Emergency Medical Services Management of Bronchospasm in the United States: A Cross-Sectional Analysis and Nationwide Quality Assessment.

Background/Objective: Bronchospasm, caused by asthma and other related conditions, is a significant cause of morbidity and mortality commonly managed by emergency medical services (EMS). We aimed to evaluate the quality of prehospital management of bronchospasm by EMS in the US.Methods: The National EMS Information System Public Release Research dataset, a nationwide convenience sample of prehospital patient care report data from 2018 to 2019, was used to capture 9-1-1 activations where patients aged ≥2 years were treated and transported by EMS for suspected bronchospasm. First, we described the extent to which EMS care met eight quality measures identified from available statewide EMS protocols, existing quality measures, and national guidelines. Second, we quantified the extent of risk-standardized agency-level variation in administration of inhaled beta agonists and systemic corticosteroids using logistic regression models, accounting for patient characteristics, severity, and clustering by agencies. Third, we compared rates of completed prehospital interventions between pediatric (age <18 years) versus adult patients using two-sample t-tests.Results: A total of 1,336,988 EMS encounters for suspected bronchospasm met inclusion criteria. Median age of patients was 66 years, with only 4% pediatric; 55% were female. Advanced life support (ALS) units managed 94% of suspected bronchospasm. Respiratory rate (98%) and pulse oximetry (96%) were documented in nearly all cases. Supplemental oxygen was administered to hypoxic patients by 65% of basic life support (BLS) and 73% of ALS units. BLS administered inhaled beta-agonist therapy less than half the time (48%), compared to 77% by ALS. ALS administered inhaled anticholinergic therapy in 38% of cases, and systemic corticosteroids in 19% of cases. Pediatric patients were significantly less likely to receive supplemental oxygen when hypoxic, inhaled beta-agonists, inhaled anticholinergics, or systemic corticosteroids.Conclusions: We found important gaps in recent EMS practice for prehospital care of suspected bronchospasm. We highlight three targets for improvement: inhaled beta-agonist administration by BLS, systemic corticosteroid administration by ALS, and increased interventions for pediatric patients. These findings indicate important areas for research, protocol modification, and quality improvement efforts to improve EMS management of bronchospasm.

Improving rates of successful extubation: Medications.

This chapter focuses on the pharmacological management of newborn infants in the peri-extubation period to reduce the risk of re-intubation and prolonged mechanical ventilation. Drugs used to promote respiratory drive, reduce the risk of apnoea, reduce lung inflammation and avoid bronchospasm are critically assessed. When available, Cochrane reviews and randomised trials are used as the primary sources of evidence. Methylxanthines, particularly caffeine, are well studied and there is accumulating evidence to guide clinicians on the timing and dosage that may be used. Efficacy and safety for doxapram, steroids, adrenaline and salbutamol are summarised. Management of term infants, extubation following surgery, accidental and complicated extubation and the use of cuffed endotracheal tubes are presented. Overall, caffeine is the only drug with a substantial evidence base, proven to increase the likelihood of successful extubation in preterm infants; no drugs are needed to facilitate extubation in most term infants. Future studies might further define the role of caffeine in late preterm infants and evaluate medications for post-extubation stridor, bronchospasm or apnoea not responsive to methylxanthines.

The Effect of Albuterol Spray on Hypoxia and Bronchospasm in Patients with Chronic Obstructive Pulmonary Disease (COPD) under General Anesthesia: A bouble-Blind Randomized Clinical Trial.

Background: Patients with chronic obstructive pulmonary disease (COPD) experience an increased risk of perioperative pulmonary complications. The aim of this study was to evaluate the effect of albuterol spray on hypoxia and bronchospasm in patients with COPD under general anesthesia. Methods: This single-center, double-blind, parallel-group, randomized clinical trial was performed on 120 smoking patients with COPD who were referred to 5 Azar Educational Hospital in Gorgan, Northern Iran, in 2021. Twenty minutes before general anesthesia and also after completion of surgery and before extubation, 60 patients in the intervention group were inhaled with 2 puffs of albuterol spray. In the control group, patients were inhaled with 2 puffs of placebo spray. In perioperative period, the occurrence of wheezing, bronchospasm, coughing, hemodynamic changes, postoperative shivering, dyspnea, and nausea and vomiting were evaluated in all patients. The Consolidated Standards of Reporting Trials (CONSORT) checklist was used to report important aspects of this study. Results: The mean age of the patients was 52.34 ±8.95 years, and 115 (95.8%) of them were males while the rest were females. The difference between systolic blood pressure before induction of anesthesia (after administration of albuterol spray) between the group receiving albuterol spray and the group not receiving it was statistically significant (p=0.04). Also, the difference between the mean arterial oxygen saturation before tracheal extubation (after re-administration of albuterol spray) between the albuterol spray group and the non-albuterol group was statistically significant (p = 0.03). Wheezing and recurrent cough after induction of anesthesia and after extubation (after albuterol spray administration) was lower in the albuterol group than in the control group (p<0.05). No significant side effects were detected in the albuterol-treated group. Conclusion: According to the results of this study, it seems that the prophylactic use of albuterol spray is useful in reducing the incidence of wheezing and recurrent cough before induction of anesthesia in COPD patients with smoking.

