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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.

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., Competing Interests: Declaration of competing interest The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2023 Maddah S.M, et al.)

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., (© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

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.

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., (Copyright © 2022 American Academy of Physician Associates.)

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., (© 2022 Revista Medica del Instituto Mexicano del Seguro Social.)

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., (© 2021 John Wiley & Sons Ltd.)

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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

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 β2-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 β2-adrenergic agonist should be considered for salbutamol-induced lactic acidosis and promptly discontinued especially when there were no common potentials.

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.

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 - R smax , dynamic compliance - C dyn 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 R smax in 3 h of continuous infusion of the study drugs., Results: Ketamine use was not associated with greater reduction in R smax when compared with fentanyl, either after 3 h (0 cm H 2 O L-1 s-1 ± 6 vs. -3 cm H 2 O L-1 s-1 ± 7.7, respectively; P = 0.16) or after 24 h (-3 cm H 2 O L-1 s-1 ± 17 vs. -3.5 cm H 2 O 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.

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., (Copyright © 2018 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

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.

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., (© 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Benign airway stenosis is a clinical challenge because of recurrent granulation tissues. Our previous study proved that a Chinese drug, β-elemene, could effectively inhibit the growth of fibroblasts cultured from hyperplastic human airway granulation tissues, which could slow down the progression of this disease. The purpose of the present study is to find out the mechanism for this effect. We cultured fibroblasts from normal human airway tissues and human airway granulation tissues. These cells were cultured with 160 μg/ml normal saline (NS), different doses of β-elemene, or 10 ng/ml canonical Wnt/β-catenin pathway inhibitor (Dickkopf-1, DKK-1). The proliferation rate of cells and the expression of six molecules involved in canonical Wnt/β-catenin pathway, Wnt3a, glycogen synthase kinase-3β (GSK-3β), β-catenin, α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and Collagen I (Col-I), were measured. At last, we used canonical Wnt/β-catenin pathway activator (LiCl) to further ascertain the mechanism of β-elemene. Canonical Wnt/β-catenin pathway is activated in human airway granulation fibroblasts. β-Elemene didn't affect normal human airway fibroblasts; however, it had a dose-responsive inhibitive effect on the proliferation and expression of Wnt3a, non-active GSK-3β, β-catenin, α-SMA, TGF-β, and Col-I of human airway granulation fibroblasts. More importantly, it had the same effect on the expression and nuclear translocation of active β-catenin. All these effects were similar to 10 ng/ml DKK-1 and could be attenuated by 10 mM LiCl. Thus, β-elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway. This pathway is possibly a promising target to treat benign tracheobronchial stenosis., (© 2018 The Author(s).)

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome (CSS), is a small vessel vasculitis associated with eosinophilia and asthma. Clinical manifestations commonly seen in patients presenting with EGPA range from upper airway and lung involvement to neurological, cardiac, cutaneous, and renal manifestations. Treatment for severe presentations includes steroids, cyclophosphamide, plasmapheresis, and recently, rituximab. Rituximab is associated with a good response in the treatment of vasculitis, but a variable response for the control of allergic symptoms. Here, we report a 16-year-old female patient with severe EGPA (gastrointestinal and cutaneous vasculitis, rhinitis and asthma) refractory to conventional treatment. She was treated with rituximab, which enabled rapid control of the vasculitis component of the disease, but there was no response to rhinitis and asthma. Additionally, she developed severe bronchospasm during rituximab infusion. Sequential rituximab and omalizumab were initiated, leading to remission of all manifestations of vasculitis, rhinitis, and asthma, in addition to bronchospasm related to rituximab infusion.

