of Life After Ureteroscopy

Fig. 10.1

Wisconsin stone-QOL questionnaire. (With permission. Please visit www.urology.wisc.edu/wisqol for further information on using the WISQOL and to register for its use)

Analgesia and Narcotic Use After URS

Given the narcotic epidemic and the multitude of negative side effects associated with narcotic pain medication, urologists and patients alike are considering other treatment options of postoperative pain control (Table 10.1). Deaths due to prescription narcotic pain medication have tripled since 1999 with a staggering 16,235 reported fatalities in 2013 [8]. Common reported side effects of opioid pain medication include constipation, nausea, vomiting, physical dependence, tolerance, dizziness, sedation, and respiratory depression. Black box warnings for hydrocodone-acetaminophen include addiction, abuse, misuse, respiratory depression, accidental ingestion, neonatal opioid withdrawal syndrome, CYP450 3A4 interaction, risks with concomitant benzodiazepines or central nervous system depressants (sedation, respiratory depression, coma, death), and hepatotoxicity [9]. Fortunately, patients after URS may be managed with or without narcotics, and there is evidence to suggest that using other forms of pain control, such as nonsteroidal anti-inflammatory drugs (NSAIDs) , are effective and do not pose risk for addiction. For renal colic, it has been shown that intramuscular diclofenac was superior to both intravenous (IV) paracetamol and IV morphine in a randomized controlled trial [10]. Data presented at AUA 2018 by Sobel et al. revealed that 73% (151/206) of patients could be discharged after ureteroscopy without narcotic pain medication [11]. The authors found that elevated BMI, chronic kidney disease, and fibromyalgia were associated with a postoperative narcotic requirement. Diclofenac was used as the narcotic-free alternative in this study, and patients who received it had a lower rate of phone calls and refill requests. It is still important to discuss with patients the risks of NSAIDs like diclofenac which include black box warnings for cardiovascular (e.g., stroke, myocardial infarction) and gastrointestinal risk (ulcers, bleeding, gastric perforation). However, diclofenac has been shown to have less adverse effects than aspirin, only 7% more than placebo, but similar to ibuprofen in a study on osteoarthritis using the same dose as has been our practice after ureteroscopy (50 mg TID) but for 4–6 weeks or more [12]. Intravenous acetaminophen has shown promise in some studies on renal colic, but data is conflicting and limited [13]. Additionally, IV acetaminophen is not available as a generic, which presents a cost challenge ($42.48/1 g vial) for wider use [14]. Patients with contraindications to NSAIDs may certainly benefit from a short course of an opioid pain medication, but urologists must prescribe the medication thoughtfully with care to avoid overprescribing practices. A recent study of 74 consecutive patients found that the median opioid pill use after URS was 10 but by day 6 postoperatively was down to 0 with patients only using half of the total number of prescribed pills [15]. One opioid option for patients in whom NSAIDs are contraindicated is tramadol. Tramadol , a centrally acting analgesic, has two separate mechanisms of action. While it is a weak μ opioid agonist, it also inhibits norepinephrine and serotonin reuptake which activates descending monoaminergic spinal inhibition of pain [16]. Both IV and oral tramadol are effective with minimal adverse effects in patients with moderate or severe postoperative pain which may be due to its dual mechanisms of action [17]. The most common reported side effects occurring in 1.6–6.1% of patients are nausea, dizziness, drowsiness, sweating, vomiting, and dry mouth. Most importantly, tramadol has no clinically significant cardiac or respiratory effects at recommended doses in adult or pediatric patients and is unlikely to lead to abuse or dependence. It is our practice to prescribe a limited number of tramadol pills after URS for patients who cannot take NSAIDS due to allergy, renal dysfunction, cardiac disease, or bleeding tendencies.

