​Kembara Xtra - Medicine - Enuresis

​Kembara Xtra - Medicine - Enuresis 
Introduction 
Classification – Primary nocturnal enuresis (NE): eighty percent of all cases; individual who has never established urinary continence on consecutive nights for a period of less than six months. – Secondary nocturnal enuresis (NE): twenty percent of cases; return of enuresis after at least six months of urine continence.
NE: "intermittent nocturnal incontinence" after the age of 5 years, which is considered to be the expected age of bladder control.
– Primary monosymptomatic NE (PMNE) is characterized by bedwetting in the absence of a previous history of bladder dysfunction or other symptoms related to the lower urinary tract (LUT).
— Bedwetting with lower urinary tract (LUT) symptoms such as frequency, urgency, daytime wetting, hesitation, straining, weak or intermittent stream, posturination dribbling, lower abdominal or genital discomfort, or sensation of incomplete emptying is considered to be a case of nonmonosymptomatic neuroendocrine enuresis (NMNE).
ALERT
Adult-onset neuroendocrine enuresis in the absence of daytime urinary incontinence is a significant symptom that requires comprehensive urologic evaluation and treatment.
The following system(s) are affected: the neurological system, renal and urologic
Bedwetting; sleep enuresis; nocturnal incontinence; main NE are all synonyms for this condition.


Incidence and Prevalence 

Incidence: varies according to the medical history of the family Spontaneous resolution: 15% of cases per year
Very frequent; it affects 5 million to 7 million children in the United States; 10 percent of 7-year-olds have it; 3 percent of 11- to 12-year-olds do; 0.5–1.7 percent of 16- to 17-year-olds do; boys are 1.5 to 2 times more likely to be affected than girls; nocturnal bites are three times more likely than day bites (3:1)
Considerations Regarding the Aged
Infrequent; frequently linked to daytime incontinence, also known as diurnal enuresis (the older term for this condition).


Causes and effects: etiology and pathophysiology 
NE is brought on by three elements that interact with one another to bring about the condition. These factors are a disturbance of sleep arousal, a limited nocturnal bladder capacity, and nocturnal polyuria.
Both organic and functional factors (listed below); numerous hypotheses, none of which have been definitively proven
● Detrusor instability

 Insufficiency of arginine vasopressin (AVP); lower nocturnal AVP or decreased AVP stimulation as a result of an empty bladder (Bladder distension promotes AVP).
Delayed maturation of the central nervous system; Severe NE with some evidence of interaction between bladder overactivity and brain arousability; association with children who have severe NE and frequent cortical arousals in sleep; Organic urologic causes in 1–4% of enuresis in children; these include urinary tract infection (UTI), occult spina bifida, ectopic ureter, lazy bladder syndrome, irritable

NE can happen at any point of the sleep cycle.
Genetics The inheritance pattern most typically associated with NE is autosomal dominant, and it has a high penetrance of 90%.
one third of all instances are considered to be sporadic.
Seventy-five percent of the children who suffer from enuresis have a first-degree relative who also has the illness.
Higher rates in monozygotic as compared to dizygotic twins (68% vs. 36%) If both parents had NE, the risk in offspring is 77%; the risk drops to 44% if only one parent is affected. The age of resolution of the parent is frequently used as a reliable indicator of when a child's enuresis should resolve.


A history of enuresis in the family is one of the most prominent risk factors for secondary enuresis. Other risk factors include emotional and environmental stressors, such as death or divorce.

 Encopresis and/or constipation Organic disease: accounting for 1% of cases of monosymptomatic NE (including both urologic and nonurologic causes)
Psychological disorders - The likelihood of having a comorbid disorder increases with the presence of secondary neuroendocrine neoplasia. These disorders include major depression, anxiety, social phobias, conduct disorder, hyperkinetic syndrome, and internalizing disorders.
– Association with attention deficit hyperactivity disorder; symptoms become more prominent between the ages of 9 and 12 years old – Altered mental status or impaired mobility



Conditions That Often Occur Together 
Obstructive sleep apnea syndrome, in which atrial natriuretic factor blocks the renin-angiotensin-aldosterone pathway, which ultimately results in diuresis. This syndrome affects 10–54% of people.
Constipation (between 33 and 75 percent)
Behavioural issues, notably attention deficit hyperactivity disorder (ADHD) in 12–17%

 Dysfunctional voiding or overactive bladder (accounting for up to 41% of cases)

● UTI (18–60%)

History of the Presenting Problem Voiding and stooling habits (voiding diary); problems with constipation Age at which symptoms first appeared, how long they lasted, and how severe they were
Psychosocial history (including patient, parental, school/bullying, and other relevant factors); Family history of enuresis; Investigation and treatment history (where applicable);

