A Systematic Review of the Evidence for CompleteDecongestive Therapy in the Treatment ofLymphedema From 2004 to 2011Bonnie B. Lasinski, MA, PT, Kathryn McKillip Thrift, BS, DeCourcy Squire, PT,Melanie K. Austin, MPH, Kandis M. Smith, PhD, Ausanee Wanchai, RN, PhD,Jason M. Green, PhD, Bob R. Stewart, EdD, Janice N. Cormier, MD, MPH,
Jane M. Armer, RN, PhD, FAAN
Objective: To critically analyze the contemporary published research that pertains to theindividual components of complete decongestive therapy (CDT), as well as CDT as abundled intervention in the treatment of lymphedema.Data Sources: Publications were retrieved from 11 major medical indices for articlespublished from 2004-2010 by using search terms for lymphedema and managementapproaches. Literature archives of the authors and reference lists were examined through2011.Study Selection: A research librarian assisted with initial literature searches by usingsearch terms used in the Best Practice for the Management of Lymphoedema, plus expandederms, for literature related to lymphedema. Authors sorted relevant literature for inclusionnd exclusion; included articles were sorted into topical areas for data extraction andssessment of level of evidence by using a published grading system and consensus process.he authors reviewed 99 articles, of which 26 met inclusion criteria for individual studiesnd 1 case study did not meet strict inclusion criteria. In addition, 14 review articles and 2onsensus articles were reviewed.ata Extraction: Information on study design and/or objectives, participants, out-
omes, intervention, results, and study strengths and weaknesses was extracted fromach article. Study evidence was categorized according to the Oncology Nursing Societyutting Evidence into Practice level of evidence guidelines after achieving consensusmong authors.ata Synthesis: Levels of evidence were only moderately strong, because there were few
andomized controlled trials with control groups, well-controlled interventions, and preciseeasurements of volume, mobility and/or function, and quality of life. Treatment interven-
ions were often bundled, which makes it difficult to determine the contribution of eachndividual component of treatment to the outcomes achieved.onclusions: CDT is seen to be effective in reducing lymphedema. This review
ocuses on original research about CDT as a bundled intervention and 2 individualomponents, manual lymph drainage and compression bandages. Additional studiesre needed to determine the value and efficacy of the other individual components ofDT.
PM R 2012;4:580-601
INTRODUCTION
Lymphedema (LE) is a swelling of the soft tissues that results from the accumulation ofprotein-rich fluid in the extracellular spaces. It is caused by decreased lymphatic transportcapacity and/or increased lymphatic load. The severity of LE is usually graded by using thescale (Table 1) from the International Society of Lymphology [1]. LE is a chronic, progres-sive condition that impairs mobility and joint movement as the swollen areas increase in size
and weight, often causing postural alterations and pain as the individual struggles to
B.B.L. Lymphedema Therapy and The Boris-Lasinski School, Woodbury, NYDisclosure: nothing to disclose
K.M.T. The Dr. Vodder Schools, Victoria, Brit-ish Columbia, Canada/Walchsee, AustriaDisclosure: nothing to disclose
D.S. Complex Lymphatic Therapy Coursesand Piedmont Hospital Lymphedema Pro-gram, Atlanta, GADisclosure: 3, Emory University Physical Ther-apy School, Lighthouse Lymphedema Net-work, Thomas Hovatter Lymphedema Aware-ness day; 9, Lymphology Association of NorthAmerica Board member
M.K.A. University of Missouri Sinclair Schoolof Nursing, Columbia, MODisclosure: nothing to disclose
K.M.S. University of Missouri Sinclair Schoolof Nursing, Columbia, MODisclosure: nothing to disclose
A.W. University of Missouri Sinclair School ofNursing, Columbia, MODisclosure: nothing to disclose
J.M.G. University of Missouri Sinclair Schoolof Nursing, Columbia, MO; Department ofComputer Science, College of Engineering,University of Missouri, Columbia, MODisclosure: nothing to disclose
B.R.S. University of Missouri Sinclair Schoolof Nursing, Columbia, MODisclosure: nothing to disclose
J.N.C. MD Anderson Cancer Center, Univer-sity of Texas, Houston, TXDisclosure: nothing to disclose
J.M.A. Ellis Fischel Cancer Center, DC116.05 Suite 415, 115 Business Loop 70West, University of Missouri Sinclair School ofNursing, Columbia, MO 65211. Address cor-respondence to: J.M.A.; e-mail: [email protected]: nothing to disclose
Disclosure Key can be found on the Table ofContents and at www.pmrjournal.org
Submitted for publication March 27, 2012;accepted May 8, 2012.
hysical Medicine and RehabilitationVol. 4, 580-601, August 2012
perform activities of daily living. Even a relatively “minimal”LE can alter body image and cause significant impairments inphysical and psychosocial function and quality of life (QOL).
Complete decongestive therapy (CDT) is currently recog-nized as the standard of care in LE treatment [1-3]. Ideally,the initial intensive phase of CDT is performed daily untilmaximal volume reduction and normalization of tissue tex-ture is achieved [3]. CDT consists of (1) an average of 60minutes of manual lymph drainage (MLD), a specializedgentle massage to stimulate the lymphatic system; (2) multi-layer, short-stretch compression bandaging (CB) with foamor layers of fabric padding of the affected limbs, also knownas multilayer limb bandages (MLLB) or CB; (3) exercises toenhance lymphatic pumping; (4) meticulous skin care of theaffected areas; and (5) fitting of appropriate compressiongarments (CG) to maintain the reductions achieved throughtreatment. Patient education in self-care is critical for success-ful long-term outcomes. Unfortunately, reimbursement forCDT has been hampered by a lack of rigorous researchevidence.
