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The effects of antimuscarinic agents on the activity of the cardiac autonomic nervous system in children with functional overactive bladder

  • Mir Sohail Fazeli
    Affiliations
    British Columbia Children's Hospital Research Institute, Vancouver, Canada

    Evidinno Outcomes Research Inc, Vancouver, Canada
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  • Mir-Masoud Pourrahmat
    Affiliations
    British Columbia Children's Hospital Research Institute, Vancouver, Canada

    Department of Medicine, University of British Columbia, Vancouver, Canada
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  • Jean-Paul Collet
    Affiliations
    British Columbia Children's Hospital Research Institute, Vancouver, Canada

    Beijing Tiantan Hospital, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
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  • Kourosh Afshar
    Correspondence
    Corresponding author. British Columbia Children's Hospital, 4480 Oak Street, Ambulatory Care Building, Room K0-109, Vancouver, British Columbia, V6H 3V4, Canada. Tel.: +1 (604) 875 2000 ext. 7959.
    Affiliations
    British Columbia Children's Hospital Research Institute, Vancouver, Canada

    Department of Urologic Sciences, University of British Columbia, Vancouver, Canada
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      Summary

      Background

      Functional overactive bladder disorder is one of the most prevalent presentations of bladder and bowel dysfunction in children, and it is associated with lower overall cardiac autonomic and parasympathetic activity. Antimuscarinics are the most frequently used pharmacological agents for treatment of children with functional overactive bladder disorder; however, there is a gap in the literature in describing the effect of antimuscarinics on the autonomic profile of this population.

      Objective

      The aim of the study was to assess the cardiac parasympathetic activity before and after 12 weeks of oxybutynin treatment in children with overactive bladder.

      Methods

      This was a single-institution prospective cohort study. Cardiac autonomic activity was assessed during storage and voiding phases of the bladder function via spectral analysis of heart rate variability and impedance cardiography. The primary outcome measure was high frequency, a proxy for parasympathetic nervous system activity. Parameters of uroflow study, severity of symptoms, and quality of life outcomes were also assessed.

      Results

      Ten children (7 females) diagnosed with overactive bladder with a median age of 10 years (range = 6–14) were followed up for a median treatment duration of 11.8 weeks (range = 6–19.4). After treatment, there was a significant reduction in high frequency during the storage phase (median change = −24.17%, p = 0.047). No change was observed in the other outcome measures except for the overall Symptom Score for Dysfunctional Elimination Syndrome after treatment (5-point decrease, p = 0.034) (Summary Table).

      Discussion

      The findings of the present follow-up study suggest that the use of oxybutynin in children with overactive bladder is associated with a significant reduction in the activity of the parasympathetic nervous system. The clinical implications of this finding are important because similar autonomic profiles (as markers of chronic stress) have been shown to be associated with increased inflammation and are found in major chronic diseases. The authors caution making a clinical connection between the heart rate variability profile of the patients in this study and patients with chronic diseases because oxybutynin is usually not administered as long-term treatment for overactive bladder.

      Conclusion

      Summary TableAutonomic and uroflowmetric profile at baseline and post-treatment.
      Baseline Post-treatment Relative change from baseline to post-treatment (%) P-value
      Autonomic variables
      High frequency (ms2/Hz) 672.58 (303.74–1053.63) 540.09 (283.54–671.67) −24.17 (−55.37 to −10.74) 0.047
      Total power (ms2/Hz) 1159.81 (767.35–1560.37) 1106.96 (868.53–1238.00) −13.00 (−40.00 to 12.25) 0.333
      Pre-ejection period (ms) 112.12 (107.42–115.35) 112.35 (105.06–121.11) 1.19 (−4.94 to 5.61) 0.767
      Heart rate (beats/min) 78.61 (74.89–83.65) 84.44 (73.09–87.18) 5.31 (−0.50 to 9.23) 0.139
      Uroflowmetric variables
      Peak urinary flow rate (ml/s) 11.4 (5.2–22.2) 10.8 (5.6–15.1) −36.1 (−57.2 to 183.9) 0.508
      Calculated peak urinary flow index
      • Franco I.
      • Shei-Dei Yang S.
      • Chang S.J.
      • Nussenblatt B.
      • Franco J.A.
      A quantitative approach to the interpretation of uroflowmetry in children.
      0.7 (0.3–1.0) 0.6 (0.4–0.9) −17.3 (−52.0 to 160.7) 0.646
      Average urinary flow rate (ml/s) 4.4 (2.2–9.8) 2.5 (1.2–5.0) −41.2 (−82.7 to 87.8) 0.139
      Calculated average urinary flow index
      • Franco I.
      • Shei-Dei Yang S.
      • Chang S.J.
      • Nussenblatt B.
      • Franco J.A.
      A quantitative approach to the interpretation of uroflowmetry in children.
      0.6 (0.4–1.2) 0.4 (0.1–0.7) −50.0 (−76.2 to 27.9) 0.241
      Voided volume (ml) 82.5 (27.6–128.6) 45.6 (25.3–92.4) −58.2 (−71.3 to 199.2) 0.646
      Postvoid residual (mL) 0 (0–13.8) 10.0 (0–66.3) 0.345
      Calculated ratio of actual to expected bladder capacity
      • Franco I.
      • Shei-Dei Yang S.
      • Chang S.J.
      • Nussenblatt B.
      • Franco J.A.
      A quantitative approach to the interpretation of uroflowmetry in children.
      0.23 (0.18–0.46) 0.34 (0.14–0.74) −8.3 (−69.9 to 270.6) 0.374
      Uroflow curve, n abnormal (%) 5/9 (56) 8/8 (100) N/A
      BBD score 23 (19–31) 18 (14–22) 0.034
      PinQ score 37 (26–49) 35 (13–48) 0.206
      Values are medians (interquartile range). P-values are reported using the Wilcoxon signed-rank test.
      BBD = bladder and bowel dysfunction, N/A = not applicable, PinQ = Pediatric Incontinence Quality-of-Life questionnaire.

      Keywords

      Abbreviations:

      ANS (autonomic nervous system), BBD (bladder and bowel dysfunction), HF (high frequency), HRV (heart rate variability), ICG (impedance cardiography), N/A (not applicable), OAB (overactive bladder), PinQ (Pediatric Incontinence Quality-of-Life questionnaire), PNS (parasympathetic nervous system), PVR (postvoid residual volume), SNS (sympathetic nervous system)
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