PHYSICAL EXAM ENT: examination for adenotonsillar hypertrophy, which is related with sleep apnea. Abdomen: enlarged bladder, kidneys, fecal lumps, or impaction. Back: look for dimpling or tufts of hair on sacrum.
Genital urinary exam: meatal stenosis, hypospadias, epispadias, and phimosis in males; vulvitis, vaginitis, labial adhesions, and ureterocele at introitus in females; indications of abuse in both sexes.
Examination of the rectal mucosa for tone, fecal soiling, and fecal impaction
a neurologic examination, with particular focus on the lower extremities


Differential Diagnosis Primary Neutropenia Delayed Physiological Urinary Control Urinary Tract Infection (Both)
– An undetected case of spina bifida – Obstructive sleep apnea (both)
– Idiopathic detrusor instability – Myelopathy or neuropathy that was not diagnosed in the past (for example, multiple sclerosis, tethered cord, or epilepsy)
- Abnormalities of the anatomy of the urinary tract, such as ectopic ureters
Secondary NE: Acute stress from a tense circumstance (the most likely underlying cause)
– Neurologic disease, namely neurogenic bladder (for example, spinal cord injury) – Obstruction of the bladder outflow

Results From the Laboratory 
Initial Tests (lab, imaging)
Urinalysis is the only test that must be performed on children.
Urinalysis and urine culture: a urinary tract infection (UTI), pyuria, hematuria, proteinuria, glycosuria, and poor concentrating ability (low specific gravity) may imply an organic cause, particularly in adults.
Imaging of the urinary system is not typically required in most cases.
Renal and bladder ultrasounds if clinical findings are abnormal or if the condition appears in adults.
Rarely is it necessary to perform an intravenous pyelogram, voiding cystourethrogram (VCUG), or retrograde pyelogram.

if there is a reason to suspect spinal dysraphism, have an MRI.


Additional Examinations, as well as Other Important Factors
Secondary enuresis (if not diagnosed as being caused by psychosocial factors): blood glucose, BUN, creatinine, thyroid-stimulating hormone (TSH), urine culture
Imaging and urodynamic investigations can be helpful in diagnosing urinary tract infections (UTIs) in children who have significant daytime symptoms, a history of UTIs, suspected structural abnormalities, or refractory cases.
Diagnostic Procedures and Other Urodynamic investigations Could Be Helpful Urodynamic investigations could be helpful for adults and NMNE.

The most typical findings for interpreting the test are dysfunctional voiding, detrusor instability, and reduced bladder capacity.

Management 

It is recommended that nonpharmacologic methods be tried first, before resorting to prescribing medicine.

 It has been discovered that straightforward behavioral therapies, including as timed wakening, positive reinforcement, bladder training, and dietary adjustments, are beneficial, but to a lesser extent than alarms or drugs; these interventions have been shown to achieve dryness in 15–20% of instances.– Please explain the three pathophysiologic elements (poor nocturnal bladder capacity, fragmented sleep, and increased nocturnal urine production) that contribute to the condition.
- Suggest maintaining normal drinking habits throughout the daylight hours and cutting back on consumption two hours before going to bed.
- Make getting a full night's sleep at bedtime a priority every night.
– A predetermined time for urination before going to bed – A predetermined time for getting up throughout the night to urinate – Nightlights to guide the way to the toilet
— A system that awards points for dry nights
Wearing pull-ups over ordinary underwear or fabric underwear that already has a waterproof barrier built into it is recommended.
"Cleanliness training" consists of the youngster assisting with the replacement of damp bedding.
Do not embarrass or penalize the child for wetting the bed; rather, involve the youngster in the process of removing soiled bedding and clothing and washing them.
Enuresis that is secondary:
– Referral to behavioral counseling if there is a suspicion. – Stool softeners and cathartics if there is constipation present. – Combined therapy (such as an enuresis alarm, bladder training, motivational therapy, and pelvic floor muscle training) is more effective than each component alone or than pharmacotherapy.

 Enuresis alarms (bells or buzzers) – Considered first line of defense; most effective treatment; success rate of 66–70%; must be used nightly for two to four months; offers cure; significant parental involvement; disrupts sleep for the entire family; if successful, it should be used until 14 consecutive dry nights are achieved.

Options can be found in the "Patient Education" section.

The First Line Of Defense Is Medication
Desmopressin is a synthetic counterpart of vasopressin that reduces the amount of urine that is produced during the night.
● Intranasal DDAVP: adults only, 20 mg (2 sprays) intranasally before bedtime
It has been reported that children who took intranasal versions of desmopressin experienced severe hyponatremia, which led to seizures and even death in some cases. As a result, the FDA advises against its usage in children.
● Oral DDAVP: safe in children. Tablets of 0.2 milligrams should be taken before going to bed on an empty stomach. If this dose does not prove effective after 14 days, the dose can be increased to 0.4 milligrams.
- At its peak effectiveness in one hour; the effect can linger anywhere from eight to ten hours.
– If the treatment is successful, it can be continued for three months before being halted for two weeks so that a dryness test can be performed.
– A high risk of relapse after quitting an addictive substance without participating in a structured withdrawal program. In the event that a recurrence takes place, oral desmopressin can be recommended for an additional three-month block.
Children who are experiencing an acute condition that affects their fluid or electrolyte balance (such as fever, vomiting, diarrhea, or strenuous activity) should have their doses suspended.
- A success rate of 60–70%, with 30% of youngsters exhibiting a full reaction and 40% exhibiting a partial response.
Considerations Relating to Children
The Food and Drug Administration (FDA) strongly discourages the use of intranasal versions of desmopressin in children because there have been reports of severe hyponatremia leading to convulsions and even deaths.


