Patient Encounter 2 Part 2 Medical History Physical Examination Diagnostic Tests and Creating a Care Plan

PMH: Unremarkable pregnancy/delivery. All developmental milestones within normal limits. Two episodes of AOM treated with no sequelae. Current on all immunizations

FH, SH: Noncontributary

Meds: None

ROS: (+) nocturnal incontinence 5 nights/week or more; (-) vaginal itching, UTIs, urgency, frequency, dysuria, lower abdominal fullness

VS: BP_/_mm Hg, P_bpm, RR /min, T 37.0°C (98.6°F)

Resp: Within normal limits CV: Within normal limits

Abd: Soft, nontender, nondistended; (+) bowel sounds; bladder not palpable Neuro: Within normal limits (gross sensory, motor, reflexes) GU: Within normal limits per inspection only Rectal: Deferred

Labs: Urinalysis within normal limits

Given this additional information, what is your assessment of this patient's condition? Identify your treatment goals for this patient.

What nonpharmacologic and pharmacologic alternatives are available to the patient? What initial treatment would you suggest?

In the absence of an identified cause and comorbidities, monosymptomatic nocturnal enuresis is present which can be amenable to nonpharmacologic and pharma-cologic therapies (Fig. 53-1). Nonpharmacologic therapy should be utilized initially, provided that the patient and family are sufficiently motivated. Use of one nonpharmacologic method at a time is reasonable, provided that each is given an adequate trial period. If response is suboptimal after 6 months, a different method should be substituted or added. There is some evidence to justify combination therapy. There is no consensus as to when pharmacologic therapy should be added to or substituted for nonpharmacologic therapy. Considering that pharmacotherapy is inferior to select nonpharmacologic treatment modalities in pediatric enuresis, pharmacotherapy will be most valuable in patients who are not candidates for nonpharmacologic therapy due to nonadherence or who do not achieve the desired outcomes on nonpharmacologic therapy alone.

FIGURE 53-1. Enuresis treatment protocol. (DDAVP, desmopressin; HS, at bedtime; D/C, discontinue; prn, as needed.)

Nonpharmacologic Treatment38

The standard first-line therapy is supportive in nature. This involves education about the condition, demystification, and assurance that the parents do not punish the child for enuresis. Journal keeping, fluid restriction, and nighttime awakenings of the child to pre-empt "accidents" make for a high level of caregiver involvement. The behavioral treatments of enuresis are explained in Table 53-6. Alarms, overlearning, and dry-bed training are the most complex and effective nonpharmacologic treatments available and compare favorably to pharmacologic therapy. A 3- to 6-month trial is recommended. Once dryness is achieved, relapse rates are low.

Measures that do not help include:

• Bladder stretching exercises (done by delaying voiding despite the urge to do so)

Hypnotherapy

Table 53-6 Behavioral Treatments for Enuresis

Lirtlng Procedure whwoln (he caregiver takes ttie thlldi to the tollel at tegula inlervalE. during 1he night toulnate milliout hj8y dwak-nlrtg Ip'il i?r htn Mkjht awakwwig Procedure wheieln (he caregiver fuly awakens ihe c «1 void shortly before he 01 she woukl usually have wel the bed; onculfUKtiild is Consistently dry, the fioquenty of jvyakuniog drops m {lc* single awakenings) the 1 c:i .11 r. 1 K iir.idiiHlly moved to eirln'i in the nghr £e, c V riii 10 hedi imit unril (he 1: Ink! ii dry awakened 1 four aftei going to bed Alaiin fln mrm devite and a moiitune-switrvt senior ait used in connbiftjliiri, wirli (he serwr Doing fljted «nda Ihe sheen, o* mone commonly, attached to the child's pajamas or underweai near [he urelhia OvtrKMl nlrvi T hii rl UymiWrKCCl iir a ill iriiirtuin of 2 nttkS ji'lti (he illMI) I ||1S rCOJOWf Hie child <)i f. it* f NU U liri kt