Ethnopharmacological Relevance: Sophora tonkinensis (Leguminosae, ST) is a traditional herbal plant in Korea and China. Its roots and rhizomes have been used to dissipate heat, to clear toxic material and to treat acute pharyngolaryngeal infections and sore throats., Aim of Study: In this study, we tried to investigate the anti-inflammatory and anti-asthmatic effects of a purified extract (SKI3301) from Sophora tonkinensis using in vitro enzyme assay models and ovalbumin (OVA)-induced asthma animal models., Materials and Methods: The effect of SKI3301 on pro-inflammatory enzymes such as 5-lipoxygenase, phosphodiesterase 3 & 4, and thromboxane synthase was assayed in vitro. BALB/c mice were sensitized with OVA/Alum ip injection and nebulized with OVA to induce airway inflammation. Bronchoalveolar lavage (BAL) fluid was collected and analyzed for leukocytes infiltration and IL-5 production along with lung histopathology. Guinea pigs passively sensitized with anti-OVA antiserum were used to investigate the effect of SKI3301 on bronchospasm in vitro and in vivo., Results: SKI3301 potently inhibited the activities of 5-lipoxygenase, phosphodiesterase 3 & 4, and thromboxane synthase. Orally administered SKI3301 attenuated the total leukocytes and eosinophil infiltration and IL-5 level in BAL fluids. Histopathological changes associated with lung inflammation were also reduced by SKI3301. SKI3301 inhibited OVA-induced contraction of isolated trachea from sensitized guinea pigs. SKI3301 also protected OVA-induced bronchoconstriction in the sensitized guinea pigs. Maackiain, one of 3 major components of SKI3301, was effective in inhibiting 5-lipoxygenase and OVA-induced airway inflammation., Conclusion: In this study, SKI3301 potently inhibited pro-inflammatory enzymes and attenuated OVA-induced bronchospasm in animal model of allergic asthma. These results suggest that SKI3301 may have therapeutic potential for allergic asthma., (Copyright © 2017. Published by Elsevier B.V.)

Adenosine contributes to the pathophysiology of respiratory disease, and adenosine challenge leads to bronchospasm and dyspnoea in patients. The equilibrative nucleoside transporter 1 (ENT1) terminates the action of adenosine by removal from the extracellular environment. Therefore, it is proposed that inhibition of ENT1 in respiratory disease patients leads to increased adenosine concentrations, triggering bronchospasm and dyspnoea. This study aims to assess the translation of in vitro ENT1 inhibition to the clinical incidence of bronchospasm and dyspnoea in respiratory disease, cardiovascular disease and healthy volunteer populations. Four marketed drugs with ENT1 activity were assessed; dipyridamole, ticagrelor, draflazine, cilostazol. For each patient population, the relationship between in vitro ENT1 [ 3 H]-NBTI binding affinity (K i ) and [ 3 H]-adenosine uptake (IC 50 ) to the incidence of: (1) bronchospasm/severe dyspnoea; (2) tolerated dyspnoea and; (3) no adverse effects, was evaluated. A high degree of ENT1 inhibition (≥13.3x K i , ≥4x IC 50 ) associated with increased incidence of bronchospasm/severe dyspnoea for patients with respiratory disease only, whereas a lower degree of ENT1 inhibition (≥0.1x K i , ≥0.05x IC 50 ) associated with a tolerable level of dyspnoea in both respiratory and cardiovascular disease patients. ENT1 inhibition had no effect in healthy volunteers. Furthermore, physicochemical properties correlative with ENT1 binding were assessed using a set of 1625 diverse molecules. Binding to ENT1 was relatively promiscuous (22% compounds K i <1μM) especially for neutral or basic molecules, and greater incidence tracked with higher lipophilicity (clogP >5). This study rationalises inclusion of an assessment of ENT1 activity during early safety profiling for programs targeting respiratory disorders., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Idiopathic pulmonary hemosiderosis is primarily a disorder of childhood, which is characterized by hemoptysis, iron deficiency anemia, and diffuse parenchymal infiltrates on chest x-ray secondary to recurrent attacks of alveolar hemorrhage. It can be diagnosed by showing hemosiderin laden macrophages in bronchoalveolar lavage fluid after other specific causes of diffuse alveolar hemorrhage are definitely excluded. A 5-year-old male patient was admitted to our clinic with sudden-onset pallor during iron therapy given for anemia. While he was being investigated for clinical and laboratory signs mimicking hemolytic anemia, he developed cough and dyspnea. He had infiltrates on chest x-ray and scattered patchy infiltrates in both lungs on high-resolution computed tomography. Hemosiderin laden macrophages were identified in fasting gastric juice and bronchoalveolar lavage fluid. The patient was diagnosed with idiopathic pulmonary hemosiderosis and started corticosteroid therapy.

