adenotonsillectomy complications: a meta-analysis · analysis, and manuscript preparation; drs...

Adenotonsillectomy Complications:A Meta-analysisGraziela De Luca Canto, DDS, MsC, PhDa,b, Camila Pachêco-Pereira, DDSb, Secil Aydinoz, MDc, Rakesh Bhattacharjee, MDd,Hui-Leng Tan, MBBSe, Leila Kheirandish-Gozal, MD, MScd, Carlos Flores-Mir, DDSC, MSc, DSc, RCDC(C)b, David Gozal, MD, MBA, FAAPd

abstract BACKGROUND AND OBJECTIVE: Complications after adenotonsillectomy (AT) in children have beenextensively studied, but differences between children with and without obstructive sleepapnea (OSA) have not been systematically reported. Our objective was to identify the mostfrequent complications after AT, and evaluate if differences between children with andwithout OSA exist.

METHODS: Several electronic databases were searched. A partial gray literature search wasundertaken by using Google Scholar. Experts were consulted to identify any missingpublications. Studies assessing complications after AT in otherwise healthy children wereincluded. One author collected the required information from the selected articles. A secondauthor crosschecked the collected information and confirmed its accuracy. Most of the selectedstudies collected information from medical charts.

RESULTS:A total of 1254 studies were initially identified. Only 23 articles remained after a 2-stepselection process. The most frequent complication was respiratory compromise (9.4%),followed by secondary hemorrhage (2.6%). Four studies compared postoperativecomplications in children with and without OSA, and revealed that children with OSA havenearly 5 times more respiratory complications after AT than children without OSA (odds ratio= 4.90; 95% confidence interval: 2.38–10.10). In contrast, children with OSA are less likely tohave postoperative bleeding when compared with children without OSA (odds ratio = 0.41;95% confidence interval: 0.23–0.74).

CONCLUSIONS: The most frequent early complications after AT are respiratory compromise andsecondary hemorrhage. Based on the current limited evidence, children with OSA appear tohave more respiratory complications. Conversely, hemorrhage appears to be more frequent inchildren without OSA.

aDepartment of Dentistry, Federal University of Santa Catarina, Florianopolis, Santa Catarina, Brazil; bSchool of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Alberta,Canada; cGulhane Military Medical Academy, Istanbul, Turkey; dDivision of Biological Sciences, Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Chicago, Illinois;and eRoyal Brompton Hospital, Imperial College, London, United Kingdom

Dr De Luca Canto worked on study conceptualization, design, data collection, data analysis, drafted the initial manuscript, and critically reviewed the manuscript;Dr Pachêco-Pereira worked on study conceptualization, design, data collection, data analysis, and manuscript preparation; Dr Aydinoz worked on data collection, dataanalysis, and manuscript preparation; Drs Bhattacharjee, Tan, and Kheirandish-Gozal worked on data analysis and manuscript preparation; Drs Flores-Mir and Gozalworked on study conceptualization, design, data analysis, and critically reviewed the manuscript; and all authors approved the final manuscript as submitted.

www.pediatrics.org/cgi/doi/10.1542/peds.2015-1283

DOI: 10.1542/peds.2015-1283

Accepted for publication Jul 7, 2015

Address correspondence to David Gozal, MD, FAAP, Department of Pediatrics, University of Chicago, 5721 S. Maryland Ave, MC 8000, Suite K-160, Chicago, IL 60637. E-mail:[email protected]

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2015 by the American Academy of Pediatrics

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Obstructive sleep apnea (OSA) iswidely recognized as a potential causeof significant morbidity in children.1,2

OSA symptoms include habitualsnoring and reporting of disturbedunrefreshing sleep, frequentlyaccompanied by excessive daytimesleepiness, and daytimeneurobehavioral and moodproblems.3 The prevalence of OSA ismarkedly variable during childhood(1%–5%), with age, gender, andethnicity as major contributors.2,4–6

However, independently of the lowestor the highest reported prevalence,OSA is a relatively frequent conditionthat imposes a high degree of diseaseburden, thereby requiring timelydiagnosis and effective treatment.

The first-line treatment of pediatricOSA is provided through eithermedical or surgical procedures on thebasis of the underlying severity of thecondition as defined by overnightpolysomnography (PSG).3 Medicaltreatments in mild cases may includeweight loss management inoverweight children, intranasalsteroids, leukotriene modifiers, andoral or topical descongestants.3

However, in the majority of cases,adenoidectomy and tonsillectomy(AT) remains the most commonsurgical procedure performed forOSA in children,7 with more than530 000 of these procedures beingperformed annually in the UnitedStates alone.8 Similarly, AT istraditionally performed in casesfulfilling the criteria of recurrenttonsillitis, which in the pastaccounted for the majority of ATsurgeries, before being surpassed byOSA indications.9 As with mostsurgical procedures, AT involvespotential intraoperative risks andpostoperative complications. Amongthe latter, minor complicationsinclude pain, nausea, vomiting, anddehydration.10 However, moreserious complications may occur, suchas hemorrhage, respiratorydecompensation, velopharyngealincompetence, subglottic stenosis,and rarely death.11

Some authors12–16 have suggestedthat differences in the frequency ofthese complications could be presentafter AT in children with OSA andchildren without OSA. Because thesecomplications can have a significantimpact on the burden of care, thepurpose of this systematic reviewwas (1) to identify the most frequentpostoperative complication duringthe first 3 weeks after AT, and (2) tocritically evaluate the differencescomparing children with OSA andchildren without OSA. These findingsshould help in making physiciansaware of potential complications afterthis type of surgical procedures inspecific target populations.