WO ml (about IIS during [he hour heirae tjorvi rohed; aL«m iise rstonilnued urni he or she Is dry for M consec ul ive nlghls with 1 he extra llukJ Intake; is used to leduce relapse rates seen with alarm use alone Ory-heO [r.iiiiiftf this begins with an intensiveUrsT nighi cf lr.nniivi wTiich Involw»*inenwed fluil consumption, hourly awakenings, prjise when the bed is dry al hourly awakenings, ancj, when the dlaim goes, off, a miH rep*riand jncltlejnllnrt^ Irjiiaig fchild tliarn 'S wt,1! i.lOthr.'S arnl lnvl r«n"r!v HHflfltaS (lie belt ii'^'t^ [tn1 going to bed .ill: I aflsr each wii 1 ing, the chid eiigjges in 7G practice iii.its of appropriate lolleting :i/■.. positive practice), for each prKtice Irlal, the chid Its In beet counts to id, aiises and alhMnplslo urinate In the (diet, lilt" rentw toljcitOii ¡vlw.tflH.'rH niighLivthikJ r> m+fi mXc. uiiwlly jbcsfl 3 houn jr^ liitthikfiijj gone to bertaftcr adry nlghl, the mght awakening moves up 50 minutes earllei; ft Is discontinued when II is-schedutJ to occur \ hour jfler btyflimc; af(n 7 comfculiw dry nighls. thealaim is Jiscom^iut'dl but Is lelnswwd if tvo cfisodes ct wni ing occur In a i-weok poriocf

Dietary changes Desensitization to allergens

Acupuncture Chiropractic

Pharmacologic Treatment

The two primary agents used to treat enuresis are DDAVP and imipramine (Table 53-7). DDAVP is the drug of choice in pediatric enuresis. Anticholinergics have a limited role (Table 53-7). Other agents have been studied with inconclusive results.40

.4142 Desmopressin '

A synthetic analogue of ADH, DDAVP was first studied in enuresis in the 1970s. It was approved by the FDA in 1990 for the treatment of nocturnal enuresis in children at least 6 years of age. It decreases the number of wet nights per week by a mean of 1.34. The between-study variability in response to DDAVP is quite large, with a frequency of wetting ranging from 10% to 91% of patients, but only 25% become completely dry on the drug. Response is dose-independent for the nasal formulation (20 = 40 = 60 mcg); however, 20 mcg is the minimum dose resulting in therapeutic benefit. Response is dose-dependent for the oral formulation (e.g., the number of wet nights fell 27%, 30%, and 40% with 0.2-, 0.4-, and 0.6-mg doses, compared to 10% with placebo in one study). Benefit exists only as long as the patient takes DDAVP, with relapse rates of up to 94% after discontinuation. Insufficient data are available to judge the relative efficacies of the two formulations. DDAVP appears to work better with monosymptomatic versus polysymptomatic enuresis. The oral route is generally preferred since nasal congestion and sinusitis can reduce the bioavailability (BA) of the nasal formulation. DDAVP is an ideal agent for rapid-onset, short-term use such as attendance at camp or going on a "sleepover." If the desire is for long-term therapy and if it is sufficiently effective short-term, a 3- to 6-month trial is reasonable. At the end of this period, the drug should be tapered off by 0.1 mg (oral) or 10 mcg (nasal) per month. Relapse is less likely with a tapered withdrawal compared to an abrupt discontinuation. The following factors should be considered in individuals with partial responses to DDAVP: suboptimal dosing, poor adherence, poor BA (change nasal to oral preparation), and poor fluid/dietary habits (i.e., fluid restriction and high protein intake during the day and liberal salt and fluid intake after suppertime).43 In individuals with presumed DDAVP resistance (i.e., poor response to usual doses or deterioration after a good response has been established), oral furosemide 0.5 mg/kg in the early morning may be useful. Furosemide works by reversing the abnormal cir-cadian rhythm of renal tubular sodium handling which is common in such individu-als.44 In 12 patients with DDAVP-resistant enuresis, furosemide 0.5 mg/kg once daily in the morning was added to DDAVP therapy. In 9/12 (75%), enuresis events were reduced to less than one wet night per month. In the remaining three patients, although events were reduced from baseline (7 wet nights/week), they were still wet 2, 3, and 6 nights per week. Two of these three patients exhibited signs/symptoms of overactive bladder and one of the two patients had to discontinue furosemide therapy due to the increased frequency of daytime symptoms.44 Side effects to DDAVP are minor and infrequent.45 The most serious complication, water intoxication, is extremely uncommon when DDAVP is used to treat enuresis, with only 48 reported cases, all due to the nasal formulation.45 However, electrolyte monitoring is recommended if intercurrent illness complicates the situation. Children should also not drink more than 8 ounces (about 240 mL) of fluid at suppertime, 8 ounces (240 mL) in the evening, and none in the 2 hours prior to bed in order to reduce the risk of water intoxication.

