Physiotherapy for pain and disability in adults with complex regional pain syndrome

103 Pages·2016·0.9 MB·English

CochraneDatabaseofSystematicReviews
Physiotherapy for pain and disability in adults with complex
regional pain syndrome (CRPS) types I and II (Review)
SmartKM,WandBM,O’ConnellNE
SmartKM,WandBM,O’ConnellNE.
Physiotherapyforpainanddisabilityinadultswithcomplexregionalpainsyndrome(CRPS)typesIandII.
CochraneDatabaseofSystematicReviews2016,Issue2.Art.No.:CD010853.
DOI:10.1002/14651858.CD010853.pub2.
www.cochranelibrary.com
Physiotherapyforpainanddisabilityinadultswithcomplexregionalpainsyndrome(CRPS)typesIandII(Review)
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAINLANGUAGESUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Figure1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Figure2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Figure3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
AUTHORS’CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
CHARACTERISTICSOFSTUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
DATAANDANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Analysis1.1.Comparison1Gradedmotorimageryversususualcare,Outcome1Painintensity(post-treatment). . 94
Analysis1.2.Comparison1Gradedmotorimageryversususualcare,Outcome2Function(0to11patientspecific
functionalscale)(post-treatment). . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
CONTRIBUTIONSOFAUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
DECLARATIONSOFINTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
DIFFERENCESBETWEENPROTOCOLANDREVIEW . . . . . . . . . . . . . . . . . . . . . 101
Physiotherapyforpainanddisabilityinadultswithcomplexregionalpainsyndrome(CRPS)typesIandII(Review) i
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
[InterventionReview]
Physiotherapy for pain and disability in adults with complex
regional pain syndrome (CRPS) types I and II
KeithMSmart1,BenedictMWand2,NeilEO’Connell3
1PhysiotherapyDepartment,StVincent’sUniversity Hospital, Dublin, Ireland. 2Schoolof Physiotherapy,TheUniversity ofNotre
DameAustralia,Fremantle,Australia.3DepartmentofClinicalSciences/HealthEconomicsResearchGroup,InstituteofEnvironment,
HealthandSocieties,BrunelUniversity,Uxbridge,UK
Contact address: Keith M Smart, Physiotherapy Department, St Vincent’s University Hospital, Elm Park, Dublin, 4, Ireland.
[email protected].
Editorialgroup:CochranePain,PalliativeandSupportiveCareGroup.
Publicationstatusanddate:New,publishedinIssue2,2016.
Reviewcontentassessedasup-to-date: 15February2015.
Citation: Smart KM, Wand BM, O’Connell NE. Physiotherapy for pain and disability in adults with complex regional
pain syndrome (CRPS) types I and II. Cochrane Database of Systematic Reviews 2016, Issue 2. Art. No.: CD010853. DOI:
10.1002/14651858.CD010853.pub2.
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ABSTRACT
Background
Complexregionalpainsyndrome(CRPS)isapainfulanddisablingconditionthatusuallymanifestsinresponsetotraumaorsurgery.
Whenitoccurs,itisassociatedwithsignificantpainanddisability.Itisthoughttoariseandpersistasaconsequenceofamaladaptive
pro-inflammatoryresponseanddisturbancesinsympathetically-mediatedvasomotorcontrol,togetherwithmaladaptiveperipheraland
centralneuronalplasticity.CRPScanbeclassifiedintotwotypes:typeI(CRPSI)inwhichaspecificnervelesionhasnotbeenidentified,
andtypeII(CRPSII)wherethereisanidentifiablenervelesion.Guidelinesrecommendtheinclusionofavarietyofphysiotherapy
interventionsaspartofthemultimodaltreatmentofpeoplewithCRPS,althoughtheireffectivenessisnotknown.
Objectives
TodeterminetheeffectivenessofphysiotherapyinterventionsfortreatingthepainanddisabilityassociatedwithCRPStypesIandII.
Searchmethods
We searched the following databases from inception up to 12 February 2015: CENTRAL (the Cochrane Library), MEDLINE,
EMBASE,CINAHL,PsycINFO,LILACS,PEDro,WebofScience,DAREandHealthTechnologyAssessments,withoutlanguage
restrictions,forrandomisedcontrolledtrials(RCTs)ofphysiotherapyinterventionsfortreatingpainanddisabilityinpeopleCRPS.
Wealsosearchedadditionalonlinesourcesforunpublishedtrialsandtrialsinprogress.
Selectioncriteria
We includedRCTs of physiotherapy interventions (including manual therapy,therapeuticexercise,electrotherapy,physiotherapist-
administered education and cortically directedsensory-motor rehabilitation strategies) employedin either astand-alone fashion or
incombination,comparedwithplacebo,notreatment,anotherinterventionorusualcare,orofvaryingphysiotherapyinterventions
comparedwith eachotherinadultswithCRPSIandII.Ourprimary outcomesofinterestwerepatient-centredoutcomesofpain
intensityandfunctionaldisability.
Physiotherapyforpainanddisabilityinadultswithcomplexregionalpainsyndrome(CRPS)typesIandII(Review) 1
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Datacollectionandanalysis
Tworeviewauthorsindependentlyevaluatedthosestudiesidentifiedthroughtheelectronicsearchesforeligibilityandsubsequently
extractedallrelevantdatafromtheincludedRCTs.Tworeviewauthorsindependentlyperformed’Riskofbias’assessmentsandrated
thequality ofthebodyofevidence forthemainoutcomesusing theGradingofRecommendations Assessment,Developmentand
Evaluation(GRADE)approach.
