Nebulized hypertonic-saline vs epinephrine for bronchiolitis: Proof of concept study of cumulative sum (CUSUM) analysis

• Published in: Indian pediatrics 2012-07, Vol.49 (7), p.543-547
• Main Authors: Gupta, Neeraj, Puliyel, Ashish, Manchanda, Ayush, Puliyel, Jacob
• Format: Article
• Language: English
• Subjects: Bronchiolitis - drug therapy; Bronchodilator Agents - administration & dosage; Data Interpretation, Statistical; Epinephrine - administration & dosage; Female; Humans; Infant; Infant, Newborn; Male; Maternal and Child Health; Medicine; Medicine & Public Health; Nebulizers and Vaporizers; Pediatric Surgery; Pediatrics; Prospective Studies; Research Paper; Saline Solution, Hypertonic - administration & dosage
• ISSN: 0019-6061; 0974-7559
• DOI: 10.1007/s13312-012-0122-5

Objective To apply cumulative sum (CUSUM) to monitor a drug trial of nebulized hypertonic-saline in bronchiolitis. To test if monitoring with CUSUM control lines is practical and useful as a prompt to stop the drug trial early, if the study drug performs significantly worse than the comparator drug. Design Prospective, open label, controlled trial using standard therapy (epinephrine) and study drug (hypertonic-saline) sequentially in two groups of patients. Setting Hospital offering tertiary-level pediatric care. Patients Children, 2 months to 2 years, with first episode of bronchiolitis, excluding those with cardiac disease, immunodeficiency and critical illness at presentation. Interventions Nebulized epinephrine in first half of the bronchiolitis season ( n = 35) and hypertonic saline subsequently ( n = 29). Continuous monitoring of response to hypertonic-saline using CUSUM control-charts developed with epinephrine-response data. Main outcome measures Clinical score, tachycardia and total duration of hospital stay. Results In the epinephrine group, the maximum CUSUM was +2.25 (SD 1.34) and minimum CUSUM was −2.26 (SD 1.34). CUSUM score with hypertonic-saline group stayed above the zero line throughout the study. There was no statistical difference in the post-treatment clinical score at 24 hours between the treatment groups {Mean (SD) 3.516 (2.816): 3.552 (2.686); 95% CI: −1.416 to + 1.356}, heart rate {Mean (SD) 136 (44): 137(12); 95% CI: −17.849 to +15.849) or duration of hospital stay (Mean (SD) 96.029 (111.41): 82.914 (65.940); 95% CI: −33.888 to +60.128}. Conclusions The software we developed allows for drawing of control lines to monitor study drug performance. Hypertonic-saline performed as well or better than nebulized epinephrine in bronchiolitis.