Twenty-four-hour urine NE level as a predictor of the therapeutic response to metoprolol in children with recurrent vasovagal syncope

  • Qingyu Kong
  • Xiaofei Yang
  • Zhifeng Cai
  • Yanyan Pan
  • Minmin Wang
  • Mengmeng Liu
  • Cuifen ZhaoEmail author
Original Article



Vasovagal syncope (VVS) is a heterogeneous disorder that creates challenges for treatment. Metoprolol is an important therapeutic option for children with VVS.


The study examined the predictive value of 24-h urine norepinephrine (NE) levels in the assessment of the therapeutic efficacy of metoprolol for recurrent VVS in children.


Thirty-eight children with recurrent VVS and 20 healthy children were enrolled in our study. Twenty-four-hour urine NE levels were measured by LC-MS-MS. VVS children were diagnosed by BHUTT and/or SNHUTT, and received metoprolol treatment for 3 months. Symptom scoring was utilized to evaluate the therapeutic effect. A ROC curve was used to investigate the predictive value of 24-h urine norepinephrine levels.


There exists significant correlation between 24-h urine NE levels and supine systolic and diastolic blood pressures. The 24-h urine NE levels of responders (40.75 ± 12.86 μg/24 h) were higher than those of nonresponders (21.48 ± 6.49 μg/24 h), and there was a significant difference between the two groups (P < 0.001). A ROC curve of the predictive value of 24 h urine NE levels revealed that the area under the curve was 0.926. A cutoff value for 24-h urine NE level of 34.84 μg/24 h produced both high sensitivity (70%) and specificity (100%) in predicting the efficacy of metoprolol therapy for VVS.


Patients with high 24-h urine NE levels have higher supine systolic and diastolic pressures and more effective responses to metoprolol. A 24-h urine norepinephrine level of > 34.84 μg/24 h was an indicator of the effectiveness of metoprolol therapy for VVS in children.


Children Metoprolol Norepinephrine Recurrent vasovagal syncope Urine 





vasovagal syncope


liquid chromatography-tandem mass spectrometry


baseline head-up tilt test


sublingual nitroglycerin-provocative head-up tilt test


receiver-operating characteristic


heart rate


blood pressure


systolic blood pressure


diastolic blood pressure


orthostatic intolerance


area under the curve


confidence interval


oral rehydration salts



We thank the Beijing Harmony Health Medical Diagnostics Co., Ltd., for contributing to these studies.

Authors’ contributions

QYK: data acquisition and analysis, writing. ZFC, MMW: performed the experiments. YYP, MML: data acquisition. CFZ: review and editing. All authors read and approved the final manuscript.


This study was supported in part by grants from the National Natural Science Foundation of China (No. 30900730) and Technology Development Plan of Shandong Province (2014GSF118066). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Consent for publication

Not applicable.

Ethics approval and consent to participate

This study was approved by the ethics committee of Qilu Hospital of Shandong University, and all participants’ guardians were fully informed of the purpose and methods of the study.


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Copyright information

© Royal Academy of Medicine in Ireland 2019

Authors and Affiliations

  1. 1.Department of Pediatrics, Qilu HospitalShandong UniversityJinanChina
  2. 2.Department of PediatricsYidu central hospital of WeifangWeifangChina
  3. 3.Department of PediatricsQilu Children’s Hospital of Shandong UniversityJinanChina

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