Mainresults
Weincluded18RCTs(739participants)thattestedtheeffectivenessofabroadrangeofphysiotherapy-basedinterventions.Overall,
therewasapaucityofhighqualityevidenceconcerningphysiotherapytreatmentforpainanddisabilityinpeoplewithCRPSI.Most
includedtrialswereat’high’riskofbias(15trials)andtheremainderwereat’unclear’riskofbias(threetrials).Thequalityofthe
evidencewasveryloworlowforallcomparisons,accordingtotheGRADEapproach.
Wefoundverylowqualityevidencethatgradedmotorimagery(GMI;twotrials,49participants)maybeusefulforimprovingpain
(0to100VAS)(meandifference(MD)−21.00, 95%CI−31.17to−10.83)andfunctional disability (11-pointnumericalrating
scale)(MD2.30, 95%CI1.12to3.48), atlong-term(sixmonths)follow-up,inpeoplewithCRPSIcomparedtousualcareplus
physiotherapy; very low quality evidence that multimodal physiotherapy (one trial, 135 participants) may be useful for improving
’impairment’atlong-term(12month)follow-upcomparedtoaminimal’socialwork’intervention;andverylowqualityevidencethat
mirrortherapy(twotrials,72participants)providesclinicallymeaningful improvementsinpain(0to10VAS)(MD3.4, 95%CI
−4.71to−2.09)andfunction(0to5functionalabilitysubscaleoftheWolfMotorFunctionTest)(MD−2.3,95%CI−2.88to
−1.72)atlong-term(sixmonth)follow-upinpeoplewithCRPSIpoststrokecomparedtoplacebo(coveredmirror).
There was low to very low quality evidence that tactile discrimination training, stellate ganglion block via ultrasound and pulsed
electromagnetic field therapy compared to placebo, and manual lymphatic drainage combined with and compared to either anti-
inflammatoriesandphysicaltherapyorexercisearenoteffectivefortreatingpainintheshort-terminpeoplewithCRPSI.Lasertherapy
mayprovidesmallclinicallyinsignificant,short-term,improvementsinpaincomparedtointerferentialcurrenttherapyinpeoplewith
CRPSI.
Adverseeventswereonlyrarelyreportedintheincludedtrials.NotrialsincludingparticipantswithCRPSIImettheinclusioncriteria
ofthisreview.
Authors’conclusions
Thebestavailable data showthatGMIand mirrortherapymay provide clinicallymeaningful improvementsinpain andfunction
in people with CRPS I although the quality of the supporting evidence is very low. Evidence of the effectiveness of multimodal
physiotherapy, electrotherapy and manual lymphatic drainage for treating people with CRPS types I and II is generally absent or
unclear.Largescale,highqualityRCTsarerequiredtotesttheeffectivenessofphysiotherapy-basedinterventionsfortreatingpainand
disabilityofpeoplewithCRPSIandII.Implicationsforclinicalpracticeandfutureresearchareconsidered.
PLAIN LANGUAGE SUMMARY
Physiotherapyforpainanddisabilityinadultswithcomplexregionalpainsyndrome(CRPS)typesIandII
Background
Complexregionalpainsyndrome(CRPS)isapainfulanddisablingcondition.Mostcommonlyitaffectsaperson’sarmandhandor
legandfootandmayoccurafteratraumaticinjury.TherearetwotypesofCRPS:CRPSIinwhichthereisnonerveinjury,andCRPS
IIinwhichthereisanerveinjury.Guidelinesrecommendphysiotherapy,whichcouldincludedifferentkindsofexercisetherapyor
electrotherapyforinstance,alongwithothermedicaltreatmentsfortreatingthepainanddisabilityassociatedwithCRPS.However,
wedonotknowhowwellthesetreatmentswork.
Reviewquestion
WhichtypesofphysiotherapytreatmentareeffectiveforreducingthepainanddisabilityassociatedwithCRPSinadults?
Studycharacteristics
Physiotherapyforpainanddisabilityinadultswithcomplexregionalpainsyndrome(CRPS)typesIandII(Review) 2
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Wesearchedforclinicaltrialsofphysiotherapyupto12February2015.Weincluded18trialsthathad739participantswithCRPSI.
InmostofthesetrialstheparticipantshadCRPSIofthearmandhand.Wedidnotfindanyclinicaltrialsthatincludedparticipants
withCRPSII.
Keyresults
OverallwedidnotfindanygoodqualityclinicaltrialsofphysiotherapyaimedatreducingthepainanddisabilityofCRPSIinadults.
Mostincludedtrialswerenotwelldesignedandcontainedonlysmallnumbersofpatients.Wedidfindsomelowqualitytrialssuggesting
thattwobroadlysimilartypesofrehabilitationtraining,knownas’gradedmotorimagery’(GMI)and’mirrortherapy’,mightbeuseful
forreducingthepainanddisabilityassociatedwithCRPSIaftertraumaticeventsorsurgeryorastroke.Fromthelimitedevidence
availableitappearsthatsometypesofelectrotherapy,suchasultrasoundandpulsedelectromagneticfieldtherapy,aswellasatypeof
massagetherapyknownasmanuallymphaticdrainage,arenoteffective.Moststudiesdidnotreportonadverseeventsandsowedo
notknowifthesetreatmentshaveanyharmfulside-effects.
