Pediatric Nocturnal Enuresis Secondary to Airway Obstruction from Cleft Palate Repair Kenneth C. Nowak, MD' Dudley J. Weider, MD2

Summary: Nocturnal enuresis in children can at times be alleviated or resolved completely with surgery on the upper airway. We present a report of a 7-year-old boy in whom nocturnal enuresis began immediately after reconstructive surgery of the pharynx that caused upper airway obstruction. Enuresis diminished immediately and stopped following an adenoidectomy but resumed secondary to adenoid regrowth after more than a year of dry nights. Nocturnal enuresis was immediately and permanently relieved by adenoidectomy revision. We review the relevant literature and discuss possible physiologic relationships between upper airway obstruction and bladder and renal function. Clin Pediatr. 1998;37:653-658

Introduction recent years, nocturnal enuresis as a sequela of obstructive sleep apnea (OSA) or partial airway obstruction in pediatric and adult populations has been reported in the literature. It was originally documented in this context by Simmons et all in 1977. They reported an 8-year-old boy and a 15-year-old girl in whom enuresis resolved immediately after treatment of airway obstruction with adenotonsillectomy and tracheostomy, respectively. Weider et al23 presented two case series of pediatric patients with upper airway obstruction and enuresis. In

The first study included 35 patients who ranged in age from 3.5 to 11 years. Of those patients 26 (74%) had cessation of their enuresis within 6 months of adenotonsillectomy. All patients with secondary enuresis and the majority of patients with primary enuresis had immediate postoperative reduction of enuresis.2 A later study reviewed 115 children from ages 3 to 19 years and showed a 76% success rate overall with surgical intervention, which consisted of adenotonsillectomy for 111 of the children and nasal surgery for four children. Again, all 12 patients with secondary nocturnal enuresis responded to airway restorations Several other investi-

'Section of Otolaryngology, Department of Surgery, Stanford University, Stanford, California; 2Section of Otolaryngology, Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.

Reprint requests and correspondence to: Dudley Weider, MD, Section of Otolaryngology, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756-0001. 1998 Westminster Publications, Inc., 708 Glen Cove Avenue, Glen Head, NY 11545, U.S.A.

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gators have noted the relationship between OSA and enuresis.Y7 Enuresis has also been reported in adult sleep apnea syndrome, although less commonly than in the pediatric population. Three cases have been documented recently,8-'0 two of these in the urologic literature. Unlike most pediatric cases, increased weight was involved in the OSA, and treatment consisted primarily of

continuous positive airway

(CPAP) or imipramine. In each patient the enuresis resolved with treatment of the OSA. Two patients had immediate relief from enuresis with treatment. Unique to all these cases, both pediatric and adult, is the documentation of partial upper airway obstruction or OSA in association pressure

with enuresis.

Nocturnal enuresis is defined involuntary voiding more than twice a month after the age of 4 to 6 years without the presence of urogenital defects." Nocturnal enuresis is typically divided into

as

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Nowak, Weider the categories of primary and secondary. Primary enuresis occurs when a child has never developed bladder control; this occurs in 80% of cases. Secondary enuresis is the loss of bladder control after a 6-month dry period.1' Both forms of nocturnal enuresis have occurred in relation to upper airway obstruction in children.2,3 However, few pediatric reviews mention airway obstruction as a potential etiology. In addition, Mark and Frank"l note that differentiation of primary versus secondary enuresis has no impact on prognosis. However, Weider et a13 reported a 100% cure rate for secondary enuretics (12 patients), as compared with a 68% to 71% cure rate in primary enuretic groups

treated with adenotonsillectomy. The above-cited urologic review of enuresis addresses the vast majority of enuretic cases that do not involve OSA. While the prevalence of OSA in enuretic patients is unknown, these patients are an important subpopulation whose prognosis and treatment are dictated by their underlying condition. The aim of this article is to increase the understanding of upper airway obstruction and its connection to nocturnal enuresis in the pediatric population. By documenting a novel case presentation, we hope to increase the awareness of the existence of chronic airway obstruction in children and the symptoms, such as enuresis, that may accompany it. In addition, for children whose chief complaint is related to enuresis, we hope to encourage a workup that includes a thorough history, including the recognition of symptoms of obstructive apnea and/or hypopnea, and a complete head and neck examination.

