Behavior, cognition, and quality of life after adenotonsillectomy for pediatric sleep-disordered breathing: Summary of the literature

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1 Otolaryngology Head and Neck Surgery (2008) 138, S19-S26 LITERATURE REVIEW Behavior, cognition, and quality of life after adenotonsillectomy for pediatric sleep-disordered breathing: Summary of the literature Susan L. Garetz, MD, Ann Arbor, MI OBJECTIVE: To summarize published studies that evaluate whether adenotonsillectomy performed for sleep-disordered breathing in children is associated with improvements in behavior, cognitive function, and quality of life, whether those improvements show correlation with polysomnographic parameters, and suggest how future studies may provide additional clinically significant information. METHODS: A computerized search of the medical literature was performed for articles published between 1950 and March 2007 with the use of the OVID Medsearch database. RESULTS: Analysis revealed 25 articles that satisfied the inclusion and exclusion criteria. All studies showed improvement in one or more of the specified outcome measures including general or disease specific quality of life, behavioral problems including hyperactivity and increased aggression or neurocognitive skills, such as memory, attention, or school performance. Limited correlation was often seen between improvements in outcome measures and polysomnographic variables. CONCLUSION: Current studies strongly suggest adenotonsillectomy performed for sleep-disordered breathing in children is associated with improvements in quality of life, behavior, and cognitive function, but large, randomized, controlled studies are needed to provide definitive evidence of the benefits of this commonly performed surgical procedure in the general population American Academy of Otolaryngology Head and Neck Surgery Foundation. All rights reserved. In the mid-20th century, over a million tonsillectomies a year were performed on children in the United States, largely for the indication of recurrent infection. In recent 1 decades the number of tonsillectomies has decreased, but it remains one of the most commonly performed pediatric surgical procedures. Currently adenotonsillectomy (AT) is performed with increasing frequency for obstructive instead of infectious indications. 2 In a recent survey of practice patterns, otolaryngologists responded that of over 20,000 pediatric AT performed in the previous year, nonmutually exclusive indications included obstructed breathing of any type in 59% of cases, recurrent infections in 42%, and obstructive sleep apnea (OSA) in 39%; this indicates that obstructed breathing now rivals recurrent infection as the 3 most common surgical indication for AT. Sleep disordered breathing (SDB) is a common entity in children 4-6 and includes a range of nocturnal breathing abnormalities. Milder forms include primary snoring, defined as habitual snoring not associated with oxygen desaturation 7 or arousals from sleep, and upper airway resistance syndrome (UARS), characterized by increases in negative intrathoracic pressure and arousals from sleep not generally 8 associated with oxygen desaturation or airflow restrictions. SDB also includes OSA, which is characterized by repeated episodes of nocturnal airflow restriction (hypopneas) or obstruction (apneas) in association with arousals from sleep, oxygen desaturation, and possible hypercapnia. 9 Although the criteria for OSA in children remains somewhat controversial, an apnea index (AI) of greater than 1 per hour or apnea/hypopnea index (AHI) greater than 5 per hour on overnight polysomnography (PSG) is generally considered abnormal. 10,11 Snoring has been reported in 3% to 12% of the pediatric population. The incidence of pediatric UARS, which requires the use of less widely available esophageal pressure monitoring (Pes) for diagnosis, remains unknown but has been suggested to be equal to or higher 8 than the incidence of OSA. OSA is thought to affect 1% to 3% of children. 4,5,14,15 Some studies report an increased incidence of SDB in certain ethnic minorities such as African Americans 6,16 as well as in children who are overweight, 6,17 which also causes an increased prevalence in 18 ethnic groups with higher obesity rates. Data also indicate that SDB in obese children is less amenable to resolution after surgical intervention Whereas OSA has been associated with systemic and 22 cardiovascular sequelae such as failure to thrive, systemic hypertension, 23,24 cor pulmonale, or left ventricular hypertrophy, even the less severe forms of SDB have been associated with decreased cognitive skills, quality of life (QOL), 31,32,34 and behavioral disturbances 29,33-35 in children. The question therefore arises whether AT done for obstructive indications is effective in ameliorating the decreased QOL and adverse behavioral and cognitive consequences of SDB. Received April 29, 2007; accepted June 27, /$ American Academy of Otolaryngology Head and Neck Surgery Foundation. All rights reserved. doi: /j.otohns