Boris et al [4] and Ko et al [5] conducted seminalresearch in the 1990s that demonstrated the value of CDTin patients who adhered to the self-care regimen afterintensive therapy over longer periods of follow-up [4] andwith larger samples than those generally found [5]. Boriset al [4] conducted a retrospective study of a 4-weekintensive course of CDT in 119 patients (56 unilateralupper extremity, 38 unilateral lower extremity, 23 bilat-eral lower extremity, and 2 bilateral upper extremity) with36-month follow-up. Initial volume reductions averaged62.6% in patients with unilateral upper extremity LE and68.6% in patients with 1 affected leg. After 36 months’
Table 1. Stages of lymphedema*
Stage
, latency:limb atrisk
Lymph stasis is presentNo clinical signs of lymphedemaIndividual may experience intermittent ache,fatigue, heaviness in limb at risk
1 Edema pits on pressureSwelling reduces completely on elevationNo clinical fibrosis presentVariable time to progression to stage 2
2 Edema no longer pitsSwelling does not completely reduce onelevation
Clinical fibrosis is presentCan be combination of pitting andnonpitting edema: mixed stage I � II
3 Skin becomes thickened and leatheryHypertrophy of subcutaneous tissues developPapillomas and warts develop on skinTissue bulges and skin folds developLess common in upper extremity
Reproduced with permission from [1].
follow-up, the average reduction increased to 63.8% for
unilateral upper and remained at 62.7% for unilaterallower extremity LE. Patients with bilateral LE maintainedtheir initial reductions.
Ko et al [5] conducted a prospective study of 299patients with LE (149 upper extremity and 150 lowerextremity) treated with CDT for an average of 15.7 days.LE reductions averaged 59.1% for the patients with upperand 62.7% for patients with lower extremity LE. Theaverage follow-up was 9 months, and 86% of the patientswere adherent and maintained 90% of their initial reduc-tions, whereas nonadherent subjects lost 33%. Patientadherence with compression and decongestive exercisescorrelated with maintaining and improving treatment re-sults [4,5].
CDT is criticized as time consuming, costly, and not wellresearched. Although identified as the criterion standardmanagement approach for LE, the level of evidence ratingby the International Lymphoedema Framework (www.lympho.org) for MLD was “C: experienced common sensejudgment” (Oncology Nursing Society Putting Evidenceinto Practice [PEP] level: “effectiveness not established”(Oncology Nursing Society, Pittsburgh, PA), and for CBwas “B: limited supporting research evidence” (PEP level:“likely to be effective”). Stakeholders require evidence tosupport the intensity of initial treatment as well as theimportance of each component of the regimen in achievingoutcomes that lead to improved function and QOL. There-fore, the American Lymphedema Framework Project(ALFP) (www.alfp.org) undertook an extensive review ofthe literature that pertains to the management of LE from2004 to 2011 with the following aims: (1) to provideevidence for the second edition of Best Practice Documentfor the Management of Lymphoedema, a document pub-lished in 2006, based on literature reviewed through 2004(Tables 2 and 3) [6]; and (2) to inform efforts to elevate thelevel of evidence for LE treatment.
In 2009, the Medicare Evidence Development and Cov-erage Advisory Committee (MEDCAC) met to review thecurrent evidence for a variety of LE treatment modalities.The MEDCAC concluded that the existing evidence givesreasonable confidence that these commonly used proto-cols for the treatment for LE are effective: (1) CDT (includ-ing MLD, compression bandaging and/or garments, exer-cise, skin care), (2) CDT in conjunction with a sequentialpump, and (3) CB systems, CGs, and sequential pumps.However, it was recognized that there remains a paucity ofhigh-level evidence that supports best practices in themanagement of LE. The Centers for Medicaid and Medi-care Coverage and Analysis Group will use the 2009MEDCAC analysis [7] in revising policies to coordinatecoverage for LE treatment. Therefore, it is imperative todocument the levels of evidence in the contemporary
literature, 2004-2011, and beyond, both for best practices
582 Lasinski et al EVIDENCE FOR COMPLETE DECONGESTIVE THERAPY IN LYMPHEDEMA
Table 2. Review articles and consensus document included in CDT systematic review
Study Topic Time Frame No. Reviewed Conclusions
Cheifetz andHaley [52],2010
Review of articles onmanagement ofBCRL by using theSackett levels ofevidence
2005-2009 21 articles (11 onCDT and 10 onexercise; also 9 onrisk factors)
Several treatment options exist for LEmanagement. Although the literature doesnot identify which treatment is superior,education, exercise, and MLD are importantcomponents of a successful treatmentprogram for reducing edema and increasingfunction. The article did not review the role ofcompression.
evoogdt et al[31], 2009
Review of treatmentmodalities for BCRL
1980-2005 15 articles CDT is an effective therapy for LE, but the roleof each component is unclear; higher qualitystudies are needed. Five of the studiescovered IPC; several studies included armelevation, but none focused on it. Theresearchers concluded from the literatureavailable that the long-term effect of IPC andthe benefits of elevation on LE are not yetproved. One RCT reviewed showed higherreduction of LE by the MLD group than thegroup without MLD and similar reduction insubjective symptoms between the groups.