Onthewhole,becauseofthelimitednumberandlowqualityofavailabletrialsforthevariousphysiotherapytreatments,wecannot
besureifanyofthephysiotherapytreatmentsweevaluatedareeffectivefortreatingthepainanddisabilityofCRPSIinadults.Itis
possiblethatsometreatments,suchasGMIormirrortherapy,mightbeeffective.Furtherhighqualityclinicaltrialsofphysiotherapy
areneededinordertofindoutifanyofthedifferenttypesofphysiotherapytreatmentareeffectiveatimprovingpainanddisabilityin
peoplewithCRPS.
BACKGROUND 1. continuingpaindisproportionatetoanyincitingevent;
2. thepresenceofclustersofvarioussymptomsandsigns
reflectingsensory(e.g.hyperaesthesia,allodynia),vasomotor
(e.g.asymmetriesoftemperatureorskincolour,orboth),
Descriptionofthecondition
sudomotor(e.g.oedemaoralteredsweatingorboth),motor(e.g.
Complexregionalpainsyndrome(CRPS)isapersistent,painful reducedrangeofmotion,tremor)ortrophic(e.g.alteredhairor
anddisablingconditionthatusually,butnotexclusively,manifests nails,orboth)disturbances;and
in response to acute trauma or surgery (Goebel 2011; Shipton 3. theabsenceofanyothermedicaldiagnosisthatmight
2009).TheInternationalAssociationfortheStudyofPain(IASP) betteraccountforanindividual’ssymptomsandsigns.
introducedthediagnostic label’CRPS’inthe1990sinorderto The pathophysiological mechanisms underlying CRPS are not
standardiseinconsistenciesinterminologyanddiagnosticcriteria fullyunderstood (Harden 2010). Current understanding impli-
(Merskey1994).Twosub-categoriesofCRPShavebeendescribed: catesmultiplemechanismsincludingcomplexcontributionsfrom
CRPStypeI(CRPSI)(formerlyandvariouslyreferredtoasreflex a maladaptive pro-inflammatory response and a disturbance in
sympatheticdystrophy(RSD),algodystrophy,Sudek’satrophy)in sympatheticallymediatedvasomotorcontrol,togetherwithmal-
which no nerve lesion is present and CRPS type II (CRPS II) adaptiveperipheralandcentralneuronalplasticity(Bruehl2010;
(formerlyreferredtoascausalgia,algoneurodystrophy),inwhich Bruehl2015;Marinus2011;Parkitny2013).Furthermore,mech-
a co-existing nerve lesion (as determined by nerve conduction anisms, and in consequence symptoms and signs, may vary be-
studies or surgical inspection for example) is present (Coderre tweenindividualsandwithinindividualsoverthetimecourseof
2011;Todorova2013). thedisorder,thusheighteningthecomplexity(Marinus2011).
CRPSischaracterisedbysymptomsandsignstypicallyconfined TheincidenceofCRPSisnotaccuratelyknownbutpopulation
toabodyregionorlimb,butwhichmaybecomemorewidespread estimatesindicateanincidenceofsomewherebetweenfiveand26
(vanRijn2011).ThediagnosticcriteriaforCRPSoriginallypro- casesper100,000person-years(Marinus2011).Alikelyconserva-
posed by the IASP (Merskey 1994) have since been revised in tive11-yearperiodprevalencerateforCRPSof20.57per100,000
response to their low specificity and potential to over-diagnose peoplehasbeenreported(Sandroni2003).CRPSisthreetofour
casesofCRPS.TheBudapestcriteriaproposedbyHarden2010 timesmorelikelytooccurinwomenthaninmen,andalthough
haveenhanceddiagnosticaccuracyandarenowwidelyaccepted itmayoccuratanytimethroughoutthelifespanittendstooc-
(Goebel2011).ThediagnosisofCRPSisclinical(Goebel2011) curmorefrequentlywithincreasingage(Shipton2009).Genetic
andthecardinalfeaturesinclude: susceptibility may serveas anaetiological riskfactor for thede-
Physiotherapyforpainanddisabilityinadultswithcomplexregionalpainsyndrome(CRPS)typesIandII(Review) 3
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
velopmentofCRPS(deRooij2009).Inindividualswhodevelop (e.g.gradedmotorimagery(GMI),mirrortherapy,sensorymotor
CRPSafterafracture,intra-articularfracture,fracture-dislocation, retuning,tactilediscriminationtraining).
pre-existingrheumatoidarthritis,pre-existingmusculoskeletalco-
morbidities(e.g.low-backpain,arthrosis)(Beerthuizen2012)and
limbimmobilisation(Marinus2011)mayincreasetheriskofits
development.Psychologicaltraits,suchasdepression,anxiety,neu-
Howtheinterventionmightwork
roticismandanger,havesofarbeendiscountedasriskfactorsfor
thedevelopmentofCRPS(Beerthuizen2009:Lohnberg2013), The precise mechanismsof action through which various phys-
althoughfurtherprospectivestudiesarerequiredtosubstantiate iotherapyinterventionsarepurportedtorelievethepainanddis-
thisassertion(Harden2013). abilityassociatedwithCRPSarenotfullyunderstood. Theories
PeoplewithCRPSexperiencesignificantsufferinganddisability underpinningtheuseofmanualtherapiestorelievepaininclude
(Bruehl2010;Lohnberg2013).Preliminarydatasuggestthatin- the induction of peripheral or central nervous system-mediated
terferencewithactivitiesofdailyliving,sleep,workandrecreation analgesia,orboth(Bialosky2009;Goats1994).Therapeuticex-
iscommonandfurthercontributestoadiminishedqualityoflife ercise may induce analgesia, via endorphin-mediated inhibition
(Galer2000;Geertzen1998;Kemler2000;Sharma2009). (Nijs2012),andimprovefunction,andbyextensiondisability,by
Studiesintothecourse ofCRPSpresentcontradictory findings. restoringrangeofmovementataffectedjointsandimprovingneu-
Whilstsomestudieshavereportedcompleteandpartialsymptom romuscularfunction(Kisner2002).Theoriesunderlyingtheuse
resolution within one year (Sandroni 2003; Zyluk1998), other ofelectrotherapymodalitiesforpainreliefvariouslyincludespinal
studies have indicated more protracted symptoms and impair- cord-mediatedelectro-analgesia,heat-orcold-mediatedanalgesia
mentslasting fromthreeto nine years(de Mos 2009; Geertzen and anti-inflammatory effects(Atamaz 2012; Robertson 2006).
