SPECIFIC FACTORS OF NOCTURIA: A SPECIALIST PERSPECTIVE An interview with Eric S. Rovner, MD Eric S. Rovner, MD, is Associate Professor of Urology at the Medical University of South Carolina in Charleston. Dr Rovner received his medical degree at Albert Einstein College of Medicine and completed an internship in surgery and residency in urology at the Hospital of the University of Pennsylvania in Philadelphia. Previous faculty appointments include Assistant Professor of Urology in Surgery and Assistant Professor of Surgery in Radiology at the University of Pennsylvania School of Medicine. He is a member of several national, international, regional, and local societies, including the American Urological Association and the American Association of Clinical Urologists. Dr Rovner is a published author or coauthor of over 50 peerreviewed research articles and various editorials, reviews, and chapters, in addition to an invited lecturer at national and international meetings. His areas of interest include urinary incontinence, interstitial cystitis, and overactive bladder. A senior clinical editor for Advanced Studies in Medicine (ASiM) interviewed Dr Rovner to discuss different methods for diagnosing and treating nocturia. ASiM: In urology and urogynecology practice, what are some important considerations in patients with nocturia? Dr Rovner: When considering the individual with nocturia, it is critically important to recognize that this condition does not represent a single entity with a single underlying pathophysiology. Nocturia is associated with several potential etiologies. When one looks back 30 or 40 years, especially in the male, physicians were, to some degree, naïve and even simplistic in that we attributed nocturia to benign diseases of the prostate or sometimes, I suppose, even malignant diseases of the prostate. As the years progressed, we have gained a much better understanding of nocturia and its multifactorial origin and thus, multifactorial treatments. Nocturia has many causes, including most commonly nocturnal polyuria and detrusor overactivity. However, there are many medical conditions that result in nocturia secondarily. ASiM: How serious do you think these considerations are? In your opinion, is this condition underreported? Dr Rovner: Nocturia is currently defined by the International Continence Society as 1 or more times voiding per night. This is a very a broad and inclusive definition. As such, it may very well be underreported; however, the prevalence of the condition is not as important as the actual number of individuals with the symptom who desire therapy. This is the bigger issue. How many individuals with nocturia times 1 desire an intervention or would present to a physician with such a request primarily? It is such a highly prevalent symptom with such a wide range of bothersomeness attributed to it. It is very likely that most individuals with lesser degrees of nocturia are reasonably healthy without considerable bothersomeness or a medically relevant secondary cause for their nocturia. However, having said this, even a single episode of nocturia can be quite debilitating to some individuals. In addition, as noted previously, nocturia can be secondary to a serious medical problem. These include conditions, such as undiagnosed diabetes or heart disease. Therefore, the seriousness of the nocturia depends on the circumstances under which the patient comes for evaluation. If, in fact, the patient comes for evaluation because he or she is considerably bothered by the symptoms, this is 1 set of circumstances. If another physician refers the patient to me because of a concern about a secondary urologic or nonurologic condition causing the nocturia, this is another set of circumstances. S24 Vol. 6 (1A) January 2006
ASiM: Then it is highly prevalent over the course of many different causative factors? Dr Rovner: Yes, it is only a problem if the person considers it as such or they have a serious underlying condition causing the problem. Most individuals with 1 episode of nocturia may not choose to come to their physician to have it evaluated. They may simply choose to live with it. ASiM: What is the role of primary care physicians (PCPs) in diagnosing nocturia or nocturnal frequency? What are some best practices in the referral process? Dr Rovner: The role of the PCP with respect to nocturia is in the identification of symptoms, and then selecting the patients who have the symptom and who desire therapy or identifying those individuals who may have an important secondary medical condition causing the symptom. If the nocturia is not likely secondary to an underlying medical condition, the level of interest among PCPs in addressing this problem is quite variable. Understandably, PCPs have a lot on their plates and unless they have a specific interest in the lower urinary tract, this may not be an area in which they want to pursue further diagnostic evaluation. However, it is within the role of a PCP to evaluate the patient for systemic disorders that can present with complaints of nocturia, including endocrine disorders, vascular disorders, and cardiac disorders. Beyond that, the pursuit of urologic disorders varies considerably from PCP. Many of my primary care colleagues