arki et al [53],2009
Effectiveness and costof current treatmentpractices for treatingBCRL in Finland
1991-2006 14 RCTs The main problems that the researchers foundwith the studies that they reviewed were poormethodology, including small sample sizesand high risk of bias. They found that CB hadsome effectiveness but that the studies didnot establish the effectiveness of othermodalities, such as laser (2 studies; decreaseof LE was not analyzed). IPC (4 studies): nosignificant difference between IPC and nointervention; no significant differencebetween MLD and CG vs IPC and CG; nosignificant difference between IPC and CG vsSLD and CG; greater decrease between IPCwith CG vs IPC without CG. Electricalstimulation (1 study): no significant differencebetween CG with vs CG without electricalstimulation.
ligman et al[51], 2004
Evidence base fortreatment of BCRL
1988-2000 10 RCTs Articles on physical therapies and on medicalinterventions were reviewed as well asquestionnaires to oncologists and therapistsfor their recommendations and/or opinions.On the basis of the studies and the survey ofhealth care practitioners, the researchersrecommended the use of compressiongarments with an added benefit of MLD. In 1study reviewed, IPC compared with nointervention did not show a significantdifference. Another study examined MLD as astrategy to prevent the onset of LE andshowed a nonstatistically significantadvantage to the use of MLD vs CG. Thereview researchers found most of the studiesinconclusive because of poor study designand/or small sample size and recommended
further research.
583PM&R Vol. 4, Iss. 8, 2012
Table 2. Continued
Study Topic Time Frame No. Reviewed Conclusions
Leal et al [32],2009
Review of treatmentmodalities for BCRL
1951-2009 18 studies Within the therapeutic modalities used for LEtreatment, CDT undoubtedly has the strongestscientific support. Its application, togetherwith IPC, has demonstrated efficacy. Newtechniques with satisfactory results are beingstudied, such as HVES and laser therapy.Combined techniques produce the mostbeneficial effects, depending on thephysiopathology of the LE. Selection of bestcombination of therapies is based on adetailed assessment of individual cases. MLDwas not found to be an effective stand-alonetreatment; CB is needed in combination withMLD for optimal effectiveness.
McCallin et al[30], 2005
Effectiveness oftreatment for BCRL
1980-2004 20 articles The researchers reviewed studies on CDT andon individual components (MLD, CB, exercise,CG) and on adjuncts to treatment (laser,IPC). They found the studies methodologicallylimited. The weight of the evidence showedeffectiveness of CDT but failed to stronglydemonstrate the role of the individualcomponents. The researchers concluded thatstudies of MLD, exercise, skin care, and laserwere limited in number and suggest thatindividuals with stage II or III LE may benefitfrom the addition of MLD to their treatmentregimen. They concurred with otherresearchers who conclude that larger studieswith longer follow-up examining individualcomponents of CDT are needed.
1980-1996 13 articles Researchers modified Sackett rules ofevidence to assess their study results.
Level 1 recommendation: CG reduced limbsize after 6 mo use; Level crecommendations: elevation alone is notuseful; CDT does tend to reduce limbs;therapies with combined modalities (eg, CDTplus IPC) also showed promise.
Meneses andMcNees [55],2007
Upper extremity LEafter treatment forbreast cancer: areview of literature
1997-2006 86 articles cited Although LE is not a curable condition, ways toprevent skin breakdown and relieve sufferingare available. Risk factors for LE includeaxillary node dissection (vs smaller risk insentinel node biopsy), weight gain, infection,and injury. Patients aware of LE can takeprecautions to lower their risk. Results ofstudies show reduced QOL with LE. Althoughmethodology in studies is sometimes weak,CDT appears to be helpful in reducing
lymphedema.
P
584 Lasinski et al EVIDENCE FOR COMPLETE DECONGESTIVE THERAPY IN LYMPHEDEMA
Table 2. Continued
Study Topic Time Frame No. Reviewed Conclusions
Moseley et al[28], 2007
Review ofconservativetherapies for BCRL
1977-2004 43 studies Studies on CDT and on MLD, compression,laser, oral drugs, exercise, and elevation werereviewed for quality of evidence andeffectiveness of treatment. Treatments byhealth care professional had better resultsthan self-care, but self-care was better thanno care and important for maintenance ofresults. MLD and compression had greatestbenefit, followed by pumps, MLD alone, oraldrugs, laser, compression, exercise, elevation,and self-MLD. Level of evidence was poor,and there is a need for larger, better-designed clinical trials.
Badger et al[50], 2004
RCTs that testedphysical therapieswith a follow-upperiod of at least 6mo
Only 3 (representing N � 150) of 36 reviewedstudies met established criteria. Each hadlimitations: different interventions were notreplicated, and findings are unable to becompared. One crossover study of MLDfollowed by self-administered massage vs notreatment concluded that improvementsseen in both groups were attributable to theuse of compression sleeves and that MLDprovided no extra benefit at any point duringthe trial. Another trial looked at hosiery vs notreatment and had a very high dropout rate,with only 3 of 14 participants in theintervention group finishing the trial and only 1of 11 in the control group. The researchersconcluded that wearing a compressionsleeve is beneficial. The bandage-plus-hosieryvs hosiery-alone trial concluded that, in thismixed group of participants, bandage-plus-hosiery resulted in a greater reduction inexcess limb volume than hosiery alone andthat this difference in reduction wasmaintained long term. There is a great needfor well-designed RCTs to determine the bestapproaches to managing LE.
artsch et al[39], 2008
CVI and LE 1997-2007 174 references A low level of compression (10-30 mm Hg) iseffective in managing venous leg edema.Moderate compression (30-40 mm Hg) iseffective in healing ulcers, preventing post-thrombotic syndrome, and managing LE.There is little evidence on the differentialeffect of elastic and short stretch CB.Sustained pressure of 60 mm Hg in supineposition decreased arterial blood flow. Ifpressure �40 mm Hg is needed, then inelasticmaterial provides greater working pressure
and lower resting pressure on the limb.
