Adenotonsillectomie bij kinderen met OSA
Uitgangsvraag
Bij welke patiënten is behandeling met adenotonsillectomie (ATE) geïndiceerd?
Aanbeveling
Pas (adeno)tonsillectomie of tonsillotomie toe bij kinderen met OSA zonder comorbiditeit om slaapgerelateerde ademhalingsklachten te verminderen.
Controleer als KNO-arts postoperatief op basis van symptomatologie of de OSA verbeterd is. Wees bewust dat bij de groep kinderen met obesitas, craniofaciale malformaties, anatomische variaties van het aangezicht, het syndroom van Down, oudere kinderen met OSA en andere groepen kinderen met verhoogd risico op OSA (o.a. neuromusculaire- en metabole aandoeningen) OSA kan persisteren na adenotonsillectomie. Verricht in deze groep laagdrempelig een PSG.
Overwegingen
Voor- en nadelen van de interventie en de kwaliteit van het bewijs
Op basis van de geïncludeerde studies kunnen er met redelijke zekerheid conclusies getrokken worden over de (on)gunstige effecten van adenotonsillectomie vergeleken met tonsillotomie of watchful waiting bij kinderen met OSA. De bewijskracht van de studies die adenotonsillectomie vergeleken met tonsillotomie of watchful waiting werd echter wel beperkt door imprecisie en risico op bias (overall bewijskracht volgens GRADE is redelijk). Er zijn geen studies gevonden die rapporteerden over de vergelijking tussen adenotonsillectomie en adenotomie.
Voor de cruciale uitkomstmaat apneu/hypopneu index (AHI) is bewijs gevonden dat adenotonsillectomie vergeleken met watchful waiting het aantal apneus/hypopneus per uur verlaagde bij kinderen met OSA. Dit verschil was klinisch relevant en de kwaliteit van dit bewijs is hoog. Wanneer adenotonsillectomie vergeleken werd met tonsillotomie, werd er geen verschil gevonden in afname van de AHI. De kwaliteit van dit bewijs was redelijk. Behandeling met adenotonsillectomie of tonsillotomie lijkt dus geen verschillend effect te hebben op het aantal apneu of hypoapneu episodes per uur.
Voor de cruciale uitkomstmaat zuurstofdesaturatie (Oxygen Desturation Index, ODI) is bewijs gevonden dat adenotonsillectomie (vergeleken met watchful waiting) geen verschil opleverende tussen de groepen. De kwaliteit van dit bewijs was laag. Voor de vergelijking tussen adenotonsillectomie en tonsillotomie kon geen conclusie worden getrokken met betrekking tot de cruciale uitkomstmaat zuurstofdesaturatie, omdat geen van de geïncludeerde studies gegevens rapporteerde over deze uitkomstmaat.
Voor de belangrijke uitkomstmaat kwaliteit van leven is bewijs gevonden dat adenotonsillectomie (vergeleken met watchful waiting) kwaliteit van leven verbeterde bij kinderen met OSA. In de meeste gevallen werd dit gemeten de met de OSA-18 vragenlijst. Dit verschil was klinisch relevant en de kwaliteit van dit bewijs is redelijk. Wanneer adenotonsillectomie vergeleken werd met tonsillotomie, werd er geen verschil gevonden (verschil) in kwaliteit van leven. Behandeling met adenotonsillectomie of tonsillotomie lijkt dus geen verschillend effect te hebben op de kwaliteit van leven van kinderen. De kwaliteit van dit bewijs was redelijk.
Voor de belangrijke uitkomstmaat cardiovasculaire risico’s werd gekeken naar een verandering in gewicht en bloeddruk vóór versus na de behandeling. Voor deze uitkomstmaat is bewijs gevonden dat adenotonsillectomie (vergeleken met watchful waiting) gewicht waarschijnlijk niet veranderde en de diastolische en systolische bloeddruk mogelijk verhoogde bij kinderen met OSA. Echter, de kwaliteit van dit bewijs was laag en moet in vervolgonderzoek met grotere patiënten aantallen bevestigd worden. Er waren geen studies die adenotonsillectomie vergeleken met tonsillotomie voor deze uitkomstmaat.
Belangrijk is te noemen dat de (adeno)tonsillectomie volgens Sluder enkel in Nederland wordt uitgevoerd. Derhalve is de internationale literatuur niet een op een te vertalen naar de Nederlandse praktijk. De verwachting is echter dat er geen verschil zal zijn ten aanzien van de cruciale en belangrijke uitkomstmaten van deze literatuuranalyse.
Daarnaast zijn er in een aanzienlijk deel van de besproken studies alleen kinderen geïncludeerd met mild en matig obstructief slaapapneu, alleen Borgström en Sjölander hebben kinderen met een ernstig OSA (AHI tot 30) geïncludeerd (Borgström, 2017; Sjölander, 2020). De verwachting is dat bij kinderen met ernstig slaapapneu het effect van een adenotonsillectomie groter zal zijn. Reden om deze kinderen niet te includeren kan zijn geweest, dat dit niet medisch ethisch verantwoord werd geacht.
Bijwerkingen en complicaties zijn geen uitkomstmaat in de verrichtte literatuuranalyse. De belangrijkste, in zeldzame gevallen fataal verlopende, complicatie van een (adeno)tonsillectomie is een nabloeding. De kans op een nabloeding na tonsillectomie volgens Sluder bij kinderen is 1:50-1:200, en na een klassieke (dissectie)tonsillectomie 1:25 (1,5-4,2%). Ook kan er postoperatief sprake zijn van smaakverandering door beschadiging van de n. glossopharyngeus (IX) in de onderpool van de tonsilnis, (incidentie 8%). Zeldzaam zijn respiratoire complicaties, velofaryngeale insufficiëntie en spraakstoornissen (richtlijn Ziekten van adenoïd en tonsillen (ZATT) (2014)).
Er is internationale literatuur die beschrijft dat na tonsillotomie de normale dagelijkse bezigheden sneller hervat kunnen worden dan na tonsillectomie. Mogelijk is er een milde afname van complicaties, waarvoor medische interventie nodig is in de eerste week na chirurgie. Het is niet duidelijk of er bij een tonsillotomie minder perioperatief bloedverlies is en er is geen verschil in gemiddelde pijnscores tussen kinderen die een tonsillectomie ondergingen versus die een tonsillotomie ondergingen. Over een mogelijk verschil tussen de ingrepen met betrekking tot het recidiveren van slaapgebonden ademhalingsstoornissen was geen duidelijkheid. Ook is het onduidelijk of er verschil is in ziekte specifieke kwaliteit van leven op de korte middellange en lange termijn na de beide ingrepen (Blackshaw 2020).
Niet behandelen van OSA zou kunnen leiden tot cardiovasculaire, endotheliale, metabole, endocriene, neurocognitieve en psychologische consequenties op de lange termijn.
Wij verwijzen voor een beschouwing van eventueel onderliggende mechanismen die tot deze consequenties kunnen leiden naar de richtlijn OSA in volwassenen (richtlijn Obstructief Slaapapneu (OSA) bij volwassenen (2018)).
Bij gezonde kinderen die geen klinische verbetering vertonen na adenotonsillectomie dient een postoperatief P(S)G verricht te worden. Er zijn populaties die speciale aandacht behoeven: Overweeg laagdrempelig een pre- en postoperatief PSG te verrichten bij kinderen met comorbiditeiten die gepaard gaan met een verhoogd risico op OSA of op persisterend OSA na chirurgie zoals obesitas, neurologische of neuromusculaire aandoeningen (bijvoorbeeld chiari malformatie, cerebrale parese), craniofaciale aandoeningen, en (complexe) genetische aandoeningen (zoals achondroplasie, Beckwith-Wiedermann syndroom, Down syndroom, mucopolysaccharidose, Prader Willi).
Voor specifieke patiëntenpopulaties kunnen specifieke therapeutische opties geïndiceerd zijn, bijvoorbeeld bij craniofaciale malformaties. De richtlijn kinderen met craniofaciale aandoeningen beveelt aan om kinderen met syndromale craniofaciale synostoses tot de leeftijd van 6 jaar jaarlijks te screenen met een PSG type 1 en behandeling van licht OSA te starten bij bijkomende klachten door middel van een niet-invasieve behandeling of een beperkt invasieve behandeling zoals ATE. Bij kinderen met een syndromale craniosynostose en een ernstig OSA wordt aangeraden een LeFort III operatie of een monobloc advancement te overwegen, eventueel in combinatie met een mandibula advancement.
De richtlijn kinderen met syndroom van Down adviseert bij ieder regulier follow up consult te vragen naar symptomen van OSA en bij een positieve respons en sterkte verdenking te verwijzen naar een KNO-arts voor adenotomie en/of tonsillectomie en/of aanvullende behandeling.
Bij kinderen met Down Syndroom, met CPAP falen en persisterend OSA na eerdere (A)TE, lijkt nervus hypoglossus stimulatie een veelbelovende therapeutische optie (Coloway, 2020; Diercks, 2018; Yu, 2022). Een ander optie voor deze specifieke groep kan tongbasischirurgie zijn (bijvoorbeeld lingual tonsillectomy) (Camacho, 2017; Ishman, 2018; Prosser, 2017). Het is mogelijk dat voorkeurslichaamspositie van kinderen met Downsyndroom tijdens de slaap een beschermend effect op de luchtweg kan hebben, meer onderzoek is echter nodig (Santoro, 2021).
Bij kinderen met obesitas dienen additionele behandelingsstrategieën, reeds in de preoperatieve fase, gericht te zijn op de behandeling van overgewicht.
De kans op residuaal OSA na chirurgie (adenotonsillectomie) is in obese kinderen hoger dan in niet-obese kinderen. Er zijn aanwijzingen dat dit meer uitgesproken kan zijn in rugligging, voor deze groep kan behandeling met een slaappositietrainer een overweging zijn (Tholen, 2021; Selvadurau, 2020).
Waarden en voorkeuren van patiënten (en evt. hun verzorgers)
Naast recidiverende tonsillitiden is het optreden van een verstoorde slaap, met anamnestisch of bewezen OSA een van de belangrijkste redenen om een (A)TE te verrichten bij kinderen. Doel van de ingreep is dan het verbeteren van de kwaliteit van de slaap op korte termijn, maar ook het voorkomen van OSA geïnduceerde schade op de lange termijn.
De impact van een operatie op een kind dient besproken te worden en afgewogen worden tegen het verwachte nut van de operatie. Er moet goed worden overwogen of een operatie echt nodig is wegens de impact die een operatie heeft op een kind. De patiënt en ouders dienen voorafgaand aan de behandeling duidelijke informatie te krijgen over de voor- en nadelen en de mogelijke uitkomsten van de operatie. Vervolgns kunnen ouders en patiënten samen met de zorgverlener een beslissing nemen/een plan maken.
Kosten (middelenbeslag)
De kosten voor ATE zijn relatief beperkt ten opzichte van andere chirurgische ingrepen. Er is geen Nederlandse literatuur beschikbaar over de kosteneffectiviteit van ATE voor OSA. In de ZATT richtlijn (2014) wordt de kosteneffectiviteit van ATE voor recidiverende tonsillitiden wel beschreven. In termen van ‘numbers needed to treat’ (NNT) voorkomt een tonsillectomie over een periode van twee jaar 3,5 episoden van tonsillitis. De berekende kosten voor een afname van 3,5 episoden van tonsillitis in twee jaar tijd is 261 pond (95% CI 161-586) per episode. Nabloedingen na de ingreep die heringreep en/of opname vereisen waren geen onderzochte uitkomstmaat (Wilson, 2012). Een soortgelijke kostenanalyse werd door Buskens (2007) verricht in de NATAN studie. De kosten in de operatie groep waren 47% hoger dan de kosten in de watchful waiting groep, namelijk gemiddeld €252 per persoonsjaar meer bij een geopereerd kind.
Tripathi (2011) heeft gekeken naar de kosteneffectiviteit van adenotomie of adenotonsillectomie voor de behandeling van pediatrisch OSA bij kinderen met sikkelcelziekte. Kinderen die een adenotomie of adenotonsillectomie ondergingen hadden minder bezoeken op de polikliniek (voor OSA) en er was sprake van een afname van cerebrovasculaire ischemie (CVA, TIA). De kosten voor acute zorg daalden significant in de interventiegroep, na een initiële toename van kosten ten tijde van de ingreep. Bagwell (2018) heeft gekeken naar de kosteneffectiviteit van intracapsulaire tonsillectomie versus klassieke (dissectie)tonsillectomie. Zij concluderen dat een klassieke (dissectie)tonsillectomie een hogere kosteneffectiviteit heeft dan een intracapsulaire tonsillectomie. De kosten van een klassieke (dissectie) tonsillectomie zijn hoger dan de kosten van een intracapsulaire tonsillectomie, maar de effectiviteit van de eerste zou ook groter zijn. Dit verschil is echter minimaal.
