The opioid misuse epidemic continues to sweep the globe, with countries like the United States struggling to curtail reflexive prescribing patterns, particularly postoperatively. The AUA white paper on opioid use highlights patient education, nonopioid adjuncts, and prescribing the fewest number and lowest potency of opioid when required.¹ Clinically, most patients with ureteral stents experience some morbidity including lower urinary tract symptoms of urgency, frequency, dysuria, incontinence, hematuria, and flank pain.² Beyond the individuals themselves, the societal impact of ureteral stents is extensive, including emergency department (ED) presentation, readmissions, unplanned clinic calls, and visits, as well as the financial implications from impaired ability to work.

Over the past 5 decades that these stents have been utilized, numerous studies have explored patient education, pain predictive models, mindfulness, oral and intramuscular medications (including alpha-blockers, beta-3 agonists, anticholinergics, gabapentinoids, nonsteroidal anti-inflammatory drugs [NSAIDs], calcium channel blockers, and combinations), and periureteral/intraureteral medications (lidocaine, onabotulinumtoxinA, hyaluronic acid, chondroitin, phosphodiesterase inhibitors, NSAIDs), as well as stent properties (length, diameter, position, material, antirefluxing, and drug-eluting), all in an effort to reduce patient morbidity. So, what works, what doesn’t work, and what may help?

There remains strong evidence for the use of oral alpha-adrenoreceptor antagonists, antimuscarinics, and oral pain medications like NSAIDs in patients without contraindications.³ Alpha-receptors in the ureter, bladder trigone, bladder neck, and prostatic smooth muscle in males can be targeted with alpha-blockers to dilate the ureter, decrease ureter vermiculation, and reduce bladder outlet resistance and subsequent intravesical voiding pressures and reflux. Meta-analyses of well-designed randomized controlled trials (RCTs) utilizing validated surveys (eg ureteral stent symptom questionnaire [USSQ]) show improvement in urinary symptom and pain scores when comparing alpha-blockers to placebo.

Similarly, there are RCTs examining antimuscarinic treatment alone and in combination with alpha-blockers which show improved pain symptoms (abdominal, flank, and urethral) along with lower urinary tract symptoms of urgency and incontinence compared to placebo. Additional meta-analyses show improved validated voiding symptom scores (eg International Prostate Symptom Score) and pain and quality of life scores when comparing combination alpha-blocker and antimuscarinic therapy to placebo. Extensive literature on pain management for acute renal colic has identified the effectiveness and benefits of NSAIDs with or without acetaminophen compared to placebo and opioid medications.⁴ In general, the synergistic effect of combining acetaminophen and NSAIDs for pain management has been well documented, although there are no well-designed ureteral stent pain-specific studies that compare these drugs alone versus in combination to placebo. However, with a reasonably safe short-term (<5 days) prescribing profile these nonopioid pain medications remain valuable options in patients suffering from stent pain.⁴

Other medications like pregabalin and beta-3 agonists (mirabegron) individually or as adjuncts to alpha-blockers and antimuscarinics have been studied with varied results.⁵ Two prospective randomized multicenter studies examined daily mirabegron with 1 showing reduced validated USSQ scores and stent-related pain compared to placebo. The other study found that mirabegron has no impact on USSQ stent-related scores; however, patients using this medication required less analgesic use.⁶ In 1 RCT, pregabalin in combination with antimuscarinic improved USSQ greater than either drug alone compared to the control group; however, further studies are required to examine the optimal use of pregabalin in concert with alpha-blockers, NSAIDs, and anticholinergics for stent-specific pain.

In the realm of stent design and placement, increased morbidity has been seen when distal stent positioning crosses midline with some studies highlighting improved quality of life and voiding symptoms by reducing the total amount of material within the bladder and appropriate stent length selection (eg intraureteral stent, pigtail suture stent).⁷ In contrast, there is no evidence that proximal end and stent diameter have a significant impact on stent symptoms.⁸ Multiple small studies have shown improvements in USSQ and pain scores when utilizing pigtail suture stent versus conventional double-J ureteral stents including reduced analgesic requirements; however, a criticism of these studies is that placement of the ureteral stent in an uncomplicated ureteroscopy case is not required and further well-designed studies on patients that require stent placement are required.^7,9 There are some small RCTs that support stent tolerability could vary with stent material (eg silicone vs nonsilicone), although further studies are again needed to identify patient selection and clinical application/cost analyses of these findings to make recommendations, and the ideal minimal-pain ureteral stent has yet to be designed and proven.

There is evidence that establishing a specific opioid-free pathway for ureteroscopy care may increase the ability to discharge patients without opioids.¹⁰ Two large academic practices in the U.S. implemented opioid-free ureteroscopy pathways >5 years ago and reported early success utilizing specific patient counseling and educational stent pain expectations along with alpha-blocker, NSAID, acetaminophen, and phenazopyridine prescriptions.¹⁰ However, studies examining phenazopyridine’s local analgesic effect within the urinary system for stent pain have not shown a clear clinically significant benefit. A followup study after >2 years of implementation of these opioid-free pathways did show a maintained success rate of 90% of patients being discharged with ureteral stents without an opioid.¹⁰

Overall, ureteral stent placement continues to play a crucial role in the safe management of many urological patients worldwide. However, the ideal stent design and material are not yet known and there is a paucity of studies examining novel oral, intramuscular, intraureteral, and drug-eluting medication recommendations that provide an evidence-based reduction in stent morbidity. Further studies examining the combination of beta-3 agonist medication with other pain management adjuncts are needed, although there is some early evidence that mirabegron may improve stent symptoms. There is evidence supporting the use of alpha-blockers, antimuscarinics, NSAIDs, and acetaminophen pain adjuncts in eligible patients which may be further supported by implementing opioid-free care pathways that guide patient expectations and stent-related education.