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Patient Report This 7-year-old boy was referred to the plastic surgery service at the Dartmouth-Hitchcock Medical Center (DHMC) inJune 1987 for evaluation of velopharyngeal insufficiency secondary to a partial submucosal cleft palate and bifid uvula. The patient had a history of mouth breathing and sleep apnea, with persistent snoring and occasional apneic periods through the night. He had also occasionally wet the bed through age 5 but had not done so since. He received speech therapy for nasal speech and occupational therapy for poor coordination. His behavior in school was good, despite conductive hearing difficulties secondary to recurrent otitis media, which had required bilateral myringotomy and tube placement 2 years earlier. He took Dilantin for petit mal seizures, which were diagnosed when he was 3 years of age. Approximately 2 weeks after his initial visit to the DHMC, the patient was admitted for surgical repair of his cleft palate. Repair was performed by elevating a flap of pharyngeal mucosa and suturing it to the soft palate, which allowed functional occlusion of the nasopharynx during speaking and swallowing. At that time the patient's tonsils were very large. After completion of the procedure and extubation, he had difficulty maintaining an airway and was reintubated. Examination revealed occlusion of the newly formed oropharynx by the hypertrophied tonsils. A tonsillectomy was performed and the patient was extubated without difficulty. Immediately postoperatively the patient developed nightly enuresis accompanied by snoring and persistent signs of sleep apnea, such as the appearance of

holding his breath when asleep (Figure 1). In addition, his daytime and nighttime mouth breathing became extremely noisy. Approximately 1 year later the patient was again referred to the DHMC for symptoms of airway obstruction, which had persisted since his previous surgery. His examination was remarkable for 4+ adenoids. Radiographs of the lateral neck confirmed this finding, which, with his reconstructed palate, fully obstructed his nasopharynx. An adenoidectomy was performed approximately 2 months later. By 2 weeks after this operation, the patient's nocturnal enuresis was diminished and intermittent, and his breathing had improved. Nocturnal enuresis varied from continuous to intermittent until it stopped completely, approximately 18 months postoperatively. A remnant of adenoid tissue was noted in the right nasopharynx. He was temporarily lost to follow-up owing to family relocation. The patient did well for approximately 3 years, until July 1991, when his nocturnal enuresis returned suddenly. His loud nighttime breathing and snoring had resumed. Examination revealed adenoid hypertrophy, which had reoccluded most of the nasopharynx. The patient's enuresis occurred sporadically for approximately 2 years, until an adenoidectomy revision was performed in October 1993 in concert with a submucous resection. The patient's nocturnal enuresis resolved completely coincident with the surgery (Figure 1). The patient was last seen in November 1995. He had had no nocturnal enuresis since the revision adenoidectomy in 1993. He remains an intermittent mouth breather but has near-normal speech and hearing. The pharyn-

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Figure 1. The frequency of nocturnal enuresis and its correlation to patient age and the events leading to airway obstruction and relief of obstruction.

geal flap continues to interfere somewhat with nighttime breathing, and thus complete release is under consideration.

Discussion To our knowledge this is the first reported case of the development of nocturnal enuresis secondary to an iatrogenic airway obstruction. The mechanism of obstruction in this patient was near-complete nasopharyngeal occlusion resulting from the palate surgery superimposed on an unrecognized large adenoid mass. Before surgery the child had symptoms of upper airway obstruction, due mainly to adenotonsillar hypertrophy, which, with the velopharyngeal insuffliciency, allowed both oropharyngeal and nasopharyngeal airflow, although

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restricted. Postoperatively, nasal obstruction became complete and oropharyngeal airflow was compromised significantly. On the basis of our previous experience with children with secondary nocturnal enuresis, we expected and achieved cessation of nocturnal enuresis following adenoidectomy.3 Most patient reports regarding nocturnal enuresis describe gradual development of the symptom over several months.1-38-10 Unique to the present case is the acute nature of the enuresis, which developed the first postoperative day (Figure 1). This demonstrates that airway obstruction was the probable etiology for the patient's enuresis. Most children who develop secondary enuresis from airway obstruction do so over time. The condition results

from the gradual tonsillar and adenoid hypertrophy, which is responsible for most pediatric upper airway obstruction and has a peak incidence between the ages of 2 and 5 years. The acute onset of enuresis in our patient further supports airway obstruction as an

etiology for enuresis. This patient also demonstrates that the resolution of enuresis associated with airway obstruction is often immediate and dramatic. This patient's enuresis had decreased significantly within 2 weeks of his adenoidectomy and later resolved completely (Figure 1). Most patient series demonstrate the complete cessation of enuresis with treatment of airway obstruction.2,4' 12-4 In fact, a number of patients showed near-complete resolution on the first day after treatment.2,3,-10