Nebulized colistin as the adjunctive treatment for ventilator-associated pneumonia: A systematic review and meta-analysis.

PURPOSE: Nebulized colistin (NC) is a potential therapy for ventilator-associated pneumonia (VAP); however, the clinical efficacy and safety of NC remain unclear. This study investigated whether NC is an effective therapy for patients with VAP. MATERIALS AND METHODS: We performed a search in Web of Science, PubMed, Embase, and the Cochrane Library to retrieve randomized controlled trials (RCTs) and observational studies published at any time until February 6, 2023. The primary outcome was clinical response. Secondary outcomes included microbiological eradication, overall mortality, length of mechanical ventilation (MV), length of intensive care unit stay (ICU-LOS), nephrotoxicity, neurotoxicity, and bronchospasm. RESULTS: Seven observational studies and three RCTs were included. Despite exhibiting a higher microbiological eradication rate (OR,2.21; 95%CI, 1.25-3.92) and the same nephrotoxicity risk (OR,0.86; 95%CI, 0.60-1.23), NC was not significantly different in clinical response (OR,1.39; 95%CI, 0.87-2.20), overall mortality (OR,0.74; 95%CI, 0.50-1.12), MV length (mean difference (MD),-2.5; 95%CI, -5.20-0.19), and the ICU-LOS (MD,-1.91; 95%CI, -6.66-2.84) than by the intravenous antibiotic. Besides, the risk of bronchospasm raised significantly (OR, 5.19; 95%CI, 1.05-25.52) among NC. CONCLUSION: NC was associated with better microbiological outcomes but did not result in any remarkable changes in the prognosis of patients with VAP.

Outpatient administration of naxitamab in combination with granulocyte-macrophage colony-stimulating factor in patients with refractory and/or relapsed high-risk neuroblastoma: Management of adverse events.

BACKGROUND: Naxitamab is a humanized GD2-binding monoclonal antibody that received accelerated approval from the U.S. Food and Drug Administration for refractory or relapsed high-risk neuroblastoma limited to bone or bone marrow. Trial 201 (NCT03363373) is an ongoing global clinical trial to evaluate the efficacy and safety of naxitamab in combination with granulocyte-macrophage colony-stimulating factor in this population. AIMS: Here, we review the safety profile and adverse event (AE) management associated with naxitamab administration in a pediatric population, based on Trial 201 protocol guidelines and clinical trial experience. METHODS AND RESULTS: At least 50% of patients experienced pain, hypotension, bronchospasm, cough, vomiting, diarrhea, nausea, and tachycardia, with the following reported at grade ≥3 AEs for at least 10% of patients: pain, hypotension, urticaria, and bronchospasm. These AEs were generally manageable in the outpatient setting using premedications, supportive therapies, and appropriate monitoring post-infusion. Algorithms were established for infusion-related AEs, including hypotension and bronchospasm, to provide guidance to investigators for early recognition and timely intervention, including medication and infusion rate modification or interruption, or treatment discontinuation, based on AE severity. Educating patients and caregivers on what to expect regarding premedication at home, experience during the infusion cycle, and post-infusion monitoring helps optimize naxitamab treatment and supportive therapies and may reduce treatment burden. CONCLUSION: This article highlights the protocol-based recommendations for the management of acute AEs associated with outpatient naxitamab treatment in Trial 201. The authors recommend close monitoring and timely implementation of measures to ensure that patients can remain on treatment and obtain maximum clinical benefit from naxitamab therapy.

Albuterol: Still first-line in rescue therapy?