are fully capable of and interested in evaluating nocturia and initiating appropriate therapy. It really depends on their level of comfort with disorders of the lower urinary tract. There are many PCPs with the knowledge and comfort in initiating primary therapy for urologic causes of nocturia. They have been doing this for years for some patients with nocturia as a result of benign prostatic hyperplasia by prescribing pharmacologic agents, such as α blockers or 5-α reductase inhibitors. If this initial empiric course of therapy is ineffective, then referral to a specialist might be indicated. Whether this reflects a best practice scenario is unclear. Best practice would depend on many factors, including cost, access to healthcare specialists, patient satisfaction, and the economics in each local microeconomic environment in which people practice. On the other hand, it is important to remember that PCPs would certainly be the key healthcare professional for identifying and then subsequently treating a variety of secondary, nonurologic causes of nocturia, such as congestive heart failure (CHF) or diabetes. ASiM: Describe a patient with nocturia. How might patient history and physical examination differ when diagnosing nocturia and determining the cause? Describe the differential diagnoses that predominate in your practice in patients presenting with nocturia. Dr Rovner: A 75-year-old female has symptoms of nocturia for 8 or 9 years, and she doesn t have much in the way of daytime problems. She wakes up 3 or 4 times at night and has urgency and occasionally leaks on the way to the bathroom, but she has essentially no daytime problems. She might go to the bathroom 4 or 5 times during her waking hours. She is a very active 75-year-old with no other significant medical history except well-controlled, mild essential hypertension. She has not had prior lower urinary tract or gynecological surgery. The first time I examine her is in the afternoon, and on physical examination she has some pitting edema about the ankles. She doesn t have clinical evidence suggestive of CHF. Pelvic examination reveals no vaginal prolapse, and her bladder is palpably empty. She has a normal urine analysis, and she takes hydrochlorothiazide in the evening for her hypertension. The most notable factor in the history for the patient described is that her symptoms are present only at night; she has an essentially normal voiding pattern during the day. On physical examination, she has lower extremity edema, which suggests venous insufficiency. She is aware of this and notes that it has gotten a little worse over the past few years. Nevertheless, she does relate that when she wakes up in the morning her lower extremity swelling is almost completely gone. In addition, she may note that at the end of the day her shoes don t fit as well as they did when she put them on in the morning. Diagnostic considerations as causes of her nocturia might be related to the venous insufficiency, the diuretic usage, or both. It is unlikely that she has overactive bladder (OAB) given her lack of symptoms during the day. The normal urine analysis is helpful in discounting infection or bladder cancer among other possibilities as a likely cause of her symptoms. The venous insufficiency may be the cause of her lower extremity edema and, in turn, the nocturia. Once supine, the fluid accumulation in her legs may Advanced Studies in Medicine S25
be reabsorbed, recirculated, and result in increased urine production at night. On the other hand, afternoon or evening dosing of the diuretic may result in the rapid production of urine during sleeping hours, which could be contributing to her nocturia. ASiM: What might be the next step with this patient? Dr Rovner: I find the most helpful diagnostic aid, in addition to aid in monitoring therapy, to be a voiding diary voiding diary being generally characterized as a record of how often the patient urinates and the volumes and times at which he or she urinates. On my voiding diary, I have several columns; the patient puts the time of each voided event, the volume of each voided event, the type of fluid and food intake throughout the day, and the time of each intake. The patient also includes whether he or she has experienced an episode of urgency associated with each void and, finally, an episode of incontinence associated with each void. With respect to evaluating nocturia specifically, I ask the patient to record the time that he or she goes to sleep and the time that he or she wakes up. That tells me everything I need to know about the patient s voiding symptoms in his or her own environment. It is crucial to understand that a significant limitation of a voiding diary is that patients often modify their behavior unwittingly while filling out the diary. It is accepted that there exists a subtle process of behavior modification that occurs simply by filling out a voiding diary. However, I specifically tell patients not to change their voiding habits whether they actually do this is another story. ASiM: Is the diary kept over the course of one 24- hour period or several days? Dr Rovner: In my practice, I like to utilize a 3-day diary. This is more a personal bias than a result of any evidence-based