Aanvaardbaarheid, haalbaarheid en implementatie
(Adeno)tonsillectomie is gangbare en verzekerde ingreep, die normaliter voor iedereen in Nederland goed toegankelijk is. Elke Nederlandse KNO-arts kan de ingreep verrichten en de ingreep duurt kort (afhankelijk van de gebruikte methode). Tonsillotomie is in Nederland nog slechts op enkele locaties beschikbaar.
Rationale van de aanbeveling: weging van argumenten voor en tegen de interventies
De bevindingen die gevonden werden in de literatuur komen overeen met de algemene opvatting dat bij verdenking op pediatrisch obstructief slaapapneu bij kinderen zonder comorbiditeit de eerste keus van behandeling vaak een adenotonsillectomie is. Of deze behandeling ook daadwerkelijk moet worden uitgevoerd is afhankelijk van de inschatting van de behandelend KNO-arts. Andere aspecten die van invloed kunnen zijn op pediatrisch obstructief slaapapneu zoals obesitas dienen tevens in overweging te worden genomen. Speciale aandacht dient tevens besteed te worden aan kinderen met craniofaciale malformaties, anatomische variaties van het aangezicht, het syndroom van Down, neuromusculaire- en metabole aandoeningen en oudere kinderen met OSA. De kno-arts dient postoperatief te controleren of de symptomatologie van OSA verbeterd is. Indien er sprake is van aanhoudende klachten dient er een postoperatief poly(somno)graphie verricht te worden. Bij kinderen met obesitas, craniofaciale aandoeningen, anatomische variaties van het aangezicht en neuromusculaire en metabole aandoeningen zou er zowel een pre- als postoperatief PSG moeten plaatsvinden. Bij craniofaciale syndromen is er vaak sprake van obstructie van de luchtweg op meerdere niveaus, waarbij het effect van een adenotonsillectomie in de regel lager is.
Onderbouwing
Achtergrond
(Adeno)tonsillectomie (het verwijderen van de (neus- en) keelamandelen wordt in Nederland veel gebruikt als behandeling voor obstructief slaapapneu (OSA) bij kinderen. Een mogelijk alternatief is om een afwachtend beleid te voeren. Buiten Nederland wordt bij deze indicatie regelmatig een tonsillotomie verricht in plaats van een tonsillectomie. Een tonsillotomie betreft het deels verwijderen van de keelamandelen. Bij zeer jonge kinderen of kinderen met kleine keelamandelen wordt soms gekozen voor het uitvoeren van enkel een adenotomie (het verwijderen van alleen de neusamandel). In deze module wordt de effectiviteit van deze verschillende vormen van behandeling beoordeeld.
Conclusies
(Adeno)Tonsillectomy versus watchful waiting
AHI (crucial)
|
High GRADE |
Adenotonsillectomy reduces the number of apnea/hypopnea events as measured by the AHI when compared with watchful waiting in children with OSA.
Sources: Au, 2021; Fehrm, 2020; Waters, 2020; CHAT-study (Marcus, 2013; Baumert, 2016) |
ODI (crucial)
|
Low GRADE |
Adenotonsillectomy may result in little to no difference in the number of episodes of oxygen desaturation below 3% per hour of sleep, when compared with watchful waiting in children with OSA.
Sources: Au, 2021; Fehrm, 2020 |
Quality of life (important)
|
Moderate GRADE |
Adenotonsillectomy likely increases improvement of quality of life when compared with watchful waiting in children with OSA.
Sources: Au, 2021; Fehrm, 2020; CHAT-study (Marcus, 2013); Waters, 2020 |
Cardiovascular risks (important)
|
Low GRADE |
Adenotonsillectomy may result in little to no difference in weight change when compared with watchful waiting in children with OSA.
Adenotonsillectomy may result in an increase in systolic and diastolic blood pressure when compared with watchful waiting in children with OSA.
Sources: Au (2021), CHAT study (Marcus, 2013) |
(Adeno)Tonsillectomy versus tonsillotomy
AHI (crucial)
|
Moderate GRADE |
Adenotonsillectomy may result in a similar reduction of the number of apnea/hypopnea events as measured by the AHI when compared to adenotonsillotomy in children with OSA.
Sources: Blackshaw (2020), Sjölander (2020) |
ODI (crucial)
|
- GRADE |
No evidence was found regarding the effect of adenotonsillectomy on ODI when compared with adenotonsillotomy in children with OSA.
Sources: - |
Quality of life (important)
|
Adenotonsillectomy likely results in little to no difference in change in quality of life when compared with adenotonsillotomy in children with OSA.
Sources: Blackshaw (2020), Sjölander (2020) |
Cardiovascular risks (important)
|
- GRADE |
No evidence was found regarding the effect of adenotonsillectomy on cardiovascular risks (weight change and blood pressure) when compared with adenotonsillotomy in children with OSA.
Sources: - |
Samenvatting literatuur
Description of studies
The Cochrane review of Blackshaw (2020) analyzed RCTs in which the effectiveness of (adeno)tonsillectomy was compared to the effectiveness of (adeno)tonsillotomy in children aged 2 to 16 years old with obstructive sleep disordered breathing. Several databases were searched for relevant RCTs. The search was executed in July 2019. In total, 19 relevant studies were included in the Cochrane review, of which 5 studies reported one of the prespecified outcomes. Age of the children participating in the RCTs varied from 2 to 10 years old. Four studies reported quality of life as an outcome measure (QoL; Borgstorm, 2017; Densert, 2001; Derkay, 2006, Ericsson, 2009), and two studies reported on AHI-score (Borgstorm, 2017; Kordeluk, 2016). The four studies reporting on QoL used various assessment methods, varying from the OSA-18 questionnaire (Borgstorm 2017; Ericsson 2009), validated questionnaires (Derkay, 2006) and the Visual Analogue Scale (Densert, 2001). The follow-up period of the different studies varied from 3 to 24 months. Blackshaw subdivided the follow-up periods into short-term (0 to 6 months), medium term (7 to 12 months), and long term (13 to 24 months). Due to the different outcome and measurement instruments, it was not possible to pool the results. Moreover, the authors conclude that the evidence is of very low quality, according to the GRADE method, because of “very serious limitations in study methodology, serious imprecision and suspected publication bias”. The authors conclude that it is therefore not possible to draw conclusions on the difference between the two operations regarding QoL for the various follow-up periods. In the studies of Kordeluk (2016) and Borgstorm (2017), the effect of the two different surgical procedures on AHI-score was assessed. AHI-score was measured at 6 months (short term) and 12 months (medium term), respectively. Both studies reported no evidence of a difference in change of AHI scores between children who underwent tonsillectomy or tonsillotomy. According to the author, evidence for this outcome was considered to be of very low certainty, due to imprecision of the evidence and publication bias, with only a small number of studies reporting on this outcome.
Au (2021) performed an RCT on the effect of early surgical intervention, as compared to a watchful waiting condition, on inattention and behavioral outcomes in children with mild OSA. The study was a single center study, executed in a hospital in China (Hong Kong) from December 2010 to December 2018. Non-obese children aged 6 to 11 years, with mild OSA (OAHI 1 to 5 events/hour) were eligible to participate. The early surgical intervention consisted of various surgical procedures. The surgery was either adenotonsillectomy or tonsillectomy, with or without turbinate reduction. In total, results from 35 children in the early surgery condition and 36 children in the watchful waiting condition were analyzed. Outcomes were assessed at 9 month follow up and included the AHI, ODI, weight change and blood pressure. Moreover, quality of life was measured with the OSA-18 questionnaire. The per-protocol analysis and high drop-out rates introduced some concerns regarding the risk of bias of this study.
Fehrm (2020) performed a parallel 2-armed RCT to determine whether adenotonsillectomy (ATE) is more effective than watchful waiting for the treatment of mild to moderate OSA in otherwise healthy children. The study was conducted at a hospital in Sweden from December 2014 to December 2017. Children aged 2 to 4 years, visiting the otorhinolaryngologist for mild to moderate OSA were invited to participate. In total 25 children underwent ATE and 28 children received watchful waiting as treatment. The groups were comparable at baseline. Outcomes included AHI, ODI and quality of life assessed with the OSA-18 questionnaire. Outcomes were assessed at 6-month follow-up and compared between children who received ATE and children who were assigned to watchful waiting. A subgroup analysis comparing the treatment effect of ATE between children with mild OSA versus children with moderate OSA, was also performed. The overall risk of bias for this study is low.
Sjölander (2020) executed an RCT regarding the difference between tonsillotomy and tonsillectomy on the effect on behavioral symptoms in children suffering from OSA. The study was conducted at one hospital in Sweden from November 2011 and April 2015. Children aged 2 to 6 years suffering from OSA were eligible to participate. 37 children underwent tonsillotomy (ATT) and 31 children underwent tonsillectomy (ATE). At 1 year follow-up outcomes were assessed. Outcome measures AHI and OSA-18 score were reported. The risk of bias for this study is low.
Waters (2020) studied whether adenotonsillectomy, as treatment for mild or moderate OSA in preschool children, compared to a waitlist control condition improves cognitive function. The study had a randomized controlled design and was executed in three tertiary children’s hospitals in Australia between 2014 and 2017. Children aged 3 to 5 years with mild or moderate OSA were included. In total 72 children received adenotonsillectomy and 69 children received the waiting list condition as treatment. At 12-month follow-up outcomes were assessed. Primary outcome of the study was cognitive functioning. Secondary outcomes were parent’s rating of child’s behavior and quality of life and PSG measures, including the AHI. The risk of bias for this study was low.
Seven articles described results from the CHAT trial. The CHAT-trial was a multi-center single blinded randomized controlled trial on the effectiveness of early adenotonsillectomy on different neuropsychological and health outcomes as compared to watchful waiting with supportive care in children with mild to moderate OSA. The study was conducted at six centers in the USA between January 2008 through September 2011. Children aged 5 to 9 years, with confirmed OSA and a history of snoring were eligible to participate. Relevant exclusion criteria were extreme obesity and severe OSA. In total 226 children were assigned to early adenotonsillectomy and 227 children to the watchful waiting condition. Outcomes were assessed at 7-month follow-up. The trial had multiple outcomes, which are described in different articles. Primary outcome was neurocognitive functioning (reported in Marcus, 2013; Taylor, 2016). Secondary outcomes included sleep apnea measured by PSG and expressed in AHI score (reported in Marcus, 2013; Baumert, 2016), quality of life measured with the PedsQL (reported in Marcus, 2013), OSA-18 score and cardiorespiratory outcomes (reported in Baumert, 2016; Liu, 2017; Liu., 2018). Some articles report a sub analysis of the outcomes, for example stratification of the results by AHI threshold (reported in Giroushetti, 2021) or comparison of demographics associated to sleep-quality at follow-up (reported in Magnusdottir, 2021). Loss to follow-up and incomplete outcome data differ among the various outcomes but vary between 181 to 196 patients for the intervention group and 171 to 203 patients for the control group. The large variety of articles challenges verifying whether all predefined outcomes were reported and there is some inconsistency between the articles regarding the loss to follow-up and missing data. This introduces some concerns regarding the risk of bias for these studies.
Results
Tonsillectomy vs. watchful waiting
Five RCTs were included in the analysis of the literature for the comparison of tonsillectomy with watchful waiting in children with (suspicion of) OSA. One of these studies is the CHAT-study, of which two publications were included. Because these publications refer to the same dataset, they are handled as one RCT (Au, 2021; Waters, 2020; Fehrm, 2020; CHAT-study: Marcus, 2013; Baumert, 2016).
Apnea Hypopnea Index (AHI)
Four studies reported the outcome AHI. In three RCTs AHI scores were reported (Au, 2021; Waters, 2020; CHAT-study (Marcus, 2013; Baumert, 2016)), and in one study obstructive AHI (OAHI) was reported (Fehrm, 2020).
Au (2021) reported a mean ± SD change in AHI from baseline to 9 month follow up of -1.1 ± 2.3 events per hour in the 35 children who received surgical intervention, compared with a change of 0.2 ± 4.4 events per hour in the watchful waiting group (n=36). At baseline, the AHI was 3.5 ± 1.6 events per hour in the surgical intervention group and 3.3 ± 1.6 events per hour in the watchful waiting group. These results reflect a mean difference in AHI of -1.30 (95% CI -2.93 to 0.33) events per hour in favor of the adenotonsillectomy group. Thus, AHI was reduced more after surgical intervention (note: all surgical interventions were pooled) compared with watchful waiting.
