Nocturia in the elderly: A wake-up call

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Nocturia in the elderly: A wake-up call
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Vincent Varilla, MD
Renato V. Samala, MD, FACP
Diana Galindo, MD, FACP, AGSF
Jerry Ciocon, MD, FACP, AGSF

Nocturia is common, but elderly patients infrequently volunteer this complaint, and even when they do, some clinicians may dismiss it as simply a part of aging. Nevertheless, nocturia causes significant distress and impairment of quality of life. It is associated with very serious consequences such as depression, social isolation, and a higher risk of death.

In this article, we review the concepts behind frequent nighttime voiding in older adults. We will start with two case scenarios to aid in understanding these concepts; near the end of the article, we will discuss the most appropriate management strategies for these two patients.

CASE SCENARIOS

Case 1: An 82-year-old man with fatigue

An 82-year-old obese white man with a history of hypertension, diabetes, and benign prostatic hyperplasia comes in to see his primary care provider, complaining of fatigue. He wakes up tired and has difficulty completing his daytime tasks. He gets up every 1 to 2 hours at night to urinate and has slow urinary flow and a feeling of incomplete bladder emptying.

See related patient education material

He says his wife has been increasingly bothered by his loud snoring. Recently, he had a car accident when he fell asleep while driving.

Case 2: An 85-year-old woman with incontinence

An 85-year-old white woman is in her family physician’s office with a primary complaint of waking up at least four times at night to urinate, and often ends up soaking her bed or adult diapers. She is bothered by urinary urgency and frequency during the day as well. She denies dysuria and hematuria.

She has a history of hypertension and urinary incontinence, and she has seven children. Her current medications are diltiazem (Cardizem), metoprolol (Toprol), and oxybutynin (Ditropan).

In these two cases, what would account for the nocturia? What would be the best way to help these patients?

THE NORM, NOT THE EXCEPTION

Although nocturia is defined as an awakening by the need to urinate even once in a night, many experts consider that it begins to be clinically significant only when the patient voids at least twice during the night.1

In older adults, nocturia is the norm rather than the exception. Studies done between 1990 and 2009 found that 68.9% to 93% of men age 70 and older get up at least once a night to void. The prevalence in women is somewhat lower, at 74.1% to 77.1%.2 Clinically significant nocturia is present in a majority of the elderly: more than 60% of both men and women.3

An Austrian study4 reported that elderly men got up to urinate a mean of 2.8 times per night, while women got up significantly more often—3.1 times. Women were also bothered more by this symptom, and their quality of life was significantly more decreased.

In another study,5 whites had a significantly higher nocturia ratio (ratio of nighttime urine volume to the 24-hour urine volume) than Asians. Asians, on the other hand, had a significantly higher nocturnal bladder capacity index than whites. (See below for definitions of the various indices of nocturia.) This information implies that nocturia may be a more prominent problem for elderly whites than for other racial groups.

In an epidemiologic study in Sweden,6 the death rate was as much as twice as high in both men and women who had three or more nocturnal voids, even after taking into account the influence of cardiac disease, diabetes mellitus, and stroke.

If nocturia is not addressed in the physician-patient encounter, patients may try to “self-manage” it by restricting their fluid intake or by limiting their social exposure,7 with limited success and with unwanted social isolation.

WHAT CAUSES NOCTURIA?

In almost all cases of nocturia in elderly people, the cause is multifactorial (Table 1).

Advancing age is primary among these factors. Age-related structural changes in the urinary system include decreased functional bladder capacity, a decreased maximum urinary flow rate,6 a decreased ability to postpone urination,8 and an age-related increase in postvoiding residual urine volume.9 The aging kidney is also less able to concentrate urine. Also implicated are histologic changes in the detrusor muscle10 that lead to diminished bladder compliance and, together with detrusor overactivity, result in increased urinary frequency.

Nocturnal polyuria or nocturnal urine overproduction is common in patients with nocturia.11

Although the pathophysiology of nocturnal polyuria is still unclear, some investigators believe that low levels of antidiuretic hormone (ADH) at night are involved, reflecting an alteration in the circadian rhythm seen in diurnal plasma arginine vasopressin levels.12 In patients with nocturnal polyuria, ADH levels drop to very low or undetectable levels at night, which increases nocturnal urine output. In some extreme cases, the low to absent levels of ADH increase nocturnal voiding to 85% of the total 24-hour urine volume.13

Other causes of nocturnal polyuria include mobilization of fluids in patients with edema,14 and autonomic dysfunction. Other biochemical changes that contribute to nocturia include a decrease in nighttime plasma melatonin levels, an increase in nighttime plasma catecholamine levels, an increase in nighttime plasma natriuretic peptide levels, an increase in blood pressure, and an increase in total urine volume.15

A decreased ability to store urine also leads to nocturia. This is caused by decreased nocturnal bladder capacity, more irritative symptoms, and comorbid conditions such as overactive bladder, pelvic floor laxity resulting in pelvic organ prolapse, and, in men, benign prostatic hyperplasia.

Neural inputs to the bladder can also be impaired, as in patients who have diabetes mellitus or spinal stenosis, leading to chronic urinary retention, detrusor dysfunction, nocturia, and incontinence.

 

 

WHICH PATIENTS ARE AT RISK?

Nocturia is associated with a number of risk factors (Table 2).

Obesity is associated with a higher incidence of moderate to severe nocturia.15 Studies have shown that the higher the body mass index, the greater the number of nighttime voids, especially in women.16

Habitually eating at night, with poor daytime appetite, is shown to be associated with increased nighttime diuresis.

Obstructive sleep apnea17 and untreated depressive symptoms such as frequent napping18 are also associated with moderate to severe nocturia.19

Higher systolic blood pressures are associated with more urine production at night. Plasma ADH regulation is also altered, which contributes to nocturnal polyuria.21

Other comorbid conditions associated with nocturia include recurrent cystitis, lung disease, congestive heart failure, neurodegenerative conditions (eg, Alzheimer disease and parkinsonism), and chronic kidney disease.21

Drugs associated with nocturia include cholinesterase inhibitors (for dementia),22 beta-blockers,23 and calcium channel blockers.24

Lifestyle factors. Alcohol and coffee have shown either no or only a mild diuretic effect. Smoking has not been shown to be associated with nocturia.15

Seasonal differences also exist, with increased frequency of nocturia in the winter.25

WHAT ARE THE CLINICAL CONSEQUENCES OF NOCTURIA?

Nocturia’s effects are varied and are very important to address (Table 3).

Quality of life can be profoundly affected, and if nocturia is left untreated, it may lead to morbidity and even death. Elderly patients may feel simultaneously debilitated, frustrated, distressed, and puzzled. Nocturia may also increase their fear of falling and may negatively affect personal relationships.26

Falls, injuries. Nocturia exposes elderly patients to injuries such as hip fractures due to falling, significantly increasing the incidence of this injury.26 This occurs as elderly patients get up from bed and walk to the bathroom to void.27 In addition, during the day, superficial and fragmented sleep leads to daytime sleepiness and impaired perception and balance, also increasing the risk of falls.28 The complications of immobility and the need for surgery in many cases lead to debility, increased risk of infections, decubitus ulcers, and death. The risk of hip fractures can lead elderly patients with nocturia to associate this symptom with a fear of falling and can alter their concept of their own age (“Nocturia makes me feel old”),29 further diminishing quality of life.

The estimated medical cost of nocturia-associated falls in the elderly is about $1.5 billion per year, part of the $61 billion in lost productivity due to nocturia in adults.30

Long-term complications (eg, debilitation, poor sleep, obesity, decreased energy), increase the overall mortality rate, especially in patients who report voiding more than three times per night.29 Elderly patients with nocturia also have a greater need for emergency care.31

Nocturia also complicates other comorbid conditions, such as dementia, which increases the risk of urinary incontinence.32 In patients who have had a stroke, nocturia is the most frequent lower urinary tract symptom, and represents a major impact on daily life.33

Sleep disturbance is another important consequence. In one survey,34 nocturia was cited as a cause of poor sleep four times more often than the cause cited next most often, ie, pain. Because the elderly patient is awakened from sleep numerous times throughout the night, nocturia leads to more fatigue,35 lower energy levels, and poorer quality of sleep.36 Depression may be linked to poor sleep, as men with two or more nocturnal episodes were shown to be six times more likely to experience depression.

