OBJECTIVE: To study the changes in dynamic compliance (Cdyn), ventilation/perfusion (V˙/ Q˙) mismatch and haemodynamic variables in hypoxaemic anaesthetized horses whose PaO2 increased following salbutamol inhalation.
METHODS: Retrospective, clinical, cohort study.
METHODS: A group of 73 client-owned horses treated with salbutamol when PaO2 <100 mmHg (13.3 kPa) during anaesthesia.
METHODS: Horses were divided into two groups: responders (R), where PaO2 after salbutamol ≥1.2 PaO2 before treatment (i.e. ≥20% increase), and non-responders (NR), where PaO2 after salbutamol <1.2 PaO2 before treatment. Demographic data and intraoperative variables before treatment were compared between R and NR. Cdyn, arterial to end-tidal carbon dioxide difference [P(a-E´)CO2], estimated ratio of dead space to tidal volume (est.VD/VT), estimated shunt fraction (F-shunt), heart rate, systolic, mean and diastolic arterial pressure and dobutamine requirements were compared before and after treatment within R and NR. For each variable, the difference (Δ) between values pre- and posttreatment was calculated and compared between groups R and NR. Numerical data were compared using univariate or bivariate analysis and categorical data were compared using chi-square test; p < 0.05.
RESULTS: Of the 73 horses 50 were classified as R while 23 horses were classified as NR. There was no statistical difference between R and NR for demographic data or initial intraoperative variables except for body weight [R: 531 (170-715) kg, NR: 540 (420-914) kg]. While salbutamol did not alter Cdyn in either group, it significantly decreased P(a-E´)CO2, est.VD/VT and F-shunt in R only. ΔP(a-E´)CO2, Δest.VD/VT and ΔF-shunt were significantly greater in R (-17.8%, -19.0% and -24.1%, respectively) than in NR (11.5%, 6.6% and -0.3%, respectively).
CONCLUSIONS: In hypoxaemic anaesthetized horses responding to inhaled salbutamol by a ≥1.2 increase in PaO2 no change in Cdyn was detected, but indicators of V˙/ Q˙ mismatch improved.

OBJECTIVE: To compare the efficacy of inhaled salbutamol with salmeterol for the treatment of arterial hypoxaemia in anaesthetized horses.
METHODS: Prospective, randomized, clinical study.
METHODS: A total of 108 client-owned horses (American Society of Anesthesiologists status I-V) anaesthetized for elective and emergency procedures.
METHODS: Horses were premedicated with acepromazine [intramuscularly 0.1 mg kg-1 or intravenously (IV) 0.05 mg kg-1] and xylazine (0.6 mg kg-1 IV). Midazolam (0.06 mg kg-1 IV) and ketamine (2.2 mg kg-1 IV) were combined to induce anaesthesia, and isoflurane in oxygen/air mixture (inspired oxygen fraction 0.7) was used for maintenance of anaesthesia. Mechanical ventilation was initiated without delay using the following ventilator settings: tidal volume 10 mL kg-1, respiratory rate 8 breaths minute-1, inspiratory-to-expiratory time ratio 1:2, no positive end-expiratory pressure. If arterial blood gas analysis revealed PaO2 < 100 mmHg (13.3 kPa), the administration of either inhaled salbutamol (2 μg kg-1) or salmeterol (0.5 μg kg-1) was randomly assigned Blood gas analysis was repeated 15 and 30 minutes after treatment. The intervention was considered successful when PaO2 after treatment ≥ 1.2 × PaO2 before treatment (i.e. ≥20% increase). PaO2 at 15 and 30 minutes was compared between groups using Mann-Whitney U test; p < 0.05 was considered significant.
RESULTS: Of the 108 horses, 60 were administered salbutamol, 65% and 60% responded successfully at 15 and 30 minutes, increasing their initial PaO2 by 38% and 44%, respectively. The other 48 horses were administered salmeterol, 35% responded successfully at 15 and 30 minutes, increasing their initial PaO2 by 3% and 4%, respectively. PaO2 was significantly higher after salbutamol than after salmeterol at 15 and 30 minutes.
CONCLUSIONS: Using the described protocol, inhaled salbutamol was more effective than salmeterol in improving PaO2 in anaesthetized horses with value < 100 mmHg (13.3 kPa).

Interindividual variability, influenced by patient-specific factors including age, weight, gender, race, and genetics, among others, contributes to variations in therapeutic response. Population pharmacokinetic (popPK) modeling is an essential tool for pinpointing measurable factors affecting dose-concentration relationships and tailoring dosage regimens to individual patients. Herein, we developed a popPK model for salbutamol, a short-acting β2-agonist (SABA) used in asthma treatment, to identify key patient characteristics that influence treatment response. To do so, synthetic data from physiologically-based pharmacokinetic (PBPK) models was employed, followed by an external validation using real patient data derived from an equivalent study. Thirty-two virtual patients were included in this study. A two-compartment model, with first-order absorption (no delay), and linear elimination best fitted our data, according to diagnostic plots and selection criteria. External validation demonstrated a strong agreement between individual predicted and observed values. The incorporation of covariates into the basic structural model identified a significant impact of age on clearance (Cl) and intercompartmental clearance (Q); gender on Cl and the constant rate of absorption (ka); race on Cl; and weight on Cl in the volume of distribution of the peripheral compartment (V2). This study addresses critical challenges in popPK modeling, particularly data scarcity, incompleteness, and homogeneity, in traditional clinical trials, by leveraging synthetic data from PBPK modeling. Significant associations between individual characteristics and salbutamol\'s PK parameters, here uncovered, highlight the importance of personalized therapeutic regimens for optimal treatment outcomes.