ABSTRACT: Albuterol has been a cornerstone of asthma treatment for several decades, but evidence suggests that it may be overused at the expense of more efficacious treatment. Albuterol may not even be appropriate for sole first-line rescue medication in some patients. Inflammatory mechanisms have been shown to play a role early in the course of developing bronchospasm, suggesting that inhaled corticosteroids should be included as part of initial rescue treatment. Newer biologics target inflammatory cytokine pathways, which may be needed in patients with moderate to severe disease. Evidence-based recommendations for the management of asthma and bronchospasm are continuing to evolve.

[Ketamine as a treatment of bronchospasm due to an anaphylaxis. A case report]. / Ketamina como tratamiento de broncoespasmo asociado a anafilaxia. Reporte de un caso.

Background: Ketamine is used in intravenous anesthesia for the maintenance in the general anesthesia. It has characteristics to prevent the difficult of breathing due to bronchospasm, as well as the delivery of histamine associated with asthmatic attack. These effects come from the direct action in the bronchial muscle, as well as from the potentiation of its catecholamines, which is why its use is very controversial, given that there are not enough trials to back it up. Moreover, the effect of ketamine on bronchospasm due to anaphylactic reaction has not been studied. The election treatment is epinephrine and there are factors associated with its use. The objective was to present the case of a patient with a history of allergic reaction to midazolam, who presented bronchospasm due to the administration of this drug, and who received unconventional treatment with positive outcomes. Clinical case: We present the case of a young female with a history of allergies to medicines, specifically to benzodiazepines, who presented bronchospasm and oxygen saturation drop after receiving a dose of midazolam into her eye while she was working. The use of ketamine was proposed after adrenaline, a beta-agonist, inhaled anticholinergics, a steroid and antihistamine drugs were used. Conclusion: Trials are needed in order to demonstrate the efficacy of ketamine in this particular context; however, the outcome in this case was positive.

Introducción: la ketamina es utilizada en anestesia intravenosa en el mantenimiento en la anestesia general. Su efecto cuenta con propiedades para prevenir la dificultad respiratoria asociada a broncoconstricción y la secreción de histamina asociada a crisis asmática. Estos efectos derivan de la acción directa en el músculo bronquial, así como de la potencialización de las catecolaminas, por lo que su uso muy controversial, ya que hasta el día de hoy no hay suficientes estudios que lo sustenten. Además, el efecto de la ketamina en el broncoespasmo debido a anafilaxia no está estudiado. El tratamiento de elección es la epinefrina y hay factores que están asociados en el éxito de esta. El objetivo fue presentar el caso de una paciente con antecedente de alergia a midazolam, que presentó broncoespasmo al estar en contacto con este y a la que se le administró tratamiento no convencional con resultados favorables. Caso clínico: presentamos el caso de una mujer joven con antecedentes de alergias a medicamentos, específicamente a benzodiacepinas, la cual presentó broncoespasmo y caída de la saturación posteriores al contacto con midazolam intraocular mientras laboraba. Se propuso la utilización de ketamina posterior a adrenalina, betaagonista y anticolinérgicos inhalados, esteroide y antihistamínico. Conclusión: es necesario hacer estudios que demuestren la eficacia de la ketamina en este contexto en particular; en este caso, los resultados fueron positivos.

Aerosolized drug delivery in awake and anesthetized children to treat bronchospasm.

Bronchospasm is a common respiratory adverse event in pediatric anesthesia. First-line treatment commonly includes inhaled salbutamol. This review focuses on the current best practice to deliver aerosolized medications to awake as well as anesthetized pediatric patients and discusses the advantages and disadvantages of various administration techniques. Additionally, we detail the differences between various airway devices used in anesthesia. We highlight the unmet need for innovation of orally inhaled drug products to deliver aerosolized medications during pediatric respiratory critical events such as bronchospasm. It is therefore important that clinicians remain up to date with the best clinical practice for aerosolized drug delivery in order to prevent and efficiently treat pediatric patients experiencing life-threatening respiratory emergencies.

Effect of tramadol on extubation response and quality of emergence following Supratentorial surgery: A randomised controlled trial.

