Acute Genitourinary System Related Pain
Wesley R. Pate
Natalie P. Tukan
Introduction
There are many causes of acute genitourinary pain, ranging from very common conditions like urinary tract infections to more rare diagnoses like testicular torsion. The etiology of pain can sometimes be clearly delineated based on history and physical exam, while other conditions require more testing to differentiate between diagnostic possibilities. Management can vary widely depending on the diagnosis and can include a variety of treatments including oral and parenteral analgesics, surgical procedures, antibiotics, and local and regional anesthetic techniques. This chapter, while not exhaustive, will focus on the background, diagnosis, and treatment of several of the most important causes of acute genitourinary pain.
Urinary Tract Infections
Background
Urinary tract infections (UTIs) are one of the most common infections in adults. They can involve the lower urinary tract confined to the bladder (cystitis) and/or the upper urinary tract with infection of the renal parenchyma (pyelonephritis).1 Infections in otherwise healthy individuals with normal urinary tracts are the most common and are referred to as uncomplicated UTIs. Complicated UTIs are associated with factors like structurally or functionally abnormal urinary tracts, immunocompromised hosts, and nosocomial infections. Infection in males is generally considered a complicated UTI.2
Women have a tenfold greater incidence of UTI compared to men throughout the reproductive years until declining to a 2:1 difference in older adulthood.3 The lifetime risk of UTI for women is estimated at 60%.4 The gender difference in infection rates can be explained by women’s short urethras facilitating migration of perineal bacteria into the bladder, whereas men’s longer urethras have more ability to clear bacteria through voiding before reaching the bladder.3 Recent sexual activity is also an important risk factor for infection, as this further facilitates the transit of bacteria through the urethra.3 Pyelonephritis is usually caused by an ascending infection from the lower urinary tract but can be caused by hematogenous or lymphatic spread, although this is very rare in healthy, nonhospitalized patients.1 Ultimately, host factors related to genetic variations and anatomic, physiologic, or functional urologic abnormalities (like neurogenic bladder, diabetes, or incomplete voiding) play a large role in whether bacteria entering the bladder are likely to bind to mucosal surfaces and cause infection.1,3
More than three-quarters of outpatient UTIs and more than 90% of cases of pyelonephritis in young, healthy women are caused by Escherichia coli, with other gram-negative rods comprising normal colonic flora contributing to most of the remaining infections.3,5 Staphylococcus saprophyticus is also a causative bacteria in about 10% of sexually active women.3
Symptoms and Diagnosis
Acute bacterial cystitis generally presents with symptoms of dysuria, urinary frequency, and urinary urgency due to bacteria irritating the urethral and bladder mucosa. More rare presenting symptoms include suprapubic tenderness or hematuria.1 The differential diagnosis for cystitis includes other acute pathologies like pyelonephritis, urethritis, bladder calculi, acute bacterial prostatitis (ABP), or vaginitis. Chronic urinary tract etiologies like interstitial cystitis, chronic pelvic pain syndrome, or overactive bladder are additional diagnostic considerations.6
Acute pyelonephritis most commonly presents with flank pain, systemic symptoms like fever and chills, and may also have lower urinary tract symptoms, although presentation can vary widely.5 In addition to distinguishing pyelonephritis from cystitis, the differential diagnosis includes other urinary tract causes like urolithiasis, gynecologic etiologies like pelvic inflammatory disease, and abdominal pathologies like appendicitis or cholecystitis. Urolithiasis is particularly likely if the flank pain radiates to the groin.5 Increased vaginal discharge would suggest that a gynecologic etiology is more likely, and imaging is important to elucidate suspected abdominal pathology.