Table 10.1

Recommended medications to prescribe post URS

Medication	Recommended use	Mechanism of action	Major side effects	Dosing
Diclofenac (Voltaren) [64]	Post URS and stent pain	NSAID: Inhibits cyclooxygenase, reducing prostaglandin and thromboxane synthesis	Stroke, myocardial infarction, GI ulcers and bleeding, gastric perforation	50 mg PO TID
Tramadol (Ultram) [65]	For patients with contraindications to NSAIDs	Central opioid agonist and weakly inhibits norepinephrine/serotonin reuptake	Nausea, dizziness, drowsiness, sweating, vomiting, dry mouth	50 mg PO q6
Tamsulosin (Flomax) [66]	Stent pain with concurrent NSAID use	Alpha-1a adrenergic receptor antagonist, relaxing smooth muscle, and improving urine flow	Orthostatic hypotension, floppy iris syndrome, syncope, dizziness, abnormal ejaculation	0.4 mg PO qd
Oxybutynin (Ditropan) [67]	Stent-related bladder spasms	Muscarinic receptor antagonist relaxes bladder smooth muscle, inhibits involuntary detrusor muscle contractions	Dry mouth, dry eyes, constipation	10 mg PO qd
Phenazopyridine (Pyridium) [28]	Post URS and stent dysuria	Produces topical analgesia of urinary tract	Orange hue to bodily fluids	1.5 PO TID
Hydrocodone-acetaminophen (Norco) [9]	Refractory pain and contraindications to other medications	Opioid agonist, producing analgesia and sedation	Addiction, respiratory depression, hepatotoxicity, constipation	2.5–10 mg PO q4-6h

In addition to NSAID or narcotic pain medications, use of an alpha blocker for patients who have a ureteral stent placed at the time of URS does decrease bothersome LUTS and flank pain [18]. Tamsulosin is well tolerated with side effects of asthenia in 0–3% of patients (i.e., weakness) and dizziness in 1–2% of patients in a study of 0.2, 0.4, and 0.6 mg dosing, and the 0.4 mg dose was found to be most effective and comparable to placebo [19]. However, tamsulosin should be avoided in patients with cataracts who may require ophthalmologic surgery due to the risk of floppy iris syndrome, which is much higher for tamsulosin than for other alpha blockers such as alfuzosin [20]. However, fortunately tamsulosin has been found to be safe in pregnant women who have limited options for analgesia based on a limited patient study [21].

Another class of medication that has shown a benefit to patients after URS and stent placement are anticholinergics such as oxybutynin . Patients should be cautioned about the typical anticholinergic side effects seen with medications like oxybutynin that include dry mouth (most common side effect), dry eyes, and constipation [22]. Anticholinergics should be avoided in the elderly due to concern for central nervous system side effects, with one exception. Trospium displays anticholinergic properties but has the lowest penetration of the blood-brain barrier in the anticholinergic class and can therefore be tolerated by many elderly individuals [23]. Anticholinergics are also a poor option in men who have benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) with elevated post-void residual urine volumes (i.e., >150 mL) due to the theoretical potential for urinary retention. Through a similar effect as anticholinergic medication , although not an anticholinergic, belladonna and opium suppositories can also limit bladder contraction and spasms through a local narcotic mechanism . A recent randomized, double-blind placebo-controlled study demonstrated that immediate postoperative administration of a belladonna and opium suppository does improve quality of life and urinary symptoms after URS and stent placement [24]. Much investigation has also gone into the beta-3 receptor agonist mirabegron and benefits for patients with stone disease. Prior studies have confirmed the presence of β-1, β-2, and β-3 adrenergic receptors in human ureteral smooth muscle, and the same authors determined β-2 and β-3 receptor stimulation causes ureteral smooth muscle relaxation [25, 26]. Multiple prospective, randomized controlled trials (NCT02744430, NCT02095665, NCT02462837) are currently underway assessing mirabegron’s effectiveness in medical expulsive therapy or in relieving stent-related symptoms. Anecdotally, we have noted success using this medication for stent discomfort. This medication has minimal side effects, but caution is advised in patients with uncontrolled hypertension as it can increase blood pressure [27].

