Tonsillectomy or adenotonsillectomy versus non-surgical management for sleep-disordered breathing in children

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the effectiveness and safety of tonsillectomy with or without adenoidectomy (also called (adeno)tonsillectomy) compared to non-surgical management for SDB in children.

Background

Description of the condition

Sleep-disordered breathing (SDB) is a spectrum of disease that affects both children and adults and ranges in severity from primary snoring to obstructive sleep apnoea syndrome (OSAS). Primary snoring, the mildest expression of SDB, is not associated with arousal from sleep or episodes characterised by below normal levels of oxygen saturation in arterial blood. In contrast, OSAS, the most severe expression of SDB, involves repeated episodes of restricted breathing (hypopnoea) or complete obstruction (apnoea), or both, with reduction in the normal levels of oxygen saturation in arterial blood and arousal during sleep (Nespoli 2013).

SDB is a common condition in the paediatric population, with an estimated prevalence of primary snoring and OSAS in children ranging from 8% to 27% and 1% to 5%, respectively (Marcus 2012; Shine 2005). Obesity is a well-established risk factor for SDB (Shelton 1993; Shine 2005). Since childhood obesity rates are rising in many Western countries, the prevalence of SDB is expected to increase in the coming years.

In children, hypertrophy of the tonsils and adenoid tissue is thought to be the most important cause of SDB; it causes narrowing of the airway, which is a particular problem during sleep when the muscles of the pharynx relax, leading to partial or complete obstruction of the airway (Marcus 2005).

An overnight sleep study (polysomnography) is considered the most comprehensive investigation for diagnosing OSAS (Marcus 2012). In many countries, however, this test is not routinely performed in children with a suspected diagnosis of OSAS because of its high cost, labour-intensive nature and limited availability (Marcus 2012). Therefore, in everyday practice the severity of SDB is usually assessed with a clinical history and examination, with or without overnight pulse oximetry (Brietzke 2004).

SDB has a considerable impact on children's quality of life, comparable to that of juvenile rheumatoid arthritis (Baldassari 2008), and has been linked with behavioural and neurocognitive morbidities (Beebe 2006; Owens 2009; Tauman 2011). Cognitive assessments show that children with SDB score six points lower on average compared to those without SDB on the Wechsler Preschool and Primary Scale Intelligence IQ test (Gottlieb 2004). This difference persists when only children with symptoms of SDB, rather than polysomnogram-diagnosed OSAS, are analysed. Children with SDB have also been shown to be more likely to suffer from behavioural problems, such as hyperactivity, emotional lability and aggression, than children without SDB (Rosen 2004). Furthermore, children with untreated OSAS, the most severe form of SDB, are at risk of severe health problems, including failure to thrive and cardiovascular diseases such as hypertension, cor pulmonale and left ventricular hypertrophy (Marcus 2001).

Description of the intervention

Intervention

Surgical removal of the tonsils with or without removal of the adenoids, called (adeno)tonsillectomy, is a common surgical procedure in children (Erickson 2009). In tonsillectomy the palatine tonsils are removed from their investing tissue in the oropharynx; it can be performed by blunt dissection, guillotine, bipolar electrocautery, laser, microdebrider or coblation according to the surgeon's preference. Adenoidectomy involves the removal of the adenoid (pharyngeal tonsil) from the nasopharynx; common techniques include curettage or suction cautery. The operation involves a general anaesthetic and can be performed as a day case or with an overnight stay (Cooper 2013; Lalakea 1999; Marcus 2012). Certain children undergoing surgery for SDB are at increased risk of peri- and postoperative respiratory compromise (Baugh 2011; Lipton 2003; Robb 2009; Schwengel 2009). Guidelines from the American Academy of Pediatrics (Marcus 2012) and the UK Royal College of Paediatrics and Child Health (Royal College of Paediatrics and Child Health 2009) recommend overnight observation for high-risk cases, such as young children (below four years of age), those with certain comorbidities (cardiac and/or craniofacial abnormalities, neuromuscular disorders) or in children with severe OSAS (e.g. an oxygen saturation level in arterial blood of 80% or lower or an Apnoea/Hypopnoea Index (AHI) greater than 24).

Throat pain and reduced oral intake are common following (adeno)tonsillectomy, with over 50% of children still experiencing pain three days after the operation despite analgesia. Vomiting and nausea occur less frequently, with one in 10 children reporting vomiting several days postoperatively (Stanko 2013). The most common complication is postoperative bleeding, which may occur in up to 5% of children (Baugh 2011). Over the past decade there has been increasing interest in partial removal of the tonsils, known as tonsillotomy, which may be associated with lower postoperative morbidity and fewer complications than complete removal of the tonsils (tonsillectomy). Several randomised controlled trials (RCTs) have compared tonsillectomy and tonsillotomy for SDB in children (Walton 2012), but this comparison will be addressed in a separate Cochrane review.