I
ClsQ
585PM&R Vol. 4, Iss. 8, 2012
Table 2. Continued
Study Topic Time Frame No. Reviewed Conclusions
Poage et al[2], 2008
Level of evidence forLE management
1997-2007 218 articles Common limitations were found in many of thestudies reviewed, including small sample sizes,lack of randomized control groups, impreciseintervention standardization within and acrossgroups, imprecise or diverse measurementapproaches, and limited follow-up. Longerfollow-up time frames are needed beforedefinitive conclusions can be reachedregarding interventions for patients at risk foror with LE.
Shrubb andMason [40],2006
Review of literature onDVT in the generalpopulation toconsider applicabilityto the populationwith LE: DVT and legLE
1986-2005 21 articles Difficulties with research: heterogeneouspopulations, lack of knowledge about LE,care based on symptom management. Someof the studies reviewed were of patientsreceiving palliative care, some of them bed-bound, and so extrapolating conclusions fromthem to the ambulatory LE population wasproblematic. Compression stockings areeffective in managing DVT in ambulatorypatients. MLLB is superior to off-the-shelf CG,with a better fit and comfort for patients.Patients with LE may need higher pressurethan patients with DVT.
in document(developed bygroup consensuspanel fromliterature reviewand consensus ofsubject matterexperts)
The document attempts to amalgamate thebroad spectrum of protocols advocatedworldwide for the diagnosis and treatment ofperipheral LE into a coordinatedproclamation that represents the internationalcommunity. No treatment method has reallyundergone a satisfactory meta-analysis (letalone rigorous, randomized, stratified, long-term, controlled study). With thisunderstanding, the absence of definitiveanswers and optimally conducted clinicaltrials and with emerging technologies andnew approaches and discoveries on thehorizon, some degree of uncertainty,ambiguity, and flexibility along withdissatisfaction with current LE evaluation andmanagement is to be expected.
LF Framework[6], 2006
Consensus documentof the ILF
2006 101 citations The BPD was derived from a U.K. NationalConsensus on Standards of Practice forpeople who are at risk of or who have LE. Theconsensus process was launched in 2002 bythe ILF with input from national patientsupport groups, patients with LE, nationalprofessional LE groups, clinical experts, andindustry. The document was reviewed by aninternational panel of experts and endorsedby key national LE organizations.Recommendations were derived byconsensus with classification according to theU.K. NHS Health Technology Assessmentmodel for guideline development.
DT � manual lymphatic drainage, compression bandaging; BCRL � breast cancer treatment–related lymphedema; LE � lymphedema; MLD � manualymphatic drainage; IPC � intermittent pneumatic compression, pump; RCT � randomized controlled trial; CB � compression bandaging using padding andhort-stretch bandages and garments, exercise, skin care; CG � compression garment; SLD � simplified/self-MLD; HVES � high-voltage electrical stimulation;OL � quality of life; CVI � chronic venous insufficiency; DVT � deep vein thrombosis; MLLB � multilayer limb bandaging; ISL � International Society of
Lymphology; ILF � International Lymphoedema Framework; BPD � best practices document; NHS � National Health Service.
586 Lasinski et al EVIDENCE FOR COMPLETE DECONGESTIVE THERAPY IN LYMPHEDEMA
Table 3. Articles detailed in CDT systematic review
Jeffs [29], 2006 Retrospective 168 of 263 BCRL ND Perometer
Kasseroller andBrenner [27]2009
Prospective RCT 61 BCRL, 2 groups: CB �alginate
LVF classificationU/E
TM every 4 cm, cyl
587PM&R Vol. 4, Iss. 8, 2012
Table 3. Continued
Intervention F/U Results Strengths Weakness
Standard therapy:CG (32-40 mmHg); exinstruction;education in skincare andprecautions;standard therapyplus MLD group:MLD 8 times in 2wk andinstruction indaily SLD
Only 38 patients hadf/u at 12 mo
No significant difference in thereduction in LE over timebetween the 2 groups; resultsfrom pooled data showedthat LE reduction after 1 mowas statistically significantcompared with the baseline;over time, further slightimprovement but notsignificant
Repeated measurements;control group; power of90% sample
SS; NB; MLD 8 timesin 2 wk and waspart of 1 h Tx,including SLDteaching
CB � CG vs CGalone
24 wk CB � CG was 2 times aseffective as CG alone
SI; 6 mo f/u MNS
Vod Var MLD 5times/wk for 2wk, with orwithout CB
No funding for f/u No significant difference in %reduction of swellingbetween groups: MLD only:LV loss 80.6% � 0.2% vs MLD� CB: LV loss 72.6% � 0.2%,mean (SD)
No dropouts in eithergroup
SS, NR, NB, NLTF
CB to L/E ofsubjects withand without LE
24 h Pressure under CB reduced37% in normal subjects and48% in subjects with LE; LVloss was 2.6% (60 mL) innormal subjects and 1.2% (50mL) in subjects with LE
