Pharmacological Provocation of Outflow-Tract Tachycardia in a Patient With Brugada Syndrome.

We present a case of a symptomatic patient with Brugada syndrome, who had sustained right ventricular outflow tract tachycardia after pronounced exercise-induced ST segment elevation in V1 and V2. In electrophysiological study he developed right ventricular outflow tract tachycardia provoked by combined infusion of ajmaline and orciprenaline. After ablation no further arrhythmia was provoked by pharmacological stimulation.

Cromoglycate, reproterol, or both--what's best for exercise-induced asthma?

OBJECTIVE: International guidelines recommend short- (SABA) or long-acting b-agonists for the prevention of bronchoconstriction after exercise (EIB) in patients with exercise-induced asthma (EIA). However, other drugs are still in discussion for the prevention of EIB. We investigated the efficacy of a combination of inhaled sodium cromoglycate and the ß-mimetic drug reproterol versus inhaled reproterol alone and both versus inhaled placebo in subjects with exercise-induced asthma (EIA). METHODS: The study aimed to prove the preventive effect of a combination of 1-mg reproterol and 2-mg disodium cromoglycate (DSCG) and its single components vs. placebo, measuring the decrease of FEV1 after a standardized treadmill test in 11 patients with recorded EIA. The study medication was twice as high as those of drugs which are commercially available (e.g., Allergospasmin®, Aarane®). RESULTS: The results revealed that the combination of reproterol and DSCG was significantly effective against a decrease of FEV1 after a standardized exercise challenge test (ECT) compared to placebo. The short-acting b-agonist reproterol alone had almost the same effectiveness as the combination of reproterol and DNCG. The difference between the combination with DNCG and reproterol alone was less than 10% and insignificant (p 0.48). DNCG alone did not show a difference in the effectiveness compared to placebo. CONCLUSION: Prevention of EIA with the combination of reproterol and DSCG or with reproterol only is effective. An exclusive recommendation in favor of the combination cannot be given due to the low difference in the effectiveness versus reproterol alone. Due to the limited number of subjects and some probands showing protection under DSCG, it cannot be completely excluded that there is some preventive power of DSCG in individual cases.

Is electrical stimulation during administration of catecholamines required for the evaluation of success after ablation of atrioventricular node re-entrant tachycardias?

OBJECTIVES: The purpose of this study was to answer the question of whether stimulation after administration of catecholamines is mandatory for identifying unsuccessful ablations of atrioventricular node re-entrant tachycardia (AVNRT). BACKGROUND: The success of radiofrequency (RF) catheter ablation in AVNRT is confirmed in many centers by noninducibility of tachycardias during stimulation after the administration of catecholamines. METHODS: A total of 131 patients (81 women and 50 men; mean age 53.6 +/- 13.7 years [range 20 to 77]) were studied. Electrical stimulation was performed without and with the beta-adrenergic amine Orciprenaline (metaproterenol) before and after RF catheter ablation. RESULTS: In 100 patients (76.3%; confidence interval [CI] 68.1% to 83.3%) an AVNRT was inducible without administration of Orciprenaline. Thirty minutes after the initially successful ablation in 95 patients, tachycardia was inducible in none of these patients, not even after Orciprenaline administration. In the 31 patients (23.7%; CI 16.7% to 31.9%) in whom there was no tachycardia inducible before ablation, Orciprenaline was given, and the stimulation protocol was repeated. In only five patients (3.8%; CI 1.3% to 8.7%) was there still no tachycardia inducible. After an initially successful ablation in the 26 patients who had inducible tachycardias with Orciprenaline before ablation, no tachycardia could be re-induced. After Orciprenaline, the tachycardia was inducible again in only one patient. CONCLUSIONS: Only patients who require catecholamines for tachycardia induction before ablation need catecholamines for control of the success of the ablation of AVNRT.

Comparison of two regimens of beta-adrenergics in acute asthma.

