Nocturia (derived from Latin nox, night, and Greek [τα] ούρα, urine), also called nycturia (Greek νυκτουρία), is defined by the International Continence Society (ICS) as “the complaint that the individual has to wake at night one or more times to void.” The pathophysiology of nocturia is multifaceted and can be complex and its cause remains unclear in a significant number of patients.
In order to diagnose nocturia, the nocturnal urine volume (NUV) of patients must be known. The ICS defines NUV as “the total volume of urine passed between the time the individual goes to bed with the intention of sleeping and the time of waking with the intention of rising.” Thus, NUV excludes the last void before going to bed, but includes the first morning void. A main factor of nocturia is the intention of the patients when wakening; whether the patient is awakened with the intention to void or if the patient voids after being awakened for some other reason. The latter not classified as nocturia. Although every patient does not need treatment, most people seek treatment for severe nocturia, waking up to void more than 2-3 times per night. Another important factor of nocturia is defining the sleep period of the patients. This can affect the evaluation of nocturia because the number of nocturnal voids depends partly on how many hours an individual actually sleeps. On average, sleep time is 8 hours per night but may vary between individuals.
Studies show that 5-15% of people who are 20-50 years old, 20-30% of people who are 50-70 years old, and 10-50% of people 70 years old and up, experience two or more symptoms of nocturia per night. From these studies, it can be seen that nocturia becomes more common as people grow older. More than 50 percent of men and women over the age of 60 have been measured to have nocturia in many communities. Even more over the age of 80 are shown to experience symptoms of nocturia every night. Also, as people get older, the faster nocturia symptoms seem to worsen. Although there are no substantial differences between men and women having symptoms of nocturia, data shows that there is a higher prevalence in younger women than younger men and older men than older women.
Causes of nocturia can fall under two categories: irregular levels of hormones that are involved in water balance of the body and vesical problems.
Two major hormones that regulate the body’s water level are arginine vasopressin (AVP) and atrial natriuretic hormone (ANH). AVP is an antidiuretic hormone that is produced in the hypothalamus but stored in and released from the posterior pituitary gland. It is activated when the body needs to retain water and does so by increasing water absorption in the collecting ducts of the kidney nephron; subsequently decreasing urine production. ANH, on the other hand, is released by heart muscle cells in response to high blood volume. When activated, ANH releases water, subsequently increasing urine production.
Nocturia can be separated into four underlying pathophysiological processes: global polyuria, nocturnal polyuria, bladder storage disorders, or mixed etiology. The first two processes are due to irregular levels of AVP or ANH, while the third process is a vesical problem.
Global polyuria is the continuous overproduction of urine which is not only limited to sleep hours. Global polyuria occurs in response to increased fluid intake and is defined as urine outputs of greater than 40 mL/kg/24 hours. The common causes of global polyuria are primary thirst disorders such as diabetes mellitus and diabetes insipidus (DI). DI is caused by irregular water levels in the body. Urination imbalance may lead to polydipsia or excessive thirst to prevent circulatory collapse. Central DI is caused by low levels of AVP that helps regulates water levels. In nephrogenic DI, the kidneys do not respond properly to the normal amount of AVP. Diagnosis of DI can be made by an overnight water deprivation test. This test requires the patient to eliminate fluid intake for a fixed period of time, usually around 8-12 hours. If the first morning void is not highly concentrated, the patient is diagnosed with DI. Central DI usually can be treated with a synthetic replacement of AVP, called desmopressin. Desmopressin is taken to control thirst and frequent urination. Although there is no substitute for nephrogenic DI, it may be treated with careful regulation of fluid intake.
Nocturnal polyuria is defined as an increase in urine production during the night but with a proportional decrease in daytime urine production that results in a normal 24-hour urine volume. With the 24-hour urine production within normal limits, nocturnal polyuria can be translated to having a nocturnal polyuria index (NPi) greater than 35% of the normal 24-hour urine volume. NPi is calculated simply by dividing NUV by the 24-hour urine volume. Similar to the inability of control urination, a disruption of arginine vasopressin (AVP) levels has been proposed for nocturia. Compared with the normal patients, nocturia patients have a nocturnal decrease in AVP level. Other causes of nocturnal polyuria include diseases such as congestive heart failure, nephritic syndrome and hepatic failure; or lifestyle patterns such as excessive nighttime drinking. The increased airway resistance that is associated with obstructive sleep apnea may also lead to nocturnal polyuria. Obstructive sleep apnea have shown to have increases in renal sodium and water excretion that are mediated by elevated plasma ANH levels.