Comparator

We will include all types of non-surgical management of SDB that are commonly used in daily clinical practice.

  • Lifestyle interventions: dietary advice, exercise programmes.

  • Medical management: intranasal and oral corticosteroids, leukotriene receptor antagonists.

  • Mechanical interventions: continuous positive airway pressure (CPAP).

  • Watchful waiting: observation and monitoring.

Recent evidence has suggested that children with OSAS have raised local and systemic inflammatory markers, which causes proliferation of lymphoid tissue within the tonsils and adenoids (Kim 2009). Intranasal and systemic corticosteroids aim to increase airway patency by reducing the inflammatory response occurring in the oropharynx. Leukotriene levels have also been shown to be higher in the adenotonsillar tissue of children with OSAS compared to those with tonsillitis (Goldbart 2004). This is why the use of leukotriene receptor antagonists such as montelukast has been suggested to have beneficial effects in children with SDB (Friedman 2011). Other non-surgical management options for SDB involve non-invasive ventilatory support (e.g. CPAP) and reducing the effort of breathing with weight loss regimes.

How the intervention might work

In children, hypertrophy of the tonsils and adenoid tissue is thought to be the most important cause of SDB. Therefore, removal of the adenoid and tonsils, i.e. adenotonsillectomy, is widely considered an effective treatment for SDB in children. Non-randomised and uncontrolled studies have shown improvements in objective and subjective measures of sleep, behaviour, cognition and quality of life (Garetz 2008). A 2009 systematic review, however, showed that (adeno)tonsillectomy may not be curative, with only two out of three children achieving complete polysomnographic resolution (Friedman 2009).

Why it is important to do this review

There is convincing evidence of an association between childhood SDB and adverse health outcomes. Consequently, the identification and implementation of an effective treatment for this common condition in children should prevent those outcomes and improve health. With (adeno)tonsillectomy offering significant improvements in sleep as measured by subjective measures (e.g. parental reporting) and objective measures such as polysomnography, the operation is nowadays considered a valuable first-line treatment for SDB in children. However, the potential benefits of (adeno)tonsillectomy in children, a surgical procedure performed under a general anaesthetic, should be carefully balanced against the risks, including the risk of adverse events. We aim to systematically review the clinical effectiveness and safety of (adeno)tonsillectomy compared to non-surgical management for SDB in children.

Objectives

To assess the effectiveness and safety of tonsillectomy with or without adenoidectomy (also called (adeno)tonsillectomy) compared to non-surgical management for SDB in children.

Methods

Criteria for considering studies for this review

Types of studies

Randomised controlled trials (RCTs) assessing the effectiveness of (adeno)tonsillectomy versus non-surgical management for SDB in children.

Types of participants

Children up to the age of 16 years with SDB. We will include RCTs in which the diagnosis of SDB is based upon polysomnography, pulse oximetry or a clinical history and examination. We will exclude RCTs that include children with central SDB (e.g. SDB related to neurological conditions or brain injury).

Types of interventions

Intervention

Tonsillectomy with or without adenoidectomy, i.e. (adeno)tonsillectomy, irrespective of the surgical technique used.

Comparator

Non-surgical management. We will include all types of non-surgical management of SDB such as lifestyle interventions, including those aimed at weight reduction, medical treatments such as intranasal and oral corticosteroids, mechanical interventions, including continuous positive airway pressure (CPAP), and no treatment (watchful waiting).

Types of outcome measures

We will analyse the primary and secondary outcomes listed below in this review, but they will not be used as a basis for including or excluding studies.

Primary outcomes
  1. Disease-specific quality of life (using any validated instrument, such as Obstructive Sleep Apnoea 18 (OSA-18) or Obstructive Sleep Disorders 6-survey (OSD-6) - see the Spruyt 2011 review for a comprehensive list) and/or a disease-specific symptom score (using any validated instrument, such as the Paediatric Sleep Questionnaire - see the Spruyt 2011 review for a comprehensive list).

  2. Adverse events and complications of treatment and comparators. Measures of morbidity include complications of surgery, such as haemorrhage and number of days with postoperative pain, and adverse events and morbidity related to non-surgical treatment.

Secondary outcomes
  1. Generic quality of life (using any validated instrument - see the Hullmann 2011 review for comprehensive list).

  2. Respiratory events during sleep as measured by the Apnoea/Hypopnoea Index (AHI) using polysomnography.

  3. Other measures of respiratory events during sleep (e.g. respiratory disturbance index (RDI), oxygen desaturations, respiratory event-related arousals).

