Reduced Reflex Autonomic Responses following Intradetrusor OnabotulinumtoxinA Injections: A pre/post study in Individuals with Cervical and Upper Thoracic Spinal Cord Injury

Abstract

Importance: Urodynamic studies (UDS) can provoke autonomic dysreflexia (AD) in individuals with spinal cord injury (SCI) at and above the sixth thoracic (T6) spinal segment potentially leading to profound vagally mediated heart rate reductions. Intradetrusor onabotulinumtoxinA injections have been shown to reduce AD events during UDS in this cohort but evidence is lacking whether this treatment can improve reflex autonomic responses. Objective: To assess the effects of intradetrusor onabotulinumtoxinA injections on heart rate variability (HRV) responses to UDS in individuals, 18-65 years of age, with chronic (>1-year) SCI at or above T6 with confirmed neurogenic detrusor overactivity and AD during UDS. Design, Setting, and Participants: This cohort study used participants from our recent prospective phase IV clinical trial. Individuals were screened at an academic medical centre between November 2014 and December 2019. After enrollment, participants underwent UDS prior to (i.e., baseline) and one month after intradetrusor onabotulinumtoxinA injections (post-treatment). Interventions: OnabotulinumtoxinA (200 U) was injected into the detrusor muscle at 20 sites (10 U/site). Main Outcomes and Measures: Continuous electrocardiogram (ECG) and blood pressure (BP) recordings were used to assess RR-interval, time and frequency domain metrics of HRV (a surrogate marker of autonomic nervous system activity), and AD pre- and post-intervention. Results: A total of 19 participants with SCI (5 women; mean [SD] age 42 [8.3] years) with complete ECG and BP data sets were suitable for autonomic analysis. During baseline UDS, an increase in RR-interval (adjusted mean difference, -0.08; 95% CI, -0.14 to -0.03; P=0.002) as well as time and frequency domain metrics of HRV were detected. Vagally mediated increases in high frequency (HF) power during UDS were larger in participants with cervical SCI compared to upper thoracic SCI (adjusted mean difference, 20.3; 95% CI, 3.3 to 37.2; P=0.013). Intradetrusor onabotulinumtoxinA injections significantly reduced time domain metrics of HRV and HF power (adjusted mean difference, 9.1; 95% CI, 3.1 to 15.1, P<0.01) responses to UDS across all participants. Conclusions and Relevance: Changes in HRV during UDS could be a potential indicator of improved autonomic cardiovascular function following interventions such as intradetrusor onabotulinumtoxinA injections.