Effects of Ipratropium Bromide Nebulizer Solution with and without Preservatives in the Treatment of Acute and Stable Asthma* David H. Bryant, M.D., F.G.G.R;

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Peter Rogers, B. SCI

In a recent study, it was suggested that the preservatives in ipratropium bromide nebulizer solution may cause a paradoxic bronchoconstrictor response in 20 percent or more of patients with stable asthma. The frequency of this response in patients with acute asthma is unlmown. The aim of this study was to examine the acute effects of the usual dose of nebulized ipratropium bromide (0.25 mg) in patients with either stable or acute asthma using formulations with and without added preservatives. Twenty-five patients with stable asthma and 25 patients with acute asthma were studied. Each subject was given preservative-containing ipratropium bromide, preservative-Cree ipratropium bromide, pH 7 preservative-free ipratropium bromide, and saline solution in random order using a double-blind crossover technique with at least 4 h between drug administrations. Very frequent measurements of FEVI were made for 30 min after each drug administration and then 5 mg of a1buterol was nebulized and the FEVI was measured again after another 30 min. Changes in FEVI were expressed as

a percentage of the predicted FEVI' Paradoxic bronchoconstriction to ipratropium was detected in only one patient with acute asthma (12 percent fall in FEVI ) but in DOne of the patients with stable asthma. A 6 percent fall in FEVI change occurred with the saline solution in this subject suggesting that the response may have been a nonspecmc one due to increased bronchial responsiveness. The mean response (± 1 SD) to a1buterol plus either preservativecontaining ipratropium, preservative-free ipratropium, or pH7 preservative-free ipratropium was significantly greater (pO.05) between the mean ( ± 1 SD) baseline FEV. value prior to each of the tests of the patients with stable (1.79±O.52 L, 1.80±O.55 L, 1.81±O.52 L, 1.78±O.53 L) or acute asthma (1.24 ± 0.47 L, 1.26 ± 0.46 L, 1.25 ± 0.44 L, 1.22±O.43 L). Similarly, there was no significant difference among the age, sex, and atopic status of the two groups of patients although those with acute asthma did have a greater responsiveness to histamine (pO.05). The subjects' FEV. responses are expressed as actual values in Table 2. There was no significant difference in either subject group between the responses to the different ipratropium solutions or to albuterol after ipratropium (p>0.05), although the mean FEV. response to a1buterol after saline solution was signifiCHEST I 102 I 3 I SEPTEMBER, 1992

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FIGURE 1. FEV. changes (± SE) in patients with acute asthma. Treatment A = preservative-free ipratropium bromide; treatment B = ipratropium bromide with preservative; treatment C = pH 7 preservative-free ipratropium bromide.

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FIGURE 2. FEV. changes (± SE) in patients with stable asthma. Treatment A = preservative-free ipratropium bromide; treatment B = ipratropium bromide with preservative; treatment C = pH 7 preservative-free ipratropium bromide.

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