SI accuratemeasurements
SS; HS; only 24-h f/u
CB to U/E,measured sub-bandagepressure overtime; measuredLV change overtime
24 h 9.2% volume reduction withlow pressure CB; 4.8%reduction with high pressureCB; low pressure toleratedbetter; all CB lost pressureover time
SI addressed patientcomfort over time;compared with high orlow pressure CB; QOLmeasured
SS, only 24-h f/u
CDT, includingVod Var MLD vsCDT without MLD3 times/wk for 4wk
None listed Reduced excess volume:55.7% in MLD group, 36% innon-MLD group
12 mo 100% experienced reduction:70% reduction in patients withlimb edema; 40% reductionin patients with complexconditions; 30% reduction inpatients with mild swellingdoing home care
Large sample; perometerincreased; reliability
NC, NR
CDT with VodMLD 2 times/dfor 5 d for 3 wk; 3weekends: IPC �CB or IPC � CB
None listed MLD group reduced 44.1%-46.1%; CB only groupreduced 37.2%-38.6%; mild LEsubjects in MLD groupreduced the most
BA; sample size chosenfor 80% power
SS, NLTF, 10%dropout
60-90 min CDT, 5times/wk untilplateau
None listed Reduction of excess LV forboth groups: 22%, nontumor:range �21% to 164% inmedian of 12 visits. Similarreductions took longer forpatients with active tumors:range of �23% to 72% inmedian of 15 visits
Included patients onchemotherapy
CDT, 30 min VodVar MLD, 5times/wk, mean11.8 d
None listed More swelling associated withhigher BMI, longer duration,but all groups reduced 36%-38%
Large sample size NB, NC; LE notdefined
CDT: 30 min VodVar MLD Tx 11 d;then HP of dailyCG, CB 3 nights/wk, MLD 1-3times/wk
426 patients (80%) at6 mo; 356 patients(66%) at 12 mo
Volume decreasedsignificantly with meanabsolute volume reduction of407 (range, 374-440 mL); CBand CG factor in continuedreduction �10% in 28% ofpatients who were availablefor follow-up
Repeated and LTE; largesample size; HS and Tx;IP; QT
NR; 34% of patientslost to f/u at 12mo
Group A: 45 minVod MLD, 5times/wk for 3 wkthen a 6-wknontreatmentperiod, then SLDdaily for 3 wk;group B: SLDdaily for 3 wk,then 6-wknontreatmentperiod, then 45min Vod MLD0.5/wk for 3 wk;both groups: CG.skin care, andinformationabout LE
None listed MLD led to significantdecrease of excess LV andreduced dermal thickness,improved emotional function,dyspnea, and sleepdisturbance, but other QOLsubscales did not achievestatistical significance; SLDdid not result in significantchanges in any outcomemeasurements
Control group; repeatedmeasures; includedtruncal
SS, NB
60 min CDT, 6/wkuntil plateau
None listed U/E lost 54% after first day, 8%more after second day,plateaued at 59.1% in 4 d(range, 2-10 d); L/E lost 55.5%after first day, 11% more aftersecond day, plateaued at73.5% in 5 d (range, 2-17 d)
Japanese subjectshad lower BMIthan subjects inU.S. studies; NC,NB
Ex only vs ex andCG
24 h Immediate increase in volumeafter ex; at 24 h, no significantdifference from baseline orbetween the groups
SS
45-60 min MLD 5times/wk,2-4 wk � CB, ex,fit with CG;home programSLD, ex, CG; CB
1 mo 43.6% average volumedecrease; trend towarddecreased QOL withincreased LV and statisticallysignificant increase QOL withLV decrease
HS, multi-site MNS; NC; bias;researchersscored QOLquestionnaire; 8subjects lost in f/u
3 nights/wk
590 Lasinski et al EVIDENCE FOR COMPLETE DECONGESTIVE THERAPY IN LYMPHEDEMA
Table 3. Continued
Study Design Sample Define LE Measurements
Effectiveness not establishedHwang et al[48], 2007
Prospective 7 U/E; 13 L/E ND Lymphoscintigram
Johansson et al[20], 1998
Prospective RCT 24 BCRL (12 MLD; 12IPC)
More than 10%differencebetween arms
Volumetry, arm mobility,strength, and subjectiveassessment
Johnstone et al[22], 2006
Retrospective 11 patients (no. ofpatients who returnedfor f/u of 82 seen)
ND F/U TM every 4 cm, cyl
Karadibak et al[23], 2008
Prospective 62 BCRL �2 cm TM every 3 cm,volumetry
Kim et al [12],2007
Prospective 53 BCRL ND TM at 6 sites, TC
Liao et al [24],2004
Prospective 18 U/E, 12 L/E �2 cm TM, every 10 cm, TC
Mondry et al[13], 2004
Prospective 20 BCRL �2 cm, �200 mL TM every 2 inches in bothdirections fromolecranon
591PM&R Vol. 4, Iss. 8, 2012
Table 3. Continued
Intervention F/U Results Strengths Weakness
Lymphoscintigramat baseline, CDT,then 1-y follow-up on results
12 mo Those with good results fromCDT after 1 y (skin condition,decrease in reportedsymptoms and a volumereduction of at least 15%)had had lymphoscintigramsthat showed a lack ofcollateralization and/or amain lymph vessel beforetreatment
Blinded SS, LE not defined,not stated if 15%reduction is oflimb volume oredema volume
Part I: 2 wk CG,patients wererandomized; partII: group 1, 45min MLD for 2wk; group 2, 2 hIPC at 40-60 mmHg for 2 wk
None listed During part II, significantreduction in MLD group 15%(P � .001); and, in the IPCgroup, 7% (P � .03); only theMLD group reported a furtherdecrease of tension andheaviness; both groupssignificantly decreased armvolume but no significantdifference between the 2groups