The patient is not the only person who loses sleep: so do the patient’s family members or sleeping partner.7 It is therefore not surprising that sleep disruption caused by nocturia has been cited as a principal reason for admitting older relatives to care homes.37

The risk of death is higher for elderly patients with coronary heart disease if they have nocturia. The causative link is the hemodynamic changes (increases in blood pressure and heart rate) that accompany awakening and arising, which may cause cardiovascular strain and lead to cardiovascular events. The 12-year survival rate has been shown to be significantly lower in patients with nighttime voiding, making nocturia a highly significant independent predictor of death in coronary heart disease patients.38

HOW TO EVALUATE AN OLDER ADULT WHO PRESENTS WITH NOCTURIA

A thorough history and physical examination are crucial in diagnosing nocturia. The goal is to identify any treatable underlying condition, such as diabetes mellitus, obstructive sleep apnea, diabetes insipidus, overactive bladder, benign prostatic hyperplasia, urinary tract infection, and congestive heart failure. Laboratory tests and imaging studies can help rule out these underlying conditions.

Other important facets in the history that must be elicited are medication use, patterns of fluid intake, and a history of other urinary complaints.39

A voiding diary and indices of nocturia

A voiding diary is extremely useful and should be used whenever possible. Episodes of incontinence, time of voids, volume voided, and frequency and volume of fluid intake are recorded. From the raw data, one can determine the following:

Total nocturnal urine volume, ie, the sum volume of the nighttime voids

Maximum voided volume, ie, the largest single recorded volume voided in a 24-hour period

Nocturia index, ie, the total nocturnal urine volume divided by the maximum voided volume. A nocturia index greater than 1 shows that nocturnal urine production is greater than the functional bladder capacity. Clinically significant nocturia is observed in patients with a nocturia index of 2.1 or greater.

Nocturnal polyuria index, ie, total nocturnal urine volume divided by the 24-hour urine output. A nocturnal polyuria index higher than 33% implies nocturnal polyuria.40

Nocturnal bladder capacity index, ie, the actual number of nightly voids minus the predicted number of nightly voids, which in turn is calculated as the nocturia index minus 1.

It is especially important to encourage patients to make a voiding diary, as some patients may find this cumbersome, and compliance can be low unless its importance is emphasized. A diary over 7 days usually gives meaningful data. The results from the diary typically confirm the presence of nocturnal polyuria or a decrease in bladder capacity, influencing management.41

 

 

WHAT ARE THE TREATMENT OPTIONS?

Therapy must be directed at the primary cause, addressing any underlying conditions that can contribute to nocturia. Examples39:

  • Tight control of blood sugar for patients with diabetes mellitus
  • Treatment of diabetes insipidus
  • Referral for patients with primary polydipsia
  • Management of hypercalcemia and hypokalemia
  • A survey of medications
  • Treatment of infections.

Nonpharmacologic measures

Tailored behavioral therapy can also be instituted, but the patient needs to have realistic expectations, as these measures are rarely effective alone.

Avoiding nighttime fluid intake, including alcohol and caffeine, has shown promise.

Wearing compression stockings and elevating the legs in the afternoon decrease the retention of fluid that otherwise would return to the circulation at night.

Identifying and eliminating nighttime influences that disturb sleep has variable efficacy. The use of continuous positive airway pressure helps to treat sleep apnea. Moderate exercise, reducing nonsleep time spent in bed,42 and sleeping in a warm bed43 to decrease cold diuresis have also been shown to improve sleep quality.44 Patients with nocturia may have a disrupted circadian rhythm, and phototherapy may help resynchronize the diurnal rhythm and melatonin secretion.

Pharmacotherapy

Pharmacotherapy of nocturia includes desmopressin (DDAVP) to manage nocturnal polyuria and antimuscarinic agents to manage the patient’s decreased ability to store urine. Alpha-blockers such as tamsulosin (Flomax) and 5-alpha-reductase inhibitors such as finasteride (Proscar) are used for men with benign prostatic hyperplasia. Novel and second-line therapies include diuretics such as furosemide (Lasix), cyclooxygenase-2 inhibitors, as well as botulinum toxin injected directly into the detrusor muscle for overactive bladder.45

Desmopressin in a low oral dose (0.1–0.4 mg) at bedtime can be initiated and the response assessed. Patients with nocturnal polyuria and disorders of the vasopressin system have been found to be more sensitive to desmopressin therapy.46 Fluid retention and hyponatremia can complicate therapy, and desmopressin must be avoided in patients with liver cirrhosis, renal failure, or congestive heart failure.47

Antimuscarinic agents are effective for patients who have lower urinary tract symptoms and for those with a diminished ability to store urine. They act by decreasing both voluntary and involuntary bladder contractions by blocking muscarinic receptors on the detrusor muscle. This reduces the bladder’s ability to contract and the urge to urinate, thereby increasing bladder capacity.48 These agents include oxybutynin (Ditropan), tolterodine (Detrol), solifenacin (Vesicare), and propiverine (not available in the United States).

Diuretics are being used as second-line agents or for patients who cannot tolerate desmopressin.49 Hydrochlorothiazide is taken 8 hours before bedtime to prevent water accumulation before the early sleeping hours.50 Furosemide has also led to a reduction in the mean number of nocturnal voids.51 The effect of these drugs on nocturia are especially beneficial to patients with concomitant hypertension or cardiovascular disease.

Cyclo-oxygenase-2 inhibitors such as celecoxib (Celebrex)52 and other nonsteroidal anti-inflammatory drugs such as diclofenac (Voltaren, others)53 and loxoprofen (not available in the United States)54 have been shown to decrease urine production, detrusor muscle tone, and inflammation, especially in men with benign prostatic hyperplasia.

Botulinum toxin has been used, usually in patients refractory to first-line treatment.44

Referral to specialists is guided by underlying causes. Referral to a pulmonologist or sleep specialist may be helpful if the patient has obstructive sleep apnea. Referral to a urologist may be prudent if the patient has benign prostatic hyperplasia, and a gynecologist can address issues such as pelvic relaxation.

Table 4 summarizes the treatment strategies for nocturia.

CASES REVISITED

The first patient described above has nocturia caused by several concomitant diseases, ie, hypertension, diabetes, benign prostatic hyperplasia, and obstructive sleep apnea. In addition to controlling his blood pressure and blood sugar, his primary care provider referred him to a pulmonologist, who confirmed obstructive sleep apnea with polysomnography and prescribed nightly use of a continuous positive airway pressure apparatus. A few weeks later, the patient’s nocturia had improved significantly, and his level of fatigue had decreased.

Apart from hypertension, the second patient’s nocturia was mostly attributed to her existing urinary incontinence. Recognizing that her current antihypertensive regimen may worsen nocturia, her family physician changed it to enalapril (Vasotec) and doxazosin (Cardura) and counseled her to restrict her fluid intake 2 hours before bedtime. She was also referred to a gynecologist, who found a moderate degree of cystocele and treated her with a collagen injection. Her nocturia improved significantly.

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  41. Jaffe JS, Ginsberg PC, Silverberg DM, Harkaway RC. The need for voiding diaries in the evaluation of men with nocturia. J Am Osteopath Assoc 2002; 102:261–265.
  42. Yoshimura K, Terai A. Classification and distribution of symptomatic nocturia with special attention to duration of time in bed: a patient-based study. BJU Int 2005; 95:1259–1262.
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  48. Andersson K. Treatment of the overactive bladder syndrome and detrusor overactivity with antimuscarinic drugs. Continence 2005; 1:1–8.
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Author and Disclosure Information

Vicent Varilla, MD
Department of Medicine, University of Connecticut Health Center, Farmington

Renato V. Samala, MD, FACP
Department Geriatrics, Cleveland Clinic Florida, Weston

Diana Galindo, MD, FACP, AGSF
Department of Geriatrics, Cleveland Clinic Florida, Weston

Jerry Ciocon, MD, FACP, AGSF
Department of Geriatrics, Cleveland Clinic Florida, Weston

Address: Jerry Ciocon, MD, Cleveland Clinic Florida, 3250 Meridian Parkway, Weston, FL 33331; e-mail cioconj@ccf.org and jocjay@aol.com

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Cleveland Clinic Journal of Medicine - 78(11)
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Nephrology
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Author(s)
Vincent Varilla, MD
Renato V. Samala, MD, FACP
Diana Galindo, MD, FACP, AGSF
Jerry Ciocon, MD, FACP, AGSF
Author(s)
Vincent Varilla, MD
Renato V. Samala, MD, FACP
Diana Galindo, MD, FACP, AGSF
Jerry Ciocon, MD, FACP, AGSF
Author and Disclosure Information

Vicent Varilla, MD
Department of Medicine, University of Connecticut Health Center, Farmington

Renato V. Samala, MD, FACP
Department Geriatrics, Cleveland Clinic Florida, Weston

Diana Galindo, MD, FACP, AGSF
Department of Geriatrics, Cleveland Clinic Florida, Weston

Jerry Ciocon, MD, FACP, AGSF
Department of Geriatrics, Cleveland Clinic Florida, Weston

Address: Jerry Ciocon, MD, Cleveland Clinic Florida, 3250 Meridian Parkway, Weston, FL 33331; e-mail cioconj@ccf.org and jocjay@aol.com

Author and Disclosure Information

Vicent Varilla, MD
Department of Medicine, University of Connecticut Health Center, Farmington

Renato V. Samala, MD, FACP
Department Geriatrics, Cleveland Clinic Florida, Weston

Diana Galindo, MD, FACP, AGSF
Department of Geriatrics, Cleveland Clinic Florida, Weston

Jerry Ciocon, MD, FACP, AGSF
Department of Geriatrics, Cleveland Clinic Florida, Weston

Address: Jerry Ciocon, MD, Cleveland Clinic Florida, 3250 Meridian Parkway, Weston, FL 33331; e-mail cioconj@ccf.org and jocjay@aol.com

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Related Articles
Do you get up a lot at night to go to the bathroom?