METHODS

This systematic review was doneadhering to the Preferred ReportingItems for Systematic Reviews andMeta-Analyses checklist.17

Diagnostic Terminology

All terms that indicated OSA,1

including sleep disordered breathing(SDB), sleep-related breathingdisorder, and OSA syndrome, were allconsidered synonymous of OSA forthis submission.

Protocol and Registration

The systematic review protocol wasregistered at the InternationalProspective Register of SystematicReviews18 under numberCRD42015016102.

Study Design

A systematic review that evaluated(within 3 weeks) postoperativecomplications after AT in childrenwith OSA and children without OSAaimed at answering 2 specificquestions:

1. What are the most frequent im-mediate postoperative complica-tions after AT?

2. Do children with OSA and childrenwithout OSA differ in the fre-quency of immediate post-operative complications after AT?

Eligibility Criteria

Inclusion Criteria

• Clinical studies that evaluated(within 3 weeks) postoperativecomplications after AT in childrenwith OSA and children without OSA(0–18 years old).

• No language restriction was set.Complications were defined as anydeviation from the usualpostoperative recovery course thatrequired intervention. All reportedcomplications were reviewed todetermine type, occurrence time, andneed for an extended hospital stayand/or intensive care unit (ICU)monitoring.19

Exclusion Criteria

The studies were excluded in 2phases.

In phase 1 (titles and abstracts) thefollowing exclusion criteria wereapplied:

1. Studies that targeted a differentcondition.

2. Studies in adults.

3. Reviews, letters, conferenceabstracts, editorials, case-seriesstudies.

4. Studies in which the cohort sampleincluded subjects previously di-agnosed with genetic syndromicpatients (eg, Down syndrome,craniofacial anomalies, neuromus-cular disorders, chromosomal ab-normality, etc), coagulationdisorders, or cerebral palsy.

In phase 2 (full-text) these additionalexclusion criteria were applied:

5. Studies that did not reveal com-plications during the first 3 weeksof follow-up.

Information Sources

Detailed individual search strategiesfor each of the following bibliographicdatabases were developed: Cochrane,Embase, Medline, PubMed, Web ofScience, and Literatura Latino-americana e do Caribe em Ciências daSaúde. A partial gray literature search

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was taken by using Google Scholar.The end search date was January 3,2015, across all databases. Thereferences cited in the selectedarticles were also checked for anyadditional references that could havebeen inadvertently omitted duringthe electronic database searches. Inaddition, experts in the field of sleep,otolaryngology, and/or respiratorymedicine were approached to identifyany missing important publication.

Experts were identified based on themain reference list, such that authorswho had (as a first/senior author). 6publications in this main searchwere contacted, and were asked toidentify the 10 most importantpublications regarding ATpostoperative complications.

Search

Appropriate truncation and wordcombinations were selected and

adapted for each database search(Supplemental Table 4). Allreferences were managed byreference manager software(RefWorks-COS, ProQuest, Bethesda,MD) and duplicate hits wereremoved.

Study Selection

The selection was completed in 2phases. In phase 1, 2 reviewers (DrsDe Luca Canto and Pachêco-Pereira)

FIGURE 1Flow diagram of literature search and selection criteria. Adapted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.17

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independently reviewed the titles andabstracts of all identified electronicdatabase citations. A third author (DrAydinoz) read all abstracts selected toreach the final decision. This wasimportant when disagreementsemerged between the 2 initialevaluators. Any studies that did notfulfill the inclusion criteria werediscarded.

In phase 2, the same 2 reviewers (DrsDe Luca Canto and Pachêco-Pereira)independently participated in phase2. The reference lists of all includedarticles were critically assessed by 1examiner (Dr De Luca Canto).Selected studies were read by bothexaminers (Drs De Luca Canto andPachêco-Pereira). Any disagreementin either phase was resolved bydiscussion and mutual agreementbetween the 3 reviewers (Drs DeLuca Canto, Pachêco-Pereira, andAydinoz).

A fourth author (Dr Gozal) wasinvolved when controversy arose inthe process of reaching a finaldecision either in phase 1 or 2. Finalselection was always on the basis ofthe full-text of the publication.

Data Collection Process

One author (Dr De Luca Canto)collected the required informationfrom the selected articles. A secondauthor (Dr Pachêco-Pereira)crosschecked all the collectedinformation and confirmed itsaccuracy. Again, any disagreement ineither phase was resolved bydiscussion and mutual agreementbetween the 3 reviewers (Drs DeLuca Canto, Pachêco-Pereira, andAydinoz). The fourth author wasinvolved as required, to enableformulation of the final decision(Dr Gozal).

Data Items

The following information wasrecorded: author(s), year ofpublication, country, study design,recruitment method, follow-uplength, sample size, participant’s age,

complication type, surgery type,results, and main conclusion. If therequired data were not complete,attempts were made to contact theauthors to retrieve the missinginformation.

Risk of Bias in Individual Studies

The methodology of selected studieswas evaluated by using the Meta-Analysis of Statistics Assessment andReview Instrument.20 Two reviewers(Drs De Luca Canto and Pachêco-Pereira) scored each item with “yes,”“no,” “unclear,” or “not applicable,”and assessed independently thequality of each included study.Disagreements between bothreviewers were resolved by a thirdreviewer (Dr Aydinoz).