medicine. I think that a single-day diary is subject to considerable variability as a result of changes in an individual s fluid intake, exercise pattern, or food intake for that single day. With a 3-day diary, I am more likely to capture a mean or an average of the patient s usual habits. ASiM: Are patients more likely to be compliant with the 3-day diary but not so with a 7-day diary? Dr Rovner: A 7-day diary may be even more accurate than a 3-day diary; however, it is quite burdensome for the patient to complete such a request. In addition, I am not sure that I will gain additional information from a 7-day diary that is not readily apparent from the 3-day diary. ASiM: What nonpharmacologic interventions would you recommend? Dr Rovner: Before recommending an intervention of any kind, I will ask the patient directly whether he or she is bothered by the nocturia to the point where he or she desires therapy. It is important to remember that individuals with voiding dysfunction may present to the healthcare practitioner for a variety of reasons; although most patients desire some sort of intervention and improvement in their symptoms, others simply want to be reassured that there are no serious underlying problems. Still other patients are referred by another healthcare practitioner for an evaluation. These represent distinct groups of patients with different goals. With our patient, if she is coming to see me but isn t particularly bothered by her nocturia to the point where intervention is desired, I will do the appropriate evaluation and reassure her. If, on the other hand, she is bothered by the nocturia and wants to see if we can improve it, then we can talk about the nonpharmacologic, nonsurgical interventions; such interventions, in general, would be fairly easy to implement. An initial intervention would be some simple behavioral modification based on the voiding diary results. Once she fills out her diary, I will have a record of her fluid intake in relation to her voiding symptoms and nocturia. For example, if she drinks, 2 or 3 glasses of water with dinner and then 2 or 3 cups of tea or coffee in the evening, we can discuss reducing her fluid intake in the evening. These are very simple behaviors that, when altered, might have a tremendous impact on her nocturia. In addition, in this particular individual we might consider elevating her legs in the evening. She clearly has some lower extremity edema and, if her diary suggested that she had nocturnal polyuria or excessive fluid output at night, then I would suggest perhaps that she raise her legs for several hours before retiring to facilitate fluid redistribution before she goes to bed. An even simpler measure would be for her to place compressive stockings or hose on her legs during the day. By using compressive hose, one can reduce the fluid buildup in the lower extremities when the individual is upright walk- S26 Vol. 6 (1A) January 2006
ing or pursuing normal daily activities. Later, when the stockings are removed at night, there is generally less excess fluid in the lower extremities. This should result in less redistribution and less nocturia. Another simple behavioral measure in this particular individual would be to shift her diuretic dosage to first thing in the morning. ASiM: How compliant are patients who have mild, moderate, or severe nocturia with nonpharmacologic interventions? Dr Rovner: It is very variable depending on the individual and his or her degree of bother. People can go to the bathroom hourly throughout the night and may or may not have a tremendous degree of bother. I can advise the patient to wear compression hose and change her diuretic dosing, but she is not going to do even the simplest intervention if she is not bothered by her symptoms. On the other hand, if the patient has recently developed nocturia, needs 8 hours of uninterrupted sleep to function the next day, and is completely incapacitated by waking up once at night, the patient will likely be very compliant. There are no known markers that I am aware of that prospectively characterize individuals who would be compliant with such behavioral programs. ASiM: Several medications normally prescribed for specific conditions can cause urinary incontinence, including nocturia. These include α-adrenergic agonists and blockers, angiotensin-converting enzyme inhibitors, anticholinergics, calcium channel blockers, and of course, diuretics, such as the thiazides and furosemide. Other than the obvious recommendation that patients limit their fluid intake before retiring, what are your management recommendations in patients whose medications include any of these agents? Dr Rovner: Clearly, there are several medications that can clinically and pharmacologically result in the aggravation of voiding symptoms, including incontinence; whether a specific medication in a certain individual results in such an outcome is not always clear. There is a tremendous amount of recall bias with respect to taking a medical history. Relating the onset of symptoms to starting a new medication, especially when the indication for the medication has no relation to the possible side effect, is a good example of this bias. I generally ask patients if their urinary symptoms began