Nocturia is common, but elderly patients infrequently volunteer this complaint, and even when they do, some clinicians may dismiss it as simply a part of aging. Nevertheless, nocturia causes significant distress and impairment of quality of life. It is associated with very serious consequences such as depression, social isolation, and a higher risk of death.

In this article, we review the concepts behind frequent nighttime voiding in older adults. We will start with two case scenarios to aid in understanding these concepts; near the end of the article, we will discuss the most appropriate management strategies for these two patients.

CASE SCENARIOS

Case 1: An 82-year-old man with fatigue

An 82-year-old obese white man with a history of hypertension, diabetes, and benign prostatic hyperplasia comes in to see his primary care provider, complaining of fatigue. He wakes up tired and has difficulty completing his daytime tasks. He gets up every 1 to 2 hours at night to urinate and has slow urinary flow and a feeling of incomplete bladder emptying.

See related patient education material

He says his wife has been increasingly bothered by his loud snoring. Recently, he had a car accident when he fell asleep while driving.

Case 2: An 85-year-old woman with incontinence

An 85-year-old white woman is in her family physician’s office with a primary complaint of waking up at least four times at night to urinate, and often ends up soaking her bed or adult diapers. She is bothered by urinary urgency and frequency during the day as well. She denies dysuria and hematuria.

She has a history of hypertension and urinary incontinence, and she has seven children. Her current medications are diltiazem (Cardizem), metoprolol (Toprol), and oxybutynin (Ditropan).

In these two cases, what would account for the nocturia? What would be the best way to help these patients?

THE NORM, NOT THE EXCEPTION

Although nocturia is defined as an awakening by the need to urinate even once in a night, many experts consider that it begins to be clinically significant only when the patient voids at least twice during the night.1

In older adults, nocturia is the norm rather than the exception. Studies done between 1990 and 2009 found that 68.9% to 93% of men age 70 and older get up at least once a night to void. The prevalence in women is somewhat lower, at 74.1% to 77.1%.2 Clinically significant nocturia is present in a majority of the elderly: more than 60% of both men and women.3

An Austrian study4 reported that elderly men got up to urinate a mean of 2.8 times per night, while women got up significantly more often—3.1 times. Women were also bothered more by this symptom, and their quality of life was significantly more decreased.

In another study,5 whites had a significantly higher nocturia ratio (ratio of nighttime urine volume to the 24-hour urine volume) than Asians. Asians, on the other hand, had a significantly higher nocturnal bladder capacity index than whites. (See below for definitions of the various indices of nocturia.) This information implies that nocturia may be a more prominent problem for elderly whites than for other racial groups.

In an epidemiologic study in Sweden,6 the death rate was as much as twice as high in both men and women who had three or more nocturnal voids, even after taking into account the influence of cardiac disease, diabetes mellitus, and stroke.

If nocturia is not addressed in the physician-patient encounter, patients may try to “self-manage” it by restricting their fluid intake or by limiting their social exposure,7 with limited success and with unwanted social isolation.

WHAT CAUSES NOCTURIA?

In almost all cases of nocturia in elderly people, the cause is multifactorial (Table 1).

Advancing age is primary among these factors. Age-related structural changes in the urinary system include decreased functional bladder capacity, a decreased maximum urinary flow rate,6 a decreased ability to postpone urination,8 and an age-related increase in postvoiding residual urine volume.9 The aging kidney is also less able to concentrate urine. Also implicated are histologic changes in the detrusor muscle10 that lead to diminished bladder compliance and, together with detrusor overactivity, result in increased urinary frequency.

Nocturnal polyuria or nocturnal urine overproduction is common in patients with nocturia.11

Although the pathophysiology of nocturnal polyuria is still unclear, some investigators believe that low levels of antidiuretic hormone (ADH) at night are involved, reflecting an alteration in the circadian rhythm seen in diurnal plasma arginine vasopressin levels.12 In patients with nocturnal polyuria, ADH levels drop to very low or undetectable levels at night, which increases nocturnal urine output. In some extreme cases, the low to absent levels of ADH increase nocturnal voiding to 85% of the total 24-hour urine volume.13

Other causes of nocturnal polyuria include mobilization of fluids in patients with edema,14 and autonomic dysfunction. Other biochemical changes that contribute to nocturia include a decrease in nighttime plasma melatonin levels, an increase in nighttime plasma catecholamine levels, an increase in nighttime plasma natriuretic peptide levels, an increase in blood pressure, and an increase in total urine volume.15

A decreased ability to store urine also leads to nocturia. This is caused by decreased nocturnal bladder capacity, more irritative symptoms, and comorbid conditions such as overactive bladder, pelvic floor laxity resulting in pelvic organ prolapse, and, in men, benign prostatic hyperplasia.

Neural inputs to the bladder can also be impaired, as in patients who have diabetes mellitus or spinal stenosis, leading to chronic urinary retention, detrusor dysfunction, nocturia, and incontinence.

 

 

WHICH PATIENTS ARE AT RISK?

Nocturia is associated with a number of risk factors (Table 2).

Obesity is associated with a higher incidence of moderate to severe nocturia.15 Studies have shown that the higher the body mass index, the greater the number of nighttime voids, especially in women.16

Habitually eating at night, with poor daytime appetite, is shown to be associated with increased nighttime diuresis.

Obstructive sleep apnea17 and untreated depressive symptoms such as frequent napping18 are also associated with moderate to severe nocturia.19

Higher systolic blood pressures are associated with more urine production at night. Plasma ADH regulation is also altered, which contributes to nocturnal polyuria.21

Other comorbid conditions associated with nocturia include recurrent cystitis, lung disease, congestive heart failure, neurodegenerative conditions (eg, Alzheimer disease and parkinsonism), and chronic kidney disease.21

Drugs associated with nocturia include cholinesterase inhibitors (for dementia),22 beta-blockers,23 and calcium channel blockers.24

Lifestyle factors. Alcohol and coffee have shown either no or only a mild diuretic effect. Smoking has not been shown to be associated with nocturia.15

Seasonal differences also exist, with increased frequency of nocturia in the winter.25

WHAT ARE THE CLINICAL CONSEQUENCES OF NOCTURIA?

Nocturia’s effects are varied and are very important to address (Table 3).

Quality of life can be profoundly affected, and if nocturia is left untreated, it may lead to morbidity and even death. Elderly patients may feel simultaneously debilitated, frustrated, distressed, and puzzled. Nocturia may also increase their fear of falling and may negatively affect personal relationships.26

Falls, injuries. Nocturia exposes elderly patients to injuries such as hip fractures due to falling, significantly increasing the incidence of this injury.26 This occurs as elderly patients get up from bed and walk to the bathroom to void.27 In addition, during the day, superficial and fragmented sleep leads to daytime sleepiness and impaired perception and balance, also increasing the risk of falls.28 The complications of immobility and the need for surgery in many cases lead to debility, increased risk of infections, decubitus ulcers, and death. The risk of hip fractures can lead elderly patients with nocturia to associate this symptom with a fear of falling and can alter their concept of their own age (“Nocturia makes me feel old”),29 further diminishing quality of life.

The estimated medical cost of nocturia-associated falls in the elderly is about $1.5 billion per year, part of the $61 billion in lost productivity due to nocturia in adults.30

Long-term complications (eg, debilitation, poor sleep, obesity, decreased energy), increase the overall mortality rate, especially in patients who report voiding more than three times per night.29 Elderly patients with nocturia also have a greater need for emergency care.31

Nocturia also complicates other comorbid conditions, such as dementia, which increases the risk of urinary incontinence.32 In patients who have had a stroke, nocturia is the most frequent lower urinary tract symptom, and represents a major impact on daily life.33

Sleep disturbance is another important consequence. In one survey,34 nocturia was cited as a cause of poor sleep four times more often than the cause cited next most often, ie, pain. Because the elderly patient is awakened from sleep numerous times throughout the night, nocturia leads to more fatigue,35 lower energy levels, and poorer quality of sleep.36 Depression may be linked to poor sleep, as men with two or more nocturnal episodes were shown to be six times more likely to experience depression.