1998;Vaneker2006).Inaddition,emergingevidencesuggeststhat Pain neuroscience education may reduce pain and disability by
peoplewith CRPS of an upper limb(which developslessoften helpingindividualstobetterunderstandthebiologicalprocesses
inresponsetoafracture)andwhoseaffectedlimbiscolderthan underlyingtheirpaininawaythatpositivelychangespainpercep-
thecontralaterallimb,mayexperiencesignificantlylongerdisease tionsandattitudes(Louw2011).Otherrehabilitationstrategies,
durationthanpeoplewithCRPSofalowerlimb(whichoccurs suchGMIormirrortherapy,mayprovidepainrelieforincrease
morecommonlyafterfracture)andwhoseaffectedlimbiswarmer mobility,orboth,byamelioratingmaladaptivesomatosensoryand
thanthecontralaterallimb(deMos2009). motorcortexreorganisation(Moseley2005;Moseley2012).
Although guidelines for the treatment of CRPS recommend an
interdisciplinarymultimodalapproach,comprisingpharmacolog-
icalandinterventionalpainmanagementstrategiestogetherwith
rehabilitation, psychological therapy and educational strategies Whyitisimportanttodothisreview
(Goebel2012;Harden2013;Perez2010;Stanton-Hicks2002),
Anumberofsystematicreviewssuggestthatphysiotherapyinter-
determining theoptimal approach to therapy remains clinically
ventions (e.g. exercise, GMI, TENS)employedin combination
challenging(Cossins2013;O’Connell2013).
withmedicalmanagementmaybebeneficialinreducingthepain
and disability associated with CRPS (Daly 2009; Smith 2005).
However,theinclusionofnon-randomisedclinicaltrialsandcase
seriesdesigns,togetherwiththeexclusionofstudiesinvolvingpeo-
Descriptionoftheintervention
ple with CRPS type II as wellas those published in alanguage
Guidelinesrecommendtheinclusion ofavarietyofphysiother- otherthanEnglish,mayhavebiasedtheseconclusions.Further-
apyinterventions aspartofthemultimodal treatmentofCRPS more,themethodologiesusedforconductingsystematicreviews
(Goebel2012;Perez2010;Stanton-Hicks2002)buttheireffec- havebeensubstantiallyrevisedinrecentyears,suchasthoserec-
tivenessisnotknown.Physiotherapyhasbeendefinedas“thetreat- ommendedwithintheGradingofRecommendationsAssessment,
mentofdisorderswithphysicalagentsandmethods”(Anderson DevelopmentandEvaluation(GRADE)approachfordescribing
2002) and for CRPS could include any of the following inter- thestrengthoftheevidence(Balshem2011),whichhasnotbeen
ventionsemployedeitherasstand-aloneinterventionsorincom- utilisedinpreviousreviews.Giventhelimitationsofexistingsys-
bination:manualtherapy(e.g.mobilisation,manipulation,mas- tematicreviews, togetherwith theavailability ofpotentiallynu-
sage, desensitisation); therapeutic exercise and progressive load- merous physiotherapy treatment strategies for CRPS, an up-to-
ingregimens(includinghydrotherapy);electrotherapy(e.g.tran- datesystematicreviewoftheevidencefromrandomisedclinical
scutaneous electrical nerve stimulation (TENS), therapeutic ul- trialsfortheeffectivenessoftheseinterventionsmayassistclini-
trasound,interferential,shortwavediathermy,laser);physiothera- ciansintheirtreatmentchoicesandinformfutureclinicalguide-
pist-administerededucation(e.g.painneuroscienceeducation);as linesthatmaybeofusetopolicymakersandthosewhocommis-
wellascorticallydirectedsensory-motor rehabilitationstrategies sionhealthcareforpeoplewithCRPS.
Physiotherapyforpainanddisabilityinadultswithcomplexregionalpainsyndrome(CRPS)typesIandII(Review) 4
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
OBJECTIVES intervention(differingonlyintheapplicationofthenon-physio-
therapycomponent)astheyareunlikelytoofferanyinsightinto
Todeterminetheeffectivenessofphysiotherapyinterventionsfor
thevalueofphysiotherapymanagement(seeDifferencesbetween
treatingpainanddisabilityassociatedwithCRPStypesIandII.
protocolandreview).
Typesofoutcomemeasures
METHODS
Primaryoutcomes
Criteriaforconsideringstudiesforthisreview
1. Changesinpainseverity/intensityasmeasuredusinga
visualanaloguescale(VAS),numericalratingscale(NRS),verbal
ratingscaleorLikertscale;
Typesofstudies 2. changesindisabilityasmeasuredbyvalidatedself-report
questionnaires/scalesorfunctionaltestingprotocols.