Summary Measures

Early (within 3 weeks) postoperativecomplications after AT wereconsidered as the main outcome. Anytype of outcome measurement wasconsidered (categorical andcontinuous variables).

Synthesis of Results

Studies that revealed postoperativeprevalence but did not directlycompare OSA and non-OSA groupswere analyzed through a meta-analysis performed with MedCalc(MedCalc Software, Ostend, Belgium).Studies that directly comparedchildren with OSA and childrenwithout OSA were analyzed througha meta-analysis by using ReviewManager 5.2 (RevMan, The NordicCochrane Centre, Copenhagen,Denmark).

Risk of Bias Across Studies

We assessed the clinicalheterogeneity (by comparingvariability among the participant’scharacteristics, type of interventionsand outcomes studied),methodological heterogeneity (bycomparing the variability in studydesign and risk of bias), andstatistical heterogeneity (bycomparing variability in the

intervention effects in the differentincluded studies).

RESULTS

Study Selection

During the initial search (phase 1),1254 different citations wereidentified across the 6 electronicdatabases. Then, aftera comprehensive evaluation of theabstracts, only 92 articles weredeemed potentially relevant, andwere selected for phase 2 assessment.An additional 60 citations fromGoogle Scholar, and another 48citations from content experts werealso considered. Of these 108 articles(not initially included among thosefrom the electronic databases), only10 were deemed appropriate forphase 2 assessments. No additionalstudy that might have beeninadvertently missed by the searchprocedures was identified afterfurther reviewing the reference list ofthe 102 studies. From theseremaining studies, 79 weresubsequently excluded (SupplementalTable 5). Thus, only 23 studies wereretained for the final meta-analysisaimed at answering the first question.From these 23 studies, only 4 studiesdifferentiated between OSA and non-OSA groups, and were used in themeta-analysis aiming to answer thesecond question. All of these articleswere identified from the mainelectronic search. A flowchart of theprocess of identification, inclusion,and exclusion of studies is shown inFig 1.

Study Characteristics

The 23 studies that were retained toaddress question 1 revealed thefollowing postoperativecomplications: respiratorycomplications,12,13,16,19,21–33

hemorrhage,15,21,25,26,28,30,34–38

pain,27,28 nausea,27,34 vomiting,27,35

refuse to drink,35 inadequate oralintake,21 dehydratation,28,29,34

fever,24,29 dysphagia,28,34 and cardiaccomplications.35




TABLE1

Summaryof

DescriptiveCharacteristicsof

Included

Studiesto

Answ

erQuestion1(n

=23)

Source

Country

Sample

Results

AdditionalData

nCharacteristics

Overall,%a

Hemorrhage,%b

RespiratoryComplications,%

Other,%

Ahmad

etal

201025

Malaysia

267

OSAor

RTor

other(unclear

ifPSGwas

performed)

7.2

Primary:1.9

Extubationfailure:0.4

Infection:1.1

Increase

inrisk

with

every1min

increase

indurationof

surgery

Secondary:1.9

Other:1.9

Primaryhemorrhage(OR:

1.05;95%

CI:

1.01–1.09

min;P

=.020)

Respiratorycomplications

(OR:

1.08;

95%

CI:1.01–1.16

min;P

=.024)

Baguleyet

al201431

Australia

100

OSA(confirm

edby

PSG)

11.0

NALeftrecovery

with

oxygen

prescribed:

11.0

Major

complications:

zero

apnea/hypopneiaindex(AHI)

cutoffabovewhich

oxygen

supplementationwas

given(OR:

1.135;95%

CI:0.99–1.3;P=.07)

Brow

n200623

Canada

54OSA(confirm

edby

PSGor

cardiorespiratorysleep

studiesor

oximetry

oraw

akecapillary

carbon

dioxidetension)

61.1

NAOverall:61.1a(reintubation,ventilation,

and/or

administrationof

racemic

epinephrineor

salbutam

ol,oxygen

administration,reintubationin

the

recovery

room

forrespiratory

comprom

ise)

NARisk

factors:Associated

medical

condition

or8.15;95%

CI:1.81–36.73

Preoperativesaturationnadirless

than

80%

OR:5.54;95%

CI:1.15–26.72

Atropine

administrationat

induction

decreasedtherisk

ofpostoperative

respiratorycomplications

(OR:

0.18;

95%

CI:0.11–1.050)

Del-Rio

Camacho

etal

201416

Spain

229

OSA(confirm

edby

PSG)

andRT

3.5

Primary:1.3

2.2

NAOSAgroup(3.23%

)vs

non-OSAgroup

(1.47%

),presentedahigher

incidenceof

respiratory

complications

(not

statistically

significant,P

=.39)

Allrespiratorycomplications

took

placeintheimmediatepostoperative

period.

Hadden

etal

201127

UnitedStates

102

OSAandothers

(unclear

ifPSGwas

performed)

100

NARespiratoryevents:26.5a

Pain:66.7a

Nausea

andvomiting:6.9a

—

Hamadaet

al201537

Japan

147

OSA(confirm

edby

home-PSG)

7.4

Primary:5.4

NANA

ATcanbe

performed

withoutmajor

complications.

