Comparison of intravenous terbutaline versus normal saline in pediatric patients on continuous high-dose nebulized albuterol for status asthmaticus. Randomised trial of intravenous salbutamol in early management of acute severe asthma in children.
To determine if the addition of intravenous terbutaline provides any clinical benefit to children with acute severe asthma already on continuous high-dose nebulized albuterol.
                We conducted a prospective, randomized, double blind, placebo-controlled trial on pediatric patients with acute severe asthma presenting to a large inner city tertiary children's emergency department. Consecutive patients between 2 and 17 years of age who failed acute asthma management and needed intensive care unit admission underwent informed consent and were enrolled into the study. Patients not requiring intubation were randomized to receive either intravenous terbutaline or intravenous normal saline while on continuous high-dose nebulized albuterol, ipratropium bromide, and systemic corticosteroids. Outcome measures included a clinical asthma severity score, hours on continuous nebulized albuterol, and duration of stay in the pediatric intensive care unit. In addition, electrocardiograms, electrolytes, lactic acid, and troponin I levels were obtained at routine intervals during the first 24 hours after admission. Patients who significantly worsened while enrolled in the study received intravenous aminophylline according to protocol.
                Forty-nine patients were enrolled in the study. Patients on terbutaline had a mean improvement in the clinical asthma severity score over the first 24 hours of 6.5 points compared with 4.8 points in the placebo group (P = 0.073). Patients on terbutaline spent 38.19 hours on continuous nebulized albuterol compared with their placebo counterparts who spent 51.93 hours (P = 0.25). The length of stay in the PICU was on average 12.95 hours longer for those patients in the placebo group as compared with the terbutaline group (P = 0.345). One patient was removed from the study for a significant cardiac dysrhythmia. This patient was in the terbutaline group and recovered without complications. Troponin I values at 12 hours and 24 hours were elevated in 3 patients each, all within the terbutaline group.
                No outcome measures demonstrated statistical significance. Outcome measures revealed a trend toward improvement in the terbutaline group. Before recommending routine use of intravenous terbutaline for acute severe asthma, further study to determine safety and efficacy is necessary. The mainstay of treatment for acute asthma in children is nebulised beta 2-adrenergic agents such as salbutamol, given with corticosteroids. However, penetration of the drug to the small airways is impeded by obstruction so intravenous salbutamol may be more effective. We assessed the use of intravenous salbutamol in the management of children with acute severe asthma in a double-blind randomised study.
                Children who presented to the Emergency Department of Westmead Hospital, Sydney, Australia with asthma were assessed with a clinical assessment scale, and those with severe acute asthma were given nebulised salbutamol at a dose of 2.5 mg (age < or = 2 years) or 5.0 mg (age > 2 years), made up to 4 mL with saline. Children who did not improve were eligible to enter phase one of the study. In this phase (0 h-2 h) treatment was by a standard protocol: nebulised salbutamol at the above dose: 4 L/min or 6 L/min continuous oxygen until oxygen saturation reached 93% in room air for at least 30 min; a bolus of intravenous hydrocortisone 5 mg/kg given over 3 min; and then 15 micrograms/kg intravenous salbutamol or saline, depending on randomised allocation. In phase two (2 h-24 h) the children were given nebulised salbutamol continuously then at 30 min, 1 h, 2 h, 3 h, and 4 h, according to need. All children were transferred to the ward once they were ready to start hourly nebulisation. All patients were followed up until discharge. The primary endpoints were recovery time (no longer requiring inhaled salbutamol) and persistent moderate to severe asthma 2 h after randomisation. Analyses were by intention-to-treat although no withdrawals occurred.
                The recovery time (time to cessation of nebulised salbutamol every 30 min) was 4 h in the 14 children allocated intravenous salbutamol compared with 11.5 h for the 15 children in the control group. 2 (14%) of the intravenous salbutamol group compared with 8 (53%) of the control group needed oxygen to maintain oxygen saturation at 93% room air. The intravenous salbutamol group were ready for discharge from the emergency department 9.7 h earlier than the control group. No clinically significant side-effects were found in either group.
                Addition of a 10 min infusion of salbutamol in the early treatment of children with acute severe asthma has the potential to curtail the clinical progression of asthma, reduce demand placed on hospital resources, and improve the quality of health care provided to the acutely sick child with asthma.
There is very limited evidence from one study (Browne 1997) to support the use of IV beta2-agonists in children with severe acute asthma with respect to shorter recovery time, and similarly there is limited evidence (again from one study Browne 1997) suggesting benefit with regard to pulmonary index scores; however this advantage needs to be considered carefully in relation to the increased side effects associated with IV beta2-agonists. We identified no significant benefits for adults with severe acute asthma. Until more, adequately powered, high quality clinical trials in this area are conducted it is not possible to form a robust evaluation of the addition of IV beta2-agonists in children or adults with severe acute asthma.