The patient is not the only person who loses sleep: so do the patient’s family members or sleeping partner.7 It is therefore not surprising that sleep disruption caused by nocturia has been cited as a principal reason for admitting older relatives to care homes.37

The risk of death is higher for elderly patients with coronary heart disease if they have nocturia. The causative link is the hemodynamic changes (increases in blood pressure and heart rate) that accompany awakening and arising, which may cause cardiovascular strain and lead to cardiovascular events. The 12-year survival rate has been shown to be significantly lower in patients with nighttime voiding, making nocturia a highly significant independent predictor of death in coronary heart disease patients.38

HOW TO EVALUATE AN OLDER ADULT WHO PRESENTS WITH NOCTURIA

A thorough history and physical examination are crucial in diagnosing nocturia. The goal is to identify any treatable underlying condition, such as diabetes mellitus, obstructive sleep apnea, diabetes insipidus, overactive bladder, benign prostatic hyperplasia, urinary tract infection, and congestive heart failure. Laboratory tests and imaging studies can help rule out these underlying conditions.

Other important facets in the history that must be elicited are medication use, patterns of fluid intake, and a history of other urinary complaints.39

A voiding diary and indices of nocturia

A voiding diary is extremely useful and should be used whenever possible. Episodes of incontinence, time of voids, volume voided, and frequency and volume of fluid intake are recorded. From the raw data, one can determine the following:

Total nocturnal urine volume, ie, the sum volume of the nighttime voids

Maximum voided volume, ie, the largest single recorded volume voided in a 24-hour period

Nocturia index, ie, the total nocturnal urine volume divided by the maximum voided volume. A nocturia index greater than 1 shows that nocturnal urine production is greater than the functional bladder capacity. Clinically significant nocturia is observed in patients with a nocturia index of 2.1 or greater.

Nocturnal polyuria index, ie, total nocturnal urine volume divided by the 24-hour urine output. A nocturnal polyuria index higher than 33% implies nocturnal polyuria.40

Nocturnal bladder capacity index, ie, the actual number of nightly voids minus the predicted number of nightly voids, which in turn is calculated as the nocturia index minus 1.

It is especially important to encourage patients to make a voiding diary, as some patients may find this cumbersome, and compliance can be low unless its importance is emphasized. A diary over 7 days usually gives meaningful data. The results from the diary typically confirm the presence of nocturnal polyuria or a decrease in bladder capacity, influencing management.41

 

 

WHAT ARE THE TREATMENT OPTIONS?

Therapy must be directed at the primary cause, addressing any underlying conditions that can contribute to nocturia. Examples39:

  • Tight control of blood sugar for patients with diabetes mellitus
  • Treatment of diabetes insipidus
  • Referral for patients with primary polydipsia
  • Management of hypercalcemia and hypokalemia
  • A survey of medications
  • Treatment of infections.

Nonpharmacologic measures

Tailored behavioral therapy can also be instituted, but the patient needs to have realistic expectations, as these measures are rarely effective alone.

Avoiding nighttime fluid intake, including alcohol and caffeine, has shown promise.

Wearing compression stockings and elevating the legs in the afternoon decrease the retention of fluid that otherwise would return to the circulation at night.

Identifying and eliminating nighttime influences that disturb sleep has variable efficacy. The use of continuous positive airway pressure helps to treat sleep apnea. Moderate exercise, reducing nonsleep time spent in bed,42 and sleeping in a warm bed43 to decrease cold diuresis have also been shown to improve sleep quality.44 Patients with nocturia may have a disrupted circadian rhythm, and phototherapy may help resynchronize the diurnal rhythm and melatonin secretion.

Pharmacotherapy

Pharmacotherapy of nocturia includes desmopressin (DDAVP) to manage nocturnal polyuria and antimuscarinic agents to manage the patient’s decreased ability to store urine. Alpha-blockers such as tamsulosin (Flomax) and 5-alpha-reductase inhibitors such as finasteride (Proscar) are used for men with benign prostatic hyperplasia. Novel and second-line therapies include diuretics such as furosemide (Lasix), cyclooxygenase-2 inhibitors, as well as botulinum toxin injected directly into the detrusor muscle for overactive bladder.45

Desmopressin in a low oral dose (0.1–0.4 mg) at bedtime can be initiated and the response assessed. Patients with nocturnal polyuria and disorders of the vasopressin system have been found to be more sensitive to desmopressin therapy.46 Fluid retention and hyponatremia can complicate therapy, and desmopressin must be avoided in patients with liver cirrhosis, renal failure, or congestive heart failure.47

Antimuscarinic agents are effective for patients who have lower urinary tract symptoms and for those with a diminished ability to store urine. They act by decreasing both voluntary and involuntary bladder contractions by blocking muscarinic receptors on the detrusor muscle. This reduces the bladder’s ability to contract and the urge to urinate, thereby increasing bladder capacity.48 These agents include oxybutynin (Ditropan), tolterodine (Detrol), solifenacin (Vesicare), and propiverine (not available in the United States).

Diuretics are being used as second-line agents or for patients who cannot tolerate desmopressin.49 Hydrochlorothiazide is taken 8 hours before bedtime to prevent water accumulation before the early sleeping hours.50 Furosemide has also led to a reduction in the mean number of nocturnal voids.51 The effect of these drugs on nocturia are especially beneficial to patients with concomitant hypertension or cardiovascular disease.

Cyclo-oxygenase-2 inhibitors such as celecoxib (Celebrex)52 and other nonsteroidal anti-inflammatory drugs such as diclofenac (Voltaren, others)53 and loxoprofen (not available in the United States)54 have been shown to decrease urine production, detrusor muscle tone, and inflammation, especially in men with benign prostatic hyperplasia.

Botulinum toxin has been used, usually in patients refractory to first-line treatment.44

Referral to specialists is guided by underlying causes. Referral to a pulmonologist or sleep specialist may be helpful if the patient has obstructive sleep apnea. Referral to a urologist may be prudent if the patient has benign prostatic hyperplasia, and a gynecologist can address issues such as pelvic relaxation.

Table 4 summarizes the treatment strategies for nocturia.

CASES REVISITED

The first patient described above has nocturia caused by several concomitant diseases, ie, hypertension, diabetes, benign prostatic hyperplasia, and obstructive sleep apnea. In addition to controlling his blood pressure and blood sugar, his primary care provider referred him to a pulmonologist, who confirmed obstructive sleep apnea with polysomnography and prescribed nightly use of a continuous positive airway pressure apparatus. A few weeks later, the patient’s nocturia had improved significantly, and his level of fatigue had decreased.

Apart from hypertension, the second patient’s nocturia was mostly attributed to her existing urinary incontinence. Recognizing that her current antihypertensive regimen may worsen nocturia, her family physician changed it to enalapril (Vasotec) and doxazosin (Cardura) and counseled her to restrict her fluid intake 2 hours before bedtime. She was also referred to a gynecologist, who found a moderate degree of cystocele and treated her with a collagen injection. Her nocturia improved significantly.

Nocturia is common, but elderly patients infrequently volunteer this complaint, and even when they do, some clinicians may dismiss it as simply a part of aging. Nevertheless, nocturia causes significant distress and impairment of quality of life. It is associated with very serious consequences such as depression, social isolation, and a higher risk of death.

In this article, we review the concepts behind frequent nighttime voiding in older adults. We will start with two case scenarios to aid in understanding these concepts; near the end of the article, we will discuss the most appropriate management strategies for these two patients.

CASE SCENARIOS

Case 1: An 82-year-old man with fatigue

An 82-year-old obese white man with a history of hypertension, diabetes, and benign prostatic hyperplasia comes in to see his primary care provider, complaining of fatigue. He wakes up tired and has difficulty completing his daytime tasks. He gets up every 1 to 2 hours at night to urinate and has slow urinary flow and a feeling of incomplete bladder emptying.

See related patient education material

He says his wife has been increasingly bothered by his loud snoring. Recently, he had a car accident when he fell asleep while driving.

Case 2: An 85-year-old woman with incontinence

An 85-year-old white woman is in her family physician’s office with a primary complaint of waking up at least four times at night to urinate, and often ends up soaking her bed or adult diapers. She is bothered by urinary urgency and frequency during the day as well. She denies dysuria and hematuria.

She has a history of hypertension and urinary incontinence, and she has seven children. Her current medications are diltiazem (Cardizem), metoprolol (Toprol), and oxybutynin (Ditropan).

In these two cases, what would account for the nocturia? What would be the best way to help these patients?