Bladder storage disorders are defined as any factors that increase the frequency of small volume voids. These factors are usually related to lower urinary tract symptoms that affect the capacity of the bladder. Patients with nocturia who do not have either polyuria or nocturnal polyuria according to the above criteria, will most likely have a bladder storage disorder that reduces their nighttime voided volume or a sleep disorder. Nocturnal bladder capacity (NBC) is defined as the largest voided volume during the sleep period. Decreased NBC can be traced to a decreased maximum voided volume or decreased bladder storage. Decreased NBC can be related to other disorders such as prostatic obstruction, neurogenic bladder dysfunction, learned voiding dysfunction, anxiety disorders, or certain pharmacological agents.
A significant number of nocturia cases occur from a combination of etiologies. Mixed nocturia is more common than many realize and is a combination of nocturnal polyuria and decreased NBC. In a study of 194 nocturia patients, 7% were determined to have simple nocturnal polyuria, 57% had decreased NBC, and 36% had a mixed etiology of the two. The etiology of nocturia is multifactorial and often unrelated to an underlying urological condition. Mixed nocturia is diagnosed through the maintenance and analysis of bladder diaries of the patient. Assessment of etiology contributions are done through formulas.
As with any patient, a detailed history of the problem is required to establish what is normal for the patient and what isn’t. The principal diagnostic tool for nocturia is the voiding bladder diary. Based on information recorded in the diary, a physician can classify the patient as having polyuria, nocturnal polyuria, or bladder storage problems. Timing of voids, number of voids, and volume of urine voided should be recorded in the diary. Volume of fluid intake and time of intake should also be recorded. Patients should include the first morning void in the NUV, however, the first morning void is not included with the number of nightly voids.
Although there is no cure for nocturia, there are many actions people can take to manage their symptoms. Prohibiting the intake of caffeine and alcohol has helped some individuals with the disorder. Compression stockings worn through the day also help in preventing fluid accumulating in the legs causing less urinary output. Drugs that increase the passing of urine can help decrease the third spacing of fluid, but they could also increase nocturia. A common action patients take is to not consume any fluids hours before bedtime, which especially helps people with urgency incontinence. However, a study on this showed that it reduced voiding at night by only a small amount and is not ideal for managing nocturia in older people. For people suffering from nocturnal polyuria, this action does not help at all because of irregular AVP levels and the inability to respond with the inhibition of increased voiding. Fluid restriction also does not help people who have nocturia due to gravity-induced third spacing of fluid because fluid is mobilized when they lie in a reclining position.
If the cause of nocturia is related to the obstruction of the prostate or an overactive bladder, surgical actions may be sought out. Transurethral prostatectomy/incision of the prostate and surgical correction of the pelvic organ prolapse, sacral nerve stimulation, clam cystoplasty, and detrusor myectomy are both treatment options and can help alleviate the symptoms of nocturia.
Desmopressin is a synthetic replacement for AVP, which is widely used for the treatment of many disorders including nocturnal enuresis and coagulation disorders. It is slowly becoming accepted as the drug needed to treat nocturia. Clinical trials testing desmopressin on nocturia patients showed that 33% of men and 46% of women treated with the drug reported a significant reduction in the number of episodes per night. Overall, the number of episodes a night and the amount of time between each episode changed significantly in favor of the patients who took desmopressin over the placebo. Also, for the patients that took the drug, many of the negative impacts of nocturia were relieved. The longer the patients were on desmopressin, the more that reported a positive effect of the drug. The only substantial negative of taking the drug seen in the trials was dilutional hyponatremia. Using this treatment in older patients and patients at risk for hyponatremia means having to monitor the serum sodium concentration because there are severe risks if the concentration falls. The treatment could also induce hyponatremia in patients who are not initially at risk for it.
Other drugs that are often used to treat nocturia include oxybutynin, tolterodine, solifenacin, and other antimuscarinic agents. These drugs are especially used in patients who suffer from nocturia due to an overactive bladder and urgency incontinence because they help bladder contractility.
Although nocturia is not a well-known disease to the general population, more than 60% of people reported it affecting their lives in a negative way. Nocturia can have a great impact on the quality of life for many individuals, especially those in an older age group who experience more symptoms. It is linked to the lack and disruption of sleep, which can cause many other issues including exhaustion, changes in mood, sleepiness, impaired productivity, less energy, increase in accidents, and cognitive dysfunctions. Twenty-five percent of falls that older individuals experience happen during the night, and 25% of these falls occur because of having to wake up to void. A recent study in Sweden observed and compared people with and without nocturia. It showed that people with the disorder experienced many of the symptoms listed about above more than the controls. In addition, nocturia can also cause a higher risk for mortality and morbidity.
A quality of life test for people who experience nocturia was recently developed. Before this test, there was no way to measure the extent of the disorder different people experienced. So far, the test can separate men who experience a different number of episodes per night. However, it has not been successfully authenticated for use in women.
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- Bergen Urological
- Nocturia Resource Centre", linked to the journal European Urology , has been providing a continuous update on nocturia, causes, consequences and clinical approaches.