Imipramine (Tofranil) is a tricyclic antidepressant that also has anticholinergic effects; it also enhances bladder capacity and has antispasmodic qualities.
- Primarily for use in adults; use in children is reserved for particularly difficult conditions and is usually started by medical professionals.
– The recommended dose for adults is 25 to 75 milligrams, while the recommended dose for children older than 6 years old is 10 to 25 milligrams taken orally before bed. The dosage should be increased by 10 to 25 milligrams every one to two weeks, and it should be continued for two to three months before being gradually reduced.
– 40% success rate, although there is a high chance of relapse after treatment is stopped.
- Prior preparation Identifying any underlying rhythm problems was recommended by the ECG.

Monotherapy with anticholinergics is not advised for use in pediatric patients.
- Oxybutynin (Ditropan, Ditropan XL, Oxytrol patch) is an anticholinergic agent, a smooth muscle relaxant, and an antispasmodic. It has the potential to increase the functional capacity of the bladder and helps with timely voiding (4).[B]
 30–50% success; recurrence rate of 50% after stopping treatment
Children older than 5 years old who have overactive bladder and have tried alarm therapy and desmopressin without success should try taking 5 mg of Ditropan before going to bed. The dosage for adults is 5 mg taken by mouth three times a day and three times a day.
 Ditropan XL dosage for adults is 5 mg orally once daily, with a maximum of 30 mg orally once daily (5- to 10-mg tablet).
 The Oxytrol patch should be applied once every three to four days (3.9 mg per patch). (Periodic trials of the medicine, such as testing it over the course of a weekend or many weeks at a time, will assist assess the medication's efficacy and whether or not it resolves the primary issue.)
Tolterodine (brand names Detrol and Detrol LA) is an anticholinergic medication that has less adverse effects than Ditropan (4).[B]
 Detrol: 1 to 2 mg orally twice daily for adults; 2 mg before bed for children older than 5 years old
○ Detrol LA: 2 to 4 mg/day


Oxybutynin should be used with caution in the following conditions: glaucoma, myasthenia gravis, gastrointestinal or genitourinary blockage, ulcerative colitis, constipation, and megacolon; older patients should take a lower dose.
Tolterodine can cause urine retention, stomach retention, constipation, and uncontrolled narrow-angle glaucoma. It also has substantial pharmacological interactions with CYP2D6, CYP3A3/4 substrates.
Desmopressin should be avoided in patients who have conditions that put them at risk for changes in their electrolytes or fluid retention (congestive heart failure [CHF], renal insufficiency). When you have gastroenteritis or another acute sickness that puts you at danger of dehydration, you should stop.
- Imipramine: Avoid use if you are taking a drug that inhibits monoamine oxidase (MAOI), you have low blood pressure, or you have an irregular heartbeat; the drug has a low toxic therapeutic ratio.
Individual usage of DDAVP and oxybutynin does not produce the same level of success as when used together in combination therapy.

Warning about imipramine because of its potential for cardiotoxicity and lethal doses

Referral Primary NE: persistent enuresis despite nonpharmacologic and pharmacologic therapies Diurnal incontinence or nonmonosymptomatic enuresis with voiding dysfunction or an underlying medical disease Referral Primary NE: persistent enuresis despite nonpharmacologic and pharmacologic therapies Referral Referral Referral Referral 

Extra Medical Intervention 
Psychotherapy for individuals and families, as well as crisis intervention

Surgical Procedures Only in cases where the condition can be treated successfully through surgery (for example, a tethered cord, an ectopic ureter, benign prostatic hypertrophy, or obstructive sleep apnea).

Acupuncture is one of the alternative therapies that only has a limited quantity of supporting facts.


Continued Patient Observation and Monitoring
When initially beginning treatment with nonpharmacologic methods, the patient should visit the clinic once every one to three months.
If an enuresis alarm is started, the patient should come back in one week to have their reaction evaluated.
If the patient is going to start DDAVP, they should come back in one to two weeks to evaluate their reaction, and then they should come back at least every three months.

Diet 
Reduce your intake of fluids and caffeine in the two hours leading up to bedtime. Avoid dairy products and drinks with added sugar in the four hours leading up to bedtime (this will lessen osmotic diuresis).


Prognosis 
In children, NE is typically self-limiting, but there is a one percent chance that it will continue into adulthood; evaluate for organic causes.

Infections of the urinary tract, perineal excoriation, and psychological disturbances (particularly in youngsters) are possible complications.