2 S20 Otolaryngology Head and Neck Surgery, Vol 138, No 1S, January 2008 Several excellent systematic reviews on the relationship of AT for SDB, behavior, QOL, and neurocognition in children have been published in recent years by Ebert and Drake and Mitchell and Kelly. This article is intended to complement the studies published in this supplement on QOL in tonsillectomy for recurrent tonsillitis by briefly summarizing the published studies on changes in behavior, QOL, and neurocognitive measures after adenotonsillectomy performed for SDB in children, including several studies published since those reviews appeared, and to suggest directions for future studies. MATERIALS AND METHODS A computerized search of the medical literature was performed with the Ovid Medsearch database for articles published between 1950 and March 2007 with the use of the key words: tonsillectomy or AT and quality of life, behavior, cognition, school, or performance. Search results were then limited to articles in the English language pertaining to human beings aged 0 to 18 years. Articles that specifically addressed changes in QOL indicators, behavior, cognitive function, or school performance after tonsillectomy or AT done primarily for sleep-disordered breathing were selected for review. The bibliographies of the selected articles were also searched manually for any articles not captured by the computerized search. Case reports, review articles, abstracts, and letters were excluded. RESULTS The search revealed a total of 232 articles. Review of those abstracts revealed 25 relevant articles that met the inclusion and exclusion criteria, with sample sizes that ranged from 19 to 297 subjects. Seventeen of the studies evaluated a single outcome variable after surgical intervention; 10 studies evaluated changes in quality of life, 4 studies examined behavioral changes, and 3 studies looked exclusively at neurocognitive improvements. Five studies evaluated changes in behavior and cognition, and two studies evaluated behavior and quality of life improvements. One study evaluated changes in all three domains: cognition, behavior, and quality of life. Early descriptive studies support a correlation between sleep-disordered breathing and behavior and cognition that improves after surgical intervention in the form of AT. Guilleminault et al 38 described 25 children with symptoms of snoring, excessive daytime somnolence, and abnormal behavior. PSG with Pes did not show obstructive sleep apnea, but increased negative esophageal pressure was seen. After AT, parents and teachers reported a decrease in behavioral symptoms in all subjects. Objective measurements of cognition (Wilkinson Addition Test) were done in a small subset of older patients and improvement was seen as well. Potsic et al 39 looked prospectively at 100 children with nocturnal obstruction from adenotonsillar hypertrophy that was not considered severe and 50 age-matched controls. Less mouth breathing and fewer behavioral problems were reported on parent questionnaires in the AT subjects after 40 surgery. Stradling et al evaluated 61 children referred for recurrent tonsillitis who also snored compared with 31 controls. A parental questionnaire revealed significant concerns about their children at baseline including increased levels of aggression, learning difficulties, and hyperactivity. Postoperative questionnaire responses were similar to those seen in 41 the control group. Gozal looked at 297 children ranked in the lowest 10th percentile of their first grade class. Nocturnal pulse oximetry and carbon dioxide measurements were used to identify 54 children with sleep-associated gasexchange abnormalities and evaluation for AT was recommended. Of those 24 children who underwent surgery, only 2 remained in the lowest 10% of their class the following year. No changes in academic performance were seen in the children with gas-exchange abnormalities who did not undergo surgery or the children without identified gasexchange abnormalities. These studies, although suggestive of improvement in key outcome measures, lacked validated objective instruments that documented either benefit from surgery or the existence of OSA. The first study in children with SDB that used a validated disease-specific QOL instrument, the Obstructive Sleep 42 Disorders 6 (OSD-6), was done by De Serres et Large al. improvement in QOL after AT was seen in 74% of 101 children at their postoperative visit and some improvement was seen in 88% of children. Studies that used other validated QOL instruments (Table 1) have shown similar improvements after AT. Mitchell et alfound short-term 43 improvements in QOL in 60 children 6 months after surgery for OSA with the Obstructive Sleep Apnea 18 (OSA-18), another validated disease-specific quality of life instrument. These improvements in QOL also appear to be long-lasting. Mitchell et al 44 showed persistent but less pronounced -im provement in QOL with the OSA-18 after a longer (9 to month) follow-up in 37 children. Flanarylooked at 55 children with adenotonsillar hypertrophy (ATH) and OSA undergoing AT with the use of both a validated general QOL instrument, the General Children s Health Questionnaire Parent Form (CHQPF-28), and the disease-specific OSA-18; she found benefits in both short-term and longterm quality of life with the disease-specific survey instrument and for the physical summary parameters of the general QOL survey. Diez-Montiel et alused the OSD-6 to 46 evaluate 101 children at least 3 years after AT, and continued improvement in disease-specific quality of life over preoperative levels was still observed. Improvements have also been shown in behavior (Table 2) and cognition (Table 3) after AT done for SDB with the use 47 of validated objective outcome measures. Ali et al compared behavior and cognition after AT in 12 children with sleep-disordered breathing based on parental question-

