 1−5, respectively (p < 0.001). Regardless of asthma severity, SABA overuse yielded a significant increase in healthcare costs per patient and year (€5,702 vs. €1,917, p < 0.001) compared with recommended use (< 2 canisters/year). Conclusions: SABA overuse yields greater costs for the Spanish National Health System. Costs increased according to asthma severity.

Continuous Flow Synthesis of Propofol

Herein, we report a continuous flow process for the synthesis of 2,6-diisopropylphenol—also known as Propofol—a short-acting intravenous anesthesia, widely used in intensive care medicine to provide sedation and hypnosis. The synthesis is based on a two-step procedure: a double Friedel–Crafts alkylation followed by a decarboxylation step, both under continuous flow.