Adverse effects of inhalation of excessive amounts of nebulized isoproterenol in status asthmaticus

Metre, Thomas E. Van

doi:10.1016/0021-8707(69)90130-0

Cited by 99 publications

(25 citation statements)

References 17 publications

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“…3). Perhaps such patients are most at risk during acute severe asthma [21,22]. While the cumulative dose of salbutamol (400 mg) used in this study appears to be small, it was administered via a large volume spacer in controlled laboratory conditions.…”

Section: Discussionmentioning

confidence: 99%

Bronchodilator tolerance: the impact of increasing bronchoconstriction

Wraight

Hancox²,

Herbison³

et al. 2003

Eur Respir J

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Chronic exposure to b-agonists causes tolerance to their bronchodilator effects, which is best demonstrated during acute bronchoconstriction. The aim of the present study was to assess whether tolerance becomes more evident with increasing bronchoconstriction, as might occur in acute asthma.In a randomised, double-blind, placebo-controlled, crossover study comprising 15 patients, the treatments were salbutamol 400 mg q.i.d. or placebo given via Diskhaler1 for 28 days with a 2-week washout between treatments. Patients attended on days 14, 21 and 28. Bronchoconstriction was induced on two of these three occasions to achieve a reduction in the forced expiratory volume in one second (FEV1) of 0 (no methacholine), 15 and 30% (using methacholine) in a randomised order. Immediately after this, salbutamol 100 mg, 100 mg and 200 mg was inhaled at 0, 5, and 10 min. FEV1 was measured over 40 min. Dose/response curves were plotted and values for the area under the curve (AUC)0-40 FEV1 were compared between treatments and by degree of bronchoconstriction.Regular salbutamol resulted in attenuation of the acute response to b-agonist, which was increasingly evident with greater bronchoconstriction. With a reduction in FEV1 of 0, 15 and 30%, the AUC0-40 FEV1 with salbutamol were 11.2, -14.6 and -35.7% respectively, compared to placebo. There was a linear relationship between the magnitude of bronchoconstriction and the between-treatment differences in AUC0-40 FEV1.Increasing bronchoconstriction conferred greater susceptibility to the effects of bronchodilator tolerance. b-agonists are widely prescribed for symptomatic relief in asthma. They are very effective as bronchodilators and as functional antagonists against a wide range of constricting stimuli. However, chronic exposure of b-adrenoceptors (b-AR) to b-agonist drugs leads to reduced responsiveness (desensitisation) and a decrease in the number of receptors (downregulation) [1].In the clinical setting, tolerance to the nonbronchodilator effects of b-agonists is readily demonstrated [2,3]. However, it has been more difficult to demonstrate tolerance to their bronchodilator effects. Reduced bronchodilator response after regular short-and long-acting b-agonists has been reported [4][5][6][7] but the findings have been inconsistent [8][9][10][11]. A possible explanation for these negative results is that bronchodilator responses were measured in patients with stable asthma in whom the margin from baseline to maximum bronchodilatation was not sufficient for the effects of tolerance to be detected.Recently, HANCOX et al. [12] have described a method that reliably demonstrates bronchodilator tolerance to b-agonists. In that study, a 36% reduction in the area under the curve (AUC) for forced expiratory volume (FEV1) was observed in patients who had been using regular inhaled b-agonist compared to placebo. Subsequently, other authors have used the same methodology to show similar effects in patients using long-acting b-agonists [13,14]. In both of these studies, measuring...

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Section: Discussionmentioning

confidence: 99%

Bronchodilator tolerance: the impact of increasing bronchoconstriction

Wraight

Hancox²,

Herbison³

et al. 2003

Eur Respir J

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“…Indirect evidence of an acute increase in reactivity following administration of P-agonists by inhalation has been described, but only in asthmatic subjects (Keighley, 1966;Eisenstadt & Nicholas, 1969;van Metre, 1969;Reisman, 1969;Paterson et al, 1971 Other studies indicate that enhanced airway reactivity can result from repeated exposure to conventional P-agonist bronchodilator drugs in asthmatic patients being treated with these agents prophylactically (Peel & Gibson, 1980;Kraan et al, 1985;Kerribijn et al, 1987;Vathenen et al, 1988;van Schayck et al, 1990;Sears et al, 1990). Regular daily use of a P-agonist has been shown to worsen the disease and make control of symptoms difficult (Sears et al, 1990) and to be associated with an increase in asthma mortality (Crane et al, 1989;Spitzer et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Enhancement of airway reactivity to histamine by isoprenaline and related β‐adrenoceptor agonists in the guinea‐pig