Objectives: To describe the effect of inhaled sevoflurane in the treatment of severe refractory bronchospasm in children., Design: Retrospective case series., Setting: Two PICUs of tertiary general university hospitals in Spain., Patients: Ten patients ranging from 5 months to 14 years old with severe bronchospasm and acute respiratory failure requiring tracheal intubation and mechanical ventilation and treated with sevoflurane from 2008 to 2015., Intervention: Inhaled sevoflurane therapy was initiated after failure of conventional medical management and mechanical ventilation. In two patients, sevoflurane was administered through a Servo 900C ventilator (Maquet, Bridgewater, NJ) equipped with a vaporizer and in the other eight patients via the Anesthetic Conserving Device (AnaConDa; Sedana medical, Uppsala, Sweden) with a critical care ventilator., Measurements and Main Results: Inhaled sevoflurane resulted in statistically significant decreases of PaCO2 of 34.2 torr (95% CI, 8.3-60), peak inspiratory pressure of 14.3 cm H2O (95% CI, 8.6-19.9), and improvement in pH of 0.17 (0.346-0.002) within 6 hours of administration. Only one patient presented hypotension responsive to volume administration at the beginning of the treatment. All patients could be extubated within a median time of 120 hours (interquartile range, 46-216)., Conclusions: Inhaled sevoflurane therapy decreases the levels of PaCO2 and peak inspiratory pressure values, and it may be considered as a rescue therapy in patients with life-threatening bronchospasm refractory to conventional therapy.

Aclidinium is a twice-daily long-acting muscarinic receptor antagonist (LAMA) with an interesting pharmacological profile. Recent evidence indicates that this LAMA, in addition to causing a significant improvement in lung function and other important supportive outcomes, such as health related quality of life, dyspnea and nighttime/early morning symptoms in patients suffering from COPD, is also able to significantly reduce the rate of exacerbations of any severity, is extremely effective in controlling the COPD symptoms, is able to reduce lung hyperinflation, and has an excellent cardiovascular safety profile. Consequently, aclidinium should be considered a first-line approach at least for the symptomatic treatment of COPD although there are still few head-to-head studies comparing this LAMA with other bronchodilators. In any case, aclidinium can be taken into account in the treatment of different COPD phenotypes (emphysema, chronic bronchitis, exacerbators and patients with overlap COPD asthma).

The carboxylate amides of 8-phenyl-1,3-dimethylxanthine described herein represent a new series of selective ligands of the adenosine A2A receptors exhibiting bronchospasmolytic activity. The effects of location of 8-phenyl substitutions on the adenosine receptor (AR) binding affinities of the newly synthesized xanthines have also been studied. The compounds displayed moderate to potent binding affinities toward various adenosine receptor subtypes when evaluated through radioligand binding studies. However, most of the compounds showed the maximum affinity for the A2A subtype, some with high selectivity versus all other subtypes. Xanthine carboxylate amide 13b with a diethylaminoethylamino moiety at the para-position of the 8-phenylxanthine scaffold was identified as the most potent A2A adenosine receptor ligand with Ki=0.06μM. Similarly potent and highly A2A-selective are the isovanillin derivatives 16a and 16d. In addition, the newly synthesized xanthine derivatives showed good in vivo bronchospasmolytic activity when tested in guinea pigs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Primary Objective: To assess the unusual use of a volatile anaesthetic for treatment of life-threatening bronchospasm in a patient with traumatic brain injury (TBI)., Research Design: Case report., Methods and Procedures: This study presents a previously healthy 30-year-old man with severe TBI and bronchospasm-induced acute hypercapnia. He was treated with inhaled isoflurane in combination with monitoring of intracranial pressure (ICP) and regional cerebral blood flow (rCBF)., Results: Three-day-long isoflurane treatment resolved drug-refractory bronchospasm, decreased airway pressure and improved gas exchange, even at a low end-tidal concentration (0.3-0.5 vol%). Although rCBF was increased by 18 ml min(-1) 100 g(-1) during isoflurane treatment, there was a significant decrease in ICP (21 (SD = 3) mmHg, 9 (SD = 5) mmHg, 2 (SD = 3) mmHg; during pre-treatment, treatment and post-treatment, respectively; p < 0.001). Improved autoregulation due to lower partial pressure of carbon dioxide, restoration of carbon dioxide reactivity, isoflurane-induced regional differences in rCBF and improved microcirculation may have been responsible for the prompt and long-lasting normalization of ICP. The patient had no TBI-related disability at 6 months post-injury., Conclusions: Isoflurane at a low dose can be an effective and safe treatment option for drug-refractory bronchospasm in a patient with traumatic intracranial hypertension, provided that multimodality neuromonitoring is used.