3 Garetz Behavior, cognition, and quality of life after... S21 Table 1 Quality of life instruments Instrument Child Health Questionnaire Parent Form-28 (CHQPF-28) Obstructive Sleep Apnea-18 (OSA-18) Obstructive Sleep Disorder-6 (OSD 6) Tonsil and Adenoid Health Status Instrument Description A 28-item generic quality of life instrument designed and validated for children that measures 14 unique physical and psychosocial domains. Scores can be reported as individual profile scores or combined as a summary score to obtain an overall value for physical and psychosocial domains. A validated, disease specific QOL survey for pediatric OSAS that consists of 18 questions divided into 5 domains: sleep disturbance, physical symptoms, emotional symptoms, daytime function, and caregiver concerns. A validated, disease-specific QOL measure to assess changes in patients with SDB. The 6 domains reflect a child s functioning with respect to: physical suffering, sleep disturbance, speech and swallowing difficulties, emotional distress, activity limitations, and level of caregiver concern relating to the child s sleep disorder and related symptoms. A validated disease-specific pediatric survey with 6 subscales that measure different aspects of health status affected by tonsil and adenoid disease: eating and swallowing, airway and breathing, infections, health care utilization, cost of care, and behavior. naires, nocturnal video, and pulse oximetry in 11 children with snoring but no obvious obstruction and 10 nonsnoring controls. The Conner s Rating Scale (Conner s), Continuous Performance Test (CPT), Wechsler Intelligence Scale (WISC), and Matching Familiar Figures test were used as outcome measures. After AT, the SDB group had reduced aggression, inattention, and hyperactivity on the Conner s as well as improved scores on the CPT; the snoring group had less hyperactivity and improved vigilance compared to 48 the nonsurgical controls. Montgomery-Downs et aleval- uated cognitive changes in a group of 19 socioeconomically at risk children with OSA before and after AT with the Differential Abilities Scale (DAS) and the Developmental Neuropsychological Assessment (NEPSY) compared with 19 controls. DAS scores in the OSA subjects were lower than those seen in controls preoperatively and improved significantly to match the control level after surgical intervention. Only the NEPSY verbal scores were found to be lower in subjects than in controls, and those scores also improved after surgery. In a noncontrolled study of 36 children who underwent 49 AT, Goldstein et al found abnormal behavior preopera - tively in 28% of patients with the Child Behavior checklist (CBCL), a standardized assessment tool for childhood behavior. These behavioral disturbances resolved in all but two patients after surgery. A significant decrease in the mean total problem score was also seen. In a larger study of 64 children before and after AT for clinically diagnosed 50 SDB, Goldstein et al found a significant improvement in disease-specific QOL after surgery with the OSA-18, as well as improvement in behavior on the CBCL. A significant correlation was seen between improvement on the 51 QOL instrument scores and behavior scores. Avior et al evaluated attention, behavior, and quality of life in 19 children with a clinical diagnosis of OSA with the Test of Variables of Attention (TOVA), the OSA-18, and the CBCL. Improvements were seen in all three measures 2 52 months after surgery. Galland et alshowed statistically significant improvement in neurocognitive function with CPT and behavior with the Behavioral Assessment System Table 2 Behavioral instruments Instrument Behavioral Assessment System for Children (BASC) Child Behavior Checklist (CBCL) Child Symptom Inventory-4 Parent checklist (CSI-4) Conner s Parents Rating Scale (Conner s) Description A group of instruments that evaluates the behaviors, thoughts, and emotions of children and adolescents and focuses on both adaptive and maladaptive behaviors. A validated instrument used to assess the behavioral problems and social competencies of children as reported by parents with the use of a 118-item questionnaire. A validated 108-item instrument for rating behavior that screens for behavior and emotional disorders in children. A validated behavioral instrument with 80 items that uses parent ratings to evaluate problem behaviors and attention deficit hyperactivity disorder.