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Nowak, Weider The immediate development of enuresis in our patient and the acute resolution in many patients with treatment of airway obstruction suggest that the physiological link is an immediate process that does not require time for adaptation. However, the pathophysiology that leads to nocturnal enuresis and its resolution are not completely clear. A disorder of sleep arousal has been postulated as an explanation of enuresis in patients with OSA. When a full bladder develops during sleep, the apneic patients are unable to awaken to urinate appropriately. Carroll and Loughlin4 found that obstructive events were rarely associated with electroencephalographic (EEG) arousal. Weider et al3 found that after surgical correction of airway obstruction some children awakened from sleep to use the bathroom, whereas preoperatively they did not. It is possible that this lack of arousal in children with upper airway obstruction may lead to enuresis. In addition to decreased arousal, renal function appears to be altered in patients with sleep apnea. Krieger et all5 observed increases in urine levels of sodium, potassium, and chloride and in overall urine flow in patients with sleep apnea, as compared with control patients. These parameters in the OSA group approached normal with the application of CPAP. Warley and Stradling'6 had similar findings. It appears that an increase in urine production, many times the bladder's normal capacity, occurs during sleep apnea and in children with nocturnal enuresis.11, 7-19 One explanation for the increased urine production during OSA in children is a lack of diurnal variation in vasopressin or antidiuretic hormone. In subjects

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without enuresis the level of antidiuretic hormone peaks through the evening hours, which decreases diuresis and increases urine osmolality. Norgaard et al'8 demonstrated that children with enuresis lost this diurnal peak of vasopressin, and urine production exceeded daytime bladder capacity by several hundred percent. They also applied this theory to enuretic patients by treating them with desmopressin, an analog of vasopressin. They demonstrated a 70% cure rate for the 34 patients tested. Based on these findings, it is plausible that the increase in urine production alone or in accompaniment with a decreased arousal state may prohibit OSA patients from controlling their nocturnal micturition. Investigators have also studied an elevation in atrial natriuretic peptide as an explanation for nocturnal enuresis in patients with sleep apnea. Atrial natriuretic peptide is released from the atrium in response to atrial distention. This hormone is strongly natriuretic by promoting renal vasodilation, suppressing aldosterone secretion, and inhibiting renin secretion. Also, distention of the atria stimulates a vagally mediated inhibition of sympathetic output to the kidneys and inhibits ADH secretion.20 One study demonstrated this finding in six of nine children with OSA and found it was reversed with CPAP treatment.17 Other reports support this finding.'2"16 Krieger et al'5 postulate two reasons for atrial distention during OSA. First, intrathoracic pressure generated to overcome upper airway obstruction draws fluid into the central venous space and leads to atrial distention. Second, hypoxia secondary to OSA may lead to pulmonary vasoconstriction and increased right heart afterload.

Thus, the secretion of atrial natriuretic peptide associated with these pathophysiologic changes may explain increased nocturnal diuresis with sleep apnea. A number of studies implicate increased intraabdominal pressure in relation to airway obstruction as a cause of enuresis.8,10 Brown et a18 refer to a case in which an adult with enuresis had increased cystometric pressure associated with her enuretic events. A study evaluating abdominal muscle behavior in children with airway obstruction demonstrated increased muscular activity during apneic events in non-REM sleep.13 It may be that increased abdominal tension associated with OSA contributes to nocturnal enuresis. Regardless of the pathophysiologic link between upper airway obstruction and nocturnal enuresis in children, it is important to note that the most common cause of pediatric OSA is adenotonsillar hypertrophy. Appropriate treatment is tonsillectomy and/or adenoidectomy for relief from airway obstruction and enuresis. This condition may also occur with a variety of causes of upper airway obstruction, including obesity, nasal septal deviation, turbinate hypertrophy, choanal stenosis, micrognathia, macroglossia, craniovertebral abnormalities, vallecular masses,12 genetic syndromes,2' and cleft palate repair on a patient with large tonsils.22 The ap propriate treatment is then directed at the cause of the obstruction. The treatments in a patient series by Weider et a13 included submucous resection, intranasal polypectomy with ethmoidectomy, turbinoplasties, and partial uvulectomies. It is important for the clinician to recognize nocturnal enuresis as a potential compo-

