The Evidence for Intravenous Theophylline Levels between 10-20mg/L in Children Suffering an Acute Exacerbation of Asthma: A Systematic Review

Abstract

BackgroundIntravenous theophyllines are a second line treatment for children suffering an acute exacerbation of asthma. Various guidelines and formularies recommend aiming for serum theophylline levels between 10-20mg/l. This review aims to assess the evidence underpinning this recommendation.MethodsA systematic review comparing outcomes of children who achieved serum theophylline concentrations between 10-20mg/l with those who did not. Primary outcomes were time until resolution of symptoms, mortality and need for mechanical ventilation. Secondary outcomes were date until discharge criteria are met, actual discharge, adverse effects and FEV1.Data sourcesMEDLINE, CINAHL, CENTRAL and Web of Science. Search performed in October 2015.Eligibility criteriaInterventional or observational studies utilizing intravenous theophyllines for an acute exacerbation of asthma in children where serum theophylline levels and clinical outcomes were measured.Findings10 RCTs and 2 observational studies were included. Children with serum levels between 10-20mg/l did not have a reduction in duration of symptoms, length of hospital stay or need for mechanical ventilation or better spirometric results compared with levels <10mg/l. Levels above 20mg/l are not associated with higher rates of adverse effects. This study is limited due to heterogeneity in the way theophylline levels were reported and poor surveillance of adverse effects across studies.ConclusionDosing strategies aiming for levels between 10-20mg/l are not associated with better outcomes. Clinicians should rely on clinical outcomes and not serum levels when using intravenous theophyllines in children suffering an acute exacerbation of asthma.

Overview of systematic reviews of therapeutic ranges: methodologies and recommendations for practice

“…The remaining reviews extracted the mean ± standard deviation of drug level achieved across participants [8, 10, 16]. One review extracted the timing of drug measurement [11], and two reviews performed separate analyses depending on the type of assay used [13, 17].…”

Aminophylline Dosage In Asthma Exacerbations in Children: A Systematic Review

“…Few studies primarily investigate the optimum dosing strategies in children [ 18 ] Therefore, we used a systematic review technique which anticipates various study designs, similar to the methodology we recently used to examine the evidence around therapeutic ranges for aminophylline [ 17 , 19 ]. We decided a priori that the most relevant study type would be a comparison of randomised controlled trials (RCTs) comparing different dosing strategies and measuring clinically relevant outcomes, but we would also include RCTs evaluating the efficacy of intravenous theophyllines compared with placebo or other treatment, with subsequent analyses performed for each comparator drug, and observational studies.…”

“…The treatment of acute asthma in children should be guided by evidence of improvement of clinically relevant outcomes [ 15 , 16 ]. A recent systematic review found no evidence to support improved efficacy of aminophylline once the serum concentration increases above the lower threshold of 10mg/L, nor increased toxicity at levels above 20mg/l [ 17 ]. As the current therapeutic range is a poor guide to efficacy, an alternative dosing strategy may improve the optimum efficacy and safety profile of aminophylline.…”

Astim Alevlenmesi̇nde Kullanilan İlaçlar

“…Aminofilin dozu düzenlenmesinde yaş, ağırlık ve önceki serum konsantrasyonunun güvenilirliği bilinmemektedir ve önemli bireysel klirens farklılıkları vardır (55,56). Önerilen serum aminofilin konsantrasyonu 10-20 mg/L olsa da yeni yapılan sistematik bir review incelemede aminofilin serum konsantrasyonunun 10 mg/L' yi geçmesinin etkinlik artışında ya da 20 mg/l'yi geçtiğinde toksisite artışında bir katkı sağladığına dair kanıt olmadığı belirtilmiştir (57). Düzey takibi gerektiği de unutulmamalıdır.…”