Objectives: To observe the effect of a single dose of tramadol 1mg/kg on haemodynamic changes related to extubation, and to assess the quality of emergence as judged by incidence of cough, laryngospasm and bronchospasm. METHODS: The double-blind randomised controlled trial was conducted at the Department of Anaesthesiology, Aga Khan University Hospital, Karachi, from 2016 to 2017, and comprised patients of either gender aged 18-65 years scheduled for elective supratentorial craniotomy under general anaesthesia. The patients were randomised to two Tramadol and Saline groups. The drug was given 45 minutes before extubation at the time of dura closure. The patients were extubated after resumption of adequate spontaneous breathing. Invasive blood pressure and heart rate were recorded one minute before reversal, at 1 minute interval for five minutes and then every 10 minute for 30 minutes after extubation. Cough, laryngospasm and bronchospasm were noted. Pain, post-operative nausea, vomiting, convulsions and conscious levels were also noted till 6 hours post-operatively. Data was analysed using SPSS 19. RESULTS: Of the 80 patients enrolled, 79(98.75%) completed the study. Of them, 38(48%) were in the Tramadol group; 27(71.1%) males and 11(28.9%) females with a mean age of 43.42±13.2 years. The remaining 41(52%) patients were in the Saline group; 28(68.3%) males and 13(31.7%) females with a mean age of 45.9±15.9 years. Intergroup comparison showed no significant difference in the extubation response (p>0.05), but the changes in blood pressure and heart rate were shorter in magnitude and duration in the Tramadol group compared to the baseline. Significant rise in blood pressure and heart rate were observed in the Saline group at 5 minutes after extubation (p=0.046). There was no difference in the quality of emergence as judged by cough or secondary complications (p>0.05). CONCLUSIONS: Tramadol 1mg/kg was considered superior in attenuating the duration and magnitude of haemodynamic response in the shape of hypertension and tachycardia during extubation, but did not affect other parameters in patients undergoing craniotomy. Clinical Trial Number: Clinical Trials.gov PRS: NCT02964416, https://clinicaltrials.gov/ct2/show/NCT02964416.

Salbutamol-induced lactic acidosis in status asthmaticus survivor.

BACKGROUND: Salbutamol-induced lactic acidosis is a rare presentation that could manifest in specific clinical context as acute asthmatic attack treatment. An increase of glycolysis pathway leading to pyruvate escalation is the mechanism of hyperlactatemia in ß2-adrenergic agonist drug. CASE PRESENTATION: A 40-year-old man who had poor-controlled asthma, presented with progressive dyspnea with coryza symptom for 6 days. He was intubated and admitted into medical intensive care unit due to deteriorated respiratory symptom. Severe asthmatic attack was diagnosed and approximate 1.5 canisters of salbutamol inhaler was administrated within 24 h of admission. Initial severe acidosis consisted of acute respiratory acidosis from ventilation-perfusion mismatch and acute metabolic acidosis resulting from bronchospasm and hypoxia-related lactic acidosis, respectively. The lactate level was normalized in 6 h after hypoxemia and ventilation correction. Given the lactate level re-elevated into a peak of 4.6 mmol/L without signs of tissue hypoxia nor other possible etiologies, the salbutamol toxicity was suspected and the inhaler was discontinued that contributed to rapid lactate clearance. The patient was safely discharged on the 6th day of admission. CONCLUSION: The re-elevation of serum lactate in status asthmaticus patient who had been administrated with the vast amount of ß2-adrenergic agonist should be considered for salbutamol-induced lactic acidosis and promptly discontinued especially when there were no common potentials.

An Innovative Method of Delivering Nebulized Medications for Perioperative Bronchospasm.

Perioperative bronchospasm is a common challenge to anesthetic care. The timely delivery of inhaled medications can be challenging, particularly in pediatric patients and in locations where dedicated resources and respiratory support teams are limited. The delivery of nebulized medication to an intubated patient in the operating room can be difficult. We present an innovative method for delivery of nebulized solutions, in which a jet nebulizer is paired with a Mapleson hyperinflation system.

Negative results for ketamine use in severe acute bronchospasm: a randomised controlled trial.

BACKGROUND: Ketamine has bronchodilation properties. The aim of the single-centre, evaluator-blinded, randomised clinical trial study was to evaluate whether continuous infusion of ketamine is associated with improvement in respiratory mechanics correlated with bronchospasm relief, as compared with continuous infusion of fentanyl. METHODS: Adult patients submitted to invasive mechanical ventilation were included if they had an acute severe bronchospasm, due to status asthmaticus or COPD exacerbation. They were randomised to ketamine or a standard IV analgesia with fentanyl, both in bolus and continuous infusion. Measurements of respiratory mechanics (airway resistance - Rsmax, dynamic compliance - Cdyn and intrinsic PEEP - PEEPi) both at baseline and 3 and 24 h after randomisation were performed. The main outcome of this study was to evaluate the improvement of Rsmax in 3 h of continuous infusion of the study drugs. RESULTS: Ketamine use was not associated with greater reduction in Rsmax when compared with fentanyl, either after 3 h (0 cm H2O L-1 s-1 ± 6 vs. -3 cm H2O L-1 s-1 ± 7.7, respectively; P = 0.16) or after 24 h (-3 cm H2O L-1 s-1 ± 17 vs. -3.5 cm H2O L-1 s-1 ± 13.7, respectively; P = 0.73). Patients randomized to the ketamine group did not have better improvements in delta PEEPi as compared with fentanyl in 3 h (P = 0.77) or in 24 h (P = 0.72). CONCLUSIONS: In this study, ketamine use was not associated with improvement in ventilatory variables associated with bronchospasm.

