Asthma Inhalers - Researches of Intravenous and Inhaled Terbutaline in the Asthma Treatment

bronchoconstrictionFlow volume loops were performed during maximal forced expiration, using a dry wedge spirometer (Floop 1 TM pulmonary function studies system, Oldelft). These were obtained with the subject breathing air and again after quiet breathing of a gas mixture of 80 percent helium and 20 percent oxygen for three minutes. The indices measured on the flow volume loops were forced expired volume in one second (FEVj), forced vital capacity (FVC), peak expiratory flow rate (PEFR), maximal midexpiratory flow rate (MMFR), and maximal expiratory flow at 50 percent of the vital capacity (MEF50). Helium responsiveness was assessed as the percentage increase in MEF50 of the helium-oxygen flow volume loop compared with that of the corresponding one breathing air.

The effects of terbutaline on pulmonary blood flow were measured by a rebreathing method introduced by Cander and Forster and used more recently by Petrini and Hyde, and also by the single-breath method originated by Krogh and Linhard and further developed by Denison and coworkers. One potential advantage of the single-breath method in asthma is that it produces less effect on airway caliber resulting from the maneuver itself than does vigorous rebreathing, which often induces bronchoconstriction. Buy asthma inhalers online to prevent asthma appearance.

The single-breath and rebreathing estimates of effective pulmonary blood flow (Q8b, Qrb) and measurement of the evenness of ventilation were made using a gas mixture containing low concentrations of the insoluble gas argon (< 5 percent) and the soluble gas difluoromonochloromethane, Freon 22 (< 3 percent). The gas concentrations were monitored at the lips using a mass spectrometer (MGA 007, TC Centronics, Ltd) and permanent records obtained with an XY recorder (Bryans 2600 A3). The slope of the alveolar plateau (phase III), and gas dilution estimates of the accessible gas volume at total lung capacity (VA) were measured from the argon tracings obtained during the single-breath maneuver. In this, gas concentrations were recorded against expired volume measured by a water-filled spirometer (Go-dart NV), during expiration at a slow constant rate following a vital capacity inspiration of the gas mixture. The slope of the alveolar plateau was measured as the percentage change in argon concentration between 750 ml and 1,250 ml of expired volume. The VA was calculated as the product of the VC and the ratio of the inspired to the mean expired argon concentration (derived by dividing the planimetrically measured area under the argon trace by the VC to give a volume-weighted average of expired concentration).

In the rebreathing procedure, the subject inspired from a bag containing the gas mixture and then rebreathed from the bag at as rapid a rate as his airways obstruction would comfortably permit.

Effective pulmonary bloodThe initial bag volume was chosen using the patient’s FEVj and FVC so that the subject rebreathed a large proportion of his VC with a 1- to 3-sec cycle. Gas concentrations were measured at the lips and recorded against time. Effective pulmonary blood flow was measured from the divergence of the soluble and insoluble gas concentrations in the time before recirculation occurred. Typical records and the measurements and equations used are shown for the single-breath procedure in Figure 1, and for the rebreathing procedure in Figure 2.

These investigations were performed in the following order: (1) pulse and blood pressure measurement; (2) singlebreath argon-Freon 22 procedure, (3) flow volume loops breathing air, (4) flow volume loops after helium-oxygen, and (5) rebreathing argon-Freon 22 procedure. The rebreathing maneuver was performed last in the series because of the tendency for it to produce changes in the airway caliber. In normal subjects, single-breath and rebreathing measurements of effective pulmonary blood flow are reproducible within ±5 percent (SD). Normal values for sitting adults are 7 to 8 L/min.

Studies

The study was performed using a double-blind crossover randomized design. Preceding a test day, no bronchodilators were given by the inhaled route for at least six hours, or by the oral or parenteral routes for at least 12 hours. Terbutaline, 2.5 mg/ml, and placebo for inhalation, and terbutaline, 0.125 mg/ml, and placebo for IV injection, were prepared in identical containers and labeled by code number only. On the first day of the study, a four-stage dose response curve was constructed for either IV or inhaled terbutaline, and on the second day the alternate route was used. On each day, after basal investigations were performed at least twice, 15 minutes apart, to establish a stable baseline, 1 ml of a solution containing either terbutaline, 2.5 mg, or placebo was given via a Bird nebulizer. At the same time, either placebo solution or terbutaline, 0.125 mg, diluted in normal saline solution was infused slowly into an indwelling IV cannula over five minutes. Pulse, blood pressure, and flow volume loops breathing air were recorded immediately after drug administration and at five-minute intervals until a plateau in FEVj^ was obtained. When this occurred, a full set of investigations was performed and the next inhalation procedure and injection given. In this way, four equal increments of the drug were given, accruing to a total dose of 10 mg by inhalation or 0.5 mg IV. The plateau effect after each dose was usually seen after 15 to 20 minutes, the whole study on any day thus being completed in about two hours. The route of administration for the first day was randomly chosen and remained constant throughout that day. The active drug was given by the alternative route on the following day, provided that the baseline FEVX was within 10 percent of that on the first day. Responses were analyzed using the Student t test for paired values and the Mann-Whitney ranking test.

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Fig1 Figure 1. Single-breath record obtained from one subject. Gas concentrations recorded against expired volume. 1-sec time signal superimposed as sharp pulsatile deflection on argon trace. Slope of alveolar plateau calculated as percentage change in argon concentration between 750 and 1,250 ml expired. Effective pulmonary blood flow (Qsb) calculated using equation shown from vital capacity (VC), pulmonary tissue ( Vt) estimated from data of Sackner et al, volume expired up to point of measurement (VE), gas solubility coefficient (a), and linear measurements (a-e) made on records. Fig2 Figure 2. Rebreathing record from one subject Gas concentrations recorded against time. Effective pulmonary blood flow (Qrb) calculated using equation shown from volume of rebreathing bag (V^), pulmonary tissue volume (Vt), and gas solubility coefficient (a), and the linear measurements (a-e) made in records.