Waters (2020) reported a mean ± SD of the AHI at 12 months follow up of 1.0 ± 0.9 events per hour in the 69 children who received adenotonsillectomy, compared with 2.1 ± 2.4 in the 72 children who were in the watchful waiting group. At baseline, the AHI was 3.0 ± 2.1 events per hour in the adenotonsillectomy group and 3.0 ± 2.5 events per hour in the watchful waiting group. These results reflect a mean difference of -1.10 (95% CI -1.69 to -0.51) events per hour in favor of the adenotonsillectomy group. Thus, AHI was reduced more after tonsillectomy compared with watchful waiting.
In the publications reporting on the CHAT-study, Baumert (2016) and Marcus (2013) report data on the AHI. Note that these results reflect the same subjects. Baumert reported that at 7 months follow-up, 169 (82%) of 206 subjects in the early adenotonsillectomy group no longer had AHI-defined OSA, i.e., AHI ≤ 2 events per hour, while in the watchful waiting group 82 (42%) of 194 children had spontaneous normalization of AHI scores. This results in a risk ratio of 1.94 (95% CI 1.63 to 2.32). Marcus (2013) reported a median (IQR) change in AHI from baseline to 7-month follow-up of -3.5 (95% CI: -7.1 to -1.8) events per hour in the 196 children who received early adenotonsillectomy, compared with -1.6 (95% CI: -3.7 to 0.5) events per hour after watchful waiting (n=204). At baseline, the median AHI was 4.8 (95% CI: 2.7 to 8.8) events per hour in the adenotonsillectomy group and 4.5 (95% CI: 2.5 to 8.9) events per hour in the watchful waiting group. Thus, results from the CHAT-study show that AHI was reduced more after early adenotonsillectomy compared with watchful waiting.
Ferm (2020) reported a mean change in OAHI at 6 months follow up of −2.9 (95% CI: −4.0 to −1.9) events per hour in the ATE group and −1.9 (95% CI: −3.0 to −0.9) events per hour in the watchful waiting group. At baseline, the OAHI was 4.8 (sd 1.0) in the ATE group and 5.1 (sd 2.2) in the watchful waiting group. This reflects a mean difference in OAHI of 1.0 (95% CI: −2.4 to 0.5) events per hour, in favour of the ATE group. Thus, AHI was reduced more after tonsillectomy compared with watchful waiting.
Taken together, the conclusions and results of the included studies all point towards a clinically relevant beneficial effect of adenotonsillectomy on AHI scores, as compared with the watchful waiting groups in children with OSA.
Oxygen Desaturation Index (ODI)
In two of the five included RCTs, ODI was measured (Au, 2021; Fehrm, 2020). The ODI is commonly used to evaluate the severity of nocturnal hypoxemia. The ODI is defined as the number of episodes of oxygen desaturation per hour of sleep, with oxygen desaturation defined as a decrease in blood oxygen saturation (SpO2) to lower than 3% below baseline. Thus, a lower ODI reflects fewer episodes of oxygen desaturation.
Au (2021) reports a mean ± SD change in ODI (% not reported) from baseline to 9 month follow up of -0.4 ± 2.0 events per hour in the 35 children who received adenotonsillectomy, compared with a change of 0.5 ± 3.9 events per hour in the watchful waiting group (n=36). At baseline, the ODI was 1.8 ± 1.7 events per hour in the surgical intervention group and 2.3 ± 2.2 events per hour in the watchful waiting group. These results reflect a mean difference of -0.90 (95% CI: -2.34 to 0.54) events per hour in favor of the surgical intervention group. Thus, ODI was reduced more after surgical intervention (note: all surgical interventions were pooled) compared with watchful waiting.
Fehrm (2020) reports a median (IQR) change in ODI (3%) score from baseline to 6 month follow up of -0.4 (IQR: -1.3 to 0.5) events per hour in the 25 children who received adenotonsillectomy, compared with a change of -1.0 (IQR: -1.9 to 0.1) events per hour in the watchful waiting group (n=27). At baseline, the ODI was 3.0 ± 2.5 events per hour in the adenotonsillectomy group and 3.7 ± 2.6 events per hour in the watchful waiting group. This reflects a mean difference of 0.5 (95% CI: -0.7 to 1.7) in favor of the watchful waiting group. Thus, ODI scores were reduced more after watchful waiting compared with tonsillectomy.
Taken together, the results point towards a difference in ODI in favor of tonsillectomy compared with watchful waiting after 6- or 9-months follow-up compared with baseline.
Quality of life
In four of the five included RCTs, quality of life was measured (Au, 2021; Fehrm, 2020; CHAT-study (Marcus, 2013); Waters, 2020).
Au (2021) measured disease specific quality of life at 9 months follow-up using the OSA-18 questionnaire, an 18-item instrument scored on a seven-point scale and totaled, providing a severity score of 18 to 126, with lower scores representing higher quality of life. Au (2021) reports a mean ± SD change in total OSA-18 score from baseline to 9 month follow up of -17.3 ± 19.7 in the 35 children who received early surgical intervention, compared with a change of -3.6 ± 14.1 in the watchful waiting group (n=36). At baseline, OSA-18 scores were 63 ± 17 in the early surgical intervention group and 56 ± 16 in the watchful waiting group. This reflects a mean difference of -13.70 (95% CI: -21.69 to -5.71) in favor of the surgical intervention group (note: all surgical interventions were pooled). Thus, OSA-18 scores were reduced more after tonsillectomy compared with watchful waiting. This difference is clinically relevant.
Fehrm (2020) reports a median (IQR) change in total OSA-18 score from baseline to 6 month follow up of -23.5 (IQR: -31.5 to -15) in the 23 children who received early surgical intervention, compared with a change of -4.5 (IQR: -12 to 1.5) in the watchful waiting group (n=26). This reflects a mean difference of -17 (95% CI: -24 to -10.0) in favor of the adenotonsillectomy group. At baseline, OSA-18 scores were 57 (IQR: 48 to 70) in the adenotonsillectomy group and 56.5 (IQR: 48 to 70) in the watchful waiting group. Thus, OSA-18 scores were reduced more after tonsillectomy compared with watchful waiting.
Marcus (2013) used the Pediatric Quality of Life Inventory (PedsQL) and OSA-18 questionnaires to measure quality of life. The PedsQL ranges from 0 to 100, with higher scores indicating better quality of life. Marcus reports a mean ± SD change in PedsQL score from baseline to 7 month follow up of 5.9 ± 13.6 in the 195 children who received early adenotonsillectomy, compared with a change of 0.9 ± 13.3 in the watchful waiting group (n=204). This reflects a mean difference of 5.00 (95% CI 2.36 to 7.64) in favor of the adenotonsillectomy group. Thus, PedsQL scores improved more after tonsillectomy compared with watchful waiting. This difference is clinically relevant. In addition, Marcus (2013) reports a mean ± SD change in total OSA-18 score from baseline to 7 month follow up of -21.4 ± 16.5 in the 193 children who received early adenotonsillectomy, compared with a change of -4.5 ± 19.3 in the watchful waiting group (n=202). This reflects a mean difference of -16.90 (95% CI: -20.44 to -13.36) in favor of the adenotonsillectomy group. Thus, OSA-18 scores were reduced more after tonsillectomy compared with watchful waiting.
Waters (2020) did not use a specific quality of life questionnaire to measure this outcome measure. However, the study did ask routine parent questions, which revealed that children in the adenotonsillectomy group had immediate and sustained improvements in sleep and “eating well,” with fewer reports of trouble breathing during sleep, snoring, and daytime sleeping. The parents also gave a rating to the question: “On a scale of 1 to 10, how would you rate your child at the moment?” At 12 months after tonsillectomy, the mean ± SD rating was 8.7 ± 1.2 in the 69 children who received early adenotonsillectomy, compared with a rating of 5.7 ± 1.6 in the watchful waiting group (n=72). This reflects a mean difference of 3.00 (95% CI 2.53 to 3.47) in favor of the adenotonsillectomy group. Thus, the parent’s rating of their child’s behavior was better after tonsillectomy compared with watchful waiting.
The results could not be combined in one meta-analysis due to difference in statistical reporting or use of different questionnaires. However, taken together, the conclusions and results of the included studies all point towards a beneficial effect of adenotonsillectomy on quality of life, as compared with the watchful waiting groups in children with OSA. Thus, adenotonsillectomy seems to improve quality of life scores more than a watchful waiting approach.
Cardiovascular risks (weight change and blood pressure)
Weight change
Au (2021) reports a mean ± SD weight change from baseline to 9 month follow up of 3.3 ± 2,1 kg in the 35 children who received early surgical intervention (adenotonsillectomy or tonsillotomy), compared with a change of 2.2 ± 1.5 in the watchful waiting group (n=36). At baseline, the children’s weight in the surgical intervention group was 27.3 ± 6.8 kg and 25.7 ± 5.4 kg in the watchful waiting group. The difference between the surgical intervention group (note: all surgical interventions were pooled) in weight change from baseline reflects a mean difference of 1.10 (95% CI: 0.25 to 1.95) in favor of the watchful waiting group, that is, in this group patients gained less weight.
In the CHAT-trial, weight change was reported at baseline and after completion of the intervention. Before adenotonsillectomy, patients (n=226) mean ± SD weight was 31.2 ± 13.0 kg compared with 31.2 ± 13.1 kg after the intervention (n=194), reflecting no difference in weight before compared with after the intervention. Before watchful waiting, patients (n=227) weighed 30.4 ± 12.4 kg compared with 30.1 ± 11.7 kg after the intervention (n=203), reflecting a decrease in weight of 0.3 kg before versus after watchful waiting. Between groups, this reflects a mean group difference of 0.3 kg, in favor of the watchful waiting group, i.e., more weight loss was reported in the watchful waiting group.
Blood pressure
Au (2021) reports a mean ± SD change in systolic blood pressure from baseline to 9 month follow up of 5.1 ± 12.4 mm Hg in the 35 children who received early surgical intervention (adenotonsillectomy or tonsillotomy), compared with a change of -1.2 ± 8.7 mm Hg in the watchful waiting group (n=36). At baseline, the children’s systolic blood pressure in the surgical intervention group (note: all surgical interventions were pooled) was 104 ± 9 mm Hg and 104 ± 8 mm Hg in the watchful waiting group. This reflects a mean difference of 6.30 (95% CI: 1.3 to 11.3) mm Hg in favor of the watchful waiting group, i.e., watchful waiting resulted in a lower systolic blood pressure.
Au (2021) reports a mean ± SD change in diastolic blood pressure from baseline to 9 month follow up of 2.9 ± 11.3 mm Hg in the 35 children who received early surgical intervention (adenotonsillectomy or tonsillotomy), compared with a change of 0.2 ± 6.9 mm Hg in the watchful waiting group (n=36). At baseline, the children’s diastolic blood pressure in the surgical intervention group (note: all surgical interventions were pooled) was 64 ± 8 mm Hg and 64 ± 6 mm Hg in the watchful waiting group. This reflects a mean difference of 2.70 (95% CI -1.67 to 7.07) mm Hg in favor of the watchful waiting group, i.e., watchful waiting resulted in a lower diastolic blood pressure.
Taken together, Au (2021) suggests early surgical intervention (adenotonsillectomy or tonsillotomy) has negative side effects on the cardiovascular outcomes weight change and blood pressure. Results from the CHAT-trial suggest there is no difference between surgical intervention (adenotonsillectomy) compared with watchful waiting on weight.
(Adeno)tonsillectomy versus tonsillotomy
Two studies (1 SR and 1 RCT) were included in the analysis of the literature for the comparison of tonsillectomy with tonsillotomy in children with (suspicion of) OSA (Blackshaw, 2020; Sjölander, 2020).
Apnea Hypopnea Index (AHI)
In the analysis of the outcome measure AHI, three RCTs were included, of which two studies were part of the systematic review by Blackshaw, 2020 (Kordeluk, 2016; Borgström, 2017), and one study was a separate RCT (Sjölander, 2020).
Kordeluk (2016) (100 randomized children; 25 (25%) included in analysis) measured respiratory events during sleep at three to six months using the AHI. The study reported a difference of -0.58 (95% CI -5.43 to 4.27) in mean change in AHI from baseline between children who underwent tonsillectomy and those who underwent tonsillotomy, favoring tonsillectomy.
Borgström (2017) (79 randomized children; 74 (94%) included in analysis) measured the AHI at 12 months follow-up. This study a mean difference of 0.83 (95% CI -3.23 to 4.88) in change scores between the groups from the polysomnography data, favoring tonsillotomy.
