Isoetharine versus albuterol for acute asthma: greater immediate effect, but more side effects.

PURPOSE: To compare the magnitudes of the immediate effects of the nebulized beta-agonists isoetharine and albuterol in the treatment of acute severe asthma. PATIENTS AND METHODS: Fifty-one adults presenting with severe asthma exacerbations (forced expiratory volumes in the first second of exhalation [FEV1] <40% of predicted) to the emergency department were randomized (double-blind) to receive hourly inhaled nebulization treatment with either isoetharine (5 mg) or albuterol (2.5 mg). The FEV1 was measured immediately before and after each nebulized treatment. Any side effects were recorded. RESULTS: Immediately after the first nebulized treatment, the isoetharine group improved its mean FEV1 (+/-SEM) by a significantly greater amount than did the albuterol group: 60% +/- 11% versus 39% +/- 5%, respectively (P <0.05). One hour later the mean FEV1 were equivalent. This pattern repeated itself after the second hourly treatment. The two groups did not differ in any outcome parameters (FEV1 at discharge, number of nebulized treatments required, the number of inpatient admissions, number of clinical relapses after discharge). More patients treated with isoetharine had side effects (36% versus 4% for albuterol, P <0.01), 1 of whom required discontinuation from the study. CONCLUSIONS: Both medications were equally effective in alleviating bronchospasm. The immediate effect of isoetharine was significantly greater, but equalized that of albuterol within an hour after treatment. There were more side effects with isoetharine.

Contribution of airway hyperresponsiveness to lower airway obstruction after extracorporeal membrane oxygenation for meconium aspiration syndrome.

OBJECTIVE: To determine whether airway hyperresponsiveness contributes to the development of lower airway obstruction in infants recovering from severe meconium aspiration syndrome treated with extracorporeal membrane oxygenation (ECMO). DESIGN: Prospective comparison study of the response to bronchodilator during the acute and convalescent phase of severe meconium aspiration. SETTING: Pediatric/neonatal intensive care unit in a tertiary care hospital. PATIENTS: Seven neonates with severe meconium aspiration syndrome that was refractory to conventional mechanical ventilation, requiring ECMO treatment. INTERVENTIONS: Evaluation of the effect of bronchodilator treatment on the airway function at a postnatal age of 14 +/- 2.7 (SEM) days, after the patients had been off ECMO for 4.6 +/- 1.4 days, and comparison with the response the same patients had shown at a postnatal age of 2.7 +/- 0.6 days, when they had been on ECMO for 1.3 +/- 0.6 days. Lung mechanics and lower airway function were measured and compared before and after administration of aerosolized isoetharine early in the course of ECMO and again several days after ECMO. Maximum expiratory flow-volume curves produced by the deflation flow-volume curve technique were used for evaluating the lower airway function, and partial passive flow-volume curves were used for measuring respiratory system compliance and resistance. MEASUREMENTS AND MAIN RESULTS: During the first test, isoetharine produced a mild increase in maximum expiratory flows at 25% (MEF25) of forced vital capacity (FVC) (48 +/- 27% compared with baseline values), without significant change in the MEF25 to FVC ratio. During the second test approximately 2 wks later (post-ECMO), isoetharine increased MEF25 by 123 +/- 29% and increased the MEF25/FVC by 40 +/- 13% compared with baseline values. The percent change in both indices was significantly higher during the second test (p < .05) than in the first test. CONCLUSIONS: Airway obstruction in infants recovering from severe meconium aspiration syndrome is partially reversible with aerosolized isoetharine, indicating that airway hyperresponsiveness contributes to the pathogenesis of airway obstruction.

Pulmonary dysfunction after primary closure of an abdominal wall defect and its improvement with bronchodilators.

To determine the extent of pulmonary dysfunction following primary closure of an abdominal wall defect, we obtained pulmonary function tests (PFT) in 11 newborn infants with gastroschisis and 6 with large omphaloceles admitted to a newborn ICU in a children's hospital. Patients were 1 to 30 days of age at the time of the PFT; all required endotracheal intubation and mechanical ventilation for operative procedures or for postoperative ventilatory support. Full-term infants (n = 21) undergoing minor surgical procedures provided comparative measurements. Flow-volume curves were obtained with manual inflation of the lungs followed by forced deflation using negative pressure, or by passive expiration, under sedation and pharmacologic paralysis. Deflation flow-volume curves gave measurements of forced vital capacity (FVC) and maximal expiratory flow at 25% of vital capacity from residual volume (MEF25). Modified passive mechanics technique gave passive expiratory curves that provided measurements of respiratory system compliance (Crs) and resistance (Rrs). Tests were done: within 48 h (period A), 3-7 days (period B), and 8-30 days after surgical repair (period C). Pulmonary function testing after nebulized 0.1% isoetharine (a bronchodilator), to test for bronchial reactivity, began midway during the study period in 15 patients. Preoperative and postoperative tests were obtained in 5 patients. Closure of an abdominal wall defect decreased FVC, Crs, and MEF25 by up to 50% of normal, reference values after surgery (P less than 0.05). FVC and MEF25 approached values of normal infants by 4 weeks, whereas Crs remained 50% lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased duration of emergency department treatment of chronic obstructive pulmonary disease exacerbations with the addition of ipratropium bromide to beta-agonist therapy.