Control group SS, NLTF; MLDgroup older andLE longer duration
60-90 min CDT for5 d/wk, toplateau; thenmaintenancephase: CG byday, CB by night,ex, SLD
Median 7.5 mo(range, 6-13 mo)
7 patients reportingcompliance had significantlybetter results at f/u (loss of3.4% edema [range, �2.8%to �10.9%]) than did 4patients reportingnoncompliance (gain of 3.4%[range, �0.05% to �6.22%])
HS; full CDT protocol used SS, NC; majority lostto f/u; LE notdefined
CDT, 60 min VodVar MLD, 5times/wk for 3wk, then HP ofCG (10-20 mmHg) and ex
12 wk for QOL Reduced 55% in intensivephase; QOL and activity levelincreased at follow-up
Full CDT protocol used NC, LV reductionnot assessed atfollow-up
CDT with 45-60min Vod MLD5/wk for 2-4 wk;HP: SLD, ex, CGdaily, with CB 3nights/wk
6 mo QOL and functional scoresmeasured by SF-36;increased after treatment;reduction of limb aftertreatment: 42%; at 6 mo,regressed to 15% reductionfrom baseline
Full CDT protocol used SS, NB, NC,adherence notmeasured
CDT, 30 min C-SMLD, 5/wk,4-21 d
None listed Pretreatment swellingcorrelated with age andduration of swelling;percentage of reduction wasnot significantly affected bythese factors: U/E reduced67.6%; L/E reduced 68.1%
SS, NC NB, noreasons given forvariation inendpoint
60-90 min CDT 5times/wk for2-4 wk
3 mo, 6 mo, 1 y Decrease 138 mL afterintensive phase; longertreatment resulted in agreater decrease but lessadherence during Tx course;QOL gradually increasedduring Tx and f/u; paingradually decreased; limbsize began increasing during
Full CDT protocol used,LTE
SS; NB; NC; did notmeasure higherthan 6 inchesproximal to theolecranon; only13 of 20 patientsleft at final f/u
f/u
rcGv
ClCFltPCivcaa
FaaaraaratAs
ethod
592 Lasinski et al EVIDENCE FOR COMPLETE DECONGESTIVE THERAPY IN LYMPHEDEMA
in LE management and to guide future research efforts tosupport the evidence base for reimbursement.
The goal of this article is to critically analyze the re-search literature from 2004 to 2011 that pertains to theindividual components of MLD and CB as well as CDT asa multicomponent LE treatment regimen. This review willexamine the methods, outcome measures, strengths andlimitations, and results of the research studies. The find-ings will then be discussed in terms of the effectiveness ofCDT treatment for LE, with recommendations for clinicalpractice and future research. Review of alternative thera-pies outside CDT is under development elsewhere; thisreview focuses on original research about CDT as a bun-dled intervention and 2 individual components, MLD andCB. Due to the selected time frame (2004-2011) and thedesire to build upon seminal research from prior years,published reviews were separately evaluated. Interna-tional non-English literature also was included if a trans-lation was available.
METHODS
A research librarian assisted with initial searches with theterms used in the Best Practice for the Management ofLymphoedema [6] plus expanded terms for all literatureelated to LE (2004-2010). The databases searched in-luded PubMed, CINAHL (CINAHL Information Systems,lendale, CA), the Cochrane Database of Systematic Re-
Table 3. Continued
Study Design Sa
O’Neill andBeatus [25],2006
Prospective 17 BCRL
Yamamoto andYamamoto[44], 2007
Retrospective 27 U/E, 55 L
Effectiveness not established: case studyWhitaker [43],2007
Single case study
CDT � manual lymphatic drainage, compression bandaging and garments,drainage; CG � compression garment; ex � exercise; SLD � simplified/senonblinded; Tx � treatment; RCT � randomized controlled trial; CB � comprintervention; MNS � measurements not standardized; BCRL � breast cancerof the Vodder method; Vod MLD � Vodder MLD; LV � limb volume; NR �water displacement; L/E � lower extremity; HS � homogenous sample; U/E �index; cyl � cylinder formula used to figure volume; IPC � intermittent pneumvolume; BA � blinded assessors; BMI � body mass index; NC � no controlsSF-36 �Short-form health survey with 36 questions; C-S � Casley-Smith m
iews (The Cochrane Collaboration, Oxford, England), v
ochrane Controlled Trials Register (The Cochrane Col-aboration, Oxford, England), PapersFirst (OCLC Onlineomputer Library Center Inc, Dublin, OH), Proceedings-irst (OCLC Online Computer Library Center, Inc., Dub-
in, OH), Worldcat (OCLC Online Computer Library Cen-er, Inc., Dublin, OH), PEDro (Centre for Evidence-Basedhysiotherapy, Sydney, Australia), National Guidelinelearing house (Agency for Healthcare Research and Qual-
ty, U.S. Department of Health and Human Services, Rock-ille, MD), ACP Journal Club (American College of Physi-ians, Philadelphia, PA), and DARE (Centre for Reviewsnd Dissemination, University of York, York, UK), as wells from our archives.