4 S22 Otolaryngology Head and Neck Surgery, Vol 138, No 1S, January 2008 Table 3 Cognition instruments Instrument Integrated Visual and Auditory Continuous Performance Test (CPT) Children s Memory Scale (CMS) Developmental Neuropsychological Assessment (NEPSY) Differential Abilities Scale (DAS) Kaufman Assessment Battery for Children (K-ABC) Matching Familiar Figures Test Tests of Variables of Attention (TOVA) Weschler Intelligence Scale for Children-Revised (WISC-R) Wilkenson Addition Test Description A validated measure of sustained attention or vigilance in which a computer button is pressed when the child sees or hears a specific word or image. A validated measure of concentration and attention in which children repeat numbers or sequences of graduated length either forwards or backwards. A series of neuropsychological tests used in various combinations to assess pediatric development for 5 functional domains: attention/ executive functions, language, sensorimotor function, visual-spatial processing, and memory and learning. A battery of tests that measure cognitive and achievement levels for children consisting of 20 subtests, 17 cognitive and 3 achievement, that also yield an overall cognitive ability score and achievement score. A validated clinical instrument to assess cognitive development and achievement in children with 16 subtests. Children are shown a drawing of a familiar object and asked to select the one that matched it from a display of similar figures differing only in small details, to measure a child s cognitive style as reflective (long response times and correct answers) or impulsive (short response times and incorrect answers). An objective, standardized neurophysiological measure of attention that measures responses to either visual or auditory simple stimuli often used to objectively confirm a diagnosis of ADHD. A validated general test of intelligence in children composed of 13 subtests divided into verbal and performance scales. A performance test in which subjects add numbers for 1 hour. The number of correct answers and number of operations performed are tabulated. for Children test (BASC) after AT for mild SDB in children despite the subjects being deemed behaviorally normal preoperatively. Improvements in behavior, like those seen in 53 QOL, appear to be long-lasting. Mitchell and Kelly showed behavioral improvements in children with documented OSA after undergoing AT with the BASC in shortterm evaluation (6 months after surgery) that were seen to persist in another study after longer term (9 to 18 month) follow-up. 54 A number of recent studies have also explored the improvements in behavior, cognition, or quality of life in 55 conjunction with PSG parameters. Friedman et al examined neurocognitive function with the Kaufman Assessment Battery for Children (K-ABC) in 39 children with documented OSA and 20 controls with no symptoms of SDB. Children with OSA had lower subtest scores as well as a lower score on the general mental processing composite scale. No correlation was seen between severity of OSA and K-ABC scores. After AT, the OSA group s neurocognitive scores reached the level seen in the control group in both the subtests and general scale. Stewart et al 56 looked at disease-specific QOL with the Tonsil and Adenoid Health Status Instrument and global QOL using the CHQPF-28 in 47 children with suspected OSA. Thirty-one children had PSG-documented OSA and underwent AT. One year later an improvement was seen in both QOL scores and PSG parameters in the children who underwent surgery, but only a moderate association between PSG findings and QOL scores was seen. Mitchell and Kelly 57 evaluated QOL in children with severe OSA and found significant improvement in general and domain QOL scores with the OSA-18 despite the lack of resolution of the 58 OSA in the majority of subjects. A study by the same authors looking at differences in QOL improvement between 43 children with severe OSA and 18 children with less severe disease showed large improvements in both general and domain scores of the OSA-18 that were not statistically different in the two groups, and another previous study 43 at the same institution showed more improve - ment in QOL in children with mild and severe OSA than in children with moderately severe disease. A study done by Tran et al 59 that looked at changes in the CBCL and OSA-18 in 42 children with documented sleep apnea on PSG found improvements in the QOL and behavior in children 3 months after undergoing AT compared with a control group of children who underwent unrelated surgical procedures who had no history of snoring. Some correlation was seen between behavioral and QOL scores preopera-

