Background
Intraoperative evaluation of ureteral patency is often performed in gynecologic and urogynecologic surgery. Many agents are used to help assess the patency, each with its own associated cost, ease of use, and adverse reactions. Some agents, such as dextrose, are used as an instillation fluid to create a viscosity difference and aid the visualization of a ureteral jet. Others, such as oral phenazopyridine or the intravenous use of sodium fluorescein and indigo carmine, cause a color change of the urine to directly aid the visualization of ureteral jets. Recently, numerous studies have examined the efficacy and surgeon satisfaction of these agents. The studies have also emphasized certain options as associated with a lower cost. However, there have not been any cost studies comparing these agents.
Objective
To compare the cost-effectiveness of the following 4 agents that are commonly used in assessing ureteral patency intraoperatively: oral phenazopyridine, dextrose instillation, intravenous sodium fluorescein, and intravenous indigo carmine.
Study Design
We constructed a decision-analytic model to compare cystoscopy using oral phenazopyridine, dextrose instillation, intravenous sodium fluorescein, and intravenous indigo carmine. Failure to see efflux resulted in work-ups for ureteral obstruction. The probabilities were obtained from published studies, and the probability of successfully seeing efflux ranged from 0.92 with oral phenazopyridine to 0.99 with intravenous indigo carmine. The costs of the agents, adverse effects, and ureteral obstruction work-ups were obtained from the University of North Carolina at Chapel Hill Department of Pharmacy, the Healthcare Cost and Utilization Project 2016 database and the FAIR Health Consumer database. The cost of a ureteral obstruction work-up used in our model ranged from $9755 for intraoperative evaluation with retrograde pyelograms and stents to $29,034 for hospitalization. Our primary outcome was the incremental cost-effectiveness ratio per unnecessary work-up for ureteral obstruction avoided. Sensitivity analyses were performed to identify the key uncertainties.
Results
Oral phenazopyridine, followed by an intravenous agent if needed, had a mean cost of $110 per patient. Dextrose averaged $151 more per patient, with only a slight improvement in avoiding unnecessary ureteral obstruction work-ups and a higher cost associated with adverse reactions (incremental cost-effectiveness ratio, $62,000). Intravenous agents cost approximately $1000 more per patient and were less effective at preventing unnecessary work-ups. Sensitivity analyses did not identify any thresholds that would significantly change the outcomes.
Conclusion
Our model suggests that oral phenazopyridine and dextrose instillation are the least expensive and the most effective agents to aid in the visualization of ureteral patency during intraoperative cystoscopy, although dextrose is associated with higher costs owing to a higher rate of adverse reactions (primarily urinary tract infections). Intravenous sodium fluorescein and indigo carmine are historically popular first-choice agents. However, they were found to be more expensive and less effective as primary agents in our model and should likely be reserved for use as secondary agents in the event that the visualization of ureteral jets is unclear with the initial use of phenazopyridine or dextrose.
Introduction
Many gynecologic, urogynecologic, and urologic surgeries require an accurate intraoperative evaluation of ureteral patency, and intraoperative cystoscopy is recommended as an initial evaluation to detect intraoperative ureteral injuries or obstructions. The estimates of the incidence of ureteral obstruction or injury for all types of pelvic reconstructive procedures have been reported to range from 0.3% to 11%, with one study reporting the true incidence of ureteral obstruction to be 5.1% in vaginal surgeries for pelvic organ prolapse. In gynecologic surgery for benign indications, the rate of ureteral injury is estimated to be between 0.08% and 0.3%. , Cystoscopy in vaginal reconstructive surgery has been reported to be an effective way to detect procedure-related ureteral injury, with a sensitivity and specificity of 94.4% and 95.5%, respectively. Moreover, universal cystoscopy after benign hysterectomy has been reported to increase the detection of delayed urologic injuries.
Why was this study conducted?
To assess the cost-effectiveness of the agents commonly used to assess ureteral patency during intraoperative cystoscopy in benign gynecologic and urogynecologic surgery.
Key findings
Oral phenazopyridine and dextrose instillation are the least expensive and the most effective first-line agents for use during cystoscopy. Intravenous agents are useful as secondary agents.
What does this add to what is known?
This study adds cost analysis to the existing data on surgeon satisfaction, ease of use, and adverse reaction rates of the agents used to assess ureteric patency during intraoperative cystoscopy.