The literature was sorted for inclusion or exclusion (seeigure 1). Selected references were sent to ALFP researchssociates who reviewed abstracts to apply broad inclusionnd exclusion criteria of LE/non-LE (Screening 1). ALFPuthors (K.M.S., M.K.A., B.R.S., J.N.C., J.M.A.) sortedelevant literature by passing Screening 1 into includednd excluded articles and topical areas (Screening 2). Fullrticles were requested for selected abstracts for furthereview. The studies were grouped by topic and assigned touthors for data extraction and to evaluate the quality ofhe evidence by using a consensus process (Screening 3).rticles from 2011 were identified by the coauthors,creened, and included, as appropriate.
Topic authors (B.B.L., K.M.T., D.S.) reviewed the rele-
Define LE Measurements
Symptoms Volumetry
ND TM at 7 points; TC;ultrasound
ND Circumference
, skin care; LE � lymphedema; f/u � follow-up; MLD � manual lymphaticSS � small sample size; plateau � no further significant reduction; NB �bandaging by using padding and short-stretch bandages; SI � standardizednt–related lymphedema; TM � tape measurement; Vod Var MLD � variationdomized; NLTF � no long-term follow-up; ND � not defined; volumetry �extremity; QOL � quality of life; LVF � location, volume difference, skin-foldpression, pump; IP � inpatient; TC � truncated cone formula used to figure
ant included library for verification of the appropriate-
“Sccrtmvwu52u
593PM&R Vol. 4, Iss. 8, 2012
ness of inclusion, and possible omissions, with rationaleprovided for each. Studies that used case series designswere included if the number of cases in the study was morethan or equal to 10. In addition, 1 individual case reporton genital LE was included due to the paucity of literaturein this area. No gray literature was included: nonrefereedarticles, abstracts, and dissertations were excluded. Intotal, 56 articles were excluded by the topic authors due toduplication, inability to obtain English translation, inade-quate sample size, insufficient level of evidence due tostudy design, and failure to meet inclusion criteria.
The level of evidence for each study was assessed by usingthe research grading system from the PEP level of evidenceguidelines (Table 4), a system judged to be both reliable andaccessible [2,8,9]. Each topic author rated all articles and thefinal rating was agreed upon by consensus.
RESULTS
Ninety-nine articles related to LE treatment were re-viewed, of which 26 studies met inclusion criteria (Table3). In addition, 1 article that did not meet study size, alongwith 14 review articles and 2 consensus documents wereincluded (see Table 2). Fifteen articles were scored aslikely to be effective” (according to PEP classification).even were randomized controlled trials (RCT) (2 withrossover), 4 retrospective, 3 prospective, and 1 case-ontrol study. Twelve studies focused on breast cancer–elated LE (BCRL) exclusively, whereas 3 included bothhe upper and lower extremities. Nine used circumferenceeasures, 2 perometry, 5 volumetry or a combination of
olumetry and circumference, 1 measured tissue thicknessith ultrasound and calipers, and 1 measured pressurender the CB. The number of subjects ranged from 29 to37. Nine studies reported no follow-up (60%), 2 had4-hour follow-up (13.3%), 1 had 6-month (6%) follow-
Table 3. Continued
Intervention F/U Resu
CDT, 30 min MLD,3-5/wk for 3-5 wkvs CB only; no excomponent
None listed Volume decreaapproximatelyincreased QOLgrip strength, d
60-90 min CDT,3-6/wk for 3-26 d(average, 6 d)U/E, 2-35 d(average, 10 d)L/E
None listed L/E reduced 73.reduced 58.7%
SLD and appliedWhitaker pouch
3 wk Scrotum circumdecreased in 2and 8.7 cm)
p, and 3 had 12-month follow-up (20%). Assessors were
not blinded to the intervention in 14 of the 15 studies, and2 measured the intervention impact on the subjects’ qual-ity of life (QOL).
Two articles were scored as “benefits balanced withharm.” One RCT of 31 subjects with BCRL studied volumechange achieved with exercise combined with wearingCGs versus exercise alone. Volume was measured by volu-metry and bioimpedance, with only a 24-hour follow-up[10]. The other was a prospective study of 57 subjects withlower extremity LE who received 2-4 weeks of MLD plusCB and exercise. Volume change was measured by circum-ference, with 1-month follow-up [11]. Both studies as-sessed the impact of intervention on subjects’ QOL. Asses-sors were not blinded in either study.
Ten articles were scored as “effectiveness not estab-lished.” Seven were prospective (1 RCT), 2 retrospective,and 1 single case study. Six focused exclusively on BCRL,3 included lower extremity LE, and a single case study ongenital LE. Eight studies measured volume reduction bycircumference, 1 by lymphoscintigram, and 1 by volume-try. QOL was assessed in 3 studies. Sample size rangedfrom 1 to 82. Four studies reported no follow-up (44.4%),1 followed-up subjects for 3 months (11.1%), and 2followed-up subjects for 6 and 12 months, respectively(22.2%). Assessors were not blinded in 9 of the 10 studies.
Individual study details are summarized in Tables 2and 3. The following are syntheses of studies by topics ofCDT as a bundled intervention, MLD alone, and CB aloneas well as QOL, special cases, lymphovenous disease, andother differential impacts of CDT.