5 Garetz Behavior, cognition, and quality of life after... S23 Table 4 Characteristics of summarized studies Study Number of cases/controls Behavioral measures Cognition measures Quality of life measures Assessment of SDB 25/0 Parent Guilleminault Wilkenson addition PSG with Pes et al 38 questionnaire test Potsic et al /50 Parent questionnaire Sleep somnography Stradling et al 40 61/36 Parent questionnaire Oximetry and video Ali et al 33 23/10 Conner s CPT, WISC-R Matching figures Oximetry and video Gozal 41 24/30 School ranking Oximetry CO2 Goldstein et al 49 36/0 CBCL Clinical De Serres et al /0 OSD-6 Clinical Goldstein et al 50 64/0 OSA-18 Clinical Flanary 45 55/0 CHQPF-28 OSA-18 Clinical Friedman et al 55 39/20 Kaufman-ABC PSG Mitchell et al 43 60/0 OSA-18 PSG Mitchell et al 44 34/0 OSA-18 PSG Mitchell, Kelly 60 30/0 OSA-18 PSG pre/post AT Avior et al 51 19/0 CBCL TOVA OSA-18 Clinical Mitchell, Kelly 57 29/0 OSA-18 PSG Tran et al 59 42/41 CBCL PSG Montgomery- 19/19 DAS, NEPSY PSG pre/post AT Downs et al 48 Stewart et al 56 31/16 CHQPF-28 Tonsil PSG pre/post AT and adenoid status Mitchell, Kelly 58 61/0 OSA-18 PSG Mitchell, Kelly 53 52/0 BASC PSG Mitchell, Kelly 54 23/0 BASC PSG Chervin et al 61 78/27 Conner s, CSI-4, Psychiatric interview CPT, CMS PSG with Pes pre/post AT Galland et al 52 61/0 BASC CPT PSG Li et al 62 40/0 CBCL, Psychiatric interview TOVA PSG pre/post AT Diez-Montiel et al /0 OSD-6 Oximetry tively and with postoperative changes in those two measures. No association was seen between extent of abnormality seen on the initial OSA-18 test and severity of OSAS. Mitchell and Kelly 60 looked at changes in QOL after AT in 30 obese children with an age and gender specific body mass index (BMI) 95% and OSA and found improvement in QOL using the OSA-18 in both the general and domain scores despite lack of resolution of OSA in the majority of subjects. Chervin el al 61 showed behavioral improvement in children 1 year after AT compared with controls using the Conner s. They also found improvements in attention with the use of objective measurements; CPT and the children s memory scale (CMS). Almost half of children in the study diagnosed with attention deficit hyperactivity disorder (ADHD) by a child psychiatrist preoperatively no longer carried that diagnosis a year after surgery. PSG measures at baseline or improvement in PSG measures after surgery were poorly predictive of which children showed either baseline abnormalities or postoperative improvement in behavior or neurocognitive functioning. Li et al 62 looked at 40 children with SDB 6 months after AT and showed significant improvements in behavior on the CBCL as well as in attention using TOVA. ADHD scores normalized in 78% of children. The improvements seen on TOVA testing did not correlate with improved AHI on PSG. These results that show lack of clear correlation between outcome measures and PSG values raise the question whether normalization of PSG measures is a useful measure of functionally significant improvements in SDB and underscores the need for more sensitive measures of sleep disruption in children. Table 4 summarizes the key elements of the studies described above. DISCUSSION Studies done in recent years show associations between AT done primarily for SDB and improvements in behavior, cog-

6 S24 Otolaryngology Head and Neck Surgery, Vol 138, No 1S, January 2008 nition, or QOL. In contrast to older studies based on descriptive reports of behavior by parents and clinical diagnosis of sleepdisordered breathing, most recent studies use standardized and validated instruments to measure QOL, behavior, and cognition with PSG to document degree of SDB. Although many of these studies show improvement in one or more outcome measures compared with control groups, none of the studies have been randomized. Many of the recent studies report the ethnic distribution of the subjects and provide statistical confirmation that the ethnic composition of subjects did not differ significantly from controls in the controlled studies. Only a few studies describe separately analyzing outcomes measures by ethnicity and report finding no significant differences in outcome by ethnicity. 