UNASSIGNED: Salbutamol is a moderately selective beta-2-adrenergic agonist. Various side effects can occur because of beta-1 and beta-2 receptor activation. Due to the large volume of distribution, it is not considered dialyzable.
UNASSIGNED: A patient with salbutamol intoxication, which developed as a result of a medical error in a patient with sepsis, Down syndrome, and liver cirrhosis, is presented. Initial treatment was partially successful and antibiotic adjustments were made. After his respiratory failure worsened, the patient needed non-invasive ventilation, and previously undiagnosed chronic obstructive pulmonary disease was suspected. He was prescribed intravenous methylprednisolone but accidently received 5 mg of salbutamol (albuterol), which led to immediate severe arrhythmic tachycardia with hemodynamic collapse. After unsuccessful cardioversion and treatment with landiolol infusion, salvage hemodialysis was commenced to decrease suspectedly highly elevated serum salbutamol levels. After 30 min, sinus rhythm with normocardia was observed. After the hemodialysis termination, no rebound tachycardia was noted, but due to severe septic shock, the hypotension was ongoing and vasoactive medications were adjusted. However, the measured levels of plasma salbutamol and data from literature do not support the view that hemodialysis was the cause of the described improvement: the total amount of the drug cleared was very small (2.8% of total dose).
UNASSIGNED: Our results confirm a large volume of salbutamol distribution; the measured levels are within observed therapeutic levels; and the measured half-life time during hemodialysis (3.1 h) is comparable to observed half-life times in therapeutic settings. The observed favorable clinical benefit associated with dialysis may be fortuitous, highlighting potential bias toward positive clinical outcomes and unproven (\"salvage\") therapies.

5q-Spinal muscular atrophy (5q-SMA) is one of the most common neuromuscular diseases due to homozygous mutations in the SMN1 gene. This leads to a loss of function of the SMN1 gene, which in the end determines lower motor neuron degeneration. Since the generation of the first mouse models of SMA neuropathology, a complex degenerative involvement of the neuromuscular junction and peripheral axons of motor nerves, alongside lower motor neurons, has been described. The involvement of the neuromuscular junction in determining disease symptoms offers a possible parallel therapeutic target. This narrative review aims at providing an overview of the current knowledge about the pathogenesis and significance of neuromuscular junction dysfunction in SMA, circulating biomarkers, outcome measures and available or developing therapeutic approaches.

BACKGROUND: Although international guidelines generally recommend the back to back use of short-acting β-agonizts (SABA) within a short time in the management of acute wheezing in children with asthma, there is still uncertainty in the evidence of short term outcome. Thus, this study aimed to investigate the efficacy of back to back and single use of inhaled SABA by lung function testing.
METHODS: This was a prospective, double-blinded, placebo controlled study conducted in children ≥6 years of age with a history of asthma. Children who presented with an acute asthma exacerbation (AAE) with a forced expiratory volume in 1 s (FEV1) between 40% to 60% were enrolled in the study if they had a first dose to SABA response of FEV1 ≥ 12%. All children were then randomly assigned either to receive two additional doses of inhaled SABA (300 µg per dose) or placebo. Spirometric analysis included forced vital capacity (FVC), FEV1, FEV1/FVC, PEF, and FEF25-75 at baseline, 15, 30, and 45 min for each group. Oxygen saturation and heart rate were monitored during the study period.
RESULTS: A total of 93 patients (inhaled SABA group; n = 48 vs. placebo group; n = 45) out of 110 enrolled patients completed the study. Baseline demographic characteristics of patients include age, gender, age of diagnosis, parental asthma, history of allergic rhinitis and atopic dermatitis, current asthma treatment, IgE and skin prick test were similar among groups. (p > .05) When lung function parameters were compared at each time interval during the study period, there were no statistical significance found in FVC, FEV1, FEV1/FVC, PEF and forced expiratory flow between 25% and 75% (FEF25-75) among groups. (p > .05) There were also no differences between groups for changes in heart rate and oxygen saturation. (p > .05) CONCLUSION: A single dose of inhaled SABA provides similar short term bronchodilator effect as back to back administration of inhaled SABA in children with AAE who showed an initial response to SABA of FEV1 ≥ 12%.

This article presents the case of a 27-year-old female patient with idiopathic congenital complete heart block who does not consent to the implantation of a cardiac pacemaker but was referred by her primary care physician for cardiological evaluation. The conduction disturbance was recognized at the age of 6 and was asymptomatic. The professional disqualification from pacemaker implantation included a detailed history of a patient\'s symptoms, an echocardiographic assessment of the heart, exercise testing and ECG Holter monitoring. The aid of salbutamol administered orally was also useful.