Many agents are used to help assess patency, each with its own associated cost, ease of use, surgeon satisfaction, and potential adverse reactions. The agents most commonly used include oral phenazopyridine (100–200 mg dose given preoperatively), intravenous (IV) sodium fluorescein (0.25–1 mL of 10% solution injected intraoperatively), and IV indigo carmine (5 mL injected intraoperatively). In addition, dextrose fluid can be instilled into the bladder during cystoscopy, creating a viscosity contrast between the fluid in the bladder and the ureteral jets. Historically, indigo carmine was a popular first-choice agent. However, during the national shortage of indigo carmine substrates and following the 2015 Drug Shortage Bulletins issued by the Food and Drug Administration, many surgeons sought alternative agents. Phenazopyridine, dextrose instillation, and sodium fluorescein emerged as proposed alternatives. The studies published since that time have examined the effectiveness, surgeon satisfaction, and safety of these agents.
In an era of increasing importance being placed on healthcare spending, it is important to keep the surgical costs in mind. Numerous studies have emphasized lower cost options for the evaluation of ureteric patency. However, a cost-effectiveness analysis has not been performed. We aimed to conduct a cost-effectiveness analysis comparing the use of oral phenazopyridine, dextrose instillation, IV sodium fluorescein, and IV indigo carmine in evaluating ureteral patency during gynecologic and urogynecologic surgery.
Materials and Methods
This study was deemed exempt from institutional review board approval. We constructed a decision-analytic model using TreeAge Pro (TreeAge LLC, Williamstown, MA) to compare cystoscopy using dextrose instillation, oral phenazopyridine, IV sodium fluorescein, and IV indigo carmine ( Figure ). For each agent, we modeled whether efflux was observed or not. As is common in clinical practice, in the event that efflux was not clearly seen with the initial use of a non-IV agent (oral phenazopyridine or dextrose instillation), we also modeled the option of an IV agent to be given intraoperatively as a secondary attempt at visualization of ureteral efflux before proceeding with further evaluation for ureteral obstruction. Failure to see efflux (a positive test result) resulted in work-ups for ureteral obstruction.
The probabilities of success for each agent and the agent-specific adverse reactions were gathered from a literature search of publications on the effectiveness of seeing a ureteral jet with the use of each agent and the reported adverse reactions for each agent ( Table 1 ). In addition to the base case probabilities used in our model, we also included the range for each estimate that was used in our sensitivity analyses. The costs are shown in Table 2 . The drug costs were obtained from the University of North Carolina at Chapel Hill Department of Pharmacy, and our costs were similar to those available in the published studies. Our model assumed that the cystoscopic time was otherwise similar among all agents. However, in the branches where the IV agents were modeled as secondary agents after an initial ureteral jet was not seen with the use of phenazopyridine or dextrose, in addition to the cost of the IV agent, additional operative time was added to the cost—on average 5 minutes if IV sodium fluorescein was chosen and 8 minutes if IV indigo carmine was chosen. , The cost of each additional minute of operating time was obtained from the published literature. We used International Classification of Diseases, Tenth Revision, Clinical Modification codes of associated diagnoses to obtain the cost data from the Healthcare Cost and Utilization Project (HCUP) 2016 database and the FAIR Health Consumer database, which uses commercial and Medicare data. To approximate the cost of a ureteral obstruction work-up, we used a range from $9755 for intraoperative retrograde pyelogram and stent placement obtained from the FAIR Health Consumer database to $29,034, the cost of the ICD-10 code for ureteral obstruction hospitalization from the HCUP 2016 database. All costs were adjusted to 2019 values using the US Bureau of Labor Statistics Consumer Price Index. Our measures of effectiveness were false positive results. Our primary outcome was the incremental cost-effectiveness ratio (ICER) per unnecessary work-up for ureteral obstruction avoided. The ICER is expressed as the ratio of the difference in the costs between the two strategies to the difference in effectiveness, and it was calculated by comparing each strategy to the next least expensive strategy listed in Table 3 . The strategies that were more expensive but equally or less effective than an alternative were considered “dominated.” Sensitivity analyses were performed using the ranges listed in Table 1 and the cost range for ureteral obstruction work-up to identify key uncertainties.
| Probability of success | Base case | 95% CI | Reference |
|---|---|---|---|
| Phenazopyridine | 0.92 | 0.88–0.95 | Strom et al, 2019 |
| Dextrose | 0.99 | 0.97–1.0 | Siff et al, 2016 |
| Sodium fluorescein | 0.97 | 0.88–1.0 | Lea et al, 2018 |
| Indigo carmine | 0.99 | 0.99–1.0 | Siff et al, 2020 |
| Probability of adverse reactions | Base case | 95% CI | Reference |
| Phenazopyridine (acute renal failure, hemolytic anemia) | 0.0001 | 0–0.0004 | Holmes et al, 2014; Chang et al, 2014 |
| Dextrose (postop urinary tract infection) | 0.23 | 0.17–0.29 | Krishingner et al, 2018 |
| Sodium fluorescein (anaphylaxis, seizure) | 0.0001 | 0.0002–0.001 | Lee et al, 2018 |
| Indigo carmine (hemolytic anemia) | 0.01 | 0–0.0004 | Siff et al, 2020 |
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