THE NORM, NOT THE EXCEPTION

Although nocturia is defined as an awakening by the need to urinate even once in a night, many experts consider that it begins to be clinically significant only when the patient voids at least twice during the night.1

In older adults, nocturia is the norm rather than the exception. Studies done between 1990 and 2009 found that 68.9% to 93% of men age 70 and older get up at least once a night to void. The prevalence in women is somewhat lower, at 74.1% to 77.1%.2 Clinically significant nocturia is present in a majority of the elderly: more than 60% of both men and women.3

An Austrian study4 reported that elderly men got up to urinate a mean of 2.8 times per night, while women got up significantly more often—3.1 times. Women were also bothered more by this symptom, and their quality of life was significantly more decreased.

In another study,5 whites had a significantly higher nocturia ratio (ratio of nighttime urine volume to the 24-hour urine volume) than Asians. Asians, on the other hand, had a significantly higher nocturnal bladder capacity index than whites. (See below for definitions of the various indices of nocturia.) This information implies that nocturia may be a more prominent problem for elderly whites than for other racial groups.

In an epidemiologic study in Sweden,6 the death rate was as much as twice as high in both men and women who had three or more nocturnal voids, even after taking into account the influence of cardiac disease, diabetes mellitus, and stroke.

If nocturia is not addressed in the physician-patient encounter, patients may try to “self-manage” it by restricting their fluid intake or by limiting their social exposure,7 with limited success and with unwanted social isolation.

WHAT CAUSES NOCTURIA?

In almost all cases of nocturia in elderly people, the cause is multifactorial (Table 1).

Advancing age is primary among these factors. Age-related structural changes in the urinary system include decreased functional bladder capacity, a decreased maximum urinary flow rate,6 a decreased ability to postpone urination,8 and an age-related increase in postvoiding residual urine volume.9 The aging kidney is also less able to concentrate urine. Also implicated are histologic changes in the detrusor muscle10 that lead to diminished bladder compliance and, together with detrusor overactivity, result in increased urinary frequency.

Nocturnal polyuria or nocturnal urine overproduction is common in patients with nocturia.11

Although the pathophysiology of nocturnal polyuria is still unclear, some investigators believe that low levels of antidiuretic hormone (ADH) at night are involved, reflecting an alteration in the circadian rhythm seen in diurnal plasma arginine vasopressin levels.12 In patients with nocturnal polyuria, ADH levels drop to very low or undetectable levels at night, which increases nocturnal urine output. In some extreme cases, the low to absent levels of ADH increase nocturnal voiding to 85% of the total 24-hour urine volume.13

Other causes of nocturnal polyuria include mobilization of fluids in patients with edema,14 and autonomic dysfunction. Other biochemical changes that contribute to nocturia include a decrease in nighttime plasma melatonin levels, an increase in nighttime plasma catecholamine levels, an increase in nighttime plasma natriuretic peptide levels, an increase in blood pressure, and an increase in total urine volume.15

A decreased ability to store urine also leads to nocturia. This is caused by decreased nocturnal bladder capacity, more irritative symptoms, and comorbid conditions such as overactive bladder, pelvic floor laxity resulting in pelvic organ prolapse, and, in men, benign prostatic hyperplasia.

Neural inputs to the bladder can also be impaired, as in patients who have diabetes mellitus or spinal stenosis, leading to chronic urinary retention, detrusor dysfunction, nocturia, and incontinence.

 

 

WHICH PATIENTS ARE AT RISK?

Nocturia is associated with a number of risk factors (Table 2).

Obesity is associated with a higher incidence of moderate to severe nocturia.15 Studies have shown that the higher the body mass index, the greater the number of nighttime voids, especially in women.16

Habitually eating at night, with poor daytime appetite, is shown to be associated with increased nighttime diuresis.

Obstructive sleep apnea17 and untreated depressive symptoms such as frequent napping18 are also associated with moderate to severe nocturia.19

Higher systolic blood pressures are associated with more urine production at night. Plasma ADH regulation is also altered, which contributes to nocturnal polyuria.21

Other comorbid conditions associated with nocturia include recurrent cystitis, lung disease, congestive heart failure, neurodegenerative conditions (eg, Alzheimer disease and parkinsonism), and chronic kidney disease.21

Drugs associated with nocturia include cholinesterase inhibitors (for dementia),22 beta-blockers,23 and calcium channel blockers.24

Lifestyle factors. Alcohol and coffee have shown either no or only a mild diuretic effect. Smoking has not been shown to be associated with nocturia.15

Seasonal differences also exist, with increased frequency of nocturia in the winter.25

WHAT ARE THE CLINICAL CONSEQUENCES OF NOCTURIA?

Nocturia’s effects are varied and are very important to address (Table 3).

Quality of life can be profoundly affected, and if nocturia is left untreated, it may lead to morbidity and even death. Elderly patients may feel simultaneously debilitated, frustrated, distressed, and puzzled. Nocturia may also increase their fear of falling and may negatively affect personal relationships.26

Falls, injuries. Nocturia exposes elderly patients to injuries such as hip fractures due to falling, significantly increasing the incidence of this injury.26 This occurs as elderly patients get up from bed and walk to the bathroom to void.27 In addition, during the day, superficial and fragmented sleep leads to daytime sleepiness and impaired perception and balance, also increasing the risk of falls.28 The complications of immobility and the need for surgery in many cases lead to debility, increased risk of infections, decubitus ulcers, and death. The risk of hip fractures can lead elderly patients with nocturia to associate this symptom with a fear of falling and can alter their concept of their own age (“Nocturia makes me feel old”),29 further diminishing quality of life.

The estimated medical cost of nocturia-associated falls in the elderly is about $1.5 billion per year, part of the $61 billion in lost productivity due to nocturia in adults.30

Long-term complications (eg, debilitation, poor sleep, obesity, decreased energy), increase the overall mortality rate, especially in patients who report voiding more than three times per night.29 Elderly patients with nocturia also have a greater need for emergency care.31

Nocturia also complicates other comorbid conditions, such as dementia, which increases the risk of urinary incontinence.32 In patients who have had a stroke, nocturia is the most frequent lower urinary tract symptom, and represents a major impact on daily life.33

Sleep disturbance is another important consequence. In one survey,34 nocturia was cited as a cause of poor sleep four times more often than the cause cited next most often, ie, pain. Because the elderly patient is awakened from sleep numerous times throughout the night, nocturia leads to more fatigue,35 lower energy levels, and poorer quality of sleep.36 Depression may be linked to poor sleep, as men with two or more nocturnal episodes were shown to be six times more likely to experience depression.

The patient is not the only person who loses sleep: so do the patient’s family members or sleeping partner.7 It is therefore not surprising that sleep disruption caused by nocturia has been cited as a principal reason for admitting older relatives to care homes.37

The risk of death is higher for elderly patients with coronary heart disease if they have nocturia. The causative link is the hemodynamic changes (increases in blood pressure and heart rate) that accompany awakening and arising, which may cause cardiovascular strain and lead to cardiovascular events. The 12-year survival rate has been shown to be significantly lower in patients with nighttime voiding, making nocturia a highly significant independent predictor of death in coronary heart disease patients.38

HOW TO EVALUATE AN OLDER ADULT WHO PRESENTS WITH NOCTURIA

A thorough history and physical examination are crucial in diagnosing nocturia. The goal is to identify any treatable underlying condition, such as diabetes mellitus, obstructive sleep apnea, diabetes insipidus, overactive bladder, benign prostatic hyperplasia, urinary tract infection, and congestive heart failure. Laboratory tests and imaging studies can help rule out these underlying conditions.

Other important facets in the history that must be elicited are medication use, patterns of fluid intake, and a history of other urinary complaints.39

A voiding diary and indices of nocturia

A voiding diary is extremely useful and should be used whenever possible. Episodes of incontinence, time of voids, volume voided, and frequency and volume of fluid intake are recorded. From the raw data, one can determine the following:

Total nocturnal urine volume, ie, the sum volume of the nighttime voids

Maximum voided volume, ie, the largest single recorded volume voided in a 24-hour period

Nocturia index, ie, the total nocturnal urine volume divided by the maximum voided volume. A nocturia index greater than 1 shows that nocturnal urine production is greater than the functional bladder capacity. Clinically significant nocturia is observed in patients with a nocturia index of 2.1 or greater.

Nocturnal polyuria index, ie, total nocturnal urine volume divided by the 24-hour urine output. A nocturnal polyuria index higher than 33% implies nocturnal polyuria.40

Nocturnal bladder capacity index, ie, the actual number of nightly voids minus the predicted number of nightly voids, which in turn is calculated as the nocturia index minus 1.

It is especially important to encourage patients to make a voiding diary, as some patients may find this cumbersome, and compliance can be low unless its importance is emphasized. A diary over 7 days usually gives meaningful data. The results from the diary typically confirm the presence of nocturnal polyuria or a decrease in bladder capacity, influencing management.41

 

 

WHAT ARE THE TREATMENT OPTIONS?

