Randomised trial of intravenous salbutamol in early management of acute severe asthma in children

Browne, Gary; Penna, Antonio S; Phung, Xan; Soo, Michael

doi:10.1016/s0140-6736(96)06358-1

Cited by 139 publications

(83 citation statements)

References 16 publications

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“…transient relaxing effect was rapidly overlapped by an additional contraction. At least in the in vivo experiments, the dose used in our study (10 g/kg ip) was close to the intravenous dose recommended for the acute relief of severe asthmatic bronchospasm in children (5). Additionally, in a previous work (35), we found that aerosolized salbutamol at therapeutic doses used in humans (2 mg/ml, 2 min) also produced the paradoxical effect.…”

Section: Discussionsupporting

confidence: 71%

Paradoxical effect of salbutamol in a model of acute organophosphates intoxication in guinea pigs: role of substance P release

Chávez¹,

Segura²,

Vargas³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Chávez J, Segura P, Vargas MH, Arreola JL, Flores-Soto E, Montaño LM. Paradoxical effect of salbutamol in a model of acute organophosphates intoxication in guinea pigs: role of substance P release. Am J Physiol Lung Cell Mol Physiol 292: L915-L923, 2007. First published December 8, 2006; doi:10.1152/ajplung.00253.2005.-Organophosphates induce bronchoobstruction in guinea pigs, and salbutamol only transiently reverses this effect, suggesting that it triggers additional obstructive mechanisms. To further explore this phenomenon, in vivo (barometric plethysmography) and in vitro (organ baths, including ACh and substance P concentration measurement by HPLC and immunoassay, respectively; intracellular Ca 2ϩ measurement in single myocytes) experiments were performed. In in vivo experiments, parathion caused a progressive bronchoobstruction until a plateau was reached. Administration of salbutamol during this plateau decreased bronchoobstruction up to 22% in the first 5 min, but thereafter airway obstruction rose again as to reach the same intensity as before salbutamol. Aminophylline caused a sustained decrement (71%) of the parathion-induced bronchoobstruction. In in vitro studies, paraoxon produced a sustained contraction of tracheal rings, which was fully blocked by atropine but not by TTX, -conotoxin (CTX), or epithelium removal. During the paraoxon-induced contraction, salbutamol caused a temporary relaxation of ϳ50%, followed by a partial recontraction. This paradoxical recontraction was avoided by the M 2-or neurokinin-1 (NK1)-receptor antagonists (methoctramine or AF-DX 116, and L-732138, respectively), accompanied by a long-lasting relaxation. Forskolin caused full relaxation of the paraoxon response. Substance P and, to a lesser extent, ACh released from tracheal rings during 60-min incubation with paraoxon or physostigmine, respectively, were significantly increased when salbutamol was administered in the second half of this period. In myocytes, paraoxon did not produce any change in the intracellular Ca 2ϩ basal levels. Our results suggested that: 1) organophosphates caused smooth muscle contraction by accumulation of ACh released through a TTX-and CTX-resistant mechanism; 2) during such contraction, salbutamol relaxation is functionally antagonized by the stimulation of M 2 receptors; and 3) after this transient salbutamol-induced relaxation, a paradoxical contraction ensues due to the subsequent release of substance P. albuterol; ␤ 2-adrenoceptor agonist; parathion; paraoxon; tachykinins; physostigmine; airway smooth muscle PARATHION IS ONE OF THE MAIN representatives of organophosphates, a family of compounds synthesized since the 1940s and still widely used all around the world in agriculture and veterinary medicine as insecticides and antihelmintics (12). To achieve biological activity, parathion must be biotransformed in the liver and other tissues into paraoxon. The latter metabolite has a very strong inhibitory capacity on acetylcholinesterase (AChE) activity (27, 36), leading to an increase in ACh...

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Section: Discussionsupporting

confidence: 71%

Paradoxical effect of salbutamol in a model of acute organophosphates intoxication in guinea pigs: role of substance P release

Chávez¹,

Segura²,

Vargas³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Oral administration of b 2 -agonist is also effective but is limited by systemic side-effects [102]. Intravenous infusion of b 2 -agonists has only shown an advantage over hourly inhaled treatment in very severe acute wheeze in young children [103].…”

Section: Pharmacological Therapymentioning

confidence: 99%

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach

Brand¹,

Baraldi²,

Bisgaard³

et al. 2008

European Respiratory Journal

746

759

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There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis.Based on the limited evidence available, inhaled short-acting b 2 -agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop.Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit.Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