Bronchial Visualization of Tetanic Contractions: A Case Report.

BACKGROUND Tetanus is a potentially fatal infectious disease which, during its evolution, creates multiple complications, usually requiring intensive management and care. CASE REPORT We present a clinical case of a 59-year-old male patient with generalized tetanus admitted to the intensive care unit. Flexible bronchoscopy revealed contraction of the bronchial demonstrating that tetany existed at the respiratory level, which rarely becomes evident. The clinical manifestations included trismus, facial paralysis, neck stiffness, and compromised respiratory function. The patient presented a state of respiratory failure that required invasive mechanical ventilation which was evaluated by bronchoscopy and that showed spasms of the bronchial musculature. The patient presented generalized tetanus in which the bronchial affectation was evaluated by bronchoscopy in the intensive care unit. In developed countries, the anti-tetanus toxoid vaccine has ostensibly decreased its incidence, while it is endemic in developing countries, and although there are measures such as vaccination that try to reduce its incidence, in Ecuador there is an increase in incidences. In this patient case, contraction of the bronchial rings was observed, demonstrating that tetany existed at the respiratory level, which rarely becomes evident. CONCLUSIONS Although muscular contractions are widespread, this clinical case evidences bronchial spams reported and visualized by bronchoscopy.

Evaluación del sulfato de magnesio en el tratamiento del broncoespasmo / Assessment of magnesium sulfate in bronchospasm treatment

Introducción: Una de las urgencias más temidas durante la instrumentación de la vía respiratoria es el broncoespasmo. El sulfato de magnesio, administrado por vía endovenosa, tiene un efecto broncodilatador al antagonizar los canales del calcio, inhibir la contracción muscular mediada por el calcio y favorecer la relajación del músculo liso bronquial. Objetivo: Evaluar la eficacia del sulfato de magnesio endovenoso en pacientes con broncoespasmo durante broncoscopias. Métodos: Estudio observacional, descriptivo y transversal en 20 pacientes, con broncoespasmo, desencadenado por manipulación de la vía respiratoria con broncoscopio flexible, tratados con sulfato de magnesio 50 mg/kg, (máximo 2 g), por vía endovenosa durante 5 min. Resultados: Predominaron los hombres entre 50-59 años (75 por ciento), todos los pacientes eran fumadores, 15 pacientes fueron clasificados como estado físico ASA III. Sufrieron broncoespasmo de intensidad moderada 60 por ciento, clasificado según la clínica y monitorización de SpO2. En 75 por ciento de los pacientes cedió el broncoespasmo tras el tratamiento sin administrar otro medicamento. No se registraron efectos adversos. Ningún paciente necesitó intubación orotraqueal para ventilación ni requirió hospitalización por más de 8 h. Conclusiones: El sulfato de magnesio es una buena opción farmacológica para el tratamiento de urgencia del broncoespasmo desencadenado por manipulación de la vía respiratoria(AU)

Introduction: One of the most feared emergencies during the instrumentation of the respiratory tract is bronchospasm. Magnesium sulfate, administered intravenously, has a bronchodilation effect by antagonizing calcium channels, inhibiting muscle contraction mediated by calcium and promoting bronchial smooth muscle relaxation. Objective: To evaluate the efficacy of magnesium sulfate administered intravenously in patients with bronchospasm during bronchoscopy. Methods: Observational, descriptive and cross-sectional study carried out with 20 patients, with bronchospasm, triggered by airway manipulation with flexible bronchoscope, treated with 50 mg/kg of magnesium sulfate, (maximum 2 g), administered intravenously for 5 min. Results: Men between 50-59 years (75 percent) predominated. All patients were smokers. 15 patients were classified with physical state ASA III. They suffered bronchospasm of mild intensity 60 percent, classified according to the clinic and monitoring of oxygen saturation. In 75 percent of the patients, the bronchospasm ceased after the treatment without administering any other medication. No adverse effects were recorded. No patient needed orotracheal intubation for ventilation or required hospitalization for more than 8 hours. Conclusions: Magnesium sulfate is a good pharmacological option for the emergency treatment of bronchospasm triggered by manipulation of the respiratory tract(AU)

Anaphylactic Bronchospasm during Induction of General Anaesthesia: A Case Report.