Finally, phenazopyridine is a medication that can improve dysuria following URS and stent placement through a local anesthetic effect. The anesthetic effect of the medication has not been shown to benefit patients who are also taking antibiotics after 2 days of therapy; however, these studies focused on individuals with urinary tract infections [28]. Phenazopyridine is well-tolerated, but patients should be informed that it will cause bodily fluids (tears, saliva, urine) to turn an orange hue because it is an azo dye [28]. It is our general practice to prescribe 3 days of the medication to patients with an indwelling stent after URS.

Stent Implications on Quality of Life After URS

Ureteral stent side effects are far too common and at times debilitating for patients, impacting health-related quality of life in 80% and causing sexual dysfunction in 32% [5]. The etiology of ureteral stent pain and urinary symptoms due to stents are not fully understood. Previously, it has been shown that a high percentage of patients with standard double-J ureteral stents have vesicoureteral reflux (VUR) on voiding cystourethrogram , 63% in the filling phase and 80% in the voiding phase [29]. The VUR associated with indwelling stents most likely contributes to the pain noted with urination, especially in high-pressure voiders such as men with benign prostatic hyperplasia. Interestingly, ureteral stent diameter has been shown by Damanio et al. to not affect stent symptoms, and in another study, ureteral stent duration did not impact pain scores [30, 31]. However, the distal curl has been linked to stent morbidity in several studies. Ho et al. found that increased stent length affects the distal curl position (not proximal), and longer stents cause more frequency and urgency [32]. Multiple studies have demonstrated that if the distal curl crosses, the midline patients have worse stent-related symptoms [33]. However, is stenting necessary and can we avoid pain post URS by eliminating the ureteral stent?

Overall, there are conflicting findings in the literature on whether or not patients experience more or less pain with or without stents after URS. Multiple studies found no difference in narcotic or analgesic use between stented and non-stented in several studies [1, 34, 35]. However, one randomized controlled trial demonstrated decreased narcotic use in patients who were not stented following uncomplicated URS for distal stones [2]. The presence of LUTS post URS is more common with stents that are in place than when they are omitted [1]. Regarding flank or suprapubic pain, this was shown to be less prevalent at postoperative day 6 in patients who were stentless after URS compared to those who were stented [3]. However, it appears that omitting a stent after URS does not completely decrease morbidity, as there are possibly more hospital readmissions with stentless URS [1, 2, 34]. Schuster et al. previously reported postoperative outcomes from 322 URS procedures with a 13.3% ER visit rate [4]. Patients who returned to the ER had operative times that were 13 min longer on average, but there were no differences in stent placement compared to those who did not return to the ER.

When stents are left in place, stent material appears to have little impact on comfort. Previous studies have compared soft and firm types of stent materials and found no differences in USSQ scores at 1 and 4 weeks postoperatively [5]. Lee et al. conducted a randomized study of five different types of stents and found that Bard inlay stents had less urinary symptoms on the USSQ, but there were no differences in pain, general symptoms scores, or narcotic use [36]. Another study found that stents with a softer distal bladder coil (Polaris™) did not lead to lower pain scores [37]. A randomized multicenter trial by Krambeck et al. found no differences in unplanned physician contact, change in pain medication, or early stent removal in patients with toradol-eluting stents compared to standard double-J stents [38]. A triclosan-eluting stent was developed and shown to reduce pain and urinary symptoms with activity, but there were no differences noted when the patient was at rest [39]. In the triclosan study, a unique symptom questionnaire was employed rather than the validated USSQ, and pain medication use was not assessed. The bottom line is a home run stent has yet to be invented.

Another decision the urologist must consider following URS is not only whether to place a stent and what size/material but also whether to leave an externalized extraction string or discard the string and retrieve the stent via cystoscopy at a later date. Leaving the externalized string aids in extraction of the stent, eliminating the need for cystoscopy stent removal. However, opponents state patient discomfort and concern for stent dislodgement as reasons to remove the extraction string. A recent study by Barnes et al. found no differences in stent-related quality of life by USSQ, in number of ER visits or phone calls or in frequency of UTI between patients who had stents with strings compared to those without and required cystoscopic extraction [40]. Anecdotally it is our practice to leave the dangle extraction string for all uncomplicated URS cases to limit patient visits and inconvenience.