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“…Outro fator relacionado ao emprego da via inalatória, e que merece referência, é a menor cooperabilidade dos pacientes na faixa etária pediátrica para realização de nebulizações. Se considerarmos que durante uma nebulização cerca de um terço do total de partículas veiculadas é disponível à via aérea, em função de uma relação alterada do ciclo respiratório (inspiração/expiração) durante a crise asmática, é de extrema importância que a técnica de realização do procedimento seja bem feita 3,11,26 . Agitação, ansiedade e baixa tolerabilidade à máscara de nebulização são situações freqüentes que acompanham pacientes pediátricos com quadro de hipoxemia, de forma a comprometer a técnica e a realização do procedimento.…”

Section: Discussionunclassified

“…Nos quadros obstrutivos intensos, uma série de fatores contribuem para a pobre deposição de ß-2 adrenérgicos inalados nas vias aéreas inferiores, dentre os quais ressaltamos baixo volume corrente e fluxo turbulento conseqüente a intensa reação inflamatória brônquica, presença de tampões mucosos e broncoespasmo. Nessas situações o emprego de drogas broncodilatadoras por via parenteral poderia ser vantajosa 3,[10][11][12] .…”

Section: J Pediatr (Rio Junclassified

Intravenous terbutaline in children

Sl²,

Zambonato³

et al. 1998

J Pediatr (Rio J)

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Objective: The authors describe their experience with the use of intravenous ß2 adrenergic (IV terbutaline) in patients admitted to a PICU with severe lower airway obstruction.Patients and methods: A retrospective study of all admissions to a PICU was conducted in Santo Antonio Hospital in Porto Alegre City (Brazil) during the winter of 1995. The files of all the patients that were treated with intravenous ß2 adrenergic as a bronchodilator were selected. The analysis included length of use, initial doses, maximal doses, associated phenomena, arterial blood gases and plasma level of potassium.Results: During the three months of study 367 patients were admitted to the PICU and 38 (10.3%) used IV terbutaline. This group of patients had a mean age of 13.8 ± 12.2 months old and used IV terbutaline for a mean length of 7.24 ± 3.6 days. The initial rate of infusion was 0.55 ± 0.25 mcg/kg/min with a mean therapeutic dose of 2.45 ± 1.18 mcg/kg/min. Twelve patients (31.5%) had increase in their heart rate (over 180 bpm) that prevented increases in the infusion rate. However this was a temporary effect. The patients under 12 months of age started with low infusion rates (0.45 ± 0.22 mcg/kg/min), when compared to children over 1 year old (0.57 ± 0.3 mcg/kg/min), p < 0.01. No patient developed pathologic heart rate attributed to the drug. The serum levels of potassium decreased significantly (p < 0.01) only in the group of patients under 1 year (4.1 ± 0.7 to 3.47 ± 0.52 mEq/L), but this difference had no clinical relevance.Comments: In view of these results the authors showed that the infusion of IV terbutaline in children is safe and presents a low risk if the criteria of administration and monitoring are followed. In this manner, IV terbutaline is an excellent therapeutic option for children with severe lower airway obstruction and no response to the conventional treatment.J. pediatr. (Rio J.). 1998; 74(6): 441-446: asthma, bronchodilators, terbutaline, ß2 adenergics, aerosoltherapy. ResumoObjetivo: Os autores descrevem sua experiência com o uso de ß2 adrenérgico (Terbutalina), por via endovenosa, em pacientes internados em UTI pediátrica com quadro grave de obstrução de vias aéreas inferiores.Pacientes e métodos: Foi realizado um estudo retrospectivo das admissões realizadas na UTI do Hospital da Criança Santo Antônio (HCSA) de Porto Alegre (RS-Brasil) durante o inverno de 1995, sendo selecionados os prontuários dos pacientes que utilizaram ß2 adrenérgi-cos endovenoso, para tratamento de broncoespasmo. Foram analisados dados referentes a tempo de uso, dose inicial, dose máxima utilizada, fenômenos associados, gasometria arterial e níveis séricos de potássio.Resultados: Nos três meses de estudo, foram admitidos 367 pacientes na UTI pediátrica, sendo que 38 (10,3%) vieram a utilizar terbutalina por via endovenosa. Esse grupo tinha uma idade média de 13,8 ± 12,2 meses e utilizou a terbutalina endovenosa por um tempo médio de 7,24 ± 3,6 dias. A taxa inicial de infusão foi de 0,55 ± 0,25 mcg/kg/min, e a dose terapêutic...

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Randomised trial of intravenous salbutamol in early management of acute severe asthma in children

Cited by 139 publications

References 16 publications

Paradoxical effect of salbutamol in a model of acute organophosphates intoxication in guinea pigs: role of substance P release

Paradoxical effect of salbutamol in a model of acute organophosphates intoxication in guinea pigs: role of substance P release

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach

Intravenous terbutaline in children

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