Weincludedrandomisedcontrolledtrials(RCTs)(includingthose
Wepresentedandanalysedprimaryoutcomesaschangeonacon-
ofparallel,cluster-randomisedandcross-overdesign)publishedin
tinuousscaleorinadichotomisedformatastheproportionofpar-
anylanguage.TranslatorsidentifiedbytheManagingEditorofthe
ticipantsineachgroupwhoattainedapredeterminedthresholdof
Cochrane Pain,PalliativeandSupportiveCareGroupevaluated
improvement.Forexample,wejudgedcut-pointsfromwhichto
studiespublishedinalanguageotherthanEnglish.Weexcluded
interpretthelikelyclinicalimportanceof(pooled)effectsizesac-
studiesinwhichparticipantswerenotrandomisedtointervention
cordingtoprovisionalcriteriaproposedintheInitiativeonMeth-
groups.
ods,Measurement,andPainAssessmentinClinicalTrials(IMM-
PACT)consensusstatement(Dworkin2008).Specifically,reduc-
tionsinpainintensitycomparedwithbaselinewerejudgedasfol-
Typesofparticipants
lows:
We included trials of adults, aged 18 years or older, diagnosed
1. lessthan15%:’noimportantchange’;
withCRPSIorII,orwithanalternativediagnosticlabelforthese
2. 15%ormore:’minimallyimportantchange’;
conditions(e.g.RSD,causalgia).Wegroupedtrialsaccordingto
3. 30%ormore:’moderatelyimportantchange’;
diagnosis (i.e.CRPS typesIandII, or mixed). Sincetheuse of
4. 50%ormore:’substantiallyimportantchange’.
formaldiagnosticcriteriaforCRPSisinconsistentacrossstudies
We planned to use the cut-points for ’minimally’, ’moderately’
(Reinders2002),weincludedtrialsthatusedestablishedorvali-
and ’substantially’ important changes to generate dichotomous
dateddiagnosticcriteria,includingtheVeldmancriteria(Veldman
outcomes,theeffectsizeforwhichwewouldhaveexpressedasthe
1993),theInternationalAssociationfortheStudyofPain(IASP)
riskratio(orrelativerisk(RR))butalackofdatadidnotpermit
criteria(Merskey1994),Bruehlcriteria(Bruehl1999),Budapest
anysuchanalyses.
criteria(Harden2010)andAtkinscriteria(Atkins2010),aswell
as studies that either predate these criteria or use non-standard
diagnosticcriteria. Secondaryoutcomes
Weplannedtoanalysethefollowingsecondaryoutcomemeasures
wheresuchdatawereavailable:
Typesofinterventions
1. changesincompositescoresforCRPSsymptoms;
We included all randomised controlled comparisons of physio- 2. changesinhealth-relatedqualityoflife(HRQoL)usingany
therapyinterventions,employedineitherastand-alonefashionor validatedtool;
incombination, compared with placebo, no treatment, another 3. changesinpatientglobalimpressionofchange(PGIC)
interventionorusualcare,orofvaryingphysiotherapyinterven- scales;
tionscomparedwitheachother,whichwereaimedattreatingpain 4. incidence/natureofadverseeffects.
or disability, or both, associated with CRPS. Weincluded trials Weplannedtoanalyseandpresentsecondaryoutcomesaschange
inwhichnon-physiotherapists(e.g.occupationaltherapists)deliv- onacontinuous scaleorinadichotomisedformatbutalackof
eredsuchphysiotherapyinterventions,asdefinedin’Description data did not permitany such analyses. For example, equivalent
oftheintervention’,andreportedtheprofessionaldisciplineofthe measuresoftreatmenteffectwithrespecttoPGIChavebeende-
cliniciandeliveringtheintervention.Afterthepublicationofour finedas:’much’or’verymuch’improved(moderatebenefit)and
Cochraneprotocol,(Smart2013)wedecidedtoexcludestudies verymuch’improved(substantial benefit)(Dworkin2008).Fu-
thatevaluatednon-physiotherapybasedinterventions(e.g.phar- tureupdatesmayallowsuchanalyseswhererelevantdataareavail-
macological) inwhich allarmsreceivedthesamephysiotherapy able.
Physiotherapyforpainanddisabilityinadultswithcomplexregionalpainsyndrome(CRPS)typesIandII(Review) 5
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Searchmethodsforidentificationofstudies 6. ClinicalTrials.gov;
7. InternationalClinicalTrialsRegistryPlatform;
8. PanAfricanClinicalTrialsRegistry;
Electronicsearches 9. EUClinicalTrialsRegister.
We identified relevantRCTs by electronicallysearching thefol-
lowingdatabases:
1. CochraneCentralRegisterofControlledTrials Datacollectionandanalysis
(CENTRAL)intheCochraneLibrary,Issue1of12,2015;
2. DatabaseofAbstractsofReviewsofEffectsintheCochrane
Library,Issue1of42015; Selectionofstudies
3. HealthTechnologyAssessmentsintheCochraneLibrary,
Tworeviewauthors(KMSandBMW)independentlyassessedthe
Issue1of42015;
titlesandabstractsofstudiesweidentifiedbythesearchstrategyfor
4. MEDLINE(OVID)(1966to11February2015);
eligibility.Iftheeligibilityofatrialwasunclearfromthetitleand
5. EMBASE(OVID)(1974to11February2015);
abstract,weassessedthefull-textarticle.Weexcludedtrialsthatdid
6. CINAHL(EBSCO)(1982to11February2015);
notmatchtheinclusioncriteria(seethe’Criteriaforconsidering
7. PsycINFO(OVID)(1806to11February2015);
studies for this review’ section). We resolvedany disagreements
8. LILACS;(1982to15February2015);
betweenreviewauthorsregardingastudy’sinclusionbydiscussion.