Sjölander (2020) measured AHI at 1 year follow up in 68 children between 2 and 6 years with OSA, of which 31 were randomized to the ATE group and 37 of the tonsillotomy group. One year after ATE, AHI showed a mean and standard deviation of 2.5 ± 2.0 compared with 4.5 ± 6.3 in the tonsillotomy group, resulting in a mean difference of -2.00 (95% CI -4.15 to 0.15), favoring tonsillectomy.
The results of the three studies could not be pooled in a meta-analysis due to different statistical reporting. However, taken together, the results do not point toward a clinically relevant difference in AHI change after ATE compared with tonsillotomy.
Oxygenation Desaturation Index (ODI)
Blackshaw (2020) and Sjölander (2020) did not report on the outcome measure ODI. Therefore, whether tonsillectomy is preferred over tonsillotomy as treatment for children with (suspicion of) OSA could not be assessed for this outcome measure.
Quality of life
Five RCTs were included to assess effects of tonsillectomy compared with tonsillotomy in children with (suspicion) of OSA on quality of life. Four of these RCTs were part of the systematic review by Blackshaw (2020).
Blackshaw (2020) reported disease-related quality of life as primary outcome measure at 0 to 6, 7 to 12, and 13 to 24 months post treatment in children aged 2 to 16 years old with obstructive sleep-disordered breathing. At 0-6 months, three RCTs were included (Derkay, 2006; Densert, 2001; Ericsson, 2009), at 7-12 months one RCT (Borgström, 2017), and at 13-24 months two RCTs (Ericsson, 2009; Densert, 2001).
Derkay (2006; 300 children included in analysis) used a validated quality of life survey evaluating physical suffering, sleep disturbance, speech or swallowing problems, emotional distress, activity limitations and caregiver concern on 0 to 6 scales and stated that at one month “no significant differences between the groups in presurgical to postsurgical changes” were observed. Further statistical data was not provided.
Densert (2001) measured snoring, apnea and well-being using a visual analogue scale (VAS) where the intensity of symptoms was marked on a 150 mm-long line. This study did not report the number of children randomized to each arm (a total of 43 children were randomized; 43 (100%) were included in analysis). At three months the mean differences from baseline scores were similar in the tonsillotomy and tonsillectomy groups for snoring (9 versus 13), apnea (9 versus 9) and well-being (11 versus 14) with no differences after tonsillotomy compared to tonsillectomy.
Ericsson (2009; 118 randomized children; 67 (57%) included in analysis) measured disease specific quality of life at six months using the OSA-18 questionnaire. The median total OSA-18 scores at six months were not different between children who underwent tonsillectomy and those who underwent tonsillotomy: 25 (IQR: 23 to 32) versus 27 (IQR: 22 to 34).
Borgström (2017) also measured disease-specific quality of life at 12 months using the OSA-18 questionnaire. There was no evidence of a difference in mean change scores between the groups at 12 months (mean difference: -1.17, 95% CI: -9.92 to 7.58).
Sjölander (2020) also measured disease-specific quality of life at 12 months using the OSA-18 questionnaire in children between 2 and 6 years with OSA. At follow-up, the mean total OSA-18 score was 31.8 ± 11.7 in the ATE group (n = 31), and 36.5 ± 11.6 in the tonsillotomy group (n = 37), reflecting a mean difference of -4.70 (95% CI: -10.26 to 0.86).
Due to the differences in instruments used to measure quality of life and in how statistics were reported (medians or means, or none at all), the results for this outcome measure could not be combined into a meta-analysis. Nevertheless, overall, there seems to be no compelling evidence for a difference in quality of life after tonsillectomy or tonsillotomy in children with OSA.
Cardiovascular risks
Blackshaw (2020) and Sjölander (2020) did not report on the outcome measure cardiovascular risks. Therefore, whether tonsillectomy is preferred over tonsillotomy as treatment for children with (suspicion of) OSA could not be assessed for this outcome measure.
Tonsillectomy versus adeno(dec)tomy
No SRs or RCTs were found that compared tonsillectomy with adenoidectomy. Therefore, whether tonsillectomy is preferred over adeno(dec)tomy as treatment for children with (suspicion of) OSA could not be assessed in this literature summary.
Level of evidence of the literature
(Adeno)Tonsillectomy versus watchful waiting
The level of evidence regarding the outcome measure Apnea Hypopnea Index was not downgraded.
The level of evidence regarding the outcome measure Oxygen Desaturation Index was downgraded by 2 levels because of inconsistency in the results (inconsistency, 1 level), and because the borders of clinical relevance were crossed (imprecision, 1 level).
The level of evidence regarding the outcome measure quality of life was downgraded by 1 level because of study limitations (risk of bias, 1 level).
The level of evidence regarding the outcome measure cardiovascular risks (weight change and blood pressure) was downgraded by two levels because of inconsistency in the conclusions (inconsistency, 1 level) and the low number of included patients (imprecision, 1 level).
(Adeno)tonsillectomy versus tonsillotomy
The level of evidence regarding the outcome measure Apnea Hypopnea Index downgraded by 1 level because of the low number of included patients (imprecision, 1 level).
The level of evidence regarding the outcome measure Oxygen Desaturation Index could not be graded due to the due to the absence of ODI reports in the included studies.
The level of evidence regarding the outcome measure quality of life was downgraded by 1 level because of study limitations (risk of bias, 1 level).
The level of evidence regarding the outcome measure cardiovascular risks could not be graded due to the due to the absence of cardiovascular risks reports in the included studies.
Tonsillectomy versus adeno(dec)tomy
No SRs or RCTs were found that compared tonsillectomy with adenoidectomy, therefore this evidence could not be graded.
Zoeken en selecteren
A systematic review of the literature was performed to answer the following question: What are the beneficial and/or harmful effects of adenotonsillectomy compared with watchful waiting, tonsillotomy, or adenotomy alone in children (0-18 years old) with (suspected) obstructive sleep apnea?
|
P (Patients) |
Children with (suspicion of) obstructive sleep apnea |
|
I (Intervention) |
Adenotonsillectomy |
|
C (Comparison) |
Watchful waiting, tonsillotomy, adenotomy |
|
O (Outcome) |
Apnea Hypopnea Index (AHI), Oxygen Desaturation Index (ODI), quality of life, cardiovascular risks |
Relevant outcome measures
The following outcome measures were considered as critical outcome measures for decision making: the Apnea Hypopnea Index (AHI) and the Oxygen Desaturation Index (ODI). Quality of life and cardiovascular risks were considered important outcome measures for decision making.
A priori, for the outcome measure quality of life, cognitive performance measures, the ability for children to focus at school, and irritability were of interest in addition to usual questionnaires measuring quality of life. The outcome measures cardiovascular risks, blood pressure and weight change were of interest as they are predictive of the long-term sequelae of OSA. The working group did not further define the outcome measures listed above but used the definitions used in the studies.
A difference of 10% on the OSA-18 questionnaire was defined as a clinically relevant difference. For dichotomous outcomes the standard GRADE limits were used as a minimal clinically (patient) important difference (i.e., relative risk (RR) of < 0.80 and > 1.25). Since there are no known minimal clinically important differences (MCIDs) for the AHI-index in the paediatric population, blood pressure and body weight, the working group concluded that it is not possible to determine a cutoff value for a clinically relevant difference.
Search and select (Methods)
The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms between 1 January 2010 and 6 December 2021. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 279 unique hits. Studies were selected based on the following criteria: systematic reviews (SRs) and randomized controlled trials (RCTs) on the effects of using adenotonsillectomy to treat children with Obstructive Sleep Apnea (OSA). Studies were initially selected based on title and abstract screening. After reading the full text, 1 systematic review (discussing five RCTs) and five RCTs were included, and 13 studies were excluded (see the Table of excluded studies for the reasons for exclusion).
Results
One SR (including five relevant RCTs) and five RCTs were included in the analysis of the literature (SR: Blackshaw, 2020; RCTs: Au, 2021; Fehrm, 2020; Sjölander, 2020; Waters, 2020). One of the five RCTs was the CHAT-trial, of which results of 2 (Baumert, 2016; Marcus, 2013) of the in total 7 publications were included in the literature summary (not included publications: Gourishetti, 2021; Liu, 2018; Liu, 2017; Magnusdottir, 2021; Taylor, 2016). Important study characteristics and results are summarized in the evidence tables. The assessment of the risk of bias is summarized in the risk of bias tables.
Referenties
- Au, C. T., Chan, K. C., Lee, D. L., Leung, N., Chow, S. M., Chow, J. S., ... & Li, A. M. (2021). Effect of surgical intervention for mild childhood obstructive sleep apnoea on attention and behavioural outcomes: A randomized controlled study. Respirology, 26(7), 690-699.
- Bagwell K, Wu X, Baum ED, Malhotra A. Cost-Effectiveness Analysis of Intracapsular Tonsillectomy and Total Tonsillectomy for Pediatric Obstructive Sleep Apnea. Appl Health Econ Health Policy. 2018 Aug;16(4):527-535. doi: 10.1007/s40258-018-0396-4. PMID: 29797301.
- Baumert, M., Pamula, Y., Martin, J., Kennedy, D., Ganesan, A., Kabir, M., ... & Immanuel, S. A. (2016). The effect of adenotonsillectomy for childhood sleep apnoea on cardiorespiratory control. ERJ Open Research, 2(2).
- Blackshaw, H., Springford, L. R., Zhang, L. Y., Wang, B., Venekamp, R. P., & Schilder, A. G. (2020). Tonsillectomy versus tonsillotomy for obstructive sleep?disordered breathing in children. Cochrane Database of Systematic Reviews, (4).
- Borgström, A., Nerfeldt, P., & Friberg, D. (2017). Adenotonsillotomy versus adenotonsillectomy in pediatric obstructive sleep apnea: an RCT. Pediatrics, 139(4).
- Buskens E, Staaij B van, Akker J van den, et al. Adenotonsillectomy or watchful waiting in patients with mild to moderate symptoms of throat infections or adenotonsillar hypertrophy: a randomized comparison of costs and effects. Arch Otolaryngol Head Neck Surg 2007;133(11):1083-8.
- Caloway CL, Diercks GR, Keamy D, de Guzman V, Soose R, Raol N, Shott SR, Ishman SL, Hartnick CJ. Update on hypoglossal nerve stimulation in children with down syndrome and obstructive sleep apnea. Laryngoscope. 2020 Apr;130(4):E263-E267. doi: 10.1002/lary.28138. Epub 2019 Jun 20. PMID: 31219619.
- Camacho M, Noller MW, Zaghi S, Reckley LK, Fernandez-Salvador C, Ho E, Dunn B, Chan D. Tongue surgeries for pediatric obstructive sleep apnea: a systematic review and meta-analysis. Eur Arch Otorhinolaryngol. 2017 Aug;274(8):2981-2990. doi: 10.1007/s00405-017-4545-4. Epub 2017 Apr 4. PMID: 28378061.
- Densert, Hilmi Desai, Alf Eliasson, Lone Frederiksen, Dan Andersson, Jan Olaison, Carl Widmark, O. (2001). Tonsillotomy in children with tonsillar hypertrophy. Acta oto-laryngologica, 121(7), 854-858.
- Derkay, C. S., Darrow, D. H., Welch, C., & Sinacori, J. T. (2006). Post-tonsillectomy morbidity and quality of life in pediatric patients with obstructive tonsils and adenoid: microdebrider vs electrocautery. Otolaryngology-Head and Neck Surgery, 134(1), 114-120.
- Diercks GR, Wentland C, Keamy D, Kinane TB, Skotko B, de Guzman V, Grealish E, Dobrowski J, Soose R, Hartnick CJ. Hypoglossal Nerve Stimulation in Adolescents With Down Syndrome and Obstructive Sleep Apnea. JAMA Otolaryngol Head Neck Surg. 2018 Jan 1;144(1):37-42. doi: 10.1001/jamaoto.2017.1871. PMID: 29098288; PMCID: PMC5833588.
- Ericsson, E., Lundeborg, I., & Hultcrantz, E. (2009). Child behavior and quality of life before and after tonsillotomy versus tonsillectomy. International journal of pediatric otorhinolaryngology, 73(9), 1254-1262.
- Fehrm, J., Nerfeldt, P., Browaldh, N., & Friberg, D. (2020). Effectiveness of adenotonsillectomy vs watchful waiting in young children with mild to moderate obstructive sleep apnea: a randomized clinical trial. JAMA otolaryngologyhead & neck surgery, 146(7), 647-654.
- Gourishetti, S. C., Hamburger, E., Pereira, K. D., Mitchell, R. B., & Isaiah, A. (2021). Baseline apnea-hypopnea index threshold and adenotonsillectomy consideration in children with OSA. International Journal of Pediatric Otorhinolaryngology, 151, 110959.