Bronchospasm represents the clinical manifestation of bronchial muscles contraction resulting in reduced alveolar air flow. Non-allergic mechanisms or anaphylaxis underlie the genesis of perioperative bronchospasm, a potential anaesthetic disaster. Early recognition and treatment are crucial. We report a rare incident of anaphylactic bronchospasm without hypotension during general anaesthesia. Urticaria appeared in chest and abdomen suggesting anaphylaxis. After the event resolved with bronchodilators, surgery continued uneventfully. Vecuronium was the most probable culprit but confirmation was not possible as the patient was lost to follow up. Rarely, perioperative anaphylaxis presents only with bronchospasm that requires prompt attention to avoid adverse outcome. Keywords: allergy; anaphylaxis; bronchial spasm; general anesthesia.

Safety of aerosol therapy in children during noninvasive ventilation with helmet and total face mask.

PURPOSE: To evaluate the consequences of using nebulized drugs in patients subjected to noninvasive ventilation (NIV) with total face mask (TFM) and helmet. DESIGN: A descriptive analytical study of a prospective patient cohort was carried out. AMBIT: Pediatric intensive care unit (PICU) of a tertiary hospital. PATIENTS: Consecutive sampling was used to include all patients admitted to the PICU and requiring NIV with helmet or TFM over a period of 29 months. No patients were excluded. INTERVENTIONS: Nebulized treatment was added according to medical criteria. VARIABLES OF INTEREST: Independent variables were age, sex, diagnosis, disease severity, ventilation parameters and nebulized drugs (if administered). Secondary outcomes were duration and failure of NIV, and length of PICU stay. RESULTS: The most frequent diagnoses were bronchiolitis (60.5%) and asthma (23%). Patients received NIV for a median of 43h. Nebulized drugs were administered in 40% of the cases during NIV, and no adverse effects were registered. Using Bayesian statistics, the calculated probability of suffering an adverse effect was 1.3% with helmet and 0.5% with TFM (high density 95% probability intervals). Patients with helmet and nebulized therapy were in more serious condition than those who did not receive nebulization; nevertheless, no differences were observed regarding the need to change to bilevel modality. With TFM, PICU stay was shorter for the same degree of severity (p=0.033), and the NIV failure rate was higher in patients who did not receive inhaled drugs (p=0.024). CONCLUSIONS: The probability of suffering an adverse effect related to nebulization is extremely low when using a helmet or TFM. Inhaled therapy with TFM may shorten PICU stay in some patients.

Futility of current urine salbutamol doping control.

AIMS: Salbutamol is used in the management of obstructive bronchospasm, including that of some elite athletes. It is claimed that high salbutamol (oral) doses may also have an anabolic effect. Therefore, inhalation of salbutamol is restricted by the World Anti-Doping Agency (WADA) to a maximal daily dose. Urine is tested for violations, but recent cases have resulted in a debate regarding the validity of this approach. It was our aim to determine whether current approaches are sufficiently able to differentiate approved usage from violations. METHODS: We extracted pharmacokinetic parameters from literature for salbutamol and its sulphated metabolite. From these parameters, a semi-physiological pharmacokinetic model of inhaled and orally administered salbutamol was synthesized, validated against literature data, and used to perform clinical trial simulations (n = 1000) of possible urine concentrations over time resulting from WADA-allowed and oral unacceptable dosages. RESULTS: The synthesized model was able to predict the literature data well. Simulations showed a very large range of salbutamol concentrations, with a significant portion of virtual subjects (15.4%) exceeding the WADA threshold limit of 1000 ng ml-1 at 1 h post-dose. CONCLUSIONS: The observed large variability in urine concentrations indicates that determining the administered dose from a single untimed urine sample is not feasible. The current threshold inadvertently leads to incorrect assumptions of violation, whereas many violations will go unnoticed, especially when samples are taken long after drug administration. These issues, combined with the dubious assertion of its anabolic effect, leads us to conclude that the large effort involved in testing should be reconsidered.