Table 53-7Dosing of Pharmacologic Treatments of Enuresis

Desmopressin

Anticholinergics

Nasal; Start with 10 meg l hour before bedtime and titrate upward in 10 meg increments every week to a maximum of 40 meg/day

Oral: Start with 0.2 mg I hour before bedtime and titrate upward in 0.1 mg increments every week to a maximum of 0,6 mg/day

Stert with 1 mg/ky/day (appr™mately 25 mg in 5- to 8-year-olds and 50 mg in older children and adolescents) and titrate in 0.5 rng/kg/day Increments every 2 weeks to a maximum of 2.5 mg/kg/day liefer to labile 53-3

Imipramine46

The TCA imipramine was first used in the treatment of enuresis in the 1960s. Although trials involving other TCAs have been performed over the years, there is insuf-

ficient evidence to assess the relative performance of these agents versus imipramine and the latter is considered the gold standard TCA in enuresis management. Its mechanism of action is unclear, although it is an anticholinergic and antispasmodic and may increase plasma ADH concentrations. Up to 80% of treated patients may respond, although the long-term continence rate is only about 25%. A patient can expect approximately one fewer wet night per week with imipramine use. As with DDAVP, benefit only occurs as long as the drug is being taken, with relapse rates after discontinuation of therapy of up to 50%. There is no significant correlation of drug concentration with response. If sufficiently effective short-term, a 4- to 6-months trial is reasonable, followed by a weaning-off period of 3 to 4 weeks. There is a high frequency of neurologic side effects in children, including lethargy, dizziness, and headache in 5%; irritability in 11%; anxiety in 10%; and sleep disturbances in 16%45 GI symptoms occur in about 25% of pediatric patients.45

Anticholinergics

Oxybutynin and tolterodine mono-therapies have no significant effect in monosymptomatic nocturnal enuresis. Oxybutynin and related agents (see adult UI section of this chapter) should be used only if the patient has concurrent daytime urgency or frequency. Combination therapy with DDAVP may also be worthwhile in patients refractory to combinations incorporating alarm therapy, DDAVP, and/or imipramine.

Comparison of Therapies

Most of the comparisons between treatments have been made by means of meta-ana-lyses conducted by the Cochrane Enuresis Collabora-tive.40,4 ,46-48 Unfortunately, most enuresis treatment studies have been so poorly designed they compromise the ability to pool studies for meta-analysis. With this in mind, the comparative efficacies of monotherapy and combination therapies using the best data available follow.

The most effective nonpharmacologic method is the use of bed alarms. Defining success as less than 1 wet night per month, the initial success rate for alarms is 66%, with long-term success after discontinuation occurring in 45% (versus 1% with no treatment). However, this method requires highly motivated families and the development of improvement is slow (over 4 to 12 or more weeks). Data are inadequate to compare the various commercial brands of alarms available to consumers or to compare alarms to other behavioral interventions. Supplementing this method with either overlearning or dry-bed training significantly reduces the already low relapse rates seen with alarms. Alarm therapy is also significantly more effective than DDAVP, evaluated at both the end of therapy and long-term. Similar findings are noted for the alarm-versus-imipramine comparison. There are conflicting data regarding the value of supplementing the alarm method with DDAVP.

The American Academy of Child and Adolescent Psychiatry and the International Children's Continence Society (ICCS) published preliminary practice guidelines for the assessment and treatment of pediatric enuresis in 2004. 5' r However, the modified algorithm of Reiner is inclusive of all potentially useful treatments and distinguishes approaches based on nocturnal urine output (nocturia), an important distinction not considered in previous recommendations.49- 1

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