- Hoberman, A., Preciado, D., Paradise, J. L., Chi, D. H., Haralam, M., Block, S. L., ... &
- Shaikh, N. (2021). Tympanostomy tubes or medical management for recurrent acute otitis media. New England Journal of Medicine, 384(19), 1789-1799.
- Ishman SL, Chang KW, Kennedy AA. Techniques for evaluation and management of tongue-base obstruction in pediatric obstructive sleep apnea. Curr Opin Otolaryngol Head Neck Surg. 2018 Dec;26(6):409-416. doi: 10.1097/MOO.0000000000000489. PMID: 30234662.
- Liu, X., Immanuel, S., Pamula, Y., Kennedy, D., Martin, J., & Baumert, M. (2017). Adenotonsillectomy for childhood obstructive sleep apnoea reduces thoraco-abdominal asynchrony but spontaneous apnoea? hypopnoea index normalisation does not. European Respiratory Journal, 49(1).
- Liu, X., Immanuel, S., Kennedy, D., Martin, J., Pamula, Y., & Baumert, M. (2018). Effect of adenotonsillectomy for childhood obstructive sleep apnea on nocturnal heart rate patterns. Sleep, 41(11), zsy171.
- Magnusdottir, S., Hilmisson, H., Raymann, R. J., & Witmans, M. (2021). Characteristics of Children likely to have spontaneous resolution of obstructive sleep apnea: results from the Childhood Adenotonsillectomy Trial (CHAT). Children, 8(11), 980.
- Marcus, C. L., Moore, R. H., Rosen, C. L., Giordani, B., Garetz, S. L., Taylor, H. G., ... & Redline, S. (2013). A randomized trial of adenotonsillectomy for childhood sleep apnea. N Engl J Med, 368, 2366-2376.
- Kordeluk, S., Goldbart, A., Novack, L., Kaplan, D. M., El-Saied, S., Alwalidi, M., ... & Joshua, B. Z. (2016). Randomized study comparing inflammatory response after tonsillectomy versus tonsillotomy. European Archives of Oto-rhino-laryngology, 273, 3993-4001.
- Prosser JD, Shott SR, Rodriguez O, Simakajornboon N, Meinzen-Derr J, Ishman SL. Polysomnographic outcomes following lingual tonsillectomy for persistent obstructive sleep apnea in down syndrome. Laryngoscope. 2017 Feb;127(2):520-524. doi: 10.1002/lary.26202. Epub 2016 Aug 12. PMID: 27515709.
- Santoro JD, Del Rosario J, Osterbauer B, Gillett ES, Don DM. Sleep positions in children with Down syndrome and obstructive sleep apnea. Sleep Med. 2021 May;81:463-465. doi: 10.1016/j.sleep.2021.03.018. Epub 2021 Mar 26. PMID: 33865077.
- Sarny, S., Habermann, W., Ossimitz, G., & Stammberger, H. (2013). What lessons can be learned from the Austrian events?. ORL, 75(3), 175-181.
- Selvadurai S, Voutsas G, Massicotte C, Kassner A, Katz SL, Propst EJ, Narang I. Positional obstructive sleep apnea in an obese pediatric population. J Clin Sleep Med. 2020 Aug 15;16(8):1295-1301. doi: 10.5664/jcsm.8496. PMID: 32807295; PMCID: PMC7446091.
- Sjölander, I., Borgström, A., Larsson, J. O., Smedje, H., & Friberg, D. (2020). Randomised trial showed no difference in behavioural symptoms between surgical methods treating paediatric obstructive sleep apnoea. Acta Paediatrica, 109(10), 2099-2104.
- Taylor, H. G., Bowen, S. R., Beebe, D. W., Hodges, E., Amin, R., Arens, R., ... & Giordani, B. (2016). Cognitive effects of adenotonsillectomy for obstructive sleep apnea. Pediatrics, 138(2).
- Tholen K, Meier M, Kloor J, Friedman N. Persistent OSA in obese children: does body position matter? J Clin Sleep Med. 2021 Feb 1;17(2):227-232. doi: 10.5664/jcsm.8902. PMID: 33094724; PMCID: PMC7853207.
- Tripathi A, Jerrell JM, Stallworth JR. Cost-effectiveness of adenotonsillectomy in reducing obstructive sleep apnea, cerebrovascular ischemia, vaso-occlusive pain, and ACS episodes in pediatric sickle cell disease. Ann Hematol. 2011 Feb;90(2):145-50. doi: 10.1007/s00277-010-1048-4. Epub 2010 Aug 17. PMID: 20714723.
- Venekamp, R. P., Mick, P., Schilder, A. G., & Nunez, D. A. (2018). Grommets (ventilation tubes) for recurrent acute otitis media in children. Cochrane Database of Systematic Reviews, (5).
- Waters, K. A., Chawla, J., Harris, M. A., Heussler, H., Black, R. J., Cheng, A. T., & Lushington, K. (2020). Cognition after early tonsillectomy for mild OSA. Pediatrics, 145(2).
- Wilson JA, Steen IN, Lock CA, et al. Tonsillectomy: a cost-effective option for childhood sore throat? Further analysis of a randomized controlled trial. Otolaryngol Head Neck Surg 2012;146(1):122-8.
- Yu PK, Stenerson M, Ishman SL, Shott SR, Raol N, Soose RJ, Tobey A, Baldassari C, Dedhia RC, Pulsifer MB, Grieco JA, Abbeduto LJ, Kinane TB, Keamy DG Jr, Skotko BG, Hartnick CJ. Evaluation of Upper Airway Stimulation for Adolescents With Down Syndrome and Obstructive Sleep Apnea. JAMA Otolaryngol Head Neck Surg. 2022 Jun 1;148(6):522-528. doi: 10.1001/jamaoto.2022.0455. PMID: 35446411; PMCID: PMC9026239.
Evidence tabellen
Research question: What are the beneficial and/or harmful effects of adenotonsillectomy compared with watchful waiting, tonsillotomy, or adenotomy in children (0-18 years old) with (suspected) obstructive sleep apnea syndrome?
Evidence table for systematic review of RCTs and observational studies (intervention studies)
|
Study reference |
Study characteristics |
Patient characteristics |
Intervention (I) |
Comparison / control (C)
|
Follow-up |
Outcome measures and effect size |
Comments |
|
SR Blackshaw 2020
[individual study characteristics deduced from [Blackshaw 2020]
|
Cochrane SR and meta-analysis of 19 RCTs (5 studies reporting relevant outcomes)
Literature search up to July 2019
A: Borgstorm (2017) B: Densert (2001) C: Derkay (2006) D: Ericsson (2009) E: Kordeluk (2016)
Study design: Double blinded (A, C, E) / single blinded (B) / non-blinded (D) parallel group design
Setting and Country: A: single-centre (hospital), Sweden B: single-centre (ENT-clinic), Sweden C: single-centre, (medical school), USA D: multi-centre (university clinics/hospitals), Sweden E: single centre (Medical Centre), Sourthern Israel
Source of funding A: non-commercial (charitable foundation) B: not described C: commercial; Medtronics Corporation (pharmaceutical company) D: non-commercial (government grant) E: not described
|
Inclusion criteria SR: - RCTs comparing the effectiveness of tonsillectomy with tonsillotomy (irrespective of surgical technique used) - children aged 2-16 with obstructive sleep disordered breathing
Exclusion criteria SR: -studies in children with central sleep disordered breathing (e.g., due to neurological conditions)
Important patient characteristics at baseline:
N at baseline (intervention/control) A: n = 79 (I: 40 / C: 39) B: n = 43 (n at intervention/control: unknown) C: n = unknown; 300 at analysis (I: 150 / C: 150) D: n = 118 (I: 32 / C: 35) E: n = 100 (I: 34 / C: 58)
Age A: 2-6 years B: 2-9 years C: 2 years and older D: 4.5-5.5 years E: 2 – 10 years
Sex: A: 67% male B: 42% male C: 45% male D: 58% male E: 63% boys
Groups comparable at baseline? |
Tonsillectomy
A: tonsillectomy B: tonsillectomy C: traditional tonsillectomy D: tonsillectomy E: standard tonsillectomy
*In addition to tonsillectomy concurrent adenoidectomy was performed in the majority of the children (D), all children (A, B, E), or whenever it was clinically indicated (C) |
Tonsillotomy
A: tonsillotomy B: tonsillotomy C: intracapsular tonsillectomy D: tonsillotomy E: partial intracapsular tonsillectomy
*In addition to tonsillotomy concurrent adenoidectomy was performed in the majority of the children (D), all children (A, B, E), or whenever it was clinically indicated (C) |
End-point of follow-up: A: 1 year B: 3 months / 2 year C: 1 month D: 6 months / 2 year E: 6 months
For how many participants were no complete outcome data available? (intervention/control) A: 6% B: 5% C: unclear D: 40% pre-trial drop-out / 6% drop-out at 6 months / 4% drop-out at 2 years E: 8% at 1 week / 73% at 6 months
|
AHI-score Mean difference (95% CI): A: 0.83 (-3.23 to 4.88) B: - C: - D: - E: -0.58 (-5.43 to 4.27)
*No pooled effects
Quality of Life (QoL) A: Measured with OSA-18; Mean difference at follow-up (95% CI): -1.17 (-9.92 to 7.58) B: no differences on VAS after tonsillotomy vs. tonsillectomy for snoring (112 vs. 104), apnea (62 vs. 66) and wellbeing (85 vs. 46) C: Measured with a validated QoL survey; no significant difference (no statistical data) D: Measured with OSA-18; Median score at follow-up (IQR) I: 25 (23 to 32) C: 27 (22 to 34) E: -
*No pooled effects
|
Author’s conclusion: “… data on long-term effects of the two operations on OSA symptoms, quality of life, and recurrence are limited and the evidence is of very low quality leading to a high degree of uncertainty about the results”
Level of evidence: GRADE Comparison: tonsillectomy vs. tonsillotomy Outcome: AHI-score GRADE: -
Outcome: QoL GRADE: Very low* (for all follow-up durations; varying from 3 to 24 months)
* “because of very serious limitations in study methodology, serious imprecision and suspected publication bias”
Sensitivity analysis: not applicable for the defined outcomes
Heterogeneity: Not applicable for the defined study outcomes
|
Evidence table for intervention studies (randomized controlled trials and non-randomized observational studies [cohort studies, case-control studies, case series])
|
Study reference |
Study characteristics |
Patient characteristics 2 |
Intervention (I) |
Comparison / control (C) 3
|
Follow-up |
Outcome measures and effect size 4 |
Comments |
|
Au (2021) |
Type of study: RCT
Country & setting: China, single-centre: at one hospital from December 2010 to December 2018
Funding: Research Grants Council, University Grants Committee
Conflicts of interest: None |
Inclusion criteria: -aged 6 – 11 years - non-obese - symptoms of habitual snoring and/or other symptoms suggestive of OSA - enlarged tonsils (> grade 1) - confirmed (by PSG) mild OSA (OAHI between 1 – 5 / hour)
Exclusion criteria: -previously undergone upper airway surgery - receiving treatment for OSA - suffering from medical conditions and/or receiving medications that could affect cognitive function and behaviour - craniofacial abnormalities
N total at baseline: I: n = 57 C: n = 57
Important prognostic factors2: (Numbers only available for participants included for analysis) Age years (± SD) I: 8.4 (± 1.6) C: 8.4 (± 1.4)
Sex: I: 54.3% male C: 69.4% male
BMI z-score mean (± SD) I: 0.12 (±0.87) C: -0.09 (±0.92)
Groups comparable at baseline? Yes
|
Early surgical intervention à Surgical condition consisting of -Adenotonsillectomy -Adenotonsillectomy + turbinate reduction - Tonsillectomy - Tonsillectomy + turbinate reduction
|
Watchful waiting
|
Length of follow-up: 9 months
Loss to follow-up: I: n = 20 (35%) (Refused surgery; refused follow-up)
C: n = 13 (23%) (Refused follow-up)
Incomplete outcome data: I: n = 2 C: n = 8 (No primary outcome)
|
Change at follow-up Mean change at follow-up (±SD) / mean difference (95% CI)
AHI I: -1.1 (± 2.3) C: 0.2 (± 4.4) Mean difference: 1.30 (-2.93 to 0.33)
ODI: I: -0.4 (± 2.0) C: 0.5 (± 3.9) Mean difference: -0.90 (-2.34 to 0.54)
OSA-18 score (QoL) I: 17.3 (± 19.7) C: -3.6 (± 14.1) Mean difference: -13.70 (-21,69 to -5.71)
|
Intervention not exclusively adenotonsillectomy Among subjects allocated to intervention: - AT: n = 13 - AT + turbinate reduction: n = 5 - tonsillectomy: n = 8 - tonsillectomy + turbinate reduction: n = 9
Authors’ conclusion: The authors conclude that PSG parameters and parent-reported symptoms improved after surgical treatment compared with watchful waiting.
|
|
Fehrm (2020) |
Type of study: RCT
Country & setting Sweden, Single-centre; at one hospital from December 2014 to December 2017.