Therapy must be directed at the primary cause, addressing any underlying conditions that can contribute to nocturia. Examples39:

  • Tight control of blood sugar for patients with diabetes mellitus
  • Treatment of diabetes insipidus
  • Referral for patients with primary polydipsia
  • Management of hypercalcemia and hypokalemia
  • A survey of medications
  • Treatment of infections.

Nonpharmacologic measures

Tailored behavioral therapy can also be instituted, but the patient needs to have realistic expectations, as these measures are rarely effective alone.

Avoiding nighttime fluid intake, including alcohol and caffeine, has shown promise.

Wearing compression stockings and elevating the legs in the afternoon decrease the retention of fluid that otherwise would return to the circulation at night.

Identifying and eliminating nighttime influences that disturb sleep has variable efficacy. The use of continuous positive airway pressure helps to treat sleep apnea. Moderate exercise, reducing nonsleep time spent in bed,42 and sleeping in a warm bed43 to decrease cold diuresis have also been shown to improve sleep quality.44 Patients with nocturia may have a disrupted circadian rhythm, and phototherapy may help resynchronize the diurnal rhythm and melatonin secretion.

Pharmacotherapy

Pharmacotherapy of nocturia includes desmopressin (DDAVP) to manage nocturnal polyuria and antimuscarinic agents to manage the patient’s decreased ability to store urine. Alpha-blockers such as tamsulosin (Flomax) and 5-alpha-reductase inhibitors such as finasteride (Proscar) are used for men with benign prostatic hyperplasia. Novel and second-line therapies include diuretics such as furosemide (Lasix), cyclooxygenase-2 inhibitors, as well as botulinum toxin injected directly into the detrusor muscle for overactive bladder.45

Desmopressin in a low oral dose (0.1–0.4 mg) at bedtime can be initiated and the response assessed. Patients with nocturnal polyuria and disorders of the vasopressin system have been found to be more sensitive to desmopressin therapy.46 Fluid retention and hyponatremia can complicate therapy, and desmopressin must be avoided in patients with liver cirrhosis, renal failure, or congestive heart failure.47

Antimuscarinic agents are effective for patients who have lower urinary tract symptoms and for those with a diminished ability to store urine. They act by decreasing both voluntary and involuntary bladder contractions by blocking muscarinic receptors on the detrusor muscle. This reduces the bladder’s ability to contract and the urge to urinate, thereby increasing bladder capacity.48 These agents include oxybutynin (Ditropan), tolterodine (Detrol), solifenacin (Vesicare), and propiverine (not available in the United States).

Diuretics are being used as second-line agents or for patients who cannot tolerate desmopressin.49 Hydrochlorothiazide is taken 8 hours before bedtime to prevent water accumulation before the early sleeping hours.50 Furosemide has also led to a reduction in the mean number of nocturnal voids.51 The effect of these drugs on nocturia are especially beneficial to patients with concomitant hypertension or cardiovascular disease.

Cyclo-oxygenase-2 inhibitors such as celecoxib (Celebrex)52 and other nonsteroidal anti-inflammatory drugs such as diclofenac (Voltaren, others)53 and loxoprofen (not available in the United States)54 have been shown to decrease urine production, detrusor muscle tone, and inflammation, especially in men with benign prostatic hyperplasia.

Botulinum toxin has been used, usually in patients refractory to first-line treatment.44

Referral to specialists is guided by underlying causes. Referral to a pulmonologist or sleep specialist may be helpful if the patient has obstructive sleep apnea. Referral to a urologist may be prudent if the patient has benign prostatic hyperplasia, and a gynecologist can address issues such as pelvic relaxation.

Table 4 summarizes the treatment strategies for nocturia.

CASES REVISITED

The first patient described above has nocturia caused by several concomitant diseases, ie, hypertension, diabetes, benign prostatic hyperplasia, and obstructive sleep apnea. In addition to controlling his blood pressure and blood sugar, his primary care provider referred him to a pulmonologist, who confirmed obstructive sleep apnea with polysomnography and prescribed nightly use of a continuous positive airway pressure apparatus. A few weeks later, the patient’s nocturia had improved significantly, and his level of fatigue had decreased.

Apart from hypertension, the second patient’s nocturia was mostly attributed to her existing urinary incontinence. Recognizing that her current antihypertensive regimen may worsen nocturia, her family physician changed it to enalapril (Vasotec) and doxazosin (Cardura) and counseled her to restrict her fluid intake 2 hours before bedtime. She was also referred to a gynecologist, who found a moderate degree of cystocele and treated her with a collagen injection. Her nocturia improved significantly.