To date there is no clear guidance on how to avoid pain and discomfort after URS. The decision to stent or not is a fluid one made by the surgeon at the time of the procedure depending on the clinical scenario. There are numerous factors at play which may swing the pendulum toward stenting or not: ureteral lumen size, use of an access sheath, ureteral edema, ureteral injury, impacted stone, prolonged operation, solitary kidney, renal insufficiency, infection, patient preference, or prior experience. If a stent is omitted, this is no guarantee the patient will have less pain or require fewer pain medications. Furthermore, if a stent is placed, there is no ideal stent design, material, dwell time, or extraction method to limit pain.

Impact of Operative Factors on Quality of Life After URS

There are numerous operative variables which may differ from case to case and may impact the amount of pain and discomfort experienced by the patient. The end result is some patients do better after URS than others undergoing the same procedure but under a different set of conditions. To address the question of whether patients who undergo ureteral dilation have more pain, Hosking et al. performed URS without stenting in 93 patients of whom 88% had balloon dilation of the distal ureter. Patients had pain less than 1 day controlled with oral medication regardless of whether balloon dilation was utilized [41]. Other investigators have found that dilation of the distal ureter for uncomplicated treatment of a distal ureteral stone does not require routine stenting, and if stents are placed, patients have been found to have increased pain, urinary symptoms, and narcotic use [2]. It follows that patients who do not tolerate stents can safely be spared a stent when distal ureteral stones are treated with uncomplicated URS, which can lead to improved quality of life postoperatively.

Bilateral URS has been shown to be safe and effective with rates of pain, complications, and stone-free rates similar to unilateral or staged procedures [42]. One study evaluated 95 bilateral URS and followed these patients for 1 month postoperatively [43]. Complications were observed in 9.7% of patients postoperatively, only 5.3% of which experienced pain necessitating either an emergency room visit or rehospitalization. The authors’ overall conclusion was that same session bilateral URS is efficacious and safe, but although most complications are minor, there may be slightly higher rates when compared to that reported for unilateral procedures. Ingimarsson et al. performed 117 same-session bilateral ureteroscopic procedures and compared the outcomes to 134 unilateral ureteroscopies [44]. Short-term complications were observed in 16.2% of patients, most commonly stent pain and discomfort in 5%. This is comparable to the unilateral group in which 6% of patients experienced stent pain and discomfort. Of the 71.8% patients that followed up at 6 weeks, there were no long-term complications. Stone-free rates with abdominal x-ray and ultrasound were 91.4% and 84.2% for patients imaged with CT scans. There was no overall difference in complication or readmission rates between the bilateral and unilateral groups. The authors concluded that bilateral ureteroscopy in a single session can be implemented as the standard of care for patients that present with bilateral stone disease.

Ureteral access sheaths are often used and are arguably safer given that there are lower intrarenal pressures for URS performed with an access sheath compared to URS performed without an access sheath [45]. Although limiting intrarenal pressure is important in all URS cases, it is most important in patients with a history of infected stones or urothelial carcinoma to avoid higher pressures which could promote pyelovenous or pyelolymphatic backflow. The ureteral access sheath also allows for repeated basket extraction of stone material to result in improved stone-free rates and improved visualization [46]. However, the use of a ureteral access sheath can result in temporary ureteral edema and in some cases ureteral perforations making the use of a ureteral stent often mandatory. A previous study demonstrated more than double the rate of emergency department visits (37% vs. 14%) when a stent was omitted after URS with an access sheath [47]. A study by Torricelli et al. reported that pre-stented patients who were left stentless after uncomplicated ureteroscopy using an access sheath had less pain than those who were stented [48]. Thus, although stent placement and its impact on postoperative recover from URS is complex, it seems that if an access sheath is used, stent placement is typically favorable unless special circumstances exist (e.g., pre-stented ureter, megaureter).