9. PEDro;(1929to15February2015);
Ifwecouldnotresolvedisagreements,athirdreviewauthor(NEO)
10. WebofScience(ISI);(1945to15February2015).
assessedrelevantstudiesandwemadeamajoritydecision.Trials
TheTrialsSearchCo-ordinator oftheCochranePain, Palliative
werenotanonymisedpriortoassessment.Weobtainedpotentially
andSupportiveCareGroupdevisedthesearchstrategies.Sheand
relevantstudies identified in the firstround of screening in full
thereviewauthorsranthesesearches.Weusedacombinationof
textandindependentlyassessedtheseforinclusionusingthesame
controlledvocabulary,i.e.medicalsubjectheadings(MeSH)and
processoutlinedabove.Wedidnotapplyanylanguagerestrictions.
free-textterms.ThesearchstrategiesareinAppendix1.
Dataextractionandmanagement
Searchingotherresources
Two review authors (KMS andBMW) independently extracted
datafromallincludedtrials.Weextracteddatausingastandard-
Referencelists isedandpilotedform.Weresolvedanydiscrepanciesanddisagree-
mentsbyconsensus.Incaseswherewecouldnotachieveconsen-
Oncompletionoftheelectronicsearcheswesearchedthereference
sus,athirdreviewauthor(NEO)assessedthetrialandwetook
listsofalleligiblestudiesinordertoidentifyadditionalrelevant
a majority decision. We extracted the following data fromeach
studies.Inadditionwescreenedthereferencelistsofkeyphysio-
includedtrial:
therapytextbooksandprevioussystematicreviews.
1. countryoforigin;
2. studydesign;
Externalexperts 3. studypopulation(includingdiagnosis,diagnosticcriteria
We sent the list of included trials to a content expert to help used,symptomduration,agerange,gendersplit);
identifyanyadditionalrelevantstudies. 4. typeofnoxiousinitiatingevent:surgery,fracture,crush
injury,projectile,stabinjury,otherornoevent;
5. typeoftissueinjured:nerve,softtissue,bone;
Unpublisheddata 6. presenceofmedicolegalfactors(thatmayinfluencethe
Inordertominimisetheimpactofpublicationbiaswesearchedthe experienceofpainandtheoutcomesoftherapeutic
followingregistersanddatabasestoidentifyunpublishedresearch interventions);
aswellasresearchinprogress: 7. concomitanttreatmentsthatmayaffectoutcome:
1. OpenGrey(SystemforInformationonGreyLiteraturein medication,proceduresetc.;
Europe); 8. samplesize:activeandcontrol/comparatorgroups;
2. DissertationAbstracts(ProQuest); 9. intervention(includingtype,parameters(e.g.frequency,
3. NationalResearchRegisterArchive; dose,duration),settingandprofessionaldisciplineofthe
4. HealthServicesResearchProjectsinProgress; cliniciandeliveringthetherapy);
5. CurrentControlledTrialsRegister(incorporatingthemeta- 10. typeofplacebo/comparatorintervention;
registerofcontrolledtrialsandtheInternationalStandard 11. outcomes(primaryandsecondary)andtimepointsassessed;
RandomisedControlledTrialNumber); 12. adverseeffects;
Physiotherapyforpainanddisabilityinadultswithcomplexregionalpainsyndrome(CRPS)typesIandII(Review) 6
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
13. authorconflictofintereststatements; ofbias(participantsblindedtoallocatedinterventionand
14. assessmentofriskofbias. unlikelythatblindingbroken;orno/incompleteblindingbut
judgedthatbothinterventionarmsreflectactiveinterventionsof
relativelyequalcredibilitydeliveredwithequalenthusiasm);
Assessmentofriskofbiasinincludedstudies unclearriskofbias(insufficientinformationprovidedtopermit
ajudgementoflow/highriskofbias);orhighriskofbias
Weassessedtheoverallriskofbiasforeachincludedtrialontheba-
(participantsnotblindedtotheallocatedinterventionand
sisofanevaluationofkeydomainsusingamodifiedversionofthe
interventionsareclearlyidentifiableascontrolandexperimental;
Cochrane’Riskofbias’assessmenttool.Weclassifiedriskofbiasas
orparticipantsblindedtotheallocatedinterventionbutlikely
either’low’(lowriskofbiasforallkeydomains),’unclear’(unclear
thatblindingwasbroken);
riskofbiasforoneormorekeydomains)or’high’(highriskofbias
5. blindingofoutcomeassessment(investigator-administered
foroneormorekeydomains),asoutlinedintheCochraneHand-
outcomes)(checkingforpossibledetectionbias).Weassessedthe
bookforSystematicReviewsofInterventions(Higgins 2011a).We
methodsusedtoblindresearchersundertakingoutcome
alsoconsideredexperimentaldesign-specific(e.g.cross-overstudy
assessments(e.g.functionaltestingprotocols)fromknowledgeof
designs)’Riskofbias’issueswhereappropriate(Higgins2011b).