Lalakeaet

al199921

UnitedStates

134

OSA(unclear

ifPSGwas

performed)andRT

5.3

Primary:1.6

Zero

Vomiting

andor

inadequate

oral

intake:3.7

Thecomplicationrate

didnotvary

significantlywith

thedurationof

postoperativeobservation(P

=.71)

Maet

al32

China

86OSA(confirm

edby

PSG)

6.8

Zero

Postoperativedesaturation:6.8

NAChildrenwith

desaturationafter

tonsilletom

yandadenotonsillectom

yhadsignificant

higher

meanBM

Izscorethan

childrenwithout

desaturation(P

=.014)

Muninnobpam

asa

etal

201228

Thailand

481

OSA(unclear

ifPSGwas

performed),RT,

peritonsillar

abscess

andothers

91.3

Primary:4.1

Anesthetic(partialairw

ayobstruction

that

needed

airw

ayintervention):1.6

Dysphagia:29.0

Theaveragelength

ofhospitalstaywas

3.6dandreadmissions3.7%

.Secondary:3.9

Dehydration:

4.6

Pain:48.1


TABLE1

Continued

Source

Country

Sample

Results

AdditionalData

nCharacteristics

Overall,%a

Hemorrhage,%b


Other,%

Nixonet

al200522

Canada

10OSA(confirm

edby

PSG)

10.0

NAInterventionforrespiratory

comprom

ise:10

NA—

Onotai

andLilly-Tariah

201330

Nigeria

100

OSA(confirm

edby

PSG),R

T,andrecurrent

earinfection

9.0

Primary:4.0

2.0

Cardiac:1.0

Mortalitywas

recorded

in3%

because

ofsevere

respiratorydistress

and

cardiacarrest.

Secondary:2.0

Perkinset

al201215

UnitedStates

9023

OSA(confirm

edby

PSG),

chronictonsillitis,

andothers

2.3

Primary:0.5

NANA

Childrenwith

OSAwerehalfas

likelyto

hemorrhagecomparedwith

chronic

tonsillitispatients(P

=.04)

Secondary:1.8

Rakoveret

al199735

Israel

363

OSA(unclear

ifPSGwas

performed),RT,

andothers

9.9

Primary:3.9

NANA

Threewas

noincrease

intherate

ofpostoperativehemorrhageandof

readmissionsam

ongthechildren

discharged

from

thehospitalafter

theoperation,

comparedwith

those

hospitalized.There

was

nocorrelationbetweentype

ofprocedure:tonsillectomyor

ATand

postoperativecomplications.

Secondary:1.9

Riaz

etal

200913

SaudiArabia

60OSA(confirm

edby

PSG)

andRT

50.0

NADesaturation,95%,cough,stridor,

laryngospasm

:41.7

Nausea

and

vomiting:8.3

Thecomplications

atextubation

(cough,laryngospasm,postoperative

nausea,and

vomiting)werehigher

inOSAgroup,butnotstatistically

significant;P

..05).

Atthetim

eof

extubation,

desaturation

was

significantlyhigher

inOSA

group(43.3%

vs6.6%

,P=.002,

OR=10.70).

Morepatientsof

OSAgrouprequired

oxygen

(63.3%

vs10%,P

,.001,

OR=15.54).

Sixchildrenfrom

OSAgrouprequired

insertionof

anoropharyngeal

airw

ay.N

ochild

from

thenon-OSA

grouprequired

it(P

=.023).

Ruboyianes

199619

UnitedStates

44OSA(confirm

edby

PSG)

32.0

Zero

Interm

ittentobstruction:2.3

NAFactorsassociated

with

developm

entof

complications

included

age,

3(P

=.10),thinbody

habitus

(P=.027),andacuteairw

ayobstruction(P

,.001).

Upperairw

ayobstruction,pulmonary

edem

a:4.5

Upperairw

ayobstruction,pneumonia:

2.3

Stridor,atelectasis:2.3

Upperairw

ayedem

a:4.5

Laryngospasm

:4.5

Transientupperairw

ayobstruction:2.3

Centralapnea:2.3

Viralbronchitis:2.3


TABLE1

Continued

Source

Country

Sample

Results

AdditionalData

nCharacteristics

Overall,%a

Hemorrhage,%b


Other,%

Sanderset

al200612

Mexico

82OSA(confirm

edby

PSG)

andRT

78.0

NAMedical

intervention(the

need

fororal

airw

ay,oxygento

keep

O 2saturations

.92%,assisted

ventilationandreintubationin

recovery:22.0

Pain:56.0

OSAgrouphadmorerespiratory

complications

than

non-OSA

(5.7vs

2.9,P=.0001).

Shakeelet

al201238

United

Kingdom

106

OSA(unclear

ifPSGwas

performed)andRT

7.6

Primary:0.9

NANA

Secondaryhemorrhageversus:

Secondary:6.7

IndicationforsurgeryOSAversus

recurrenttonsillitis(OR:

0.180;

95%

CI:0.02–1.82)

Obstructivesymptom

sto

recurrent

tonsillitis(OR:

1.004;95%

CI:

0.09–11.03)

Shottet

al198734

UnitedStates

421

OSA(confirm

edby

PSG)

3.8

Secondary:2.1

NANausea

and

vomiting:0.5

—

Dehydration:

0.7

Dysphagia:0.5

SpencerandJones

201229

UnitedStates

86OSA(unclear

ifPSGwas

performed),RT,and

chronictonsillitis

7.0

NAReactiveairw

aydisease:1.2

Dehydration:

4.7

—

Fever:1.2

Vlastoset

al201026

Greece

910

OSA(unclear

ifPSGwas

performed)

2.8

Primary:1.4

1.1

0.3

—

Wanget

al200924

China

82OSA(confirm

edby

PSG)

21.5

Zero

Airw

ayedem

awith

increasedsnoring,

mouth

breathing,andapneas

inthe

firstnight:17.1;requiredCPAP

inthe

first3d:3.7

Fever:0.7

Wonget

al200736

China

329

OSA(unclear

ifPSGwas

performed)andRT

2.4

Secondary:2.4

NAMortalityzero

—

Yeet

al200933

China

321

OSA(confirm

edby

PSG)

11.2

Zero

Overall:11.2(requiredan

oropharyngealor

nasopharyngeal

airw

ay,had

multipleepisodes

ofdesaturation,andotherrespiratory

complications)

NA—

CPAP,continuous

positiveairw

aypressure;N

A,notapplicable,w

hentheitem

was

notevaluatedby

thestudy;RT,recurrent

tonsillitis.

aData

werecalculated

byauthors.

bWeconsidered

primaryhemorrhagewhenitoccurs

inthefirst24

h,andsecondaryhemorrhagewhenitoccurs

after24

h.


TABLE2

Summaryof

DescriptiveCharacteristicsof

Included

Studiesto

Answ

erQuestion2(n

=4)

Source

Country

Placeof

Recruitm

ent

FollowUp

OSA,n

Non-OSAWith

Tonsillitis,n

MeanAge

orRange

SurgeryProcedure/

ComplicationAssessment

Location

Results

MainConclusion

Del-Rio

Camacho

etal

201416

Spain

Hospitalpediatric

department

Once

thesurgery

was

finished

93136

4.97

ATby

curettageand

tonsillectomyby

dissection

Hemorrhage:1.3%

Childrenwho

undergoAT

and

have

animmediate

postoperativeperiod

without

complications

donotn

eedto

beadmitted

toan

ICU,

even

though

they

presentsevere

OSA.

Respiratory:2.2%

OSAgroup(3.23%

)vs

non-OSA

group(1.47%

),presented

ahigher

incidenceof


(not

statisticallysignificant,

P=.39).

Complicationduring

anesthetic

recovery

andwhilethe

patientswas

inthewardor

ICU.

Allrespiratorycomplications

took

placein

theimmediate

postoperativeperiod.

Perkins

etal

201215

UnitedStates

Pediatrichospital

48h–18

d267

158

6.90

Tonsillectomyby

electrocautery

orcoblation

Childrenwith

OSAwerehalfas

likelyto

hemorrhage

comparedwith

chronic

tonsillitispatients(P

=.04).

Childrenwith

OSAmay

beless

likelyto

have

postoperative

hemorrhagethan

children

withoutOSAwith

chronic

tonsillitis.

Riaz

etal

200913

SaudiArabia

Hospitalanesthesiology

department

Once

thesurgery

was

finished

3030

6.60

ATThecomplications

atextubation

(cough,laryngospasm,

postoperativenausea,and

vomiting)werehigher

inOSA

group,butnotstatistically

significant;P

..05).

Childrenwith

OSAoperated

for

ATareat

significant

risk

ofcertainlife-threatening

perioperativeanesthetic

complications.

Atthetim

eof

extubation,

desaturationwas

significantlyhigher

inOSA

group(43.3%

vs6.6%

,P=.002,O

R=10.70).

Recovery

room

Morepatientsof

OSAgroup

required

oxygen

(63.3%

vs10%,P

,.001,O

R=15.54).

Sixchildrenfrom

OSAgroup

required

insertionof

anoropharyngealairw

ay.N

ochild

from

non-OSAgroup

required

it(P

=.023).


The sample size ranged widely from1023 to 9023 subjects.15 A summaryof the study descriptivecharacteristics can be found inTable 1. The characteristics from the4 studies selected to answer question2 can be found in Table 2.

Risk of Bias Within Studies

The studies selected to answerquestion 1 were very heterogeneous,6 of them had high risk of bias, 6 hadmoderate risk, and only 7 had lowrisk of bias. None of the studiesfulfilled all methodological qualitycriteria. The studies selected toanswer question 2 were morehomogeneous, 2 had moderate risk ofbias and 1 had low risk. Moreinformation about the risk of bias ofincluded studies can be found inTable 3 (summarized assessment)and Supplemental Tables 6 and 7(detailed assessment).

Results of Individual Studies

The results of studies selected toanswer question 1 are reported inTable 1. The results of the studiesselected to answer question 2 are

TABLE2

Continued

Source

Country

Placeof

Recruitm

ent

FollowUp

OSA,n

Non-OSAWith

Tonsillitis,n

MeanAge

orRange

SurgeryProcedure/

ComplicationAssessment

Location

Results

MainConclusion

Sanders

etal

200612

Mexico

Pediatric

otolaryngology

servicefrom

university’shospital

Until

dischargeof

recovery

room

6121

2–16

ATby

electrocautery

dissection

OSAgrouphadmore


than

non-OSA(5.7vs

2.9,

P=.0001).

Childrenwith

OSAareat

risk

forrespiratory

complications

afterAT.These

complications

donot

prolongthetim

eto

discharge.

Supraglotticobstruction,

breath

holding,and

desaturationon

anesthetic

inductionandem

ergence

werethemostcommon

complications.