The diagnosis of cystitis is primarily via urinalysis from a clean-voided midstream urine sample with pyuria and/or bacteriuria in combination with bothersome urinary symptoms. If urinary bacteria are identified in the absence of UTI symptoms, this is classified as asymptomatic bacteriuria rather than bacterial cystitis and does not require treatment except in special circumstances like pregnancy or in patients undergoing certain urologic procedures.7 For cases of suspected pyelonephritis, a urine culture is also obtained to confirm the pathogen and antimicrobial susceptibility.1 Imaging should be considered in patients more likely to have complicated infections like patients with a history of urolithiasis or known abnormal urinary tract anatomy, or patients with persistent symptoms despite appropriate antibiotic therapy.6
Treatment
The cornerstone of management for UTIs is appropriate antimicrobial treatment to eradicate the causative organism(s). Per IDSA guidelines, the first-line recommended antimicrobials in the United States for acute cystitis, depending on factors like availability and local resistance patterns, are nitrofurantoin, trimethoprim-sulfamethoxazole, and fosfomycin. For acute pyelonephritis, treatment should always be based on the antimicrobial susceptibilities from the urine culture, with inpatient parenteral vs outpatient oral treatment depending on the clinical status of the patient and comorbidities.5,8 With proper antimicrobial treatment, symptoms of cystitis are markedly improved or even completely resolved within 24 hours, and those of pyelonephritis within about 48 hours.3 Persistent fever or ongoing symptoms after this time raises concern for an alternative diagnosis like obstruction from urolithiasis or the development of a renal or perinephric abscess.5
Temporizing options for pain include analgesics like phenazopyridine and nonsteroidal anti-inflammatory drugs (NSAIDs). Phenazopyridine is an azo dye that functions as a urinary analgesic by exerting a local anesthetic action on urinary mucosa.9 Several studies examining the use of NSAIDs vs antibiotics suggest that although many women may recover with symptom management only, their symptoms resolve more quickly and have less risk of progression to pyelonephritis when treated with antibiotics, pointing toward the utility of NSAIDs as an adjunctive, rather than sole, treatment strategy.10,11,12 Patients with debilitating symptoms may also require brief therapy with opioid medications.3
In patients with recurrent UTIs, prophylactic measures are also important in managing symptoms, with several options depending on frequency and severity of infections and patient preference. These measures include patient-initiated treatment at the onset of UTI symptoms, daily antibiotic prophylaxis for between 3 and 12 months, or postcoital prophylaxis for
women whose UTIs are related to sexual activity.13 For nonantibiotic options, there is lowgrade evidence that cranberry extracts can decrease the rate of recurrent UTI, as they contain proanthocyanidins which prevent the adhesion of bacteria to the urothelium.3,13 Other tested measures like lactobacillus probiotics or increased water intake have not been shown to have any clinical effect.13
women whose UTIs are related to sexual activity.13 For nonantibiotic options, there is lowgrade evidence that cranberry extracts can decrease the rate of recurrent UTI, as they contain proanthocyanidins which prevent the adhesion of bacteria to the urothelium.3,13 Other tested measures like lactobacillus probiotics or increased water intake have not been shown to have any clinical effect.13
Urolithiasis and Renal Colic
Background
Urolithiasis refers to formation of urinary calculi, or stones, anywhere along the entire genitourinary tract. Most commonly, stones form in the collecting system that drain the kidneys, and the presence of these calculi is referred to as nephrolithiasis. Issues with stones occur when they cause obstruction of the kidney or infections within the urinary tract. Pain with stones most commonly involves the passage of a stone through the ureter, and there are patients who consider this the most painful experience of their life.
Risk factors for urolithiasis include obesity, dietary factors, diabetes mellitus, urine characteristics, family history, certain genetic conditions, and arid environments.14 Gender is also important, as stone disease affects men more than women, though the gender gap has been narrowing over time. Estimates of age distribution of urolithiasis show significant variability between studies, although overall stone disease is rare in the pediatric population.15
Recent analysis of the National Health and Nutrition Examination Survey data estimates the prevalence of kidney stones in the United States at 8.8%, with higher rates in men (10.6%) vs women (7.1%).16 Interestingly, the percentage of patients who form another stone within 5 years after an initial episode has been estimated to be as high as 30%-40%.17 The prevalence and incidence of kidney stones globally, including in the United States, has been increasing. Various reasons for this increase have been suggested, including changes in diet patterns, increased obesity rates, and increased identification of asymptomatic stones found incidentally on imaging.15,18 The majority of stones are composed of calcium oxalate, alone or in addition to calcium phosphate, with the remainder composed of uric acid, struvite, and cystine.14
Symptoms and Diagnosis
Pain from urinary calculi varies between patients and is often episodic, and the pain is intermittent and described as “colicky” as the stone moves and the ureter spasms. The stones typically cause pain when passing through the ureter, as opposed to when it is in the kidney or immobile in the ureter.19 It is unknown why the pain arises, although two theories exist: rapid dilation of the collecting system that compresses the renal parenchyma vs urinary extravasation.19 The pain also differs based on the stone location within the urinary system as a reflection of referred pain from the corresponding dermatomes. For example, in the renal pelvis and proximal ureter, pain presents in the costovertebral angle and flank and can be confused with conditions like pyelonephritis, cholecystitis, or acute pancreatitis depending on the side of the stone. In the distal ureter, pain radiates to the groin as a manifestation of referred pain from the ilioinguinal or genitofemoral nerve and needs to be distinguished from conditions like testicular torsion or epididymitis.20 A patient with stone colic will often be unable to lie still, which is in contrast to other acute abdominal pathologies, in which the patient does not move in order to prevent pain.19,20