BACKGROUND AND METHODS: Inhaled adrenergics and steroids are the main agents used in acute asthma. Dosing recommendations for adrenergics, while generally becoming more aggressive, lack prospective validation. A double blind, randomized trial of two regimens of nebulized metaproterenol was conducted in patients presenting to an Emergency Department with an acute asthma exacerbation. Asthmatics age 16-55, with no other cardio-pulmonary disease, presenting with peak expiratory flow rate (PEFR) < 30% of predicted and greater than 80 L/m were enrolled. All patients received 125 mg of methylprednisolone and theophylline, if needed, to reach therapeutic levels. The experimental group received 0.3 cc metaproterenol in 2.5 cc of saline at times 0, 20", 40", 1', 2', 3', 4', 5', 6', and 7'. The control group received metaproterenol at times 0, 1 hr, and hours 3, 5, and 7. Placebo was given to control group patients at 20", 40", 2', 4', and 6'. PEFR and vital signs were measured 10 min after each treatment. Study end points included discharge upon reaching set criteria or admission if patients were not discharged following the hour 7 treatment. RESULTS: Seventy one patients were enrolled, 40 in experimental group and 31 in the control group. The group characteristics did not differ at entry in any significant way, and the groups began with mean expected PEFR of 23.4% and 24.5%, respectively. There were no significant differences at any point in PEFR outcomes, time to discharge, or admission rate. The experimental group showed a greater increase in pulse rate and a reduced diastolic blood pressure at 20, 40 and 60 min. The experimental group had a 12- and 8-fold increase in the risk of a pulse rate > 140 at 40 and 60 min, respectively. This group also had two moderate complications, both near the 60-minute mark. These were an induction of atrial fibrillation in one patient and ischemic electrocardiographic changes in another. CONCLUSION: Three treatments in the first hour, and hourly thereafter showed no benefit over treatments initially, at one hour, and every other hour in acute, moderate, or severe exacerbation of asthma. Side effects were markedly increased in the control group. Such dosing should not be recommended as routine therapy.

Tolerability and in vivo performance of a novel freon-free metered dose inhaler for a fixed combinational product of reproterol and disodium cromoglycate.

The present study was conducted to describe and compare the in vivo performance (systemic exposure), clinical and laboratory safety of a fixed combinational product of inhaled reproterol (CAS 54063-54-6) plus disodium cromoglycate (DSCG; CAS 15826-37-6) using a novel freon (CFC)-free metered dose inhaler (MDI), which uses 1,1,1,2,3,3,3-heptafluoropropane (HFA-227; CAS 431-89-0) as propellant and polyoxyethylene glyceryl trioleate (Tagat TO; CAS 68958-64-5) as surfactant relative to the conventional freon-driven MDI Allergospasmin in healthy male and female volunteers. Twenty-four young male and female healthy subjects were randomly allocated in gender-balanced fashion to 4 parallel treatment groups with single and repeated dosing of either reproterol + DSCG by HFA- or CFC-MDI (each time N = 8) or placebo by HFA- or CFC-MDI (each time N = 4) using matched placebo devices thus allowing a double-blind (with regard to placebo) approach. Treatments consisted of a single morning dose of 2 actuations followed 4 days later by a 1 week treatment course of 2 actuations four times daily. Subjects were investigated extensively in terms of blood pressure, pulse rate, electrocardiography, spirometry, respiratory rate, body temperature, laboratory safety (haematology, clinical chemistry, urinalysis) and clinical well-being. There were no treatment, compound or device related effects for any of the tolerability and safety end points. The treatments were well tolerated. In particular, there was no irritative cough or any sign of broncho-irritation on application. Adverse events were reported in a total of 9 subjects: 3/8, 4/8, 0/4 and 2/4 subjects treated with reproterol + DSCG by HFA-MDI, reproterol + DSCG by CFC-MDI, placebo by HFA-MDI and placebo by CFC-MDI, respectively. Of these, 6 events in 6 subjects receiving the active treatments were considered probably or definitely related to the test drug administration (i.e. adverse drug reactions): after reproterol + DSCG one subject in each treatment group (HFA-MDI and CFC-MDI) complained of an unpleasant bitter taste immediately after application; one further subject in each group complained of headache. Under treatment with reproterol + DSCG by CFC-MDI one male subject complained of mild transient nausea with onset on day 5. Under treatment with reproterol + DSCG by HFA-MDI one female subject complained of mild dizziness and mildly disturbed (blurred) vision with onset on day 1. All adverse events occurred only transitory and required no treatment. Systemic exposure, evaluated by the plasma concentrations of DSCG at 1 h after application, was slightly higher with the HFA-MDI compared to the CFC-MDI. It is concluded that the safety, tolerability and in vivo performance of the newly developed freon-free MDI is at least as well tolerable as the already marketed freon-driven conventional formulation.