Galland

Blackman

1993

British J Pharmacology

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1 The effect of isoprenaline, adrenaline and salbutamol on airway reactivity to histamine was observed in anaesthetized, ventilated guinea-pigs. Airway reactivity was determined before and 20 min and 90 min after a 30-min i.v. infusion of each agonist by constructing cumulative dose-response curves from breath-by-breath measurements of the effect of different rates of i.v. infusion of histamine on lung resistance (RL) and dynamic compliance (Cdy,). 2 ( ± )-Isoprenaline infused i.v. for 30 min at a rate of 0.4 jimol h -' kg-' caused bronchodilatation and a fall in blood pressure. Recovery to starting values of RL and Cdy. occurred within 20 min of stopping the infusion. 3 Reactivity to histamine was greatly enhanced when measured 20 min and 90 min after stopping the infusion of (± )-isoprenaline. This was not an effect of the prior infusion of histamine or of the dissolving solution. 4 Infusion of (-)-isoprenaline for 30 min at a rate of 0.2 umol h-' kg-' also enhanced reactivity to histamine. However, enhancement of reactivity to histamine was not demonstrable after infusion of (+)-isoprenaline at equal or higher dose rates. 5 Infusions of bronchodilator concentrations of adrenaline and salbutamol also enhanced airway reactivity to histamine, but the bronchodilator effect of salbutamol lasted longer than that of isoprenaline or adrenaline and the development of hyperreactivity was delayed. 6 After acute bilateral vagotomy, infusion of ( )-isoprenaline enhanced airway reactivity but only at the highest dose of histamine. 7 ( ± )-Isoprenaline did not enhance contractile responses to histamine in isolated preparations of first branch bronchi. 8 We conclude that the bronchodilator effect of activating P-adrenoceptors in the airways of guineapigs is followed by a more persistent state of hyperreactivity to histamine.

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“…Sobol, Emirgil, Wadhwani & Goyal (1972) followed 32 patients with chronic obstructive pulmonary disease for 4 to 32 months (average 18 months) who used an isoprenaline nebulizer at least 5 times/day and found that bronchodilator effects did not diminish. Ayres (1973) (Keighley, 1966;Reisman et al, 1968;Van Metre, 1969). There are also some patients whose condition may deteriorate when such aerosols are used (Keighley, JournalT (1972) points out that in cases of status asthmaticus 'Bronchodilator aerosols have ceased to be effective' and 'Sympathomimetic bronchodilators, by inhalation or by injection, should be avoided unless oxygen can be administered at the same time.'…”

Section: Discussionmentioning

confidence: 99%

“…Some asthmatic patients were reported to have, no bronchodilator response to nebulized isoprenaline (Reisman, Friedman & Arbesman, 1968; Van Metre, 1969;Herxheimer, 1969Herxheimer, , 1972a. It is not certain whether this lack of response was due to tachyphylaxis or to other causes (see Discussion).…”

Section: Introductionmentioning

confidence: 99%

Lack of Cardiac or Bronchodilator Tachyphylaxis to Isoprenaline in the Dog

Minatoya

Spilker

1975

British J Pharmacology

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Tachyphylaxis to heart rate and bronchodilator effects of (±)‐isoprenaline was studied in anaesthetized open‐chest dogs by 5 procedures. Heart rate responses to a series of intravenous injections of isoprenaline were essentially unchanged before and after a 15 min infusion of isoprenaline (at 3 doses). Heart rate and bronchodilator responses in the same animal to an intravenous injection of isoprenaline were not significantly different before and after a 30 min infusion of isoprenaline (at 2 doses). Heart rate responses were relatively constant to an isoprenaline injection given every 30 min during a 4 h infusion of isoprenaline (at 3 doses), but the magnitude of the response was smallest for the largest infusion dose (highest background heart rate) and greatest for the smallest infusion dose (lowest background heart rate). Heart rate and bronchodilator responses in the same animal to isoprenaline were relatively constant during a 5 h infusion of isoprenaline (at 2 doses). Bronchodilator responses to intratracheally administered isoprenaline aerosol were essentially unchanged during a 4–5 h period using various doses and procedures. Tachyphylaxis to the heart rate or bronchodilator effects of isoprenaline was not observed. The present data give no support to the hypothesis that tachyphylaxis to isoprenaline aerosols is an important mechanism in asthma mortality.

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Adverse effects of inhalation of excessive amounts of nebulized isoproterenol in status asthmaticus

Cited by 99 publications

References 17 publications

Bronchodilator tolerance: the impact of increasing bronchoconstriction

Bronchodilator tolerance: the impact of increasing bronchoconstriction

Enhancement of airway reactivity to histamine by isoprenaline and related β‐adrenoceptor agonists in the guinea‐pig

Lack of Cardiac or Bronchodilator Tachyphylaxis to Isoprenaline in the Dog

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