Recovery

room

Increasedseverityof

OSA,low

weight,andyoungageare

correlated

with

anincreased

rate

ofcomplications.

Medical

interventionwas

more

necessaryin

OSAgroup

during

recovery

and

emergencethan

inthenon-

OSAgroup(17/61

vs1/21,

P=.05).

TABLE 3 Risk of Bias SummarizedAssessment

Source Risk of Bias

Ahmad et al25 ModerateBaguley et al31 ModerateBrown23 LowDel-Rio Camacho et al16 ModerateHadden et al27 LowHamada et al37 LowLalakea et al21 LowMa et al32 LowMuninnobpamasa et al28 ModerateNixon et al22 ModerateOnotai and Lilly-Tariah30 HighPerkins et al15 LowRakover et al35 HighRiaz et al13 ModerateRuboyianes19 HighSanders et al12 LowShakeel et al38 LowShott et al34 HighSpencer and Jones29 ModerateVlastos et al26 LowWang et al24 HighWong et al36 HighYe et al33 Moderate




synthesized below (with additionalinformation in Table 2).

Riaz et al13 reported that at the timeof extubation, desaturation wassignificantly more frequent in the OSAgroup (43.3% vs 6.6%, P = .002, oddsratio [OR] = 10.70). Othercomplications at extubation (ie,cough, laryngospasm, andpostoperative nausea and vomiting)were also more frequent in the OSAgroup, but were not statisticallysignificant (P = .999). In thepostanesthesia care unit, thefrequency of complications andmedical interventions was also higherin OSA group. More patients in the

OSA group required oxygensupplementation (63.3% vs 10%,P, .001, OR = 15.54). They concludedthat children with OSA undergoing ATare at significant risk of certain life-threatening perioperative anestheticcomplications.

Similarly, Sanders et al12 evaluated therate of complications experienced bychildren who undergo AT for OSA, thesafety of a standard anestheticprotocol for these children, andpreoperative predictors ofcomplications. They found thatchildren with OSA had morerespiratory complications thanchildren without OSA (5.7 vs 2.9,

P , .0001). Supraglottic obstruction,breath holding, and desaturation onanesthetic induction and emergencefrom anesthesia were the mostcommon complications. Increasedseverity of OSA, low body weight, andyoung age were associated with anincreased rate of complications.Medical intervention was necessary ina higher proportion of children withOSA during recovery and emergencefrom anesthesia than in the non-OSAgroup (17/61 vs 1/21, P , .05).However, both groups of children hadsimilar opioid requirements, and thetime to discharge from the recoveryroom was also similar. They concluded

FIGURE 2Forest plot question 1. Frequency of complications after AT in children (question 1). Results from 2 types of meta-analysis: fixed and random effects. A,Forest plot for all postoperative complications. Sample = 13 537. B, Forest plot for respiratory complications. Sample = 3148. C, Forest plot for primaryhemorrhage. Sample = 11 760. D, Forest plot for secondary hemorrhage. Sample = 11 090.


that children with OSA are at risk forrespiratory complications after AT, butthat these complications do not appearto prolong the time to discharge.

Del-Rio Camacho et al16 found thatwhen considering all children,complications occurred in only 3.5%of children, with 2.2% correspondingto respiratory complications. Childrenwith mild to moderate OSA (3.23% vs1.47%, P = .39) and children withsevere OSA (3.77% vs 1.70%, P = .32)presented a higher incidence ofrespiratory complications, which didnot achieve statistical significance. Allrespiratory complications took placein the immediate postoperative period.

In contrast, Perkins et al15

hypothesized that a diagnosis of OSA

may be protective againstpostoperative hemorrhage. A total of9023 tonsillectomy patients wereidentified. Of these, only 2.4%(n = 212) presented with hemorrhage.There were 48 patients (22.6%) withprimary, and 164 patients (77.4%)with secondary hemorrhage, with themajority occurring among childrenwith recurrent tonsillitis. The authorsconcluded that children with OSAwere half as likely to manifestbleeding as a complication after ATwhen compared with children withchronic tonsillitis (P = .04).

Synthesis of Results

The meta-analysis was performed in2 steps. To answer question 1, the 23

studies selected were grouped anda meta-analysis was performed. Theheterogeneity between the studiesfound in the meta-analysis was high;therefore, a random model waschoosen.39 The results from thismeta-analysis revealed that theoverall frequency of postoperativecomplications was ∼19% (totalsample = 13 537; Fig 2A). The mostfrequent postoperative complicationswere respiratory compromise (9.4%in sample = 3148 cases; Fig 2B)followed by secondary hemorrhage(2.6% in sample = 11 090 cases;Fig 2D) and primary hemorrhage(2.4% in sample = 11 760; Fig 2C).