Prospective, randomized trial of epinephrine, metaproterenol, and both in the prehospital treatment of asthma in the adult patient.

STUDY OBJECTIVE: To compare the effectiveness and incidence of adverse reactions with three treatment regimens for asthma in adults in the prehospital setting. DESIGN: Prospective, randomized clinical study. SETTING: Inner-city emergency medical service system providing basic and advanced life support and transport to 14 urban area hospital emergency departments. PARTICIPANTS: One hundred fifty-four adult asthmatic patients, 18 to 50 years old, who presented to paramedics with shortness of breath and wheezing. RESULTS: Eligible patients were randomly assigned by the base station physician to one of three treatment groups: subcutaneous epinephrine, nebulized metaproterenol, or subcutaneous epinephrine and nebulized metaproterenol. Peak expiratory flow rate (PEFR), blood pressure, heart rate, and respiratory rate were measured before and after treatment in each patient. During a 9-month period (October 1992 through June 1993), 154 patients were enrolled in the study; 53 (34%) received epinephrine, 49 (32%) received metaproterenol, and 52 (34%) received both. There were no significant differences in patient demographics, initial vital signs, or pretreatment PEFR among the three groups. The mean difference between pretreatment and posttreatment PEFR was 73 L/min and did not significantly differ among the treatment groups. Significant changes in vital signs were seen in no treatment group. CONCLUSION: Nebulized metaproterenol is as effective as subcutaneous epinephrine in the prehospital treatment of adult patients with acute asthma. The combination of these two treatments offered no additional clinical benefit in the patients we studied.

Efficacy and safety of a rapid-sequence metaproterenol protocol in the treatment of acute adult asthma.

A 6-month prospective study was performed to examine the efficacy and safety of a rapid-sequence nebulized metaproterenol regimen for the treatment of acute asthma in adults. Patients 18 years of age or older who were not pregnant and who had not received beta 2-agonist therapy were identified and started on a rapid-sequence metaproterenol regimen (15 mg) by the triage nurse. Pretreatment and posttreatment peak flow, respiratory rate, pulse rate, and blood pressure were documented. Patients also gave a pretreatment and posttreatment rating of the clinical severity of their attack using a 1-to-10 visual analogue scale. Fifty patients were entered into the study, with an average age of 38 years (range, 19 to 87 years). Data were analyzed using the Wilcoxon matched-pairs signed rank test. Patients showed statistically significant increases in peak flow (193 to 328 L/min, P < .00001) and systolic blood pressure (136 to 143 mm Hg, P < .0054). Statistically significant decreases were shown for respiratory rate (25 to 22 beats/min, P < .0001) and clinical severity (6.2 to 3.2, P < .00001). Thirty-three patients (71%) who completed the protocol experienced an increase in pulse rate. Ten (21%) had a pulse rate increase of more than 30 beats/min. Two (4.2%) had pulse rate increases of more than 40 beats/min. Four patients were removed after one or two nebulizers because of severe side effects. One patient's pulse rate increased to more than 200 beats/min. Although effective in reversing bronchospasm, the side effects of metaproterenol when used in rapid sequence are of major concern.

Metaproterenol (Alupent) metered dose inhaler in children 5-12 years of age.

This multiclinic study was performed to evaluate the safety and efficacy of metaproterenol sulfate (Alupent) metered dose inhaler in children with asthma ages 5 to 12 years. A total of 268 children completed this study according to the protocol, having received either metaproterenol or placebo for 30 consecutive days. Full spirometric testing was done pre- and postdose on Days 1 and 30 for a total duration of 6 hours on each day. The results showed that metaproterenol was consistently superior to placebo in all pulmonary function parameters measured on Days 1 and 30. This difference was statistically significant for peak values and areas under the curves for both FEV1 and FEF25-75%. There were no significant side effects noted. We conclude that metaproterenol metered dose inhaler is safe and effective in the treatment of asthma in children ages 5 to 12 years.

Dose-response relationship of inhaled metaproterenol sulfate in preschool children with mild asthma.