Introduction: Implementation of smokefree laws is followed by drops in hospital admissions for cardiovascular diseases and asthma. The impact of smokefree laws on use of non-hospital medical services has not been assessed. The purpose of this study is to evaluate the impact of Uruguay's national 100% smokefree legislation on non-hospital emergency care visits, hospitalizations for bronchospasm, and bronchodilator use., Methods: The monthly number of non-hospital emergency care visits and hospitalizations for bronchospasm, as well as monthly puffs of bronchodilators (total and per person), from 3 years prior to the adoption of the 100% smokefree policy on March 1, 2006, through 5 years after the policy were assessed using interrupted time series negative binomial regression. Data analysis was conducted in 2014., Results: The incidence of non-hospital emergency visits for bronchospasm decreased by 15% (incidence rate ratio [IRR]=0.85, 95% CI=0.76, 0.94) following implementation of the law. Hospitalizations for bronchospasm did not change significantly (IRR=0.89, 95% CI=0.66, 1.21). Total monthly puffs of salbutamol and ipratropium administered in the non-hospital emergency setting decreased by 224 (95% CI=-372, -76) and 179 (95% CI=-340, -18.6), respectively, from means of 1,222 and 1,007 before the law., Conclusions: Uruguay's 100% smokefree law was followed by fewer emergency visits for bronchospasm and less need for treatment, supporting adoption of such policies in low- and middle-income countries to reduce the disease burden and healthcare costs associated with smoking., (Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

The clinical need for novel bronchodilators for the treatment of bronchoconstrictive diseases remains a major medical issue. Modulation of airway smooth muscle (ASM) chloride via GABAA receptor activation to achieve relaxation of precontracted ASM represents a potentially beneficial therapeutic option. Since human ASM GABAA receptors express only the α4- and α5-subunits, there is an opportunity to selectively target ASM GABAA receptors to improve drug efficacy and minimize side effects. Recently, a novel compound (R)-ethyl8-ethynyl-6-(2-fluorophenyl)-4-methyl-4H-benzo[f]imidazo[1,5-a][1,4] diazepine-3-carboxylate (SH-053-2'F-R-CH3) with allosteric selectivity for α5-subunit containing GABAA receptors has become available. We questioned whether this novel GABAA α5-selective ligand relaxes ASM and affects intracellular calcium concentration ([Ca(2+)]i) regulation. Immunohistochemical staining localized the GABAA α5-subunit to human ASM. The selective GABAA α5 ligand SH-053-2'F-R-CH3 relaxes precontracted intact ASM; increases GABA-activated chloride currents in human ASM cells in voltage-clamp electrophysiology studies; and attenuates bradykinin-induced increases in [Ca(2+)]i, store-operated Ca(2+) entry, and methacholine-induced Ca(2+) oscillations in peripheral murine lung slices. In conclusion, selective subunit targeting of endogenous α5-subunit containing GABAA receptors on ASM may represent a novel therapeutic option to treat severe bronchospasm., (Copyright © 2015 the American Physiological Society.)

Background: Loxapine, a first-generation antipsychotic, delivered with a novel inhalation delivery device developed for the acute treatment of agitation in patients with schizophrenia or bipolar disorder was evaluated in subjects with asthma or chronic obstructive pulmonary disease (COPD)., Methods: Separate randomized, double-blind, parallel-arm, placebo-controlled trials compared two administrations of inhaled loxapine (10 mg) 10 hr apart with placebo in 52 subjects with asthma and in 53 subjects with COPD. A thermally-generated drug aerosol of loxapine was delivered to the deep lung for rapid systemic absorption. Controller medications were continued throughout the study, but quick-relief bronchodilators were withheld from 6-8 hr before through 34 hr after dose 1, unless indicated as rescue., Results: All airway adverse events (AEs) were of mild or moderate severity. Symptomatic bronchospasm occurred in 53.8% of subjects with asthma after inhaled loxapine and 11.5% after placebo; and in 19.2% of COPD subjects after inhaled loxapine and 11.1% after placebo. Subjects required inhaled albuterol as follows: asthma: 53.8% after inhaled loxapine and 11.5% after placebo; and COPD: 23.1% after inhaled loxapine and 14.8% after placebo. Respiratory signs/symptoms requiring treatment responded to rescue bronchodilator [forced expiratory volume in 1 sec (FEV(1)) return to within 10% of baseline] within 1 hr in 11 of 15 events in asthma subjects and four of seven events in COPD subjects, the remainder by the last spirometry., Conclusions: In subjects with either asthma or COPD, FEV(1) decline and bronchospasm can occur following inhaled loxapine, but more frequently in asthmatic subjects. Most subjects with bronchospasm responded to rescue bronchodilator within 1 hr. No treatment-related serious AE occurred. Although inhaled loxapine is contraindicated in patients with active airways disease per the current approved US labeling, these studies demonstrated that rescue bronchodilator mitigated the symptomatic bronchospasms that may occur in case of inadvertent use.