References
  1. Abrams P. Nocturia: the major problem in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction (LUTS/BPO). Eur Urol Suppl 2005; 3(6):8–16.
  2. Bosch JL, Weiss J. The prevalence and causes of nocturia. J Urol 2010; 184:440–446.
  3. Tikkinen KA, Johnson TM, Tammela TL, et al. Nocturia frequency, bother, and quality of life: how often is too often? A population-based study in Finland. Eur Urol 2010; 57:488–496.
  4. Klingler HG, Heidler H, Madersbacher H, Primus G. Nocturia: an Austrian study on the multifactorial etiology of this symptom. Neurourol Urodyn 2009; 28:427–431.
  5. Mariappan P, Turner KJ, Sothilingam S, Rajan P, Sundram M, Steward LH. Nocturia, nocturia indices and variables from frequency-volume charts are significantly different in Asian and Caucasian men with lower urinary tract symptoms: a prospective comparison study. BJU Int 2007; 100:332–336.
  6. Asplund R. Mortality in the elderly in relation to nocturnal micturition. BJU Int 1999; 84:297–301.
  7. Booth J, O’Neil K, Lawrence M, et al. Advancing community nursing practice: detecting and managing nocturia in community-living older people. Final report. 2008. Queens Nursing Institute, Scotland. http://www.qnis.co.uk/documents/Item3.2-finalreportnocturiav2.doc. Accessed 8/22/11
  8. Kawauchi A, Tanaka Y, Soh J, Ukimura O, Kojima M, Miki T. Causes of nocturnal urinary frequency and reasons for its increase with age in healthy older men. J Urol 2000; 163:81–84.
  9. Madersbacher S, Pycha A, Schatzl G, Mian C, Klingler CH, Marberger M. The aging lower urinary tract: a comparative urodynamics study of men and women. Urology 1998; 51:206–212.
  10. Elbedawi A, Yalla SV, Resnick NM. Structural basis of geriatric voiding dysfunction. I: methods of a prospective ultra structural/urodynamics study and an overview of the findings. J Urol 1993; 150:1650–1656.
  11. Weiss JP, Blaivas JG, Jones M, Wang JT, Guan Z; 037 Study Group. Age related pathogenesis of nocturia in patients with overactive bladder. J Urol 2007; 178:548–551.
  12. Natsume O, Kaneko Y, Hirayama A, Fujimoto K, Hirao Y. Fluid control in elderly patients with nocturia. Int J Urol 2009; 16:307–313.
  13. Asplund R. Pharmacotherapy for nocturia in the elderly patient. Drugs Aging 2007; 24:325–343.
  14. Sugaya K, Nishijima S, Oda M, Owan T, Miyazato M, Ogawa Y. Biochemical and body composition analysis of nocturia in the elderly. Neurourol Urodyn 2008; 27:205–211.
  15. Shiri R, Hakama M, Häkkinen J, et al. The effects of lifestyle factors on the incidence of nocturia. J Urol 2008; 180:2059–2062.
  16. Asplund R. Obesity in elderly people with nocturia: cause or consequence? Can J Urol 2007; 14:3424–3428.
  17. Hardin-Fanning F, Gross JC. The effects of sleep-disordered breathing symptoms on voiding patterns in stroke patients. Urol Nurs 2007; 27:221–229.
  18. Foley DJ, Vitiello MV, Bliwise DL, Ancoli-Israel S, Monjan AA, Walsh JK. Frequent napping is associated with excessive daytime sleepiness, depression, pain, and nocturia in older adults: findings from the National Sleep Foundation ‘2003 Sleep in America’ Poll. Am J Geriatr Psychiatry 2007; 15:344–350.
  19. Häkkinen JT, Shiri R, Koskimäki J, Tammela TL, Auvinen A, Hakama M. Depressive symptoms increase the incidence of nocturia: Tampere Aging Male Urologic Study (TAMUS). J Urol 2008; 179:1897–1901.
  20. Natsume O, Kaneko Y, Hirayama A, Fujimoto K, Hirao Y. Fluid control in elderly patients with nocturia. Int J Urol 2009; 16:307–313.
  21. Kujubu DA, Aboseif SR. An overview of nocturia and the syndrome of nocturnal polyuria in the elderly. Nat Clin Pract Nephrol 2008; 4:426–435.
  22. Hashimoto M, Imamura T, Tanimukai S, Kazui H, Mori E. Urinary incontinence: an unrecognized adverse effect with donepezil (letter). Lancet 2000; 356:568.
  23. Wagg A, Cohen M. Medical therapy for the overactive bladder in the elderly. Age Ageing 2002; 31:241–246.
  24. Williams G, Donaldson RM. Nifedipine and nocturia. Lancet 1986: 1:738.
  25. Yoshimura K, Kamoto T, Tsukamoto T, Oshiro K, Kinukawa N, Ogawa O. Seasonal alterations in nocturia and other storage symptoms in three Japanese communities. Urology 2007; 69:864–870.
  26. Asplund R. Hip fractures, nocturia, and nocturnal polyuria in the elderly. Arch Gerontol Geriatr 2006; 43:319–326.
  27. Stewart RB, Moore MT, May FE, Marks RG, Hale WE. Nocturia: a risk factor for falls in the elderly. J Am Geriatr Soc 1992; 40:1217–1220.
  28. van Balen R, Steyerberg EW, Polder JJ, Ribbers TL, Habbema JD, Cools HJ. Hip fracture in elderly patients: outcomes for function, quality of life, and type of residence. Clin Orthop Relat Res 2001; 390:232–243.
  29. Mock LL, Parmelee PA, Kutner N, Scott J, Johnson TM. Content validation of symptom-specific nocturia quality-of-life instrument developed in men: issues expressed by women, as well as men. Urology 2008; 72:736–742.
  30. Holm-Larsen T, Weiss J, Langkilde LK. Economic burden of nocturia in the US adult population. J Urol Suppl 2010; 100:332–336.
  31. Ali A, Snape J. Nocturia in older people: a review of causes, consequences, assessment, and management. Int J Clin Pract 2004; 58:366–373.
  32. Miu DK, Lau S, Szeto SS. Etiology and predictors of urinary incontinence and its effect on quality of life. Geriatr Gerontol Int 2010; 10:177–182.
  33. Tibaek S, Gard G, Klarskov P, Iversen HK, Dehlendorff C, Jensen R. Prevalence of lower urinary tract symptoms (LUTS) in stroke patients: a cross-sectional, clinical survey. Neurourol Urodyn 2008; 27:763–771.
  34. Bliwise DL, Foley DJ, Vitiello MV, Ansari FP, Ancoli-Israel S, Walsh JK. Nocturia and disturbed sleep in the elderly. Sleep Med 2009; 10:540–548.
  35. Asplund R. Nocturia: consequences for sleep and daytime activities and associated risks. Eur Urol Suppl 2005; 3(6):24–32.
  36. Hernández C, Estivill E, Prieto M, Badia X. Nocturia in Spanish patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). Curr Med Res Opin 2008; 24:1033–1038.
  37. Pollak CP, Perlick D, Linsner JP, Wenston J, Hsieh F. Sleep problems in the community elderly as predictors of death and nursing home placement. J Community Health 1990; 15:123–135.
  38. Bursztyn M, Jacob J, Stessman J. Usefulness of nocturia as a mortality risk factor for coronary heart disease among persons born in 1920 or 1921. Am J Cardiol 2006; 98:1311–1315.
  39. Appell RA, Sand PK. Nocturia: etiology, diagnosis, and treatment. Neurourol Urodyn 2008; 27:34–39.
  40. Weiss JP, Blaivas JG, Stember DS, Chaikin DC. Evaluation of the etiology of nocturia in men: the nocturia and nocturnal bladder capacity indices. Neurourol Urodyn 1999; 18:559–565.
  41. Jaffe JS, Ginsberg PC, Silverberg DM, Harkaway RC. The need for voiding diaries in the evaluation of men with nocturia. J Am Osteopath Assoc 2002; 102:261–265.
  42. Yoshimura K, Terai A. Classification and distribution of symptomatic nocturia with special attention to duration of time in bed: a patient-based study. BJU Int 2005; 95:1259–1262.
  43. Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med 2009; 37:S186–S202.
  44. Soda T, Masui K, Okuno H, Terai A, Ogawa O, Yoshimura K. Efficacy of nondrug lifestyle measures for the treatment of nocturia. J Urol 2010; 184:1000–1004.
  45. Flynn MK, Amundsen CL, Perevich M, Liu F, Webster GD. Outcome of a randomized, double-blind, placebo controlled trial of botulinum A toxin for refractory overactive bladder. J Urol 2009; 181:2608–2615.
  46. Asplund R, Sundberg B, Bengtsson P. Desmopressin for the treatment of nocturnal polyuria in the elderly: a dose titration study. Br J Urol 1998; 82:642–646.
  47. Abrams P, Mattiasson A, Lose GR, Robertson GL. The role of desmopressin treatment in adult nocturia. BJU Int 2002; 90:32–36.
  48. Andersson K. Treatment of the overactive bladder syndrome and detrusor overactivity with antimuscarinic drugs. Continence 2005; 1:1–8.
  49. Reynard JM, Cannon A, Yang Q, Abrams P. A novel therapy for nocturnal polyuria: a double-blind randomized trial of frusemide against placebo. Br J Urol 1998; 81:215–218.
  50. Cho MC, Ku JH, Paick JS. Alpha-blocker plus diuretic combination therapy as second-line treatment for nocturia in men with LUTS: a pilot study. Urology 2009; 73:549–553.
  51. Fu FG, Lavery HJ, Wu DL. Reducing nocturia in the elderly: a randomized placebo-controlled trial of staggered furosemide and desmopressin. Neurourol Urodyn 2011; 30:312–316.
  52. Falahatkar S, Mokhtari G, Pourezza F, Asgari SA, Kamran AN. Celecoxib for treatment of nocturia caused by benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled study. Urology 2008; 72:813–816.
  53. Addla SK, Adeyoju AB, Neilson D, O’Reilly P. Diclofenac for treatment of nocturia caused by nocturnal polyuria: a prospective, randomised, double-blind, placebo-controlled crossover study. Eur Urol 2006; 49:720–725.
  54. Saito M, Kawatani M, Kinoshita Y, Satoh K, Miyagawa I. Effectiveness of an anti-inflammatory drug, loxoprofen, for patients with nocturia. Int J Urol 2005; 12:779–782.
References
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  2. Bosch JL, Weiss J. The prevalence and causes of nocturia. J Urol 2010; 184:440–446.
  3. Tikkinen KA, Johnson TM, Tammela TL, et al. Nocturia frequency, bother, and quality of life: how often is too often? A population-based study in Finland. Eur Urol 2010; 57:488–496.
