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Sodium-containing versus sodium-trace preparations of IVIG for children with Kawasaki disease in the acute phase

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Abstract

Kawasaki disease (KD) is an acute systemic vasculitis that most commonly causes acquired cardiac disease in children in developed countries. The most highly recommended treatment for KD is 2 g/kg intravenous immunoglobulin (IVIG). There are two types of IVIG, sodium-containing (high-Na) and sodium-trace (low-Na) preparations. However, few studies have compared the effects of these two preparations for superiority. The purpose of this study was to compare outcomes between high and low-Na IVIG preparations in KD children using a national inpatient database in Japan. We used the Diagnostic Procedure Combination database to identify KD patients treated with IVIG between 2010 and 2017. We identified those receiving high and low-Na preparations of IVIG as an initial treatment. Outcomes included proportion of coronary artery abnormalities (CAA), IVIG resistance, adverse effects, length of stay, and medical cost. Propensity score–matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results. We identified 42,345 patients with KD. There were significant differences in proportions of CAA (2.8% vs. 3.2%; p = 0.031) and IVIG resistance (17% vs. 18%, p = 0.001) between the two groups. However, there were no significant differences in length of stay or medical cost. The instrumental variable analysis confirmed the same results as the propensity score analysis.

Conclusion: The present study suggests that high-Na IVIG is potentially effective for reducing the proportion of CAA in KD patients. Prospective studies are warranted to confirm the effectiveness observed in this study.

What is Known:

• For treatments of Kawasaki Disease in acute phase, intravenous immunoglobulin have been the most recommended to reduce fever early and prevent complications of coronary artery abnormalities. There are two types of IVIG preparations, sodium-containing IVIG and sodium-trace IVIG. However, few studies have performed comparisons to determine which preparation of IVIG is superior.

What is New:

• The present findings suggest that high-Na IVIG is associated with reductions in the proportions of CAAs and IVIG resistance in KD patients.

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Abbreviations

ADL:

Activities of daily living

ASD:

Absolute standardized difference

CAA:

Coronary artery abnormalities

CI:

Confidence interval

IQR:

Interquartile range

IVIG:

Intravenous immunoglobulin

KD:

Kawasaki disease

SD:

Standard deviation

USD:

US dollar

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Availability of data and material

Data cannot be made publicly available for ethical reasons as the data are patient data. The data are available to interested researchers upon request to the corresponding author, pending ethical approval.

Code availability

This study was analyzed using the standard packages of the Stata software version 16.1 (StataCorp LP, College Station, TX, USA).

Funding

This work was supported by grants from the Ministry of Health, Labour and Welfare, Japan (19AA2007 and 20AA2005) and the Ministry of Education, Culture, Sports, Science and Technology, Japan (20H03907).

Author information

Authors and Affiliations

  1. Department of Pediatric Cardiology, Aichi Children’s Health and Medical Center, Aichi, Japan

    Takanori Suzuki

  2. Department of Pediatrics, Fujita Health University, Aichi, Japan

    Takanori Suzuki, Tetsushi Yoshikawa & Kazuyoshi Saito

  3. Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Nobuaki Michihata

  4. Department of Biostatistics & Bioinformatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Shotaro Aso

  5. Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan

    Hiroki Matsui & Hideo Yasunaga

  6. Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan

    Kiyohide Fushimi

Authors
  1. Takanori Suzuki
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  2. Nobuaki Michihata
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  3. Shotaro Aso
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  4. Tetsushi Yoshikawa
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  8. Hideo Yasunaga
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Contributions

TS and NM conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. SA, TY, and KS conceptualized and designed the study, and coordinated and critically reviewed the manuscript for important intellectual content. HM, KF, and HY designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Nobuaki Michihata.

Ethics declarations

Ethics approval, Consent to participate, Consent for publication

This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent was waived because all data were de-identified. This study was approved by the Institutional Review Board of The University of Tokyo (approval number: 3501-(3) (December 25, 2017)).

Conflict of interest

The authors declare no competing interests.

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Communicated by Peter de Winter

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Suzuki, T., Michihata, N., Aso, S. et al. Sodium-containing versus sodium-trace preparations of IVIG for children with Kawasaki disease in the acute phase. Eur J Pediatr 180, 3279–3286 (2021). https://doi.org/10.1007/s00431-021-04096-x

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  • DOI: https://doi.org/10.1007/s00431-021-04096-x

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