whichinterventionaparticipantreceived.Weassessedthe
We assessed thefollowing key domains of risks of bias for each
methodsasateither:lowriskofbias(researchersblindedto
includedtrialusingeither’yes’,’no’or’unclear’judgements:
allocatedinterventionandunlikelythatblindingbroken);
1. randomsequencegeneration(checkingforpossible
unclearriskofbias(insufficientinformationprovidedtopermita
selectionbias).Weassessedthemethodusedtogeneratethe
judgementoflow/highriskofbias);highriskofbias(researchers
allocationsequenceaseither:lowriskofbias(anytrulyrandom
notblindedtotheallocatedintervention;orresearcherblinded
process,e.g.randomnumbertable;computerrandomnumber
totheallocatedinterventionbutlikelythatblindingwasbroken);
generator);unclearriskofbias(methodusedtogenerate
6. incompleteoutcomedata(dropout)(checkingforpossible
sequencenotclearlystated);orhighriskofbias(studiesusinga
attritionbias).Wefirstassessedforriskofattritionbiasby
quasi/non-randomprocess(e.g.oddorevendateofbirth;
evaluatingparticipantdropoutratesaccordingtojudgements
hospitalorclinicrecordnumber);
basedonthefollowingcriteria:lowriskofbias(lessthan20%
2. allocationconcealment(checkingforpossibleselection
dropoutandappearsnottobesystematic,withnumbersfor
bias).Themethodusedtoconcealallocationtogrouppriorto
eachgroupandreasonsfordropoutreported);unclearriskof
assignmentdetermineswhetherinterventionallocationcould
bias(lessthan20%dropoutbutappearstobesystematicor
havebeenforeseeninadvanceof,orduringrecruitment,or
numberspergroupandreasonsfordropoutnotreported);high
changedafterassignment.Weassessedthemethodsusedas:low
riskofbias(greaterthanorequalto20%dropout);
riskofbias(e.g.telephoneorcentralrandomisation;
7. incompleteoutcomedata(methodofanalysis)(participants
consecutivelynumberedsealedopaqueenvelopes);unclearrisk
analysedinthegrouptowhichtheywereallocated)(checkingfor
ofbias(methodnotclearlystated);orhighriskofbias(studies
possibleattritionbias).Wefurtherassessedforriskofattrition
thatdonotconcealallocation(e.g.openlist));
biasbyseparatelyevaluatingtheappropriatenessofthemethod
3. blindingofstudyparticipantsandpersonnel(checkingfor
ofanalysisemployed,usingthefollowingcriteria:lowriskofbias
possibleperformancebias).Weassessedthemethodsusedto
(participantsanalysedinthegrouptowhichtheywereallocated
blindparticipantsandcareprovidersaseither:lowriskofbias
(intention-to-treat(ITT)orasanavailablecaseanalysis);unclear
(participantsandcareprovidersblindedtoallocatedintervention
riskofbias(insufficientinformationprovidedtodetermineif
andunlikelythatblindingbroken;orno/incompleteblinding
analysiswasbasedontheprincipleofITTorperprotocol);or
butjudgedthatbothinterventionarmsreflectactive
highriskofbias(ifperprotocolanalysisusedorwhereavailable
interventionsofrelativelyequalcredibilitydeliveredwithequal
dataisnotanalysedorparticipant’sdatawereincludedingroup
enthusiasm);unclearriskofbias(insufficientinformation
towhichtheywerenotoriginallyassignedto);
providedtopermitajudgementoflow/highriskofbias);orhigh
8. selectivereporting(checkingforpossiblereportingbias).
riskofbias(participantsandcareprovidersnotblindedtothe
Weassessedstudiesforselectiveoutcomereportingusingthe
allocatedinterventionandinterventionsareclearlyidentifiableas
followingjudgements:lowriskofbias(studyprotocolavailable
controlandexperimental;orparticipantsandcareproviders
andallpre-specifiedprimaryoutcomesofinterestadequately
blindedtotheallocatedinterventionbutlikelythatblindingwas
reportedorstudyprotocolnotavailablebutallexpectedprimary
broken);
outcomesofinterestadequatelyreportedorallprimary
4. blindingofoutcomeassessment(selfreportedoutcomes)
outcomesnumericallyreportedwithpointestimatesand
(checkingforpossibledetectionbias).Weassessedthemethods
measuresofvarianceforalltimepoints);unclearriskofbias
usedtoblindstudyparticipantsself-reportingoutcomes(e.g.
(insufficientinformationprovidedtopermitajudgementoflow/
painseverity)fromknowledgeofwhichinterventiona
highriskofbias);orhighriskofbias(incompletereportingof
participantreceived.Weassessedthemethodsaseither:lowrisk
Physiotherapyforpainanddisabilityinadultswithcomplexregionalpainsyndrome(CRPS)typesIandII(Review) 7
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
pre-specifiedprimaryoutcomesorpointestimatesandmeasures Wepresentedtreatmenteffectsizesusingappropriatemetrics.We
ofvarianceforoneormoreprimaryoutcomenotreported calculatedtheriskratio(RR)with95%confidenceintervals(CIs)
numerically(e.g.graphicallyonly)oroneormoreprimary fordichotomisedoutcomemeasures,andthenumberneededto
outcomesreportedusingmeasurements,analysismethodsor treat (NNT) as an absolute measure of treatment effect where
subsetsofdatathatwerenotpre-specifiedoroneormore possible.