STUDY OBJECTIVES: To determine the benefit of the addition of ipratropium bromide to beta-agonist therapy of acute exacerbations of chronic obstructive pulmonary disease. DESIGN: The trial was randomized and double blinded. SETTING: The study was conducted in the emergency department of Parkland Memorial Hospital, a busy, inner-city, county hospital. INTERVENTIONS: Patients were treated in the medicine emergency department with either the standard regimen of nebulized isoetharine, 0.5 mL of a 1% solution (5.0 mg) diluted to 2.0 mL with normal saline every hour (control group) or with the same regimen plus ipratropium bromide, 54 micrograms (three puffs) after the first isoetharine treatment and 36 micrograms (two puffs) after the second and fourth (experimental group). A placebo metered-dose inhaler used in the same manner as the ipratropium blinded the study to both the patients and medical personnel. MEASUREMENTS AND MAIN RESULTS: The group treated with the addition of ipratropium (30) was discharged from the ED an average of 91 minutes (P less than .05) sooner than the control group (25) and required on the average one less isoetharine treatment (P less than .05). The pulmonary functions tested, forced expiratory volume in the first second, and the forced vital capacity were the same in the two groups initially and on discharge, as identical discharge criteria were used in each group. CONCLUSION: The addition of ipratropium to standard beta-agonist treatment of chronic obstructive pulmonary disease exacerbations shortens the duration of treatment required in the ED.

A randomized, controlled comparison of isoetharine and albuterol in the treatment of acute asthma.

STUDY OBJECTIVE: To determine whether treatment of acute asthma with repeated doses of nebulized albuterol leads to greater bronchodilation and lower hospital admission rate than treatment with nebulized isoetharine. DESIGN: Randomized, double-blinded, controlled trial of albuterol and isoetharine. TYPE OF PARTICIPANTS: Patients between 18 and 50 years old presenting with acute asthma. Patients were excluded if they had a history of sensitivity to the study drugs, had congestive heart failure or chronic-obstructive pulmonary disease, or were unable to perform spirometry. One hundred three patients were entered into the study. INTERVENTIONS: All patients received oxygen and methylprednisolone in addition to administration of either isoetharine or albuterol. The nebulized aerosol was given at hourly intervals for a total of three doses. MEASUREMENTS AND MAIN RESULTS: Spirometry was performed before treatment and again at 90 and 180 minutes. Initial forced expiratory volume at one minute (FEV1) was 38.1% of predicted normal for the albuterol group and 36.0% of predicted normal for the isoetharine group. At 180 minutes, FEV1 was 55.6% of predicted normal for the albuterol group and 57.1% of predicted for the isoetharine group (NS). Twenty-eight percent of the albuterol group required admission compared with 26% of the isoetharine group (NS). There was no difference in occurrence of side effects between the two groups. CONCLUSION: Repeated doses of albuterol do not lead to a greater improvement in pulmonary function or a lower hospital admission rate than treatment with isoetharine.

A controlled trial of nebulized isoetharine in the prehospital treatment of acute asthma.

Acute asthma is a potentially life-threatening disorder, recognizable to the prehospital care provider. While therapies are available to the prehospital care provider for treating acute asthma, no previous controlled studies have been performed demonstrating the treatment in the field is efficacious and safe. The authors conducted a controlled trial of the prehospital use of nebulized isoetharine in an urban emergency medical services system. Fifty-two patients with acute asthma were studied. Patients were initially evaluated with a peak flow meter. Half of the patients received isoetharine, while the control group received basic life support only. There was no difference in baseline values. Peak expiratory flow increased from 138 L/min to 148 L/min in the control group, while it increased from 149 L/min to 218 L/min in the treatment group (P less than .001). The authors conclude that paramedic treatment of acute asthma with nebulized isoetharine is effective in improving pulmonary function and clinical status during transport.

Combination of atropine and isoetharine aerosol therapy in pediatric acute asthma.