BACKGROUND: Congenital myasthenic syndromes (CMS) are among the most challenging differential diagnoses in the neuromuscular domain, consisting of diverse genotypes and phenotypes. A mutation in the Docking Protein 7 (Dok-7) is a common cause of CMS. DOK7 CMS requires different treatment than other CMS types. Regarding DOK7\'s special considerations and challenges ahead of neurologists, we describe seven DOK7 patients and evaluate their response to treatment.
METHODS: The authors visited these patients in the neuromuscular clinics of Tehran and Kerman Universities of Medical Sciences Hospitals. They diagnosed these patients based on clinical findings and neurophysiological studies, which Whole Exome Sequencing confirmed. For each patient, we tried unique medications and recorded the clinical response.
RESULTS: The symptoms started from birth to as late as the age of 33, with the mean age of onset being 12.5. Common symptoms were: Limb-girdle weakness in 6, fluctuating symptoms in 5, ptosis in 4, bifacial weakness in 3, reduced extraocular movement in 3, bulbar symptoms in 2 and dyspnea in 2 3-Hz RNS was decremental in 5 out of 6 patients. Salbutamol was the most effective. c.1124_1127dupTGCC is the most common variant; three patients had this variant.
CONCLUSIONS: We strongly recommend that neurologists consider CMS in patients with these symptoms and a similar familial history. We recommend prescribing salbutamol as the first-choice treatment option for DOK7 patients.

BACKGROUND: Activation of β2 adrenergic receptors reduces cutaneous mechanical pain thresholds in rats. While β2 adrenergic receptor activation may contribute to mechanisms that underlie temporomandibular joint pain, its effect on masticatory muscle pain sensitivity is uncertain.
OBJECTIVE: The current study sought to determine the extent to which β adrenergic receptors are expressed by masticatory muscle afferent fibres, and to assess the effect of local activation of these receptors on the mechanical sensitivity of masticatory muscle afferent fibres in rats.
METHODS: Trigeminal ganglion neurons that innervate the rat (n = 12) masseter muscle and lower lip were identified by tissue injection of fluorescent dyes and were then stained with antibodies against β1 or β2 adrenergic receptors. Extracellular recordings from 60 trigeminal ganglion neurons that innervate the masticatory muscle were undertaken in a second group of anaesthetised rats of both sexes (n = 37) to assess afferent mechanical activation thresholds. Thresholds were assessed before and after injection of the β adrenergic receptor agonists into masticatory muscle.
RESULTS: β1 and β2 adrenergic receptor expression was greater in labial skin than in masticatory muscle ganglion neurons (p < .05, one-way ANOVA, Holm-Sidak test). There was a higher expression of β2 adrenergic receptors in masticatory muscle ganglion neurons in males than in females. The mixed β agonist isoproterenol increased afferent mechanical activation threshold in male but not female rats (p < .05, Mann-Whitney test). In male rats, salbutamol, a β2 selective agonist, also increased afferent mechanical activation threshold but hydralazine, a vasodilator, did not (p < .05, Mann-Whitney test).
CONCLUSIONS: Activation of β2 adrenergic receptors decreases the mechanical sensitivity of masticatory muscle afferent fibres in a sex-related manner.

UNASSIGNED: To compare the response between different doses of nebulized magnesium sulphate along with Salbutamol in children between two to 12 years of age with status asthmaticus.
UNASSIGNED: This single blinded, randomized clinical trial was carried out at the Department of Pediatrics, Dr. Ziauddin University Hospital, Karachi, Pakistan during October 2021 to September 2022. A total of 104 children aged between 2-12 years, with the diagnosis of asthma having \"Pediatric Rapid Assessment Measure (PRAM)\" score>4 and with reactive airways were included. Children either received three back-to-back nebulization with salbutamol solution only (n=50) or salbutamol and MgSO4 with three different doses (250mg, 500mg or 750mg) after every 20 minutes for 60 minutes. The PRAM score was used as an assessment tool to clinically score asthma.
UNASSIGNED: In a total of 104 children, 53 (51.0%) were girls. The mean age was 5.25±2.86 years. No statistically significant difference was found in PRAM scores at baseline (p=0.448) and at 20-minutes (p=0.072) but significant differences were observed at 40-minutes (p=0.009), 60-minutes (p=0.011), 120-minutes (p=0.010), 6-hours (=0.034), 12-hours (p=0.018), 18-hours (p=0.033) and at 24-hours (p=0.029). The reduction in PRAM scores from baseline to 24-hours following treatment among Salbutamol, Salbutamol+ MgSo4 250mg, Salbutamol+ MgSo4 500mg and Salbutamol+ MgSo4 750mg group were 6.53±1.09, 7.22±1.09, 6.85±1.43 and 7.57±1.06 respectively (p=0.007).
UNASSIGNED: While children with status asthmaticus managed using salbutamol, with or without nebulized MgSO4, showed improved clinical outcomes, combining salbutamol with higher dosages of nebulized MgSO4 resulted in even greater clinical improvement.Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT04929626.