One would expect a longer operative time to potentially cause more postoperative pain. Ahn et al. reported outcomes on acute pain after URS in 143 consecutive patients from 2008 to 2010 and found that younger age, psychiatric illness, history of urinary tract infection, use of a stone basket, large stone size, and prolonged operative time were associated with more pain [49]. Factors that tend to prolong operative time, large stone size, and use of a basket were found to have an effect as expected in the study. A recent manuscript by the EDGE (Endourologic Disease Group for Excellence) Research Consortium found a significantly longer operative time when using a basketing vs. dusting technique (67.4 ± 53.3 vs. 35.9 ± 17.8 min, p < 0.001) [50]. However, there was no difference in postoperative complications or need for additional procedures between dusting and basketing. Also impacting operative time is stent placement which has been reported at a mean of 12 min [3]. Thus, when considering URS for larger stone burdens, the treating physician should consider longer operative times as a potential risk factor for poorly controlled postoperative pain.

Patient Factors and Rates of Emergency Room Visits, Readmissions, and Phone Calls After URS

Several baseline patient characteristics may influence recovery after URS. Patient-specific risk factors for significant pain after URS have been identified as younger age, history of psychiatric illness, and urinary tract infection [49]. A study by Penniston et al. showed that, among patients with nephrolithiasis, women have a lower healthcare-related quality of life than men after undergoing URS [51]. The authors stated in their limitations that differences in severity of stone disease between genders may have influenced their results. Also, they did point out that more women had a history of depression and musculoskeletal complaints than men in their study which likely influenced the quality of life score domains which were different between sexes (physical functioning, general health, vitality, and mental health). However, a recent publication by Ozsoy et al. demonstrated no gender differences in success or complication rates after URS [52]. As mentioned previously, ureteral access sheath use without stenting patients can result in 2.5 times the rate of ER visits compared to those with sheaths that were stented [47]. From a meta-analysis of 10 different studies with a total of 891 subjects, patients who were stented had a 4% lower rate of urologic complications, but this finding was not significant (p = 0.175) [53]. Morgan et al. reported that two-thirds of patients made postoperative contact with a healthcare provider after URS with 79% for medical reasons with pain as the primary complaint [54]. On multivariate analysis, only younger age and use of a larger ureteral access sheath were predictive factors of healthcare provider contact. The authors compared URS to TURBT in the same study and found that patients undergoing the URS were 2.5 times more likely to have a pain-related postoperative encounter than those who had TURBT . These results indicate that in certain groups of the population, quality of life is significantly decreased after URS, regardless of surgical factors.

Convalescence

The time needed to recover and return to work or regular activities is often a major patient determining factor when considering treatment options for symptomatic stone disease. A systematic review and meta-analysis compared URS to extracorporeal shockwave lithotripsy (ESWL) and percutaneous nephrolithotomy (PCNL) . Pearle et al. looked at patients who underwent URS or ESWL for less than 10 mm lower pole stones and found that the latter had superior quality of life, shorter convalescence, and less analgesic requirement (5.6 vs. 14.7 pain pills, p = 0.015) [55]. For URS vs. ESWL, mean convalescence variables assessed were all lower and better for SWL: 5.3 ± 6.1 vs. 1.9 ± 1.7 days to driving, 7.9 ± 9.8 vs. 3.2 ± 3.0 days to return to nonstrenuous activity, 8.5 ± 8.3 vs. 3.3 ± 2.7 days to return to work, and 15.6 ± 11.6 vs. 8.1 ± 10.8 days until 100% recovered. A larger number of patients were willing to have a future ESWL than URS (90% vs. 63%, p = 0.031). Of note, 89% of the patients in the URS group were stented. Singh et al. had similar findings except satisfaction with URS was higher than ESWL with more patients willing to undergo repeat URS than ESWL (84% vs. 50%, p = 0.002) [56]. The preference for URS over ESWL in the Singh study may be because the URS patients had higher stone-free rates (83% vs. 49%), and the procedure was performed under epidural/spinal anesthesia with an overnight hospital stay per institutional and societal norms. Park et al. prospectively evaluated 65 patients undergoing ESWL vs. 95 undergoing URS for a single ureteral calculus ranging from 4 to 15 mm [57]. The patients who underwent URS were stented with a 6-Fr double-J stent for 2 weeks after surgery. There was no difference in patient satisfaction between the two procedures, as well as willingness to undergo the same procedure again (ESWL 64.6% vs. URS 51.6%). However, those patients treated with ESWL experienced a significantly faster return to work compared to patients treated with URS (2.48 ± 1.12 days vs. 3.02 ± 1.20 days, respectively). The authors attributed stent placement to be a main factor in prolonging convalescence in the URS cohort. Another study prospectively randomized 91 patients with large impacted proximal ureteral stones, defined as stones >1 cm in size to antegrade (44) or retrograde (47) ureteroscopic lithotripsy [58]. Stents were place in both groups for approximately 3 weeks. Retrograde ureteroscopic lithotripsy was associated with a statistically significant shorter interval to return to normal activities than PCNL antegrade URS. (2.7 ± 0.6 days vs. 7.8 ± 0.7). Thus, although URS seems to have a longer convalescence period than ESWL, it is significantly shorter than that experienced by those undergoing PCNL .