  4. Cardiovascular disease, including hypertension, right and left ventricular dysfunction, pulmonary hypertension.

  5. Neurocognitive performance (using a validated instrument).

  6. Attention (using a validated instrument).

  7. Behaviour (using a validated instrument).

  8. School performance.

  9. Absence from school.

  10. Weight changes.

Search methods for identification of studies

We will conduct systematic searches for randomised controlled trials and controlled clinical trials. There will be no language, publication year or publication status restrictions. We will contact original authors for clarification and further data if trial reports are unclear and we will arrange translations of papers where necessary.

Electronic searches

We will identify published, unpublished and ongoing studies by searching the following databases from their inception: the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL, current issue); Ovid MEDLINE; Ovid MEDLINE In-Process & Other Non-Indexed Citations; PubMed (as a top up to searches in Ovid MEDLINE); EMBASE; CINAHL; LILACS; KoreaMed; IndMed; PakMediNet; CAB Abstracts; Web of Science; ISRCTN; ClinicalTrials.gov; ICTRP, Google Scholar and Google.

We will model subject strategies for databases on the search strategy designed for CENTRAL (Appendix 1). Where appropriate, we will combine subject strategies with adaptations of the highly sensitive search strategy designed by The Cochrane Collaboration for identifying randomised controlled trials and controlled clinical trials (as described in theCochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, Box 6.4.b. (Handbook 2011)).

Searching other resources

We will scan the reference lists of identified publications for additional trials and contact trial authors if necessary. In addition, we will search PubMed, TRIPdatabase, The Cochrane Library and Google to retrieve existing systematic reviews relevant to this systematic review, so that we can scan their reference lists for additional trials. We will search for conference abstracts using the Cochrane Ear, Nose and Throat Disorders Group Trials Register and EMBASE.

Data collection and analysis

Selection of studies

Two review authors will independently screen titles and abstracts obtained from the database searches and citations of relevant systematic review articles to assess their potential relevance for full review. Similarly, two review authors will independently review the full text of potentially relevant titles and abstracts against the inclusion and exclusion criteria. We will resolve disagreements by discussion with a third review author.

Data extraction and management

Three review authors will independently extract data from the included studies using standardised forms. We will extract the following information from each study:

  1. Characteristics of trials: setting, design, method of data-analysis.

  2. Participants: study population, number of participants in each group, patient characteristics, such as age, gender, ethnicity, body mass index (BMI).

  3. Interventions: type of surgical procedure, including pre-operative and postoperative treatment, type of non-surgical management.

  4. Outcomes: primary and secondary outcomes recorded, time points, treatment failure, recurrence rate, adverse events related to the intervention.

In case of missing information we will contact the trial authors.

Assessment of risk of bias in included studies

Three review authors will independently assess the methodological quality of the included trials. We will resolve any disagreements by discussion. We will perform 'Risk of bias' assessment using the 'Risk of bias' tool as described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Handbook 2011). We will judge the following domains as high, low or unclear risk of bias:

  • sequence generation (selection bias);

  • allocation concealment (selection bias);

  • blinding of participants and personnel (performance bias);

  • blinding of outcome assessment (detection bias);

  • incomplete outcome data (attrition bias);

  • selective outcome reporting (reporting bias); and

  • other sources of bias.

We will present the results of the 'Risk of bias' assessment in a graph and summary figure.

Measures of treatment effect

We will express dichotomous outcomes as risk ratios (RR), absolute risk differences (ARD) and number needed to treat to benefit (NNTB) with accompanying 95% confidence intervals (CI). We will express continuous outcome variables either as mean differences (MD) if reported on the same scale or as standardised mean differences (SMD) if different continuous scales have been used, with accompanying 95% CIs.

Unit of analysis issues

In case of cluster-randomised trials, we will use analysis techniques which take into account the effect of clustering as described in Chapter 16 of the Cochrane Handbook for Systematic Reviews of Interventions (Handbook 2011). If multiple observations at different time points have been made for the same outcome, we will only incorporate data at the most relevant time points.

Dealing with missing data

We will contact trial authors in order to provide additional information in case of missing data.

In primary analyses, we will only analyse the available data based on the intention-to-treat (ITT) principle. We will assess the impact of incomplete data reporting by performing scenario analyses (best and worst-case scenario). In a best-case scenario analysis we will count all participants who were lost to follow-up in the surgical group as treatment successes and all participants lost to follow-up in the control (non-surgical) group as treatment failures. In contrast, in a worst-case scenario analysis we will count all participants who were lost to follow-up in the surgical group as treatment failures and all participants lost to follow-up in the control group as treatment successes.

