Continuous infusions of terbutaline in asthma - a review

After the safety issues raised by the Salmeterol Multicenter Asthma Research Trial, concerns persist about the safety of agents that cause prolonged β-adrenoceptor stimulation in asthmatic patients. We therefore decided to revisit and review the use of continuous subcutaneous infusions of terbutaline (CSIT)-a treatment often reserved for those with severe and refractory disease.

Original studies from the 1980s included 26 patients and showed that CSIT was well tolerated with predominately cutaneous side effects despite maintaining very high serum levels of terbutaline. CSIT led to improved outcomes in approximately 75% of patients which included rises in lowest daily peak expiratory flow rate (PEFR), diminution in diurnal variation, reduction in other medication requirements, and subjective opinion of symptoms. Almost all patients demonstrating an improvement had a wide variation in their pretreatment PEFRs. However, in a retrospective follow-up of 42 patients, the only outcome to be significantly improved by CSIT was that of mean hospital admissions (p = .031). CSIT is theorized to stimulate a discrete set of β-receptors not accessible by the inhaled route as further increases in Forced expiratory volume in one second (FEV(1)) occur with concurrent nebulized therapy.

Although some findings are encouraging, they are drawn from small observational studies done at a time when the standard management of asthma was quite different from today. No randomized controlled trials exist for the use of CSIT, which remains off-license for the treatment of asthma in the United Kingdom. Clearly, prospective well-powered studies are required to fully ascertain its potential benefits and safety profile-something that is unlikely to occur given that the use of CSIT remains low and appears to be declining.