The dose-response relationship of single doses of nebulized metaproterenol sulfate 5% inhalant solution was evaluated by placebo-controlled, parallel-group study of 30 children, aged 3 to 6 years old, with stable asthma. Total respiratory resistance, the primary variable used to assess response, was measured by the forced oscillation method for a period of 6 hours from the start of inhalation. When comparisons were made between metaproterenol sulfate and saline, only 0.01 and 0.02 mL/kg showed significant bronchodilation (P less than .05) in percent change from baseline and area under the curve. However, no significant differences were seen between these doses. Moreover, the effect was sustained for 3 hours with both higher doses. Minimal side effects were observed. Metaproterenol sulfate 5% inhalant solution at a dose of 0.01 mL/kg seems to be optimal to elicit significant and sustained bronchodilatory response in preschool children with mild asthma.

Frequency of inhaled metaproterenol in the treatment of acute asthma exacerbation.

Acute asthma exacerbations are common complaints in patients who present to the emergency department. A prospective, double-blinded study was designed to evaluate how frequency of dosing of an inhaled beta-agonist, metaproterenol (Alupent inhalation solution) would affect patient response, length of stay in the ED, and admission rates. Forty-one patients initially received a 0.3-mL dose of nebulized metaproterenol followed by two additional doses of either metaproterenol or saline every 20 minutes. While there was no difference in response (forced expiratory volume in one second) in patients at 30 minutes after their arrival, there was an improved response in the metaproterenol group at 60 and 120 minutes. The length of stay in the ED was approximately the same for both groups. There was no significant difference in admission rates. No increase in undesirable side effects (eg, nausea, tremor, palpitations) was seen in the metaproterenol-treated group. Frequent dosing of metaproterenol is useful in asthmatics having acute exacerbations and leads to rapid improvement without an increase in toxicity.

An exaggerated response to beta-adrenergics.

Beta-adrenergics are used frequently in the management of asthma. Tremor has been found to be a limiting side effect with the oral or the inhaled forms. We describe one child who developed gross tremors necessitating an extensive neurologic evaluation to eliminate any other cause. With the results of a normal work-up and the reappearance of tremor when challenged again, the diagnosis of increased sensitivity to the tremorogenic effect of beta-adrenergics was made.

Hypokalemia induced by inhaled bronchodilators.

Since parenteral beta 2-adrenergic stimulation can induce hypokalemia, we postulated that administration of beta 2 adrenoreceptor agonists by inhalation could induce the same. We administered the usual clinical doses of three commonly used bronchodilators to each of six subjects receiving assisted mechanical ventilation in line with the ventilator: two beta 2-adrenoreceptor agonists, metaproterenol, 5 percent solution, and isoetharine, 1 percent solution; and the anticholinergic agent atropine as a control. Each bronchodilator was nebulized over 10 to 15 minutes in random order, four hours apart, and given to every subject. Plasma potassium was measured at five-minute intervals and arterial blood gases at 15-minute intervals, for a total of 50 minutes after administration of each bronchodilator. Following administration of each drug, plasma potassium showed an average decline. The mean decline in plasma potassium from baseline was statistically significant for metaproterenol (p = 0.04) and atropine (p = 0.001) but not for isoetharine (p = 0.09). Although there were no statistically significant differences among the declines in plasma potassium induced by the three drugs, metaproterenol caused the greatest decline (-0.6 mEq/L).

Dose-related effects of nebulized metaproterenol in asthmatic children.

The dose-related effects of inhaled 5% metaproterenol solution in asthmatic children between the ages of six and 12 years with acute bronchospasm were evaluated. Tests included FEV1.0, FEF25-75, and PEFR. For entry into the study, subjects were required to have an FEV1.0 or an FEF25-75 less than 80% of the child's predicted normal value based on height and race. Sixty children were randomly assigned in double-blind fashion to receive one of four different doses of 5% metaproterenol inhalant solution: 0.0 ml (placebo), 0.1 ml, 0.2 ml, or 0.3 ml. Drug efficacy was assessed by spirometry using a DeVilbiss Surveyor I spirometer. Spirometry was performed prior to inhalation of the test dose (baseline) and four times after inhalation: immediately after and 15, 30, and 60 minutes after inhalation. Patients in the three treated groups had significantly higher peak post-dose FEV1.0 and FEF25-75 than the placebo group but were not significantly different from one another. There was a significant relationship between dose and incidence of side effects. These results suggest that 0.1 ml (5 mg) of nebulized metaproterenol may provide as much bronchodilatation as higher doses with fewer side effects.