53,54,56 It is likely that in many of the other studies the small sample size would have made statistical determinations about outcomes in subpopulations difficult. No study specifically addressed recruitment of minority populations to ensure adequate representation. Only one study specifically looked at 60 outcome measures after surgery in obese children. The evidence that prevalence and severity of SDB and response to surgical treatment may not be uniform across ethnic groups and body weights coupled with the dramatic rise in childhood obesity mandates studies that specifically address outcomes measures in those populations. The most recent Cochrane review of the efficacy of adenotonsillectomy for the treatment of obstructive sleep apnea in children states Due to the absence of randomized 63 trial data, no results could be ascertained. This starkly underscores the need for more rigorous studies to provide definitive evidence of the efficacy of adenotonsillectomy for SDB. Large, prospective, randomized, controlled studies with sufficient representation of minority populations and obese children and comprehensive follow-up are needed to definitively establish the beneficial role of adenotonsillectomy to alleviate the cognitive and behavioral consequences of pediatric SDB and to document QOL improvements, as well as to evaluate any differences in effectiveness in obese children, ethnic minorities, or any other populations. The National Heart Lung and Blood of the National Institutes of Health has recently funded the Childhood Adenotonsillectomy Study (CHAT), which will be the first randomized, controlled study of behavioral, neurocognitive, and physiologic changes in children who undergo AT for mild-moderate sleep-disordered breathing. Recruitment for this multisite study is scheduled to begin shortly and will target recruitment of sufficient numbers of minority and obese subjects to allow the results obtained to be applied to those populations as well. 64 A meta-analysis by Brietzke and Gallaghershowed that normalization of PSG parameters occurs in 82.9% of otherwise healthy children who undergo AT. Despite recent recommendations by the American Academy of Pediatrics that all children with suspected SDB undergo PSG before 65 invasive interventions such as surgery, recent surveys indicate that otolarygologists actually order PSGs on fewer 3,66 then 10% of patients before performing AT. In adults with OSA, PSG measures have not been shown to correlate well with symptoms or QOL, either at baseline or after surgical intervention. 67 Many of the outcome studies in children detailed above also show limited correlation between behavioral, cognitive, and QOL measurements with PSG parameters either at baseline or after surgical intervention. This lack of correlation between currently available measurements of SDB and clinically relevant outcomes implies that current determinations of sleep disruption may provide inadequate assessment of actual sleep status. Investigation into more sensitive measures of disruption of sleep 68,69 or architecture by micro-arousals such as pulse transit time respiratory cycle-related electroencephalographic changes 70,71 are needed to obtain PSG data that better correlate with functional outcome measures. CONCLUSION Tonsillectomy and AT remain commonly performed surgical procedures despite a lack of definitive randomized studies proving their efficacy. It is hoped that large, multicenter, randomized, controlled studies such as the CHAT study will provide needed data about the efficacy of pediatric AT done for SDB in ameliorating the adverse effects on cognition, behavior, and QOL often seen in this common disease. Efforts must also be directed toward identifying more sensitive PSG measurements that show closer correlation with the functional disturbances seen with SDB in children. AUTHOR INFORMATION From the Department of Otolaryngology Head and Neck Surgery, University of Michigan Medical Center. Corresponding author: Susan L. Garetz, MD, Department of Otolaryngology Head and Neck Surgery, TC 1904, 1500 E Medical Center Dr, Ann Arbor MI address: garetz@med.umich.edu. AUTHOR DISCLOSURE None. REFERENCES 1. Owings MF, Kozak LJ. 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