Introduction: Acute severe asthma is a life-threatening form of bronchial constriction in which the progressively worsening airway obstruction is unresponsive to the usual appropriate bronchodilator therapy. Pathophysiological changes restrict airflow, which leads to premature closure of the airway on expiration, impaired gas exchange, and dynamic hyperinflation ("air-trapping"). Additionally, patients suffering from asthma for a prolonged period of time usually have serious comorbidities. These conditions constitute a challenge during the treatment of this disease. Therapeutic interventions are designed to reduce airway resistance and improve respiratory status. To achieve therapeutic goals, appropriate bronchodilator treatment is indispensable, and mechanical ventilation under adequate sedation may also be required. The volatile anesthetic agent, sevoflurane, meets both criteria; therefore, its use can be beneficial and should be considered., Case Presentation: A 67-yr-old Caucasian male presented with acute life-threatening asthma provoked by an assumed upper airway infection and non-steroidal anti-inflammatory drug antipyretics, complicated by chronic atrial fibrillation and hemodynamic instability. Due to frequent premature ventricular contractions, conventional treatment was considered unsafe and discontinued, and sevoflurane inhalation was initiated via the AnaConDa (Anaesthetic Conserving Device). Symptoms of life-threatening bronchospasm resolved, and the patient's respiratory status improved within hours. Adequate sedation was also achieved without any hemodynamic adverse effects., Conclusion: The volatile anesthetic agent, sevoflurane, is used widely in anesthesia practice. Its utility for treatment of refractory bronchospasm has been appreciated for years; however, its administration was difficult within the environment of the intensive care unit due to the need for an anesthesia machine and a scavenging system. The introduction of the AnaConDa eliminates these obstacles and makes the use of sevoflurane safe and simple. Our case report reveals the potential of sevoflurane as a "two-in-one" (bronchodilator and sedative) drug to treat a severe acute asthma attack.

We investigated the effects of nonselective muscarinic antagonist (atropine) and of selective muscarinic subtype 1 (M1), 2 (M2), 3 (M3) antagonists (VU0255035, methoctramine, pFHHSiD, respectively) on the contractions evoked by electrical field stimulation (EFS) or by exogenous ACh in isolated horse bronchial muscle. Atropine completely inhibited neurogenic contractions in a concentration-dependent fashion, whereas selective muscarinic antagonists induced relevant modifications only at the highest concentration tested. Experiments with selective muscarinic antagonists in combination showed that only the simultaneous blockade of M1 /M3 or M2 /M3 receptors was able to induce a nearly complete suppression of contractions. The contractions induced by exogenous ACh were competitively antagonized only by atropine (pA2 = 9.01 ± 0.05). M3 selective antagonist, up to 10(-6) m, caused a moderate concentration-dependent rightward shift of ACh curve (pA2 = 7.96 ± 0.10). These data show that M3 muscarinic receptors possess a central role in mediating cholinergic contraction of horse bronchi, while M1 and M2 receptors seem to have a cooperative role. Selective muscarinic antagonists seem unlikely to be useful against bronchoconstriction associated with airway diseases in horses. Conversely, compounds with selectivity for both M1 and M3 receptors could be as effective as traditional anticholinergics and induce fewer cardiac side effects., (© 2014 John Wiley & Sons Ltd.)

Marijuana is the most commonly used drug of abuse in the USA. It is commonly abused through inhalation and therefore has effects on the lung that are similar to tobacco smoke, including increased cough, sputum production, hyperinflation, and upper lobe emphysematous changes. However, at this time, it does not appear that marijuana smoke contributes to the development of chronic obstructive pulmonary disease. Marijuana can have multiple physiologic effects such as tachycardia, peripheral vasodilatation, behavioral and emotional changes, and possible prolonged cognitive impairment. The carcinogenic effects of marijuana are unclear at this time. Studies are mixed on the ability of marijuana smoke to increase the risk for head and neck squamous cell carcinoma, lung cancer, prostate cancer, and cervical cancer. Some studies show that marijuana is protective for development of malignancy. Marijuana smoke has been shown to have an inhibitory effect on the immune system. Components of cannabis are under investigation as treatment for autoimmune diseases and malignancy. As marijuana becomes legalized in many states for medical and recreational use, other forms of tetrahydrocannabinol (THC) have been developed, such as food products and beverages. As most research on marijuana at this time has been on whole marijuana smoke, rather than THC, it is difficult to determine if the currently available data is applicable to these newer products.