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Pediatric Nocturnal Enuresis and Cleft Palate Repair nent of pediatric upper airway obstruction. A child may not show characteristic symptoms of OSA

fit the polysomnographic criteria for diagnosis but may still have nocturnal enuresis resulting from the obstruction. One patient, despite not meeting the diagnosis for OSA, had cessation of his enuresis following adenoidectomy.2 When examining a child it is important to remember that symptoms may not correlate with tonsillar size,5 and an examination may produce negative results when the patient is awake and upright.23 Thus, it may be necessary to examine a sleeping patient to appreciate the obstruction (i.e., tonsils that appear to be ordinary size in the awake patient may actually touch each other when the patient is asleep and relaxed).22 When a child presents with enuresis, the physician must perform a thorough history regarding airway obstruction, as well as a head and neck examination. Unless investigated specifically, upper airway obstruction as an etiology for nocturnal enuresis will remain undetected.

or

Acknowledgments The authors wish to thank Carole A. Stashwick, MD, of the Department of Pediatrics, for her review of and suggestions for this manuscript. The authors also wish to thank Alicia Green, MA, for her editorial suggestions and help with the preparation of this manuscript.

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REFERENCES 1. Simmons FB, Guileminault C, Dement WC, et al. Surgical management of airway obstructions during sleep. Laryngoscope. 1977;87:326-338. 2. Weider DJ, Hauri PJ. Nocturnal enuresis in children with upper airway obstruction. Int J Pediatr Otolaryngol. 1985;9:173-182. 3. Weider DJ, Sateia MJ, West RP. Nocturnal enuresis in children with upper airway obstruction. Otolaryngol Head Neck Surg. 1991;105:427-432. 4. Carroll JL, Loughlin GM. Diagnostic criteria for obstructive sleep apnea syndrome in children. Pediatr Pulmonol. 1992;14:71-74. 5. Gaultier C. Obstructive sleep apnea syndrome in infants and children: established facts and unsettled issues. Thorax. 1995;50:1204-1210. 6. Guilleminault C, Tilkian A, Dement WC. The sleep apnea syndromes. Ann Rev Med. 1976;2:465-484. 7. Richardson MA, Seid AB, Cotton RT, et al. Evaluation of tonsils and adenoids in sleep apnea syndrome. Laryngoscope. 1980;90:1106-1110. 8. Brown MA, Jacobs MB, Pelayo R. Adult obstructive sleep apnea with secondary enuresis. West J Med. 1995; 163:478-480. 9. Everaert K, Pevernagie D, Oosterlinck W. Nocturnal enuresis provoked by an obstructive sleep apnea syndrome. J Urol. 1995;153:1236. 10. Yokoyama 0, Lee SW, Ohkawa M, et al. Enuresis in an adult female with obstructive sleep apnea. Urology. 1995;45:150-154. 11. Mark SD, FrankJD. Nocturnal enuresis. BrJUrol. 1995;75:427-434. 12. Follenius M, KriegerJ, Krauth MO, et al. Obstructive sleep apnea treatment: peripheral and central effects on plasma renin activity and aldosterone. Sleep. 1991;14:211-217.

13. PraudJP, D'Allest AM, Nedelcoux H, et al. Sleep-related abdominal muscle behavior during partial or complete obstructed breathing in prepubertal children. PediatrRes. 1989;26:347-350. 14. Suen JS, Arnold JE, Brooks LJ. Adenotonsillectomy for treatment of obstructive sleep apnea in children. Arch Otolaryngol Head Neck Surg. 1995;121: 525-530. 15. KriegerJ, ImbsJL, Schmidt M, Kurtz D. Renal function in patients with obstructive sleep apnea: effects of nasal continuous positive airway pressure.

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