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  5. Mariappan P, Turner KJ, Sothilingam S, Rajan P, Sundram M, Steward LH. Nocturia, nocturia indices and variables from frequency-volume charts are significantly different in Asian and Caucasian men with lower urinary tract symptoms: a prospective comparison study. BJU Int 2007; 100:332–336.
  6. Asplund R. Mortality in the elderly in relation to nocturnal micturition. BJU Int 1999; 84:297–301.
  7. Booth J, O’Neil K, Lawrence M, et al. Advancing community nursing practice: detecting and managing nocturia in community-living older people. Final report. 2008. Queens Nursing Institute, Scotland. http://www.qnis.co.uk/documents/Item3.2-finalreportnocturiav2.doc. Accessed 8/22/11
  8. Kawauchi A, Tanaka Y, Soh J, Ukimura O, Kojima M, Miki T. Causes of nocturnal urinary frequency and reasons for its increase with age in healthy older men. J Urol 2000; 163:81–84.
  9. Madersbacher S, Pycha A, Schatzl G, Mian C, Klingler CH, Marberger M. The aging lower urinary tract: a comparative urodynamics study of men and women. Urology 1998; 51:206–212.
  10. Elbedawi A, Yalla SV, Resnick NM. Structural basis of geriatric voiding dysfunction. I: methods of a prospective ultra structural/urodynamics study and an overview of the findings. J Urol 1993; 150:1650–1656.
  11. Weiss JP, Blaivas JG, Jones M, Wang JT, Guan Z; 037 Study Group. Age related pathogenesis of nocturia in patients with overactive bladder. J Urol 2007; 178:548–551.
  12. Natsume O, Kaneko Y, Hirayama A, Fujimoto K, Hirao Y. Fluid control in elderly patients with nocturia. Int J Urol 2009; 16:307–313.
  13. Asplund R. Pharmacotherapy for nocturia in the elderly patient. Drugs Aging 2007; 24:325–343.
  14. Sugaya K, Nishijima S, Oda M, Owan T, Miyazato M, Ogawa Y. Biochemical and body composition analysis of nocturia in the elderly. Neurourol Urodyn 2008; 27:205–211.
  15. Shiri R, Hakama M, Häkkinen J, et al. The effects of lifestyle factors on the incidence of nocturia. J Urol 2008; 180:2059–2062.
  16. Asplund R. Obesity in elderly people with nocturia: cause or consequence? Can J Urol 2007; 14:3424–3428.
  17. Hardin-Fanning F, Gross JC. The effects of sleep-disordered breathing symptoms on voiding patterns in stroke patients. Urol Nurs 2007; 27:221–229.
  18. Foley DJ, Vitiello MV, Bliwise DL, Ancoli-Israel S, Monjan AA, Walsh JK. Frequent napping is associated with excessive daytime sleepiness, depression, pain, and nocturia in older adults: findings from the National Sleep Foundation ‘2003 Sleep in America’ Poll. Am J Geriatr Psychiatry 2007; 15:344–350.
  19. Häkkinen JT, Shiri R, Koskimäki J, Tammela TL, Auvinen A, Hakama M. Depressive symptoms increase the incidence of nocturia: Tampere Aging Male Urologic Study (TAMUS). J Urol 2008; 179:1897–1901.
  20. Natsume O, Kaneko Y, Hirayama A, Fujimoto K, Hirao Y. Fluid control in elderly patients with nocturia. Int J Urol 2009; 16:307–313.
  21. Kujubu DA, Aboseif SR. An overview of nocturia and the syndrome of nocturnal polyuria in the elderly. Nat Clin Pract Nephrol 2008; 4:426–435.
  22. Hashimoto M, Imamura T, Tanimukai S, Kazui H, Mori E. Urinary incontinence: an unrecognized adverse effect with donepezil (letter). Lancet 2000; 356:568.
  23. Wagg A, Cohen M. Medical therapy for the overactive bladder in the elderly. Age Ageing 2002; 31:241–246.
  24. Williams G, Donaldson RM. Nifedipine and nocturia. Lancet 1986: 1:738.
  25. Yoshimura K, Kamoto T, Tsukamoto T, Oshiro K, Kinukawa N, Ogawa O. Seasonal alterations in nocturia and other storage symptoms in three Japanese communities. Urology 2007; 69:864–870.
  26. Asplund R. Hip fractures, nocturia, and nocturnal polyuria in the elderly. Arch Gerontol Geriatr 2006; 43:319–326.
  27. Stewart RB, Moore MT, May FE, Marks RG, Hale WE. Nocturia: a risk factor for falls in the elderly. J Am Geriatr Soc 1992; 40:1217–1220.
  28. van Balen R, Steyerberg EW, Polder JJ, Ribbers TL, Habbema JD, Cools HJ. Hip fracture in elderly patients: outcomes for function, quality of life, and type of residence. Clin Orthop Relat Res 2001; 390:232–243.
  29. Mock LL, Parmelee PA, Kutner N, Scott J, Johnson TM. Content validation of symptom-specific nocturia quality-of-life instrument developed in men: issues expressed by women, as well as men. Urology 2008; 72:736–742.
  30. Holm-Larsen T, Weiss J, Langkilde LK. Economic burden of nocturia in the US adult population. J Urol Suppl 2010; 100:332–336.
  31. Ali A, Snape J. Nocturia in older people: a review of causes, consequences, assessment, and management. Int J Clin Pract 2004; 58:366–373.
  32. Miu DK, Lau S, Szeto SS. Etiology and predictors of urinary incontinence and its effect on quality of life. Geriatr Gerontol Int 2010; 10:177–182.
  33. Tibaek S, Gard G, Klarskov P, Iversen HK, Dehlendorff C, Jensen R. Prevalence of lower urinary tract symptoms (LUTS) in stroke patients: a cross-sectional, clinical survey. Neurourol Urodyn 2008; 27:763–771.
  34. Bliwise DL, Foley DJ, Vitiello MV, Ansari FP, Ancoli-Israel S, Walsh JK. Nocturia and disturbed sleep in the elderly. Sleep Med 2009; 10:540–548.
  35. Asplund R. Nocturia: consequences for sleep and daytime activities and associated risks. Eur Urol Suppl 2005; 3(6):24–32.
  36. Hernández C, Estivill E, Prieto M, Badia X. Nocturia in Spanish patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). Curr Med Res Opin 2008; 24:1033–1038.
  37. Pollak CP, Perlick D, Linsner JP, Wenston J, Hsieh F. Sleep problems in the community elderly as predictors of death and nursing home placement. J Community Health 1990; 15:123–135.
  38. Bursztyn M, Jacob J, Stessman J. Usefulness of nocturia as a mortality risk factor for coronary heart disease among persons born in 1920 or 1921. Am J Cardiol 2006; 98:1311–1315.
  39. Appell RA, Sand PK. Nocturia: etiology, diagnosis, and treatment. Neurourol Urodyn 2008; 27:34–39.
  40. Weiss JP, Blaivas JG, Stember DS, Chaikin DC. Evaluation of the etiology of nocturia in men: the nocturia and nocturnal bladder capacity indices. Neurourol Urodyn 1999; 18:559–565.
  41. Jaffe JS, Ginsberg PC, Silverberg DM, Harkaway RC. The need for voiding diaries in the evaluation of men with nocturia. J Am Osteopath Assoc 2002; 102:261–265.
  42. Yoshimura K, Terai A. Classification and distribution of symptomatic nocturia with special attention to duration of time in bed: a patient-based study. BJU Int 2005; 95:1259–1262.
  43. Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med 2009; 37:S186–S202.
  44. Soda T, Masui K, Okuno H, Terai A, Ogawa O, Yoshimura K. Efficacy of nondrug lifestyle measures for the treatment of nocturia. J Urol 2010; 184:1000–1004.
  45. Flynn MK, Amundsen CL, Perevich M, Liu F, Webster GD. Outcome of a randomized, double-blind, placebo controlled trial of botulinum A toxin for refractory overactive bladder. J Urol 2009; 181:2608–2615.
  46. Asplund R, Sundberg B, Bengtsson P. Desmopressin for the treatment of nocturnal polyuria in the elderly: a dose titration study. Br J Urol 1998; 82:642–646.
  47. Abrams P, Mattiasson A, Lose GR, Robertson GL. The role of desmopressin treatment in adult nocturia. BJU Int 2002; 90:32–36.
  48. Andersson K. Treatment of the overactive bladder syndrome and detrusor overactivity with antimuscarinic drugs. Continence 2005; 1:1–8.
  49. Reynard JM, Cannon A, Yang Q, Abrams P. A novel therapy for nocturnal polyuria: a double-blind randomized trial of frusemide against placebo. Br J Urol 1998; 81:215–218.
  50. Cho MC, Ku JH, Paick JS. Alpha-blocker plus diuretic combination therapy as second-line treatment for nocturia in men with LUTS: a pilot study. Urology 2009; 73:549–553.
  51. Fu FG, Lavery HJ, Wu DL. Reducing nocturia in the elderly: a randomized placebo-controlled trial of staggered furosemide and desmopressin. Neurourol Urodyn 2011; 30:312–316.
  52. Falahatkar S, Mokhtari G, Pourezza F, Asgari SA, Kamran AN. Celecoxib for treatment of nocturia caused by benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled study. Urology 2008; 72:813–816.
  53. Addla SK, Adeyoju AB, Neilson D, O’Reilly P. Diclofenac for treatment of nocturia caused by nocturnal polyuria: a prospective, randomised, double-blind, placebo-controlled crossover study. Eur Urol 2006; 49:720–725.
  54. Saito M, Kawatani M, Kinoshita Y, Satoh K, Miyagawa I. Effectiveness of an anti-inflammatory drug, loxoprofen, for patients with nocturia. Int J Urol 2005; 12:779–782.
Issue
Cleveland Clinic Journal of Medicine - 78(11)
Issue
Cleveland Clinic Journal of Medicine - 78(11)
Page Number
757-764
Page Number
757-764
Publications
Cleveland Clinic Journal of Medicine
Publications
Cleveland Clinic Journal of Medicine
Topics
Geriatrics
Nephrology
Article Type
Article
Display Headline
Nocturia in the elderly: A wake-up call
Display Headline
Nocturia in the elderly: A wake-up call
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Inside the Article

KEY POINTS

  • Nocturia is multifactorial and is caused by factors that increase urine production and others that decrease the bladder’s ability to hold urine.
  • The first priority in treating nocturia is to identify and treat concomitant conditions that may be contributing to it, such as diabetes mellitus, diabetes insipidus, urinary tract infections, hypercalcemia, and hypokalemia.
  • Nonpharmacologic measures can help, but by themselves usually do not solve the problem.
  • Drug therapies for nocturia include desmopressin (DDAVP), antimuscarinic agents, alpha-blockers, and 5-alpha reductase inhibitors.
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