Seventeen hospitalized children with acute asthma, ages 7 to 15 years, were studied to determine the efficacy of simultaneous administration of atropine sulfate and isoetharine. Combination therapy was superior in 11/17 (65%) patients while isoetharine alone was superior in 4/17 (23%) patients (P = .037). We conclude that simultaneous administration of combination therapy is safe and beneficial in some children with acute asthma.

Longitudinal response of pulmonary function to bronchodilators in cystic fibrosis.

Previous studies have found that between 0 and 95% of patients with cystic fibrosis (CF) have a significant response to bronchodilators. These studies have been limited by small numbers and the measurement of response at one point in time. We analyzed the response to bronchodilators of patients with CF in a longitudinal and cross-sectional manner using pulmonary function data from 1980 to 1988. Overall, the proportion of patients with a positive response to bronchodilators was relatively large but not consistent over time. Of 573 tests in 127 persons, a positive response occurred in 68 tests of 51 patients. A negative response occurred in 19 tests of 17 patients. Only nine patients had a positive response in more than one third of their tests. The cross-sectional analysis showed variability similar to previous cross-sectional studies. Although a large proportion of patients with CF had a response to bronchodilators, the response was not consistent and may have been related to the number of tests performed. Continued longitudinal testing is necessary for valid decisions for bronchodilator use and for documenting the length, variability, and clinical significance of these responses.

Hypomania related to phenelzine and isoetharine interaction in one patient.

A case is reported of a man with apparent unipolar depression that was responsive to treatment with phenelzine who became hypomanic when isoetharine was added to treat his chronic obstructive pulmonary disease. The role of beta-adrenergic receptors in affective illness is reviewed in light of this case.

Effect of a beta-agonist nebulization on lung function in neonates with increased pulmonary resistance.

Pulmonary resistance is elevated early in preterm infants who later develop chronic lung disease. This early increase in pulmonary resistance may play a role in the development of severe bronchopulmonary dysplasia (BPD). A beta-2-agonist (isoetharine HCl) was used as an aerosol in 13 preterm infants with elevated pulmonary resistance. Their birthweight ranged from 880 to 1630 g, their gestational age from 27 to 34 weeks, and their post natal age from 3 to 18 days. All infants had required mechanical ventilation for respiratory distress syndrome and therefore were at risk to develop BPD. Pulmonary mechanics were measured before and 30 minutes after aerosol treatment, determining inspiratory and expiratory flow with a pneumotachometer and esophageal pressure through a water-filled feeding tube. The treatment was well tolerated with no significant changes in blood pressure, heart rate, or respiratory rate. Pulmonary resistance decreased significantly from 130 +/- 35 cm H2O/L/sec to 89 +/- 24 cm H2O/L/sec after the treatment. Dynamic lung compliance increased in 11 of the 13 infants. It is concluded that beta-2-agonist nebulization is effective in reducing the early increase in pulmonary resistance that occurs in preterm infants who are at risk of developing BPD. This effect may be due to relaxation of bronchial smooth muscle, to improved mucociliary transport, and to a reduction in peribronchial edema.

A study of isoetharine mesylate in patients with chronic bronchial asthma.

We performed a double-blind, random crossover study to investigate the respiratory effects of a single dose isoetharine mesylate (IM), administered by a metered aerosol canister in 19 subjects with mild, stable asthma. In addition, we studied the influence of the dose (number of actuations) and the mode of administration (delay between actuations) on these respiratory effects. The protocol consisted of a screening day and four test days: (1) one inhalation IM (2) two inhalations IM (3) one inhalation placebo (P), and (4) two inhalations P. In addition, the first nine asthmatics paused one minute between inhalations whereas the last ten paused five minutes between inhalations. Lung function was assessed using maximal and partial expiratory flow volume curves. Measurements were taken prior to aerosol delivery and for six hours after aerosol. Significant differences between IM and P were seen for up to two hours. The maximum effect was observed at 15 minutes, corresponding to a 23% and 25% increase in FEV1 from baseline with one and two puffs, respectively (P less than .001). The differences between one and two actuations were, in general, not significant. No significant differences were observed between individuals who waited one versus five minutes between inhalations. We conclude that IM aerosol results in significant improvement compared with placebo for two hours. Differences between one and two inhalations and the interval between two inhalations did not, in general, lead to enhanced effectiveness of this drug in the group of asthmatics studied.

Effect of a treatment protocol on the efficiency of care of the adult acute asthmatic.