Funding: Grants from the Stockholm County Council (ALF project), the ACTA Oto-Laryngologica Foundation, and the Samaritan Foundation for Pediatric Research.
Conflicts of interest: Dr Fehrm reported grants from the Samaritan Foundation for Pediatric Research, from the ACTA Oto-Laryngologica Foundation, and from the Stockholm City Council |
Inclusion criteria: - Aged 2-4 years - History or symptoms of habitual snoring, apneas and/or restless sleep - Mild to moderate OSA (OAHI-score: > 2; < 10) - Tonsil hypertrophy of 2 to 4 (according to Brodksy)
Exclusion criteria: - craniofacial abnormalities - neuromuscular disease - chromosomal abnormality - previous adenotonsillar surgery - bleeding disorder, - cardiopulmonary disease
N total at baseline: I: n = 29 C: n = 31
Important prognostic factors2: Age months (± SD) I: 39 (±8) C: 37 (±11)
Sex: I: 51.7% male C: 61.2% male
BMI z-score mean (± SD) I: 0.2 (±1.4) C: 0.2 (±1.1)
Groups comparable at baseline? Yes
|
Adenotonsillectomy
|
Watchful waiting
|
Length of follow-up: 6 months
Loss to follow-up: I: n = 4 (14%) (Not received the intervention, could not go through with measurements, declined further participation)
Control: C: n = 3 (10%) (Discontinued the intervention, declined further participation)
Incomplete outcome data: Some missing data on individual outcomes in both treatment groups, missings are similar across the groups.
|
Change at follow-up Median change at follow-up (IQR) / Mean difference (95% CI)
OAHI (obstructive apnea–hypopnea index) I: −2.9 (−4.0 to −1.9) C: −1.9 (−3.0 to −0.9) Mean difference: −1.0 (−2.4 to 0.5)
Central AHI I: -0.5 (-1.2 to 0.3) C: -0.5 (-1.2 to 0.2) Mean difference: 0.1 (-0.9 to 1.1)
ODI (3%) I: -0.4 (-1.3 to 0.5) C: -1.0 (-1.9 to -0.10) Mean difference: 0.5 (-0.7 to 1.7)
OSA-18 score (QoL) I: -23.5 (-31.5 to 15) / -1.24 C: -45 (-12 to 1.5) / -0.36 Mean difference: -17.0 (-24 to -10) /
|
Authors’ conclusion: The authors conclude that children with moderate OSA should be considered for early ATE, while watchful waiting could be an alternative for otherwise healthy children with mild OSA. |
|
Sjolander (2020) |
Type of study RCT
Country & setting Sweden, single-centre; at one hospital from November 2011 and April 2015
Funding: Not reported
Conflicts of interest None |
Inclusion criteria: -Aged 2-6 years -AHI > 5 and < 30 events per hour
Exclusion criteria: -Craniofacial abnormalities - neuromuscular disease - chromosomal abnormalities - obesity (body mass index z score > 1.67), - previous adenotonsil surgery - bleeding disorder, - cardiopulmonary disease - history of recurrent tonsillitis
N total at baseline: I: n = 39 C: n = 40
Important prognostic factors: Age months (range) I: 42 (25-80) C: 44 (29-74)
Sex: I: 66% male C: 70%% male
BMI z-score mean (± SD) not reported
Groups comparable at baseline? Yes
|
Adenotonsillotomy
|
Adenotonsillectomy |
Length of follow-up: Intended follow-up period: 1 year
Intervention: 14.3 months Control: 15.1 months
Loss to follow-up: I: n = 2 (5%) Reason: did not complete the follow-up
C: n = 9 (22%) Reason: did not complete the follow-up
Incomplete outcome data: None |
Change at follow-up Mean at follow up (± SD) / mean difference (95% CI)
AHI: I: 4.5 (± 6.3) C: 2.5 (± 2.0) Between groups: 2,00 (95% CI -4.15 to 0.15
OSA-18 score (QoL) I: 36.5 ± 11.6 C: 31.8 ± 11.7 Between groups: -4,70 (95% CI -10.26 to 0.86). |
Authors’ conclusion: The authors recommend treating children suffering from OSA with ATT since this is a more conservative treatment option with lower risks and less pain for the child, as well as lower costs as compared with ATE. |
|
Waters (2020) |
Type of study RCT
Country & Setting Australia, Multicenter; undertaken at 3 tertiary children’s Hospitals from January 2014 to 2017
Funding National health and medicinal research council, The Garnett Passe, Rodney Williams Memorial Foundation, The Golden Casket.
Conflicts of interests: None |
Inclusion criteria: -Aged 3-5 years -Children with mild or moderate OSA (OAHI-score: < 10) - Suitable for adenotonsillectomy
Exclusion criteria: -abnormal hearing test result (bilateral hearing loss .35 dB).
N total at baseline: I: n = 99 C: n = 91
Important prognostic factors:
Age months (± SD) I: 46.5 (± 8.8) C: 47.8 (± 8.8)
Sex: I: 52% male C: 63% male
BMI score Not reported
Groups comparable at baseline? Yes
|
Adenotonsillectomy |
Waiting List condition
|
Length of follow-up 12 months
Loss to follow-up: I: n =27 (27%) Reason: crossover, withdrawal, lost to follow-up, excluded
Control: C: n =22 (24%) Reason: crossover, withdrawal, lost to follow-up, excluded
Incomplete outcome data No incomplete outcome data for the selected outcomes. |
Change at follow-up mean (± SD) / mean difference (95% CI)
AHI: I: 1.0 (±0.9) C: 2.1 (±2.4) Difference: -1.11 (-1.69 – 0.51)
QoL (parent questionnaires) Rating QoL of their child on a 1-10 scale; mean (± SD) I: 8,7 (± 1,2) C: 5,7 (± 1,6) Difference: 3.00 (2.53 – 3.47) |
Authors’ conclusion: The authors concluded that there were improvements in PSG parameters and quality of life in preschool children undergoing adenotonsillectomy. |
|
CHAT-trial (Baumert, 2016; Gourishetti, 2021; Liu, 2018; Liu, 2017; Magnusdottir, 2021; Taylor, 2016; Marcus, 2013) |
Type of study RCT
Country & Setting USA, Multicenter; undertaken at six centers (paediatric sleep centres/sleep laboratories/pediatric otolaryngology clinics, general paediatric clinics, and the general community) January 2008 through September 2011
Funding: CHAT Trial is Supported by grants from the National Institutes of health
Conflicts of interests: None
|
Inclusion criteria: -aged 5-9 years -confirmed OSA (AHI> 2; OAHI > 1). - history of snoring - considered to be surgical candidate for adenotonsillectomy
Exclusion criteria - comorbidities - medications for psychiatric or behavioural disorders - recurrent tonsilitis - extreme obesity (< 2.99 for age group and sex Z-score) - severe OSA (AHI > 30; OAHI > 20 or oxyhaemoglobin saturation < 90% for > 2% of total sleep time)
N total at baseline I: n = 226 C: n = 227
Important prognostic factors:
Age years (± SD) I: 6.5 (±1.4) C: 6.5 (±1.4)
Sex: I: 46% male C: 52% male
BMI: % overweight or obese I: 48% C: 46%
Groups comparable at baseline? Yes
|
Adenotonsillectomy |
Watchful waiting with supportive care |
Length of follow-up 7 months
Loss to follow-up a: I: 18 (8%) / C: 35 (15%) b: I: 29 (13%) / C: 24 (10%) c: I: 30 (15%) / C: 23 (11%)
Incomplete outcome data a: I: 12 (6%) / C: 13 (7%) b: not reported c: I: 2 (1%) / C: 1 (< 1%) |
Change at follow-up
AHI (c): Mean (±IQR) / mean difference I: - 5.2 (-7.1 to -1.8) C: -1.6 (-4 to 1) Effect size:
AHI (c): mean change at follow-up (±SD) I: -5.3 (±6.2) C: -0.7 (±9.6) Mean difference:
Normalization of AHI at follow-up (a) I: 169/206 (82% normalized) C: 82/194 (42% normalized) RR: 1.94 (94% CI 1.63 – 2.32)
Peds-QL mean change at follow-up (c) I: 5.9 ± 13.6 C: 0.9 ± 13.3 Mean difference: 5,00 (95% CI 2.36 to 7.64)
OSA-18 score mean change at follow-up (±SD) (c) I: -21.4 (±16.5) C: -4.5 (±19.3)
|
Multiple studies reporting on outcomes of the CHAT-trial a. Baumert (2016) b. Giroushetti (2021) c. Marcus (2013)
|
Risk of bias tables
Table of quality assessment for systematic reviews of RCTs and observational studies
|
Study
First author, year |
Appropriate and clearly focused question?1
Yes/no/unclear |
Comprehensive and systematic literature search?2
Yes/no/unclear |
Description of included and excluded studies?3
Yes/no/unclear |
Description of relevant characteristics of included studies?4
Yes/no/unclear |
Appropriate adjustment for potential confounders in observational studies?5
Yes/no/unclear/not applicable |
Assessment of scientific quality of included studies?6
Yes/no/unclear |
Enough similarities between studies to make combining them reasonable?7
Yes/no/unclear |
Potential risk of publication bias taken into account?8
Yes/no/unclear |
Potential conflicts of interest reported?9
Yes/no/unclear |
|
Blackshaw 2020 |
Yes
PICO and inclusion criteria are defined |
Yes
Search period and strategy are defined, Medline is included as database |
Yes
Reason for exclusion after full text screening are reported per excluded article. |
Yes
Relevant characteristics are described per included study |
Not applicable
only RCTs included |
Yes
Risk of bias assessed for the included studies |
Not relevant for the selected outcomes |
Yes
Not sufficient number of included studies. Study protocols were checked. |
Yes
Source of funding described for the review and the included articles |
Risk of bias table for intervention studies (randomized controlled trials; based on Cochrane risk of bias tool and suggestions by the CLARITY Group at McMaster University)
|
Study reference |
Was the allocation sequence adequately generated?
Definitely yes Probably yes Probably no Definitely no |
Was the allocation adequately concealed?
Definitely yes Probably yes Probably no Definitely no |
Blinding: Was knowledge of the allocated interventions adequately prevented?
Were patients blinded?
Were healthcare providers blinded?
Were data collectors blinded?
Were outcome assessors blinded?
Were data analysts blinded?
Definitely yes Probably yes Probably no Definitely no |
Was loss to follow-up (missing outcome data) infrequent?
Definitely yes Probably yes Probably no Definitely no |
Are reports of the study free of selective outcome reporting?
Definitely yes Probably yes Probably no Definitely no |
Was the study apparently free of other problems that could put it at a risk of bias?
