Toshio Katsunuma1, Takao Fujisawa2, Takanobu Maekawa3, Kenichi Akashi4, Yukihiro Ohya5, Yuichi Adachi6, Koji Hashimoto7, Mihoko Mizuno8, Takanori Imai9, Mari S Oba10, Mayumi Sako11, Yasuo Ohashi12, Hidefumi Nakamura13. 1. Department of Pediatrics, Daisan Hospital, The Jikei University School of Medicine, Tokyo, Japan. Electronic address: tkatsunuma@jikei.ac.jp. 2. Allergy Center, Mie National Hospital, Mie, Japan. 3. Department of General Pediatrics and Interdisciplinary Medicine, National Center for Child Health and Development, Tokyo, Japan. 4. Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan. 5. Division of Allergy, Department of Medical Subspecialties, National Center for Child Health and Development, Tokyo, Japan. 6. Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan. 7. Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan. 8. Mihoko Mizuno, Department of Pediatrics, Social Medical Corporation Kojunkai Daido Hospital, Aichi, Japan. 9. Takanori Imai, Department of Pediatrics, The Showa University School of Medicine, Tokyo, Japan. 10. Department of Medical Statistics, Faculty of Medicine, Toho University, Tokyo, Japan. 11. Division for Clinical Trials, Department of Clinical Research, Center for Clinical Research and Development, National Center for Child Health and Development, Tokyo, Japan. 12. Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, Japan. 13. Department of Development Strategy, Center for Clinical Research and Development, National Center for Child Health and Development, Tokyo, Japan.
Abstract
BACKGROUND: Although the guidelines in most countries do not recommend continuous inhalation of l-isoproterenol to treat pediatric patients with acute severe exacerbation of asthma, lower dose of l-isoproterenol has been widely used in Japan. To determine whether the efficacy of low-dose l-isoproterenol was superior to that of salbutamol, we conducted a double-blind, randomized controlled trial. METHODS:Hospitalized patients aged 1-17 years were eligible if they had severe asthma exacerbation defined by the modified pulmonary index score (MPIS). Patients were randomly assigned (1:1) to receive inhalation of l-isoproterenol (10 μg/kg/h) or salbutamol (500 μg/kg/h) for 12 hours via a large-volume nebulizer with oxygen. The primary outcome was the change in MPIS from baseline to 3 hours after starting inhalation. Trial registration number UMIN000001991. RESULTS:From December 2009 to October 2013, 83 patients (42 in the l-isoproterenol group and 41 in the salbutamol group) were enrolled into the study. Of these, one patient in the l-isoproterenol group did not receive the study drug and was excluded from the analysis. Compared with salbutamol, l-isoproterenol reduced MPIS more rapidly. Mean (SD) changes in MPIS at 3 hours were -2.9 (2.5) in the l-isoproterenol group and -0.9 (2.3) in the salbutamol group (difference -2.0, 95% confidence interval -3.1 to -0.9; P < 0.001). Adverse events occurred in 1 (2%) and 11 (27%) patients in the l-isoproterenol and salbutamol groups, respectively (P = 0.003). Hypokalemia and tachycardia occurred only in the salbutamol group. CONCLUSIONS:Low-dose l-isoproterenol has a more rapid effect with fewer adverse events than salbutamol.
RCT Entities:
BACKGROUND: Although the guidelines in most countries do not recommend continuous inhalation of l-isoproterenol to treat pediatric patients with acute severe exacerbation of asthma, lower dose of l-isoproterenol has been widely used in Japan. To determine whether the efficacy of low-dose l-isoproterenol was superior to that of salbutamol, we conducted a double-blind, randomized controlled trial. METHODS: Hospitalized patients aged 1-17 years were eligible if they had severe asthma exacerbation defined by the modified pulmonary index score (MPIS). Patients were randomly assigned (1:1) to receive inhalation of l-isoproterenol (10 μg/kg/h) or salbutamol (500 μg/kg/h) for 12 hours via a large-volume nebulizer with oxygen. The primary outcome was the change in MPIS from baseline to 3 hours after starting inhalation. Trial registration number UMIN000001991. RESULTS: From December 2009 to October 2013, 83 patients (42 in the l-isoproterenol group and 41 in the salbutamol group) were enrolled into the study. Of these, one patient in the l-isoproterenol group did not receive the study drug and was excluded from the analysis. Compared with salbutamol, l-isoproterenol reduced MPIS more rapidly. Mean (SD) changes in MPIS at 3 hours were -2.9 (2.5) in the l-isoproterenol group and -0.9 (2.3) in the salbutamol group (difference -2.0, 95% confidence interval -3.1 to -0.9; P < 0.001). Adverse events occurred in 1 (2%) and 11 (27%) patients in the l-isoproterenol and salbutamol groups, respectively (P = 0.003). Hypokalemia and tachycardia occurred only in the salbutamol group. CONCLUSIONS: Low-dose l-isoproterenol has a more rapid effect with fewer adverse events than salbutamol.
Authors: Alexander G Mathioudakis; Michael Miligkos; Cristina Boccabella; Gioulinta S Alimani; Adnan Custovic; A Deschildre; Francine Monique Ducharme; Omer Kalayci; Clare Murray; Antonio Nieto Garcia; Wanda Phipatanakul; David Price; Aziz Sheikh; Ioana Octavia Agache; Leonard Bacharier; Apostolos Beloukas; Andrew Bentley; Matteo Bonini; Jose A Castro-Rodriguez; Giuseppe De Carlo; Timothy Craig; Zuzana Diamant; Wojciech Feleszko; Tim Felton; James E Gern; Jonathan Grigg; Gunilla Hedlin; Elham M Hossny; Despo Ierodiakonou; Tuomas Jartti; Alan Kaplan; Robert F Lemanske; Peter N Le Souëf; Mika J Mäkelä; Georgios A Mathioudakis; Paolo Matricardi; Marina Mitrogiorgou; Mario Morais-Almeida; Karthik Nagaraju; Effie Papageorgiou; Helena Pité; Paulo M C Pitrez; Petr Pohunek; Graham Roberts; Ioanna Tsiligianni; Stephen Turner; Susanne Vijverberg; Tonya A Winders; Gary Wk Wong; Paraskevi Xepapadaki; Heather J Zar; Nikolaos G Papadopoulos Journal: BMJ Open Date: 2021-07-02 Impact factor: 2.692