Diagnosis of stones is made with imaging, with noncontrast computed tomography considered the gold standard with reported 97% sensitivity and 98% specificity (Fig. 19.1).15 Imaging with the patient in prone position is most informative because for very distal stones at the ureterovesical junction, prone position can distinguish if the stone is still in the ureter
or has passed into the bladder.21 Ultrasonography has emerged in recent years has a low-cost and radiation-free modality; however, its role in patients with suspected renal colic remains controversial, as sensitivities and specificities that have been reported in the literature vary widely.22 A review by Ray et al. found a pooled sensitivity and specificity of 45% and 94%, respectively, for ureteric stones and 45% and 88%, respectively, for renal stones.23 Additionally, scenarios that increase difficulty of identification of stones using ultrasonography include stones <3 mm due to absence of acoustic shadow, ureteral stones that can be obscured by bowel gas, and stones that abut the echogenic renal sinus fat.22,23 Two groups of patients in which the AUA, EAU, and ACR recommend ultrasound as first-line imaging modality to avoid radiation exposure are pediatric patients (<14 years old) and pregnant patients.24,25,26 In addition to imaging, labs should include determination of white blood cell count and serum creatinine to see if leukocytosis or acute kidney injury are present, respectively. Urinalysis and urine culture should also be obtained to evaluate for urinary infection.
or has passed into the bladder.21 Ultrasonography has emerged in recent years has a low-cost and radiation-free modality; however, its role in patients with suspected renal colic remains controversial, as sensitivities and specificities that have been reported in the literature vary widely.22 A review by Ray et al. found a pooled sensitivity and specificity of 45% and 94%, respectively, for ureteric stones and 45% and 88%, respectively, for renal stones.23 Additionally, scenarios that increase difficulty of identification of stones using ultrasonography include stones <3 mm due to absence of acoustic shadow, ureteral stones that can be obscured by bowel gas, and stones that abut the echogenic renal sinus fat.22,23 Two groups of patients in which the AUA, EAU, and ACR recommend ultrasound as first-line imaging modality to avoid radiation exposure are pediatric patients (<14 years old) and pregnant patients.24,25,26 In addition to imaging, labs should include determination of white blood cell count and serum creatinine to see if leukocytosis or acute kidney injury are present, respectively. Urinalysis and urine culture should also be obtained to evaluate for urinary infection.
 FIGURE 19.1 Images from a noncontrast renal protocol CT scan of a patient with a ureteral stone in the proximal third of the left ureter (arrows) in the (A) axial and (B) coronal views. (Adapted from Pena A, Ferretti JA. Stone disease imaging: there is more to x-rays than what we see! In: Schulsinger D, ed. Kidney Stone Disease. Springer; 2015.) |
Treatment
Treatment of stones in the urinary tract first and foremost involves determination if a stone should be managed medically or surgically in the acute setting. Reasons to intervene earlier include signs of urinary sepsis with obstruction, acute kidney injury that does not respond to fluid resuscitation, obstruction in a solitary kidney, inability to tolerate oral intake, or poor pain control. Urgent intervention in the acute setting involves placement of a ureteral stent or percutaneous nephrostomy tube in order to bypass the stone and decompress the renal collecting system.27 For patients with uncomplicated ureteral stones <10 mm, American Urologic Association (AUA) guidelines suggest offering observation with pain control and aggressive fluid hydration. If the stone is in the distal ureter, patients can be offered medical expulsive therapy (MET) with the addition of alpha-adrenergic blockers.27 Management of pain is crucial in this time period, especially if the stone is to be managed medically over the course of several weeks. Options for pain control include a variety of analgesics like acetaminophen, NSAIDs, and opioids. Choice of agents depends greatly on the clinical course of the patient. Intravenous opioids and NSAIDs are often used to quickly and effectively manage severe pain in the acute setting. If a patient is to be managed medically outpatient, oral options are utilized.19 For patients who fail medical management with either re-presentation with intractable pain or do not spontaneously pass the stone after multiple weeks, surgical intervention is often pursued. Options for eradication of stone are highly dependent on stone characteristics,
location, and patient preference. Types of intervention include extracorporeal shock wave lithotripsy, ureteroscopy and laser lithotripsy, percutaneous nephrolithotomy, and rarely laparoscopic and robotic stone removal or nephrectomy.27
location, and patient preference. Types of intervention include extracorporeal shock wave lithotripsy, ureteroscopy and laser lithotripsy, percutaneous nephrolithotomy, and rarely laparoscopic and robotic stone removal or nephrectomy.27
In patients who have required ureteral stenting, side effects with the stent in place are extremely common with 80% of patients having at least one symptom.28 These include flank and suprapubic pain, hematuria, dysuria, frequency, urgency, infection, incomplete emptying, incontinence, and encrustation.28,29 The etiology of these symptoms, while not completely understood, is thought to be related to reflux of urine through the stent during voiding, as well as movement of the stent within the kidney, ureter, and bladder.30 Medications that target stentrelated pain include alpha-blockers, anticholinergics, and pregabalin.