Definitely yes Probably yes Probably no Definitely no |
Overall risk of bias If applicable/necessary, per outcome measure
LOW Some concerns HIGH |
|
Au 2021 |
Probably yes:
Reason: A randomization list developed by personnel not involved in this study, with varying block sizes of 4 to 8 was generated – not clear how randomization list was developed |
Definitely yes:
Reason: The details of the list were unknown to any of the investigators and contained in a set of sealed, sequentially numbered envelopes |
Definitely no:
Reason: due to the nature of the intervention (surgery), blinding is not possible. Outcome collectors were blinded. |
Probably no:
Reason: high drop-out rates in comparison to total no. of participants |
Probably yes:
Reason: protocol not freely available, but reported outcomes in the methods section also reported in the results |
Probably yes:
Reason: per protocol analysis – but groups were comparable at baseline. No ITT analysis performed |
Some concerns
Reason: high drop-out rates and per protocol analysis. Lack of blinding was not likely to have influenced the outcomes |
|
Fehrm 2020 |
Definitely yes;
Reason: a total of 5 enveloped from each group were mixed together to create a block of 10. |
Definitely yes
Reason: randomization was performed with sealed envelopes which were place in folders containing study information which were opened together with the caregivers and children. |
Definitely no;
Reason: Due to the nature of the intervention (surgery), blinding is impossible. |
Definitely yes;
Reason: Some loss to follow-up and missing outcomes, but missings are similar across both arms. |
Definitely yes;
Reason: All predefined outcomes in the protocol were reported |
Probably yes;
Reason: analysis was per protocol, but intention to treat analysis as sensitivity analysis (for primary outcome) No other sources of bias were identified.
|
LOW
Reason: only potential bias is in non-blinding. The lack of blinding was not likely to have influenced the outcomes. |
|
Sjolander 2020 |
Definitely yes;
Reason: envelopes were randomly mixed, giving a 1:1 ratio. |
Definitely yes:
Reason: sealed envelopes were used |
Probably yes:
Reason: due to the nature of the intervention (surgery) blinding is impossible. Only the surgeon and staff in operating room knew which surgical method was performed. The surgeon was not further involved in the study |
Probably yes:
Reason: the difference in percentage missings/lost to follow-up between the two groups is substantial (5% vs. 22%) |
Definitely yes:
Reason: all predefined outcomes in the protocol were reported |
Probably yes;
Reason: analysis by intention to treat principle, no conflicts of interest, no other sources of bias could be identified |
LOW
Reason: only potential bias due to non-blinding and higher drop-out rates. However, since parents were blinded, it is not likely that this has influenced the outcomes |
|
Waters 2020 |
Definitely yes;
Reason: used block randomization with blocks for AHI values, randomization sequence provided by a statistician |
Definitely yes:
Reason: randomization was centralized, allocation to arm was via telephone
|
Definitely no;
Reason: Due to the nature of the intervention (surgery), blinding is impossible. Some outcome assessors and analysists were blinded. |
Definitely yes:
Reason: Some loss to follow-up and missing outcomes, but missings are similar across both arms. |
Definitely yes:
Reason: all predefined outcomes in the protocol were reported |
Probably yes:
Reason: analysis by intention to treat principle, no conflicts of interest, no other sources of bias could be identified. |
LOW
Reason: only potential bias due to in non-blinding, it is not likely that this has influenced the outcome. |
|
CHAT-trial (Baumert, 2016; Giroushetti 2021; Marcus, 2013) |
Definitely yes;
Reason: randomization (stratified by age, race, and weight) was performed using a web-based procedure |
Definitely yes;
Reason: randomization was centralized, clinic sites do not have access to the randomization schedule |
Definitely no;
Reason: due to the nature of the intervention (surgery) blinding is impossible. Efforts were made to protect unblinding of individuals involved in data collection and evaluation. |
Probably yes;
Reason: different papers on different outcomes of the CHAT trials report different numbers regarding loss to follow-up and missings. However, missings are similar across both arms. |
Probably yes:
Reason: all prespecified outcomes in the protocol seem to be reported. Some outcomes are not addressed in the result section (only in appendix) (Marcus, 2013). The variety in articles reporting on this same trial makes it challenging to evaluate whether all outcomes were reported. |
Probably yes:
Reason: intention to treat principle was used, no conflicts of interest or funding by industry. Some authors collaborated with industry but report that this was not related to this trial. |
SOME CONCERNS:
Reason: a large variety of articles reporting on the same trial, creates uncertainty in terms of selective outcome reporting + some inconsistencies between the different articles (regarding loss to follow-up and missing data) |
Table of excluded studies
|
Author and year |
Reason for exclusion |
|
Di Mauro, 2021 |
more recent systematic reviews available |
|
Galluzzi, 2021 |
systematic reviews of higher quality available; only children with severe OSA included |
|
Gorman, 2017 |
more recent systematic reviews available |
|
Wang, 2015 |
more recent and higher quality systematic reviews available |
|
Wood, 2014 |
more recent and higher quality systematic reviews available |
|
Garetz, 2015 |
included in included systematic reviews |
|
Marcus, 2013 |
included in included systematic reviews |
|
Trosman, 2016 |
included in included systematic reviews |
|
Teo, 2013 |
more recent and higher quality systematic reviews available |
|
Todd, 2017 |
more recent and higher quality systematic reviews available |
|
Zhang, 2017 |
more recent and higher quality systematic reviews available |
|
Quante, 2015 |
included in included systematic reviews |
|
Venekamp, 2015 |
more recent systematic reviews available |
|
Lin, 2019 |
wrong P: only patients with OSA and adenotonsillar hypertrophy included |
|
Gourishetti, 2021 (CHAT study) |
Wrong outcome |
|
Liu, 2018 (CHAT-study) |
Wrong outcome |
|
Lui, 2017 (CHAT-study) |
Wrong outcome |
|
Magnusdottir, 2021 (CHAT-study) |
Wrong comparison |
|
Taylor, 2016 (CHATO-study) |
Wrong outcome |
Verantwoording
Autorisatiedatum en geldigheid
Laatst beoordeeld : 16-04-2024
Laatst geautoriseerd : 16-04-2024
Geplande herbeoordeling : 16-04-2029
Algemene gegevens
De ontwikkeling/herziening van deze richtlijnmodule werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd uit de Kwaliteitsgelden Medisch Specialisten (SKMS). De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.
Samenstelling werkgroep
Voor het ontwikkelen van de richtlijnmodule is in 2021 een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg voor patiënten met pediatrisch OSA.
Werkgroep
- dr. B. (Bas) Pullens (voorzitter), NVKNO, kno-arts (Erasmus MC)
- dr. M.A.J. (Marjolein) van Looij, NVKNO, kno-arts (OLVG)
- drs. C.C.A.F.M. (Christianne) Veugen, NVKNO, AIOS kno (UMCG)
- F.H. (Frea) Kruisinga, NVK, algemeen kinderarts (Amsterdam UMC)
- E.M. (Esther) Dias, NVA, anesthesioloog (Máxima Medisch Centrum)
- dr. J.W. (Jitske) Nolte, NVMKA, MKA-chirurg (Amsterdam UMC)
- E.C. (Esen) Doganer, Stichting Kind en Ziekenhuis, patiëntvertegenwoordiger, tijdelijk vervangen door:
- Anne Swinkels, Stichting Kind en Ziekenhuis (maart 2023 – augustus 2023)
- Marjolein Jager, Stichting Kind en Ziekenhuis (vanaf september 2023)
- T. (Tanja) Mast, Apneuvereniging, patiëntvertegenwoordiger
Klankbordgroep
- drs. W.J.D.M. (Wilma) van Beers, NVvO, orthodontist (tot mei 2023)
- drs. P.C.M. (Petra) Zuurbier, NVvO, orthodontist (vanaf mei 2023)
Met dank aan
- Prof. dr. K.F.M. (Koen) Joosten, kinderarts-intensivist (Erasmus MC)
Met ondersteuning van
- dr. A. (Anja) van der Hout, adviseur Kennisinstituut (vanaf september 2022)
- drs. E.R.L. (Evie) Verweg, junior adviseur Kennisinstituut (vanaf november 2022)
- dr. I. (Iris) Duif, adviseur Kennisinstituut (tot september 2022)
Belangenverklaringen
De Code ter voorkoming van oneigenlijke beïnvloeding door belangenverstrengeling is gevolgd. Alle werkgroepleden hebben schriftelijk verklaard of zij in de laatste drie jaar directe financiële belangen (betrekking bij een commercieel bedrijf, persoonlijke financiële belangen, onderzoeksfinanciering) of indirecte belangen (persoonlijke relaties, reputatiemanagement) hebben gehad. Gedurende de ontwikkeling of herziening van een module worden wijzigingen in belangen aan de voorzitter doorgegeven. De belangenverklaring wordt opnieuw bevestigd tijdens de commentaarfase.
Een overzicht van de belangen van werkgroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten.
|
Werkgroeplid |
Functie |
Nevenfuncties |
Gemelde belangen |
Ondernomen actie |
|
Pullens |
KNO arts Erasmus MC |
Voorzitter werkgroep landelijke kwaliteitsregistratie Amandeloperaties (die zal een landelijke registratie over amandeloperaties opzetten). Daarnaast voorzitter van de “educational committee” van de Europese kinderKNO vereniging ESPO |
Presentatie tegen vergoeding (sprekersfee) bij Smith & Nephew over coblatie-operaties bij amandelen |
Exclusie bij beslissingen over module aangaande coblatie-operaties bij amandelen. |
|
Veugen |
AIOS Keel-, Neus-, en Oorheelkunde UMCG |
- PhD kandidaat KNO St. Antonius Ziekenhuis/UMCU (onbetaald) - Lid Kerngroep slaapgeneeskunde van de KNO-vereniging |
Promotieonderzoek op het gebied van OSA bij volwassenen, deels gefinancierd door de industrie. Dit gaat echter om OSA bij volwassenen, derhalve hebben zij geen belang in de adviezen die voortvloeien uit de richtlijn pediatrisch OSA. |
Geen restricties |
|
Van Looij |
KNO-arts, somnoloog OLVG |
- Voorzitter Commissie Kwaliteit en Accreditatie SVNL (onbetaald) - Lid richtlijncommissie ESRS - Lid Bestuur SVNL, a.i. voorzitter (onbetaald) - Lid Commissie PrevENT, KNO-vereniging (onbetaald, vacatiegelden) - Adviserend arts voor DEKRA Certification B.V. (incidenteel) - Lid klankbordgroep van de themagroep slaapgeneeskunde van de KNO-vereniging. - Plaatsvervangend opleider van de AIOS en HAIO’s |
Geen |
Geen restricties. Niet de verwachting dat DEKRA Certification B.V. belang heeft bij product. |
|
Dias |
Anesthesioloog Máxima Medisch Centrum |
Geen |
- Sprekersfee (Johnson en Johnson) voor praatjes die niet relateren aan OSA bij kinderen - Principal investigator van Multi-Centre Clinical Trial (PREPARATION) - Wil een onderzoek opzetten naar post-operatief beloop van kinderen met obesitas en bariatrische chirurgie. |
Geen restricties |
|
Nolte |
MKA-chirurg Amsterdam UMC en Schisisteam Amsterdam |
Bestuur Nederlandse Vereniging voor Schisis en Craniofaciale Afwijkingen (NVSCA, penningmeester, onbetaald) |
Geen |
Geen restricties |
|
Kruisinga |
Algemeen kinderarts |
Geen |
Wetenschappelijk onderzoek OSA bij kinderen waaronder: diagnostische instrumenten |
Geen restricties |
|
Mast |
Medewerker ApneuVereniging t.a.v. apneu bij kinderen en t.a.v. de Löwenstein |
- Afdelingssecretaresse Thoraxcentrum Enschede (betaald) - Secretaresse hartrevalidatie bij het Thoraxcentrum |
Geen |
Geen restricties |
|
Doganer |
Junior projectmanager/ beleidsmedewerker Stichting Kind en Ziekenhuis |
Geen |
Geen |
Geen restricties |
|
Swinkels |
Junior projectmanager/ beleidsmedewerker Stichting Kind en Ziekenhuis |
Geen |
Geen |
Geen restricties |
|
Jager |
Junior beleids- en projectmedewerker Stichting Kind en Ziekenhuis |
Begeleider C bij Sherpa, betaald (3 contracturen). |
Geen |
Geen restricties |
|
Zuurbier |
- Orthodontist, deels eigenaar praktijk orthodontisten Heemstede -Orthodontist, staflid afdeling orthodontie, ACTA |
Lid wetenschappelijke commissie van de NVTS |
Geen |
Geen restricties |
|
Van Beers |
Recent met pensioen, voorheen praktijkhouder orthodontisten praktijk |
- Vice voorzitter College Tandheelkundig Specialisten - Lid VICO, visitatiecommissie orthodontisten - Lid Consilium orthodontiae - Lid LOP - Lid verantwoordingsorgaan tandarts pensioenfonds (betaald), - Zelfstandig gevestigd mediator - Ombudspersoon voor Volt Europa - Waarnemer zzp (betaald) |
Geen |
Geen restricties |
Inbreng patiëntenperspectief
Er werd aandacht besteed aan het patiëntenperspectief door inbreng van De Apneu Vereniging en Stichting Kind en Ziekenhuis in de knelpuntenanalyse en afgevaardigden van De Apneu Vereniging en Stichting Kind en Ziekenhuis in de werkgroep. De verkregen input is meegenomen bij het opstellen van de uitgangsvragen, de keuze voor de uitkomstmaten en bij het opstellen van de overwegingen. De conceptrichtlijn is tevens voor commentaar voorgelegd aan Stichting Kind en Ziekenhuis en de Apneuvereniging en de eventueel aangeleverde commentaren zijn bekeken en verwerkt.
Kwalitatieve raming van mogelijke financiële gevolgen in het kader van de Wkkgz
Bij de richtlijn is conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uitgevoerd of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling zijn richtlijnmodules op verschillende domeinen getoetst (zie het stroomschema op de Richtlijnendatabase).
