Our study has shown no advantage in giving salbu­tamol and ipratropium separately rather than together. Clinical convenience may therefore dictate that the drugs should be given together. However, our results also suggest that the addition of ipratropium to salbu­tamol provides no additional benefit over a single agent given alone. Combination salbutamol/ipratro- pium was not superior to either agent alone at one hour. When given second, ipratropium was not supe­rior to saline solution after combination. Similar conclusions were drawn from a study of eight nonacute asthmatic and bronchitic subjects. The change in PEFR which we found after saline solution is probably due to a continuing or “carry-over” effect of the salbutamol/ipratropium combination administered 60 minutes earlier, but we cannot exclude a direct effect of saline solution upon peak flow.

In contrast to an order effect of ipratropium, we found that salbutamol was equally effective whether given first or second in the sequence. There is an extensive literature supporting the use of salbutamol and other beta-agonists as the mainstay of bronchodi­lator therapy in the treatment of acute asthma, but the evidence in support of a role for ipratropium is scanty. viagra plus

Our study was limited to the initial period of treatment of the acute episode of asthma. Our data covered a period of two hours and the additional time required for two volumes of 4 ml to be nebulized, totalling a maximum of approximately 150 minutes. We were unable to draw conclusions as to the effect of drug combinations beyond this period. However, the initial period when patients present to an Emer­gency Department represents the opportunity for most effective treatment. The response to therapy during this initial period may be a predictor for the subsequent response of the patient to treatment. Such initial bronchodilator response is often used to determine whether patients are subsequently admitted to hospital.

At present, the evidence for the routine use of ipratropium in addition to a beta-adrenoceptor agonist such as salbutamol is not strong. With one exception, studies have been performed on relatively small num­bers of patients, and are not comparable to the very substantial body of evidence which supports the use of beta-agonists in acute asthma. In order to minimize the probability of type 2 errors when clinical studies are undertaken with small numbers of patients, it has been suggested that overview or meta-analysis of a number of studies should be performed. The authors of one report have combined their own data with that from some previous studies in this fashion. Their meta-analysis suggested an advantage from combined treatment. However, the deficiencies of meta-analysis are that data are aggregated which may not be directly comparable, since studies are performed in various centers and have different protocols for assessment and treatment. Because of such inherent difficulties with meta-analysis, any resulting conclusions are less robust than conclusions based upon data emanating from studies within single centers comprising large numbers of patients.
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From review of the literature and from the data presented here, we suggest that the case for the routine use of ipratropium in the treatment of acute asthma remains unproven. Further clinical studies are necessary before ipratropium can be considered to have an established place in treatment of acute asthma. Such studies should be performed upon patients with acute asthma rather than basing conclusions upon studies of patients with asthma provoked, for example, by the withholding of routine therapy or by histamine inhalation. Such clinical studies should preferably be undertaken upon large numbers of patients with acute asthma, and the analysis of the resulting data may be enhanced by incorporation of a placebo within the trial design.