Alpha-blockers are primarily utilized for treatment of hypertension and benign prostatic hyperplasia but have off-label use for MET and ureteral stent pain.30 Tamsulosin is an alphaadrenergic antagonist that targets the alpha1 receptors, which are located in the smooth muscle of the prostate, bladder neck, and ureter. Its use in MET and ureteral stent pain is related to the presence of these receptors in the ureter, with the highest density in the distal ureter.30 Their role in MET is supported by the aforementioned AUA/Endourologic Society guidelines in which their recommendation is specifically for distal ureteral stones <10 mm, as no clear benefit was demonstrated for proximal or mid-ureteral stones in their meta-analysis.27 With respect to stent discomfort, alpha-blockers help to dilate the ureteral lumen, decrease ureteral spasms and motility, relax trigonal smooth muscle, as well as decrease intravesical pressure and reflux through relaxation of the bladder neck.30 Patients should be counseled on side effects of orthostatic hypotension, dizziness, headache, fatigue, and retrograde ejaculation.
The role of anticholinergics in urology is predominantly used for overactive bladder, but they are also used in ureteral stent-related pain. Data are controversial about whether they provide a benefit as a monotherapy or in combination with alpha-blockers. Physiologically, anticholinergics are thought to decrease detrusor overactivity that is associated with bothersome voiding symptoms.30 Whether used alone or in combination with other agents, it is important to consider side effects of anticholinergics that include dementia, blurred vision, headache, dry mouth, orthostatic hypotension, ileus, and urinary retention.
Pregabalin is the last agent that has had recent evidence emerge for its role in ureteral stent pain. A study by Ragab et al. randomized 489 patients who underwent ureteroscopy with stent placement to combination anticholinergic and pregabalin, anticholinergic only, pregabalin only, and placebo. They showed that all groups had lower symptom scores than the placebo group. The hypothesis behind the role of pregabalin in stent pain is by decreasing firing of unmyelinated C fibers with mechanical irritation.31
Priapism
Background
Priapism, as defined by the American Urological Association, is a persistent penile erection lasting at least 4 hours that is either unrelated to, or continues hours beyond, sexual stimulation.32 There are three types of priapism: ischemic, nonischemic, and stuttering. Ischemic priapism is characterized by cavernosal venoocclusion, which is essentially a form of compartment syndrome. Nonischemic priapism has a high cavernous arterial inflow, and stuttering priapism is a form of ischemic priapism with periods of detumescence in between recurrent painful erections.32 Ischemic priapism lasting over 24 hours can have up to a 90% risk of longterm erectile dysfunction, making prompt diagnosis and management essential.33 Conversely, nonischemic priapism is not an emergency and usually resolves with conservative management.
Priapism is rare, with epidemiological studies from the past two decades citing incidence between 0.84 and 5.34 cases per 100 000 male person years.34,35,36 Over 95% of cases are ischemic in origin.37 Historically, ischemic priapism has been attributed to sickle cell disease in about two-thirds of pediatric cases and one-quarter of adult cases, with a greater proportion of adult cases due to alternative etiologies such as iatrogenic from intracavernosal injections for erectile dysfunction or from erectogenic medications like trazodone.33
Symptoms and Diagnosis
The diagnosis of priapism is considered to be unmistakable, with the primary goal in differentiating between ischemic vs nonischemic priapism. Key features on history, physical examination, and testing can help differentiate between the different types of priapism. Ischemic priapism is painful with a fully rigid penis, patients are more likely to have a history of hematologic abnormalities like sickle cell disease or a history of recent intracavernosal vasoactive drug injections, and cavernosal blood gases will usually be hypoxic, hypercarbic, and acidotic.32 In contrast, nonischemic priapism is rarely painful, does not cause a fully rigid erection, has normal cavernosal blood gases, and is more likely to be associated with a history of recent perineal trauma.37 Color duplex ultrasonography is considered an alternative or adjunct to cavernosal blood gas sampling; patients with ischemic priapism have little to no blood flow in the cavernosal arteries as opposed to normal to high flow in nonischemic priapism.32
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