Sexual Function

The impact of stent placement after URS on sexual function has also been extensively studied. In one report, sexual function was decreased after URS and was not shown to improve over time after stent placement, with the authors postulating that may take more time to recover than other domains assessed by the USSQ [59]. Another study used International Index of Erectile Function-5 and Female Sexual Function Index to evaluate patients after stent placement, and both male gender and longer duration of stent dwell time were associated with lower sexual function scores on multivariable analysis [60].

Joshi et al. evaluated 85 consecutive adult patients with unilateral indwelling ureteral stents using the USSQ. Results of the USSQ revealed that at 4 weeks after stent removal, 35% of patients who were sexually active experienced pain during sex (mild pain 24%, moderate to severe pain 11%). Of the patients who reported being sexually active, 70% experienced temporary sexual dysfunction, and 14% had total sexual dysfunction. Patients’ self-assessment also revealed that 18% expressed mixed feelings with overall sexual satisfaction, and 14% were completely dissatisfied with sex at the end of 4 weeks of an indwelling stent [5].

Eryildirim et al. evaluated sexual function in patients undergoing URS procedures [61]. The authors assessed 102 sexually active patients (60 male, 42 female) undergoing diagnostic and/or therapeutic URS for ureteral stone. None of these patients had stents placed after surgery. Sexual function was evaluated by using International Index of Erectile Function (IIEF) in male and Female Sexual Function Index (FSFI) forms in female cases before and at 1 month post procedure. Mean age of males was 42.07 ± 1.83, and mean age of females was 43.67 ± 2.14. There was no statistical difference in overall sexual function in males, but when subdomains of the index were considered, men showed a statistically significant dissatisfaction with sex at 1 month post URS (IIEF-IS 9.32 ± 0.46 vs. 6.66 ± 051). Females showed no overall difference in sexual function, as well as no difference in the subdivisions. The authors theorized that the differences in satisfaction noted between males and females can be attributed to male lower urinary tract symptoms resulting from neuronally rich trigon mucosa irritation, anxiety, insomnia, and depression leading to sexual dysfunction.

Importance of Patient Education and Shared Decision-Making

Managing patient expectations is critical in every aspect of medicine and is particularly important for URS. Since URS is a minimally invasive procedure, there can be a patient perception that pain should be minimal to nonexistent, but in fact many patients can experience significant discomfort postoperatively and may need additional treatment. Although minimally invasive in the sense that URS is endoscopic with no incisions, it must be stressed to patients that URS can be quite painful. Taking time to educate the patient on the delicate nature of the kidney and ureter can help manage patient expectations postoperatively. The sensitive nature of the kidney and ureter is most apparent and translatable to patients from a study that found renal colic to be more painful than childbirth among women who have experienced both [62]. Stents themselves can be quite bothersome for patients, which can result in a significant number of patient encounters with the healthcare team if they are not coached and prepared on what symptoms to expect post procedure. A helpful tool available to urologists is the MUSIC (Michigan Urological Society Improvement Collaborative) stent brochure (see Fig. 10.2). The MUSIC brochure along with other educational tools can act as a resource to patients in the postoperative period and can be provided in the preoperative period to prepare patients.