Assessment of heterogeneity

First, we will assess the level of clinical diversity between trials by reviewing the potential differences in the types of participants recruited, interventions used and outcomes measured. Next, we will assess statistical heterogeneity for each outcome using the Chi2 test, with a significance level set at P < 0.10, and the I2 statistic, with I2 values over 50% suggesting substantial heterogeneity (Higgins 2003).

Assessment of reporting biases

For each study, we will search the internet and ClinicalTrials.gov (http://clinicaltrials.gov/) for available study protocols to determine whether all a priori defined outcomes have been reported in the publications. Furthermore, we plan to assess reporting biases using funnel plots.

Data synthesis

We propose to analyse the data according to the ITT principle, i.e. we will analyse all participants in the group to which they were originally allocated.

In the absence of significant clinical diversity we will consider a meta-analysis. We will use a fixed-effect meta-analysis where no heterogeneity is present. If statistical heterogeneity is detected but unresolved by subgroup analysis, then we will use a random-effects (DerSimonian and Laird) model to provide a more conservative estimate of the effect. If we decide to refrain from pooling the trial results because of clinical diversity, we will report the effect estimates as presented by the individual trials.

Subgroup analysis and investigation of heterogeneity

If possible, we will perform subgroup analyses planned a priori for the following characteristics:

  1. SDB severity (OSAS versus less severe SDB);

  2. body weight (obese versus non-obese children);

  3. age (younger than three, three to seven and above seven years).

Sensitivity analysis

To assess the robustness of the review findings we will perform a sensitivity analysis in which only RCTs classified as having a low risk of bias are included. In further sensitivity analyses, we plan to assess whether variations in the following characteristics affect the outcome:

  • SDB definition (clinical diagnosis alone or SDB diagnosis based on respiratory events during sleep as measured by polysomnography);

  • type of surgery (tonsillectomy with or without adenoidectomy);

  • type of non-surgical management (lifestyle intervention, corticosteroid or leukotriene receptor antagonist treatment, CPAP, no treatment or watchful waiting).

Appendices

Appendix 1. CENTRAL search strategy

#1 MeSH descriptor: [Sleep Apnea Syndromes] this term only
#2 MeSH descriptor: [Sleep Apnea, Obstructive] explode all trees
#3 MeSH descriptor: [Snoring] explode all trees
#4 sleep* and (apnea* or hypopnea* or apneahypopnea* or apnoea* or hypopnoea* or apnoeic)
#5 sleep* near/3 disorder* near/3 breath*
#6 OSA or OSAS or OSAHS or SBD or SRBD or OSDB or SAHS
#7 (hypertroph* or hyperplasia or obstructive) near (tonsil* or adenoid* or adenotonsil*)
#8 snoring
#9 (nighttime or sleep* or "night time") and (((breath* or airway*) near (obstruct* or restric*)) or (mouth near/3 breath*))
#10 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9
#11 MeSH descriptor: [Tonsillectomy] explode all trees
#12 MeSH descriptor: [Palatine Tonsil] explode all trees and with qualifier(s): [Surgery - SU]
#13 MeSH descriptor: [Adenoidectomy] explode all trees
#14 MeSH descriptor: [Adenoids] explode all trees and with qualifier(s): [Surgery - SU]
#15 tonsillectom* or tonsilectom* or adenotonsillectom* or adenoidectom*
#16 MeSH descriptor: [Palatine Tonsil] explode all trees
#17 MeSH descriptor: [Adenoids] explode all trees
#18 tonsil* or adenotonsil* or adenoid*
#19 #16 or #17 or #18
#20 MeSH descriptor: [Surgical Procedures, Operative] explode all trees
#21 surg* or laser* or extract* or resect* or excis* or operat* or dissect* or remov* or coblat* or ablat*
#22 #20 or #21
#23 #19 and #22
#24 #11 or #12 or #13 or #14 or #15 or #23
#25 #10 and #24

Contributions of authors

Protocol drafted by: RPV, BJH, DC, AGMS
Screening search results: BJH, DC, RPV
Extracting data: BJH, DC, RPV
Assessing risk of bias: BJH, DC, RPV
Entering data into RevMan: BJH, DC, RPV
Carrying out analysis: BJH, DC, RPV
Interpreting the analysis: BJH, DC, RPV, HB, AGMS
Writing the review: all authors
General advice on the review: all authors

Declarations of interest

AGMS is joint Co-ordinating Editor of the Cochrane Ear, Nose and Throat Disorders Group.
BJH, DC, JL, RPV and HB declare no conflicts of interests in the current work.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • National Institute for Health Research (NIHR), UK.

    Professor Anne Schilder's team is supported by a NIHR Research Professorship Award

Notes

Split from 'Adenotonsillectomy for obstructive sleep apnoea in children' (to be withdrawn on completion of this review).

Ancillary