To answer the question 2, the 4studies12,13,15,16 that directly

FIGURE 2Continued.


compared an OSA and a non-OSAgroup, as defined by nocturnalPSG were grouped, and a meta-analysis was performed. Onlya meta-analysis with a fixed effectmodel was performed by using themethod of Mantel-Haenszel.39 Inthis meta-analysis, only data relyingon PSG-confirmed OSA and non-OSAwere considered. Because of thesecriteria, different sample sizesemerge in Tables 1 and 2 for thesame studies. To perform this meta-analysis, the studies were groupedin 2 groups, A (respiratorycomplications) and B (bleedingcomplications). The heterogeneitybetween the studies found in themeta-analysis was 0% indicatinghigh homogeneity (confirming that

we can analyze these data withfixed effect). The meta-analysis ofgroup A (respiratory complications)included 371 patients (184 withOSA and 187 without OSA) andconfirmed that children with OSAappear to have more frequentpostoperative respiratorycomplications after AT than childrenwithout OSA (OR = 4.90; 95%confidence interval (CI):2.38–10.10). In group B (bleedingcomplications), 360 children withOSA and 294 children without OSAwere included. The meta-analysisconfirmed that bleeding is morelikely to occur among childrenwithout OSA (OR = 0.41; 95% CI:0.23–0.74; Fig 3).

Risk of Bias Across Studies

Although the studies had differentstudy design (experimental anddescriptive), the main methodologicalproblem concerns the actual subjectsample. Most of the studies selected toanswer question 1 used a conveniencesample from a hospital. Even theexperimental studies did not randomlyassign participants. Besides thisparticular issue, most of theobservational studies did not performappropriate statistical analyses.

DISCUSSION

AT is a relatively common procedurein clinical otolaryngology practice andusually follows referrals from

FIGURE 2Continued.


primary care physicians.25 It is thecurrent treatment of choice fortreatment of OSA in children, whenindicated, due to its perceived efficacyand cost effectiveness.40

Currently guidelines used byclinicians to identify children who areappropriate candidates for AT haveindications based primarily onobstructive and infectious causes.41

Before 1995, the major indication forAT was recurrent tonsillitis, with OSAbeing a distant second. However, inthe past 10 years the number ofchildren referred for OSA-related ATsurgery has increased markedly,reflecting an increased awareness andimproved diagnosis of OSA by

pediatricians and other primary carephysicians.36

This systematic review investigatedthe available evidence about the mostfrequent early postoperativecomplications after AT, and alsoevaluated potential differences in theassociated complications betweenchildren with OSA and those withoutOSA. Regarding the most frequentearly postoperative complications,respiratory compromise andhemorrhage were the most frequent,followed by pain, fever, nausea andvomiting, and dehydration. Infectionand cardiac complications were rare.These results are in agreement withthe available literature.3,21,29,35,37

Mortality rates of AT have beenestimated between 1 in 16 000 and 1in 35 000 cases.42

Nixon et al22 demonstrated thatsleep-related airway obstruction isa common postoperativecomplication leading to significantoxyhemoglobin desaturations afterAT in children with severe OSA.Episodes of desaturation occurredduring the first postoperative night inall 10 children studied, and thesedesaturation episodes werepredominantly caused by upperairway obstruction. Severalmechanisms may explain ongoingupper airway obstruction after AT,including copious nasal secretions

FIGURE 2Continued.


after surgery, and reactive,postsurgical edema in the adenoidand tonsillar beds. Thus, the firstnight after AT will usually manifestmarked sleep disturbance, airwayobstruction, and desaturation.22

In this systematic review, we founda very high frequency of pain as themajor complication of AT, with someof the included studies revealingexceedingly high rates of pain,12,27,28

such that the frequency of overallpostoperative complications whenpain was included in the meta-analysis reached the vicinity of 20%,even after random effects wereaccounted for. Under thesecircumstances, the frequency ofrespiratory compromise after AT was9.4% and primary and secondaryhemorrhage prevalence was 2.4%and 2.6%, respectively. Of note,although postoperative bleeding canbe a serious complication after AT,21

it rarely requires transfusion.30 Thus,AT has substantial postoperativemorbidity, and identification ofchildren at risk for either respiratorycompromise or bleeding would be

obviously important, particularlybecause the majority of AT surgeriesare conducted in outpatient settings.

In this context, our meta-analysishighlights 2 relevant clinical practicepoints. The presence of OSAsignificantly increases the oddsfor postoperative respiratorycomplications, with children with OSAexhibiting a nearly fivefold increase inthe odds of developing respiratorycomplications when compared withchildren without OSA. These findingsconcur with previous studies thatsuggested that as the severity ofOSA increases, the probability ofrespiratory complications after ATincreases as well.43–45 Children withOSA not only had more frequentcomplications during induction andemergence from anesthesia, theywere also more likely to requiresupplemental oxygen, oral ornasal airway insertion, or assistedventilation in the immediatepostoperative period.12 Thus,identification of children at higherrisk for respiratory complicationsbefore AT can help in formulating

a safe anesthetic strategy for childrenwith OSA, and should be pursued infuture prospective large-scalestudies.13 In contrast, our meta-analysis indicated that the presenceof tonsillitis in children without OSAincreased the odds for hemorrhagiccomplications. Children without OSAwith tonsillitis appear to have 2.5-foldincreases in the odds for bleedingcomplications when compared withchildren with OSA. Perkins et al15

suggested that either OSA isprotective against postoperativehemorrhage or that recurrent tonsilinfection increases the risk forbleeding through undefinedmechanisms, most likely involvingincreased vascularity of tonsillar andsurrounding upper airway tissues.