relative to having started a new medication. In other words, did their urinary symptoms coincide with initiating this medication? Often, the patient will not have made the connection. If the patient does make a connection with medication and symptoms, then the patient is sent back to whoever prescribed that medication to ask whether there is an alternative medication. However, if it is unclear, I may check with the patient s PCP or internist. If the onset of symptoms and the initiation of the medication are related, then I will query the internist or PCP to see if there is a suitable alternative medication. If possible, the potentially problematic medication will be discontinued and the urinary symptoms monitored for resolution. ASiM: Would changing the time of the dosing of the offending medication make any difference? Dr Rovner: With respect to certain agents, such as diuretics, there is a definite relationship. Dosing of a diuretic at night often results in nocturia. If the dosing regimen can be changed to the morning, the nocturia may improve or resolve. However, sometimes changing dosing regimens is clinically not feasible. The relationship with other classes of medications may not be so obvious. ASiM: How important is it to tailor treatment to the underlying pathophysiology of nocturia? Dr Rovner: It is often extremely helpful to define the underlying pathophysiology. I think that if an individual already has been prescribed empiric behavioral therapy or even drug therapy, and the patient has not had an optimal response, then it is critically important to initiate further investigations and tailor treatment to the underlying pathophysiology. On the other hand, if the individual has had a medical evaluation and is otherwise healthy, then empiric therapy can be tried initially. ASiM: Of the available pharmacologic treatments, what are the differences in efficacy and patient compliance? Dr Rovner: For the group that suffers from detrusor overactivity or OAB, antimuscarinic therapy remains the mainstay of therapy. There is a wide variety of antimuscarinic agents available for OAB. Currently, their efficacy in nocturia is not well defined. Nevertheless, they are effective in the treatment of OAB and as a component of OAB; nocturia Advanced Studies in Medicine S27
has the potential to be effectively treated by some of these agents. ASiM: How would you traditionally follow up with the 75-year-old woman? Dr Rovner: After her initial visit, I would probably have her return in 4 to 8 weeks to assess her response subjectively and objectively with another diary. The diary will allow me an objective parameter to determine if the intervention has been at all efficacious. ASiM: Now we have treated with the stockings and behavior modification, and the patient completed another diary after 2, 3, or 4 weeks. How would you make another determination of whether you need to see her again? Dr Rovner: Well, I would assess her response and, if she were happy, I would send her back to her PCP and tell her to call me if there are any problems. If she were unhappy, we would explore some other options for treating her. With this individual, we might consider pharmacologic therapy. ASiM: Which pharmacologic therapy might you include? Dr Rovner: Based on my examination and the lack of vaginal prolapse and a nonpalpable bladder on bimanual examination, in addition to the lack of prior bladder or urethral surgery on history, it is unlikely that this female with nocturia has an obstruction or poor bladder emptying as the cause of her symptoms. Therefore, my first choice of drug therapy with this individual would likely be trial of an antimuscarinic agent. It would be dosed at bedtime, which in recent studies seems to reduce some of the adverse side effects of this class of agents, including dry mouth and constipation. I would be sure to reinforce the need to continue whatever behavior modifications were previously instituted. A suitable medication trial of 4 to 8 weeks would be given, and the patient would return to the office with another diary and symptom assessment. A decision to continue drug therapy, increase the dose, change drugs, or change therapy altogether would be based on the patient s response to the treatment and whether any adverse events were noted. If the patient was satisfied, I would refer her back to the PCP. Another alternative agent for nocturia might be a vasopressin analogue, such as desmopressin acetate. If, upon review of the initial voiding diary, the patient was found to have nocturnal polyuria that was not a result of a secondary cause, this class of agents might result in reduction of nocturia. However, in some patient groups, including the geriatric population, the administration of a vasopressin analogue, such as desmopressin acetate, is associated with some safety issues, including hyponatremia and free water overload. It is not commonly reported, but it can happen. ASiM: What would be your expectation of the antimuscarinic in this patient? Dr Rovner: My expectation would be to reduce her nocturia by approximately 33%. In someone who has nocturia associated with OAB 3 or 4 times, my expectation would be to get them at best to have nocturia 1 or 2 times. S28 Vol. 6 (1A) January 2006