Ethnopharmacological Relevance: In the traditional medicine, Cynodon dactylon (Linn.) is used in asthma, but scientific studies to provide evidence for medicinal uses are sparse. Thus this study was undertaken to provide evidence for medicinal use in asthma as a bronchodilator, and to identify active ingredient(s)., Materials and Methods: In vivo, acetylcholine (Ach)-induced bronchospasm was conducted in guinea pig while isolated rat tracheal strip was suspended in organ bath to measure the concentration response curve using multichannel data acquisition system., Results: The chloroform extract of Cynodon dactylon (CECD) protected against Ach-induced bronchospasm in guinea pigs, similar to atropine. In the in vitro studies, CECD relaxed carbachol (CCh) and high K+-induced contraction of rat tracheal strip, similar to atropine and verapamil respectively, suggesting antimuscarinic and calcium channel blocking (CCB) activities, which were confirmed by right ward shifting of CCh and Ca(+2) concentration response curve (CRC). The phosphodiestrase (PDE) inhibitory activity was confirmed by potentiation of isoprenaline-induced inhibitory response, similar to papaverine. Densitometry analyses led to the identification of scopoletin as an active ingredient. Effectively, it significantly inhibited high K+, and Ca(+2) induced contractile response, similar to verapamil. The phosphodiestrase (PDE) inhibitory activity was confirmed by direct evidence of potentiation of isoprenaline-induced inhibitory response, similar to papaverine., Conclusions: These results suggest that the bronchodilator activity of CECD is partly due to presence of scopoletin, and mediated possibly through CCB and PDE inhibition.

Minor and major allergic reactions occur during oral and maxillofacial treatment. Immediate diagnosis and pharmacologic intervention are imperative. Signs and symptoms may be variable. The early administration of epinephrine is critical., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The efficacy of systemic corticosteroids in many critical illnesses remains uncertain. Our primary objective was to survey intensivists in North America about their perceived use of corticosteroids in clinical practice., Design: Self-administered paper survey., Population: Intensivists in academic hospitals with clinical trial expertise in critical illness., Measurements: We generated questionnaire items in focus groups and refined them after assessments of clinical sensibility and test-retest reliability and pilot testing. We administered the survey to experienced intensivists practicing in selected North American centres actively enrolling patients in the multicentre Oscillation for ARDS Treated Early (OSCILLATE) Trial (ISRCTN87124254). Respondents used a four-point scale to grade how frequently they would administer corticosteroids in 14 clinical settings. They also reported their opinions on 16 potential near-absolute indications or contraindications for the use of corticosteroids., Main Results: Our response rate was 82% (103/125). Respondents were general internists (50%), respirologists (22%), anesthesiologists (21%), and surgeons (7%) who practiced in mixed medical-surgical units. A majority of respondents reported almost always prescribing corticosteroids in the setting of significant bronchospasm in a mechanically ventilated patient (94%), recent corticosteroid use and low blood pressure (93%), and vasopressor-refractory septic shock (52%). Although more than half of respondents stated they would almost never prescribe corticosteroids in severe community-acquired pneumonia (81%), acute lung injury (ALI, 76%), acute respiratory distress syndrome (ARDS, 65%), and severe ARDS (51%), variability increased with severity of acute lung injury. Near-absolute indications selected by most respondents included known adrenal insufficiency (99%) and suspicion of cryptogenic organizing pneumonia (89%), connective tissue disease (85%), or other potentially corticosteroid-responsive illnesses (85%)., Conclusions: Respondents reported rarely prescribing corticosteroids for ALI, but accepted them for bronchospasm, suspected adrenal insufficiency due to previous corticosteroid use, and vasopressor-refractory septic shock. These competing indications will complicate the design and interpretation of any future large-scale trial of corticosteroids in critical illness.