reportedprimaryoutcomeswerenotpre-specifiedorresultsfora We expressed the size of treatment effect on pain intensity, as
primaryoutcomeexpectedtohavebeenreportedwereexcluded); measuredwithaVASorNRS,usingthemeandifference(MD)
9. otherbias.Weassessedstudiesforotherpotentialsourcesof (where all studies utilised the same measurement scale) or the
bias.Wedeterminedjudgementsregardinglow/unclear/highrisk standardisedmeandifference(SMD)(wherestudiesuseddifferent
ofbiasaccordingtothepotentialconfoundinginfluenceof scales).Inordertoaidinterpretationofthepooledeffectsizewe
identifiedfactors,forexample:lowriskofbias(appearsfreeof plannedtoback-transformtheSMDvaluetoa0to100mmVAS
otherpotentiallyserioussourcesofbiase.g.noseriousstudy format on the basis of the mean standard deviation (SD) from
protocolviolationsidentified);unclearriskofbias(othersources trialsusinga0to100mmVASwherepossible.
ofbiasmaybepresentbutthereiseitherinsufficientinformation WeanalysedthedatausingReviewManager(RevMan)(RevMan
toassesswhetheranimportantriskofbiasexistsorinsufficient 2014). We plotted the results of each RCT with available data
rationaleorevidenceregardingwhetheranidentifiedproblem as point estimates with corresponding 95% CIs and displayed
willintroducebias);orhighriskofbias(resultsmayhavebeen them using forest plots. If included trials demonstrated clinical
confoundedbyatleastonepotentiallyseriousriskofbias,e.g.a homogeneityweperformedameta-analysistoquantifythepooled
significantbaselineimbalancebetweengroups;aseriousprotocol treatmenteffectsizesusingarandom-effectsmodel.Wedidnot
violation;useof’lastobservationcarriedforward’whendealing performameta-analysiswhenclinicalheterogeneitywaspresent.
withmissingdata). Similarlywepresentedsecondary outcomes, though wedidnot
Wealsoevaluatedincludedtrialsfortheadditionalsourcesofbias considerthemformeta-analysis.
associatedwith:
1. samplesize;and
2. durationoffollow-up,asrecommendedbyMoore2010. Unitofanalysisissues
Smallstudiesaremorepronetobiasbecauseoftheirinherentim-
Allincludedtrialsrandomisedparticipantsattheindividualpartic-
precisionandduetotheeffectsofpublicationbiases(Dechartres
ipantlevel.Weplannedtometa-analyseestimatesoftreatmentef-
2013;Moore2012;Nüesch2010).Inadequatelengthoffollow-
fect(andtheirstandarderrors(SE))fromcluster-RCTsemploying
up may produce an overly positive view of the true clinical ef-
appropriatestatisticalanalysesusingthegenericinverse-variance
fectivenessofinterventions, particularlyinpersistentconditions
methodinRevMan(RevMan2014),assuggestedintheCochrane
(Moore2010).Theseadditionalcriteriawerenotconsidered’key
HandbookforSystematicReviewsofInterventions(Higgins2011b).
domains’andthereforedidnotinformjudgementsofatrial’sover-
Whereweconsideredsuchtrialstohaveemployedinappropriate
allriskofbias.Weassessedthesetrialsaccordingtothefollowing
analyses,weplannedtoutilisemethodsfor’approximatelycorrect
criteria:
analysis’wherepossible(Higgins2011b).Inaddition,weplanned
1. samplesize(checkingforpossiblebiasesconfoundedby
toentercross-overtrialsintoameta-analysiswhenitwasclearthat
smallsamplesize):weassessedtrialsasbeingatlowriskofbias
datawerefreefromcarry-overeffects,andtocombinetheresults
(greaterthanorequalto200participantspertreatmentarm);
of cross-over trials with those of parallel trials by imputing the
unclearriskofbias(50to199participantspertreatmentarm);
post-treatmentbetween-conditioncorrelationcoefficientfroman
highriskofbias(lessthan50participantspertreatmentarm);
includedtrialthatpresentedindividual participantdataanduse
2. durationoffollow-up(checkingforpossiblebiases
thistocalculatetheSEoftheSMD.Thesedatamaybeentered
confoundedbyashortdurationoffollow-up):weassessedtrials
into a meta-analysis using the generic inverse-variance method
asbeingatlowriskofbias(follow-upofgreaterthanorequalto
(Higgins 2011b). Issues concerning cluster-RCTs and crossover
eightweeks);unclearriskofbias(follow-upoftwotoseven
trialsdidnotariseaswedidnotidentifyanycluster-RCTsthatmet
weeks);orhighriskofbias(follow-upoflessthantwoweeks).
theinclusioncriteriaofthisreviewandwedidnotconductany
Tworeviewauthors(KMSandBMW)independentlyundertook
quantitativeanalysesontheoneincludedcrossovertrial.Wemay
the’Riskofbias’assessments,andresolvedanydisagreementsby
includesuch analyseswhererelevantdataare availableinfuture
discussion. Iftheycouldnotreachanagreement,athirdreview
updatesofthisCochranereview.
author(NEO)undertooka’Riskofbias’assessmentandwetook
amajoritydecision.
Dealingwithmissingdata
Weattemptedtocontacttheauthorsofincludedtrialswhennu-
Measuresoftreatmenteffect
mericaldatawereunreportedorincomplete.Iftrialauthorsonly
Physiotherapyforpainanddisabilityinadultswithcomplexregionalpainsyndrome(CRPS)typesIandII(Review) 8
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.