Uit de kwalitatieve raming blijkt dat er waarschijnlijk geen substantiële financiële gevolgen zijn, zie onderstaande tabel.
|
Module |
Uitkomst raming |
Toelichting |
|
Module Adenotonsillectomie |
geen financiële gevolgen |
Hoewel uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (> 40.000 patiënten), volgt ook uit de toetsing dat het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft, het geen toename in het aantal in te zetten voltijdsequivalenten aan zorgverleners betreft en het geen wijziging in het opleidingsniveau van zorgpersoneel betreft. Er worden daarom geen substantiële financiële gevolgen verwacht. |
Werkwijze
AGREE
Deze richtlijnmodule is opgesteld conform de eisen vermeld in het rapport Medisch Specialistische Richtlijnen 2.0 van de adviescommissie Richtlijnen van de Raad Kwaliteit. Dit rapport is gebaseerd op het AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II; Brouwers, 2010).
Knelpuntenanalyse en uitgangsvragen
Tijdens de voorbereidende fase inventariseerde de werkgroep de knelpunten in de zorg voor patiënten met pediatrisch OSA. De werkgroep beoordeelde de aanbeveling(en) uit de eerdere richtlijnmodule (NVKNO, 2013) op noodzaak tot revisie. Tevens zijn er knelpunten aangedragen door De Apneu Vereniging en Stichting Kind en Ziekenhuis. Een verslag hiervan is opgenomen onder aanverwante producten.
Uitkomstmaten
Na het opstellen van de zoekvraag behorende bij de uitgangsvraag inventariseerde de werkgroep welke uitkomstmaten voor de patiënt relevant zijn, waarbij zowel naar gewenste als ongewenste effecten werd gekeken. Hierbij werd een maximum van acht uitkomstmaten gehanteerd. De werkgroep waardeerde deze uitkomstmaten volgens hun relatieve belang bij de besluitvorming rondom aanbevelingen, als cruciaal (kritiek voor de besluitvorming), belangrijk (maar niet cruciaal) en onbelangrijk. Tevens definieerde de werkgroep tenminste voor de cruciale uitkomstmaten welke verschillen zij klinisch (patiënt) relevant vonden.
Methode literatuursamenvatting
Een uitgebreide beschrijving van de strategie voor zoeken en selecteren van literatuur is te vinden onder ‘Zoeken en selecteren’ onder Onderbouwing. Indien mogelijk werd de data uit verschillende studies gepoold in een random-effects model. Review Manager 5.4 werd gebruikt voor de statistische analyses. De beoordeling van de kracht van het wetenschappelijke bewijs wordt hieronder toegelicht.
Beoordelen van de kracht van het wetenschappelijke bewijs
De kracht van het wetenschappelijke bewijs werd bepaald volgens de GRADE-methode. GRADE staat voor ‘Grading Recommendations Assessment, Development and Evaluation’ (zie https://www.gradeworkinggroup.org). De basisprincipes van de GRADE-methodiek zijn: het benoemen en prioriteren van de klinisch (patiënt) relevante uitkomstmaten, een systematische review per uitkomstmaat, en een beoordeling van de bewijskracht per uitkomstmaat op basis van de acht GRADE-domeinen (domeinen voor downgraden: risk of bias, inconsistentie, indirectheid, imprecisie, en publicatiebias; domeinen voor upgraden: dosis-effect relatie, groot effect, en residuele plausibele confounding).
GRADE onderscheidt vier gradaties voor de kwaliteit van het wetenschappelijk bewijs: hoog, redelijk, laag en zeer laag. Deze gradaties verwijzen naar de mate van zekerheid die er bestaat over de literatuurconclusie, in het bijzonder de mate van zekerheid dat de literatuurconclusie de aanbeveling adequaat ondersteunt (Schünemann, 2013; Hultcrantz, 2017).
|
GRADE |
Definitie |
|
Hoog |
|
|
Redelijk |
|
|
Laag |
|
|
Zeer laag |
|
Bij het beoordelen (graderen) van de kracht van het wetenschappelijk bewijs in richtlijnen volgens de GRADE-methodiek spelen grenzen voor klinische besluitvorming een belangrijke rol (Hultcrantz, 2017). Dit zijn de grenzen die bij overschrijding aanleiding zouden geven tot een aanpassing van de aanbeveling. Om de grenzen voor klinische besluitvorming te bepalen moeten alle relevante uitkomstmaten en overwegingen worden meegewogen. De grenzen voor klinische besluitvorming zijn daarmee niet één op één vergelijkbaar met het minimaal klinisch relevant verschil (Minimal Clinically Important Difference, MCID). Met name in situaties waarin een interventie geen belangrijke nadelen heeft en de kosten relatief laag zijn, kan de grens voor klinische besluitvorming met betrekking tot de effectiviteit van de interventie bij een lagere waarde (dichter bij het nuleffect) liggen dan de MCID (Hultcrantz, 2017).
Overwegingen (van bewijs naar aanbeveling)
Om te komen tot een aanbeveling zijn naast (de kwaliteit van) het wetenschappelijke bewijs ook andere aspecten belangrijk en worden meegewogen, zoals aanvullende argumenten uit bijvoorbeeld de biomechanica of fysiologie, waarden en voorkeuren van patiënten, kosten (middelenbeslag), aanvaardbaarheid, haalbaarheid en implementatie. Deze aspecten zijn systematisch vermeld en beoordeeld (gewogen) onder het kopje ‘Overwegingen’ en kunnen (mede) gebaseerd zijn op expert opinion. Hierbij is gebruik gemaakt van een gestructureerd format gebaseerd op het evidence-to-decision framework van de internationale GRADE Working Group (Alonso-Coello, 2016a; Alonso-Coello 2016b). Dit evidence-to-decision framework is een integraal onderdeel van de GRADE methodiek.
Formuleren van aanbevelingen
De aanbevelingen geven antwoord op de uitgangsvraag en zijn gebaseerd op het beschikbare wetenschappelijke bewijs en de belangrijkste overwegingen, en een weging van de gunstige en ongunstige effecten van de relevante interventies. De kracht van het wetenschappelijk bewijs en het gewicht dat door de werkgroep wordt toegekend aan de overwegingen, bepalen samen de sterkte van de aanbeveling. Conform de GRADE-methodiek sluit een lage bewijskracht van conclusies in de systematische literatuuranalyse een sterke aanbeveling niet a priori uit, en zijn bij een hoge bewijskracht ook zwakke aanbevelingen mogelijk (Agoritsas, 2017; Neumann, 2016). De sterkte van de aanbeveling wordt altijd bepaald door weging van alle relevante argumenten tezamen. De werkgroep heeft bij elke aanbeveling opgenomen hoe zij tot de richting en sterkte van de aanbeveling zijn gekomen.
In de GRADE-methodiek wordt onderscheid gemaakt tussen sterke en zwakke (of conditionele) aanbevelingen. De sterkte van een aanbeveling verwijst naar de mate van zekerheid dat de voordelen van de interventie opwegen tegen de nadelen (of vice versa), gezien over het hele spectrum van patiënten waarvoor de aanbeveling is bedoeld. De sterkte van een aanbeveling heeft duidelijke implicaties voor patiënten, behandelaars en beleidsmakers (zie onderstaande tabel). Een aanbeveling is geen dictaat, zelfs een sterke aanbeveling gebaseerd op bewijs van hoge kwaliteit (GRADE gradering HOOG) zal niet altijd van toepassing zijn, onder alle mogelijke omstandigheden en voor elke individuele patiënt.
|
Implicaties van sterke en zwakke aanbevelingen voor verschillende richtlijngebruikers |
||
|
|
||
|
|
Sterke aanbeveling |
Zwakke (conditionele) aanbeveling |
|
Voor patiënten |
De meeste patiënten zouden de aanbevolen interventie of aanpak kiezen en slechts een klein aantal niet. |
Een aanzienlijk deel van de patiënten zouden de aanbevolen interventie of aanpak kiezen, maar veel patiënten ook niet. |
|
Voor behandelaars |
De meeste patiënten zouden de aanbevolen interventie of aanpak moeten ontvangen. |
Er zijn meerdere geschikte interventies of aanpakken. De patiënt moet worden ondersteund bij de keuze voor de interventie of aanpak die het beste aansluit bij zijn of haar waarden en voorkeuren. |
|
Voor beleidsmakers |
De aanbevolen interventie of aanpak kan worden gezien als standaardbeleid. |
Beleidsbepaling vereist uitvoerige discussie met betrokkenheid van veel stakeholders. Er is een grotere kans op lokale beleidsverschillen. |
Organisatie van zorg
In de knelpuntenanalyse en bij de ontwikkeling van de richtlijnmodule is expliciet aandacht geweest voor de organisatie van zorg: alle aspecten die randvoorwaardelijk zijn voor het verlenen van zorg (zoals coördinatie, communicatie, (financiële) middelen, mankracht en infrastructuur). Randvoorwaarden die relevant zijn voor het beantwoorden van deze specifieke uitgangsvraag zijn genoemd bij de overwegingen. Meer algemene, overkoepelende, of bijkomende aspecten van de organisatie van zorg worden behandeld in de module Organisatie van zorg.
Commentaar- en autorisatiefase
De conceptrichtlijnmodule werd aan de betrokken (wetenschappelijke) verenigingen en (patiënt) organisaties voorgelegd ter commentaar. De commentaren werden verzameld en besproken met de werkgroep. Naar aanleiding van de commentaren werd de conceptrichtlijnmodule aangepast en definitief vastgesteld door de werkgroep. De definitieve richtlijnmodule werd aan de NVKNO, NVA, NVK en Apneuvereniging voorgelegd voor autorisatie en door hen geautoriseerd dan wel geaccordeerd.
Literatuur
Agoritsas T, Merglen A, Heen AF, Kristiansen A, Neumann I, Brito JP, Brignardello-Petersen R, Alexander PE, Rind DM, Vandvik PO, Guyatt GH. UpToDate adherence to GRADE criteria for strong recommendations: an analytical survey. BMJ Open. 2017 Nov 16;7(11):e018593. doi: 10.1136/bmjopen-2017-018593. PubMed PMID: 29150475; PubMed Central PMCID: PMC5701989.
Alonso-Coello P, Schünemann HJ, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Rada G, Rosenbaum S, Morelli A, Guyatt GH, Oxman AD; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. BMJ. 2016 Jun 28;353:i2016. doi: 10.1136/bmj.i2016. PubMed PMID: 27353417.
Alonso-Coello P, Oxman AD, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Vandvik PO, Meerpohl J, Guyatt GH, Schünemann HJ; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines. BMJ. 2016 Jun 30;353:i2089. doi: 10.1136/bmj.i2089. PubMed PMID: 27365494.
Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, Fervers B, Graham ID, Grimshaw J, Hanna SE, Littlejohns P, Makarski J, Zitzelsberger L; AGREE Next Steps Consortium. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010 Dec 14;182(18):E839-42. doi: 10.1503/cmaj.090449. Epub 2010 Jul 5. Review. PubMed PMID: 20603348; PubMed Central PMCID: PMC3001530.
Hultcrantz M, Rind D, Akl EA, Treweek S, Mustafa RA, Iorio A, Alper BS, Meerpohl JJ, Murad MH, Ansari MT, Katikireddi SV, Östlund P, Tranæus S, Christensen R, Gartlehner G, Brozek J, Izcovich A, Schünemann H, Guyatt G. The GRADE Working Group clarifies the construct of certainty of evidence. J Clin Epidemiol. 2017 Jul;87:4-13. doi: 10.1016/j.jclinepi.2017.05.006. Epub 2017 May 18. PubMed PMID: 28529184; PubMed Central PMCID: PMC6542664.
Medisch Specialistische Richtlijnen 2.0 (2012). Adviescommissie Richtlijnen van de Raad Kwalitieit. http://richtlijnendatabase.nl/over_deze_site/over_richtlijnontwikkeling.html
Neumann I, Santesso N, Akl EA, Rind DM, Vandvik PO, Alonso-Coello P, Agoritsas T, Mustafa RA, Alexander PE, Schünemann H, Guyatt GH. A guide for health professionals to interpret and use recommendations in guidelines developed with the GRADE approach. J Clin Epidemiol. 2016 Apr;72:45-55. doi: 10.1016/j.jclinepi.2015.11.017. Epub 2016 Jan 6. Review. PubMed PMID: 26772609.
Schünemann H, Brożek J, Guyatt G, et al. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from http://gdt.guidelinedevelopment.org/central_prod/_design/client/handbook/handbook.html.
Zoekverantwoording
Zoekacties zijn opvraagbaar. Neem hiervoor contact op met de Richtlijnendatabase.