A treatment protocol for patients with acute bronchospasm was introduced to an adult emergency department in an attempt to decrease treatment time and potentially decrease need for admission. The charts of all patients seen in a control year (before any protocol was in place) and the first three years of the protocol were reviewed. All care was given by medical housestaff. The first year after the protocol was introduced showed no change in either admission rate or stay in the ED. During this time, however, the protocol was used only 33% of the time. In the following two years, the protocol was used 93% of the time, and the admission rate decreased from 36.4% to 23.3% (P less than .02). The length of stay for all patients seen fell from a mean of 3.6 hours to 2.8 hours (P less than .005). The length of stay for those discharged fell from an average of 4.3 hours to 3.6 hours (P less than .02). Among the patients admitted, there was also a less striking but similar decrease from 3.0 hours to 2.4 hours. An organized treatment protocol was effective in increasing the efficiency of care given by the housestaff. The routine use of the protocol was not immediate and required time for acceptance by the housestaff.

Comparison of metaproterenol, isoetharine and salbutamol in the relief of methacholine-induced bronchospasm in dogs.

We evaluated cardiovascular effects and effectiveness of isoetharine, metaproterenol and salbutamol, when administered intratracheally to relieve methacholine-induced bronchospasm in dogs anaesthetized with 50 per cent nitrous oxide, oxygen, halothane and mechanically ventilated. Methacholine 2 micrograms X kg-1 X hour-1 was administrated first followed by halothane (1 MAC) for 30 minutes (control), then metaproterenol, isoetharine or salbutamol. Metaproterenol (15 mg) significantly decreased transpulmonary pressure to 20.1 +/- 0.5 (SE) from 22.5 +/- 1.15 cmH2O (p less than 0.025) after three min and to 15 +/- 0.5 cmH2O (p less than 0.005) after 90 min. Isoetharine (2.5 mg) decreased transpulmonary pressure after five min to 22.1 +/- 1 from 24.5 +/- 1.5 cmH2O (p less than 0.05), and to 21.75 +/- 0.55 mmH2O after 90 min. Salbutamol 25 micrograms X kg-1 decreased transpulmonary pressure to 20.7 +/- 0.75 from 24.25 +/- 1.28 after three min and to 16 +/- .5 after 90 min. The peak effects on airway pressure occurred at 15 min for metaproterenol, 25 min for salbutamol and 20 min for isoetharine. Pulmonary vascular resistance was not significantly changed during halothane anaesthesia alone but decreased significantly after metaproterenol and isoetharine infusion. Heart rate increased ten per cent after metaproterenol, three per cent after isoetharine, and five per cent after salbutamol. No arrhythmias occurred in any group. Cardiac output increased significantly to 3.25 +/- 0.2 from 1.5 +/- 0.17 L X min-1 (p less than 0.025) after metaproterenol to 3.2 +/- .025 from 1.45 +/- .009 after salbutamol and was unchanged after isoetharine. Metaproterenol and salbutamol in the presence of 1 MAC halothane anaesthesia relieved methacholine-induced bronchospasm more rapidly than did isoetharine. The onset of effect was 3 +/- 0.05 min for metaproterenol and salbutamol and 5 +/- 0.01 min for isoetharine. The effect lasted 210 +/- 10.5 min for metaproterenol, 170 +/- 12.5 min for salbutamol and 90 +/- 4.75 min for isoetharine.

Anaphylaxis following psyllium ingestion.

Psyllium is a hydrophilic agent found in many bulk laxative preparations. We report the occurrence of an anaphylactic reaction in a patient after ingestion of a psyllium-containing laxative. IgE mediation of the reaction was suggested by a positive immediate skin test to psyllium, positive passive transfer skin test, lack of skin response during passive transfer with heat treated serum, and an elevated IgE (RAST) to psyllium seed.

A method for comparing the peak intensity and duration of action of aerosolized bronchodilators using bronchoprovocation with methacholine.

The effects of aerosolized metaproterenol (1.30 mg) and isoetharine (1.02 mg) on nonspecific airway responsiveness to inhaled methacholine were quantitated and compared in 6 asthmatic subjects for 4 h after dosing. Both metaproterenol and isoetharine demonstrated bronchodilatation and reduced airway responsiveness during the first hour. Isoetharine had lost its bronchodilator effects and its effects on airway responsiveness by 2.25 h. The effects of metaproterenol on airway responsiveness had decreased by half at 2.25 h, while its bronchodilator effect remained maximal. Metaproterenol had no effect on airway responsiveness by 4 h, despite persisting bronchodilatation. Thus, for metaproterenol, there is disparity between duration of bronchodilation and suppression of airway responsiveness. Because methacholine sensitivity is a measure of nonspecific airway responsiveness, which appears to correlate with the severity of asthma, this methodology may provide more relevant information for assessment of duration of effect and estimation of appropriate dosing intervals for maintenance therapy than do more traditional methods.