Hypothesis / aims of study
A urodynamic study (UDS) is routinely utilized to evaluate lower urinary tract disorders. However, a UDS can often result in significant patient discomfort, pain, and emotional distress. Sedatives such as propofol have been trialed during UDS to improve patient experiences, however, has been shown to compromise verbal feedback and impair bladder emptying [1]. Nitrous oxide (NO) has been used for decades in pediatric and adult populations as an inhaled anesthetic to relieve periprocedural pain and anxiety. At concentrations <50%, the American Society of Anesthesiology classifies NO as minimal sedation, producing a state in which a patient responds normally to verbal commands, and maintains airway reflexes and spontaneous ventilation. When using NO at <50%, there is no requirement for anesthesia personnel, NPO status, or escort home. Additionally, NO’s rapid absorption and distribution allow for near-immediate analgesia. To date, no clinical study has investigated the role of NO for use in UDS. The aim of this study is to determine the effect of self-adjusted nitrous oxide (SANO) during UDS. We hypothesize that SANO will significantly improve patient anxiety and pain without impacting UDS tracing quality.
Study design, materials and methods
This is a single-center randomized controlled crossover trial comparing UDS with SANO or oxygen. Internal Review Board approval was obtained prior to study commencement and all patients were consented. Sample size calculation to detect difference in UDS outcomes based upon a power of 95% was determined to be 14 patients per treatment arm. Patients with cognitive impairment, benzodiazepine prescriptions, or medical conditions considered contraindications to NO were excluded. The crossover study design is shown in Figure 1. All patients received SANO during catheter placement to determine the patient-preferred NO level. Following a “washout” period of 2 minutes, the patient underwent two UDS fills, randomized to either oxygen for the first run followed by SANO for the second run, or vice versa. Both the patient and operator performing the UDS were blinded to treatment assignment. UDS interpretation was performed by two blinded urologists from two different institutions. Primary outcomes were standard UDS parameters (compliance, capacity, detrusor overactivity, voiding quality, bladder contractility, and post-void residuals (PVR)). Secondary outcomes included patient-reported pain and anxiety, measured immediately before maximum capacity during both fills, using the Visual Analog Scale for Pain (VAS-P) and the Visual Analog Scale for Anxiety (VAS-A). Patient responsiveness and tolerance of the procedure was rated by a single blinded operator performing the UDS. Wilcoxon Signed Ranks and Chi-Squared Tests correcting for repeated patients was used for analysis. An alpha of 0.05 was selected a priori. Sensitivity analysis was utilized to compare outcomes in patients given SANO or oxygen during the first or second round of UDS. Analysis was performed using R (v4.1.3) and SPSS (v29).
Results
19 participants, each with two UDS fills, were included for analysis. The median (IQR) age was 61 (42-68), and 7 (36.8%) patients were female. The median (IQR) concentration of NO administered was 37% (35.5% - 41.5%) with a median (IQR) time to effect of 170 (135 - 200) seconds. Two patients were unable to void during the oxygen run but were able to void volitionally during the SANO run. No patients experienced complications.
Between the SANO and oxygen treatments, there was no significant difference in bladder capacity, maximum flow rate, pressure at the max flow rate, detrusor overactivity and contractility, void quality, or compliance. Patients reported significantly less pain during the SANO run when compared to the oxygen run (median (IQR) VAS-P Score; 2.0 (0.0, 3.0) vs 0.70 (0.00, 1.25), p = 0.047). Lower anxiety was reported, however, this difference was not significant (median (IQR) VAS-A Score; 2.0 (0.0, 2.85)vs 1.00 (0.0, 2.15), p = 0.26). The UDS operator rated patient responsiveness and tolerance of the procedure to be significantly better than expected during runs with SANO when compared to runs with oxygen (p = 0.001 & p = <0.001, respectively) (Table 1). Sensitivity analysis adjusting for treatment randomization also demonstrated no significant difference in outcomes between treatment groups. Post-procedure survey of the patients revealed most patients (15/19, 78.9%) would prefer to receive SANO again during future UDS.
Interpretation of results
To the best of our knowledge, we present the first study demonstrating safe and effective use of NO during UDS to alleviate patient pain without compromising UDS quality. Our findings build upon our application of SANO to improve patient experience during transrectal prostate biopsies [2]. Limitations of our institution include single-institution, crossover study design. Though there is no evidence that NO used at the doses utilized in this study can impact neuronal control of the bladder, our ability to quantify changes in bladder function is limited by provider interpretation of UDS and quantitative UDS measures. Future studies will aim to identify optimal dose-response ratios and extend SANO’s application to the pediatric population.