Objective: To evaluate the antiasthmatic and antitussive properties of the aqueous leaf extract of Bryophyllum pinnatum (B. pinnatum) (BP) Lam., Methods: Ovalbumin-sensitized guinea pigs which were treated with BP for 21 consecutive days were exposed to 0.2% histamine aerosol in a glass chamber. Mucus viscosity, white blood cell and lymphocyte counts and tracheal wall morphometry were measured. Bouts of cough were counted pre and post acute exposure of extract-treated (× 7 d) guinea pigs to 7.5% citric acid aerosol in a chamber. Phenol red expectoration was estimated in mice after 7 d of daily administration of BP., Results: Doses of 200 and 400 mg/kg/day (×21 d) BP significantly increased the time for guinea pigs to experience preconvulsive dyspnoea. BP and salbutamol (0.5 mg/kg/day ×21 d) reduced mucus viscosity in the sensitized group to values comparable with controls. White blood cell, lymphocyte counts and tracheal morphometry were not significantly altered. Both doses of BP also significantly reduced the bouts of cough but only 400 mg/kg/day significantly inhibited the amount of phenol red secreted., Conclusions: BP has demonstrated antiasthmatic and antitussive properties in these rodent models. These properties may underscore its use in Nigerian ethnomedicine., (Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)

Background: Snorting or smoking heroin is a known trigger of acute asthma exacerbation. Heroin abuse may be a risk factor for more severe asthma exacerbations and intubation. Heroin and other opioids provoke pulmonary bronchoconstriction. Naloxone may play a role in decreasing opioid-induced bronchospasm. There are no known clinical cases describing the effect of naloxone on opioid-induced bronchospasm., Methods: This is an observational study in which nebulized naloxone was administered to patients with suspected heroin-induced bronchospasm. Patients with spontaneous respirations were administered 2 mg of naloxone with 3 mL of normal saline by nebulization. We describe a case series of administrations for suspected heroin-induced bronchospasm., Results: We reviewed 21 administrations of nebulized naloxone to patients with suspected heroin-induced bronchospasm. Of these, 19 patients had a clinical response to treatment documented. Thirteen patients displayed clinical improvement (68%), 4 patients had no improvement (21%), and 2 patients worsened (10%). Of the 2 patients who had clinical decline, none required intubation. Of the patients who improved, 1 patient received only nebulized naloxone and 1 patient received naloxone and albuterol together. Seven patients showed clinical improvement after the administration of albuterol, atrovent, and naloxone together as a combination. Four patients showed additional improvement when the naloxone was administered after the albuterol and atrovent combination., Conclusion: Naloxone may play a role in reducing acute opioid-induced bronchoconstriction, either alone or in combination with albuterol. Future controlled studies should be conducted to determine if the addition of naloxone to standard treatment improves bronchospasm without causing adverse effects., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Children with severe bronchospasm requiring mechanical ventilation may become refractory to conventional therapy. In these critically ill patients, isoflurane is an inhaled anesthetic agent available in some centers to treat bronchospasm. We hypothesized that isoflurane is safe and would lead to improved gas exchange in children with life-threatening bronchospasm refractory to conventional therapy., Methods: A retrospective review was conducted and included mechanically ventilated children treated with isoflurane in a quaternary pediatric ICU for life-threatening bronchospasm, from 1993 to 2007. Demographic, blood gas, ventilator, and outcome data were collected., Results: Thirty-one patients, with a mean age of 9.5 years (range 0.4-23 years) were treated with isoflurane, from 1993 to 2007. Mean time to initiation of isoflurane after intubation was 13 hours (0-120 h), and the mean maximum isoflurane dose was 1.1% (0.3-2.5%). Mean duration of isoflurane administration was 54.5 hours (range 1-181 h), with a total mean duration of mechanical ventilation of 252 hours (range 16-1,444 h). Isoflurane led to significant improvement in pH and P(CO(2)) within 4 hours of initiation (P ≤ .001). Complications during isoflurane administration included hypotension requiring vasoactive infusions in 24 (77%), arrhythmia in 3 (10%), neurologic side effects in 3 (10%), and pneumothorax in 1 (3%) patient., Conclusions: Isoflurane led to improvement in pH and P(CO(2)) within 4 hours in this series of mechanically ventilated patients with life-threatening bronchospasm. The majority of patients in this series developed hypotension, but there was a low incidence of other side effects related to isoflurane administration. Isoflurane appears to be an effective therapy in patients with life-threatening bronchospasm refractory to conventional therapy. However, further investigation is warranted, given the uncertain overall impact of isoflurane in this context.