Despite the current guidelines fromthe American Academy of Pediatrics,several important obstacles have thusfar precluded widespreadimplementation of PSG for OSA, suchas cost and reduced availability.3

However, a definitive diagnosis ofOSA requires a PSG, and our currentfindings further suggest that among

FIGURE 3Forest plot question 2. Postoperative respiratory and bleeding complications after AT in children with OSA and children without OSA. Children with OSAwere at significantly higher odds for respiratory complications (A), and conversely children without OSA were at increased odds for hemorrhage aftersurgery (B). A, Forest plot for post-AT respiratory complications. B, Forest plot for post-AT bleeding complications.


children with OSA, the risk ofpostoperative respiratorycomplications is high. Childrenwith OSA are clearly at higheranesthetic risk than are patientswith normal upper airway function.Anesthesiologists should routinelyscreen patients for snoring, airwaydysfunction, airway anatomicdisorders, and other coexistingdiseases that can increase risk fromOSA in the postoperative period.Despite the pressure to reduce costs,both surgeons and anesthesiologistsshould improve screening procedures,perhaps develop alternate surgicalapproaches, to decrease the risks.46

Thus, systematic implementation ofPSG-based OSA diagnosis couldpotentially enable delineation of PSG-based criteria that would inform ear,nose and throat (ENT) surgeons onthe presence of specific children withhigher respiratory risk, and thusimprove peri- and postoperative phaseplanning, while ascertaining that high-risk patients undergo surgery ina medical center capable of monitoringand treating more complex pediatricpatients postoperatively.3

Raman et al47 established guidelinesfor patients undergoing AT resultingin an overall reduction inunanticipated admissions. The authorsemphasize that guidelines could beuniversally applied in an outpatientscreening process for identification ofat risk surgical patients. This wouldaid in identifying those patients who

may not be ideal candidates foroutpatient surgical facilities.

Future prospective studies mayaddress the development of screeningtools for patients in need ofadditional education in normal andabnormal postoperativesymptomatology or health caresupport. This may ultimately lowerpostoperative emergency departmentvisits and overall health care costassociated with this procedure.48

Limitations

Most of the selected studies wereretrospective. Documentation ofa respiratory complication wascollected from medical charts. It islikely that minor complications thatdid not require sentinel eventreporting, hospital readmission, oroperative intervention were not takeninto account in the publishedliterature. In most studies, the criteriaused to establish the diagnosis andseverity of OSA relied on clinicalassessment, rather than PSG.Therefore, accurate stratification ofOSA severity is not possible to enableaforementioned OSA severitystratification of postoperative risk.

Notwithstanding that our findingsemanate from a meta-analysis of thepertinent published studies, cautionshould be exercised because thesample size was relatively small, andthus does not enable irrefutableevidence to unequivocally answer the2 questions from this systematic

review. This is even more noticeablefor the second question.

CONCLUSIONS

The most frequent complications afterAT include respiratory compromiseand secondary hemorrhage. Based onthe current limited evidence, childrenwith OSA appear to have morerespiratory complications after ATthan children without OSA. In contrast,hemorrhage appears to be morefrequent in children without OSA.

ACKNOWLEDGMENTS

We thank the experts who kindlyresponded to specific questionsduring the conduct of this research:Dr Karen A. Brown at McGillUniversity Health Centre and TheMontreal Children’s Hospital; DrRonald D. Chervin at the University ofMichigan; Dr Ron B. Mitchell at theUniversity of Texas Southwestern andChildren’s Medical Center Dallas; andDr Hawley E. Montgomery-Downs atWest Virginia University.

ABBREVIATIONS

AT: adenoidectomy andtonsillectomy

CI: confidence intervalICU: intensive care unitOR: odds ratioOSA: obstructive sleep apneaPSG: polysomnographySDB: sleep disordered breathing

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

FUNDING: Drs Gozal and Kheirandish-Gozal are supported by National Institutes of Health (NIH) grant HL-65270. Dr Bhattacharjee is supported by a scientist

development grant from the American Heart Association (3SDG14780079).

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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BREAKING DARWIN’S RULES: My second son loves to fish. He mostly surfcasts insalt water and fly fishes in fresh water. While he likes to catch bigger rather thansmaller fish, he is always happy just to be fishing. We do have one rule, however.Regardless of the size of the fish we catch, unless the fish is badly hurt, we alwaysrelease the fish back to thewater fromwhich it came.We usually spend a bit of timemaking sure thefish has the energy to swimawayandnot becomegame for a largerfish. Our theory is that even bigfish have the right to get bigger and lead productiveadult lives. Unfortunately, conservation policies and fishing practices of mostfishermen encourage keeping the largest fish caught.Asreported inTheNewYorkTimes (Science:August20,2015),humans tendtohuntand eat mature adult animals, those in their prime reproductive years. This is insharp distinction to what happens in the wild where the young, the small, and theweak tend to be the ones killed by other animals. Humans, as amazing predators,havechangedtherulesof somespecies from “survivalof thefittest” to “survivalof thesmallest”. This can be seen in the Atlantic cod population. Large female cod producefarmoreeggs thansmaller cod.As thecodpopulationplummeteddue tooverfishing,quotas were established so that only the largest cod could be kept. This led toselection pressure favoring the survival of smaller cod and those that bred earlierand hence, produced smaller numbers of eggs.Unfortunately, fishing and hunting practices are unlikely to change as sport fish-erman and hunters like to pose with larger fish and trophies. Still, I hope that somewill realize that the biggest is not always the best, and either return the fish to thewater or settle for smaller fish or game while hunting.

Noted by WVR, MD


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Graziela De Luca Canto, Camila Pachêco-Pereira, Secil Aydinoz, RakeshAdenotonsillectomy Complications: A Meta-analysis

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