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

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Abstract

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.

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Authors and Affiliations

  1. Department of Pediatrics and Neonatology, St Stephen’s Hospital, Delhi, India

    Neeraj Gupta, Ayush Manchanda & Jacob Puliyel

  2. Tech Guru gonzoBuzz, Singapore, Singapore

    Ashish Puliyel

  3. Department of Pediatrics, St Stephen’s Hospital, Tis Hazari, Delhi, 110 054, India

    Neeraj Gupta

Authors
  1. Neeraj Gupta
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  2. Ashish Puliyel
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  3. Ayush Manchanda
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  4. Jacob Puliyel
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Correspondence to Neeraj Gupta.

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Gupta, N., Puliyel, A., Manchanda, A. et al. Nebulized hypertonic-saline vs epinephrine for bronchiolitis: Proof of concept study of cumulative sum (CUSUM) analysis. Indian Pediatr 49, 543–547 (2012). https://doi.org/10.1007/s13312-012-0122-5

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  • DOI: https://doi.org/10.1007/s13312-012-0122-5

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