CDT
CDT is currently recognized as the criterion standard in LEtreatment [1-3], with the intensive phase of CDT, involving
(1) MLD, (2) MLLB or CB, (3) exercise, (4) skin care, and (5)
s1
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594 Lasinski et al EVIDENCE FOR COMPLETE DECONGESTIVE THERAPY IN LYMPHEDEMA
CGs. The majority of studies have considered cumulativeoutcomes of CDT as a bundled intervention, with varyingtechniques and dosages, and relatively few have consideredthe contribution of the individual components.
Acute and Long-term Management of LEwith CDT
Several studies looked at what happens after the initial inten-sive treatment is completed. Kim et al [12] conducted aprospective study with 53 subjects with BCRL, observingthem 1 and 6 months after the initiation of an intensive CDTcourse. At 1 month, subjects’ limb volume had decreased. Atthe 6-month follow-up, QOL had improved significantly,whereas limb measurements had started to increase, al-though not above baseline. Mondry et al [13] conducted aimilar prospective study of 20 subjects, with 3-, 6-, and
Rev
Renece
Revi
(n =Fina
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Screeview of titlessary for inc
SCDT & LE
iew of full teauth
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ure Search (nsearch LibraHand Search
ening 1 (n = s and abstrac
ening 2 (n =es, abstracts,clusion and s
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Screening 3+ 14 reviewf articles incafter review
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Figure 1. Literature review process for complete deconges-tive therapy (CDT) and lymphedema systematic review (2004-2011).
2-month follow-ups after an intensive phase of CDT. Swell-
ing and pain decreased with treatment, and QOL increased;longer length of treatment was associated with increasedgirth loss but decreased patient adherence. During follow-up, girth increased slightly, but QOL improved.
Vignes et al [14] followed up 537 consecutive patientsprospectively after completion of intensive treatment for 6months (426 patients) and 12 months (356 patients). Theresults correlated with adherence in using compressionsleeves by day and/or bandaging at least 3 nights a week. Anumber of subjects were lost to follow-up (34%). In addition,there was no random assignment to the follow-up compo-nents of self-MLD, sleeves, and bandages.
MLD Unbundled
Karadibak et al [15] conducted an RCT of arm edema inbreast cancer survivors in which the intervention group (n �
7) received standard CDT (including MLD) and the controlroup (n � 26) had standard therapy without MLD. Theirrial produced arm edema reduction of 36% in the controlroup without MLD and a 56% edema reduction in the MLDroup. Although this was a small trial (n � 53), it showed theLD contribution within standard CDT treatment. Williams
t al [16] conducted an RCT crossover study with 31 (16 �intervention group, 15 � control group) subjects with moresevere chronic LE who received MLD daily compared with acontrol group of subjects who performed a simplified form ofself-MLD; both groups wore compression sleeves. After 6weeks, the alternate intervention was assigned. The studyfound that MLD led to a significant reduction in swelling inboth the arm and the trunk. Andersen et al [17] conducted anRCT crossover study of 42 women with mild or early onsetBCRL and found that MLD was not a significant factor thatcontributed to further volume reduction compared withcompression alone, whereas McNeely et al [18] conducted anRCT study of 50 women with BCRL and found that MLDfollowed by compression bandaging was more beneficialthan compression bandaging alone. The group who bene-fited most from compression bandaging plus MLD werewomen with mild BCRL.
Contradictory findings in the various studies may be duein part to differences in study protocols (Table 3), whichpoints to the need for further research with consistent proto-cols, standard definitions, and longer follow-up. There wereinconsistencies in defining and measuring LE [19], a problempervasive in this body of literature (Table 3) and in widevariations of how the MLD component of CDT was appliedby both technique and dose. For example, the MLD might bethe Vodder technique [12,16,17,20], a modification of theVodder technique [15,21-23], or the Casley-Smith technique[24]. In the studies, MLD was performed 2 days a week (8weeks) [21], 3 days a week (4 weeks) [15], 3 days a week (12weeks) [23], 3-5 days a week (3-5 weeks) [25], 5 days a week
(2-4 weeks) [13,18,20,22,26], or twice a day for 22 days
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595PM&R Vol. 4, Iss. 8, 2012
Table 4. Review guidelines:matrices of levels of evidence*
PEP Card BPD Technology Assessment
reen � Go. The evidence supports the consideration ofthese interventions in practice.
Recommended for practice: interventions for whicheffectiveness has been demonstrated by strongevidence from rigorously designed studies, meta-analysis, or systematic reviews, and for whichexpectation of harm is small compared with thebenefits:● At least 2 multi-site, well-conducted RCTs with at least
100 subjects. A panel of expert recommendationderived from explicit literature search strategy;includes thorough analysis, quality rating, andsynthesis of evidence.
Likely to be effective: Interventions for whicheffectiveness has been demonstrated from a singlerigorously conducted controlled trial, consistentsupportive evidence form well-designed controlled trialsby using small samples, or guidelines developed fromevidence and supported by expert opinion.● One well-conducted RCT with fewer than 100
patients or at 1 or more study sites.● Guidelines developed by consensus or expert
opinion without synthesis or quality rating.
A: Clear researchevidence.
Good (low risk of bias). These studies havethe least bias and results are consideredvalid. A study that adheres mostly to thecommonly held concepts of high quality,including the following: a formalrandomized controlled study; cleardescription of the population, setting,interventions, and comparison groups;appropriate measurement of outcomes;appropriate statistical and analyticmethods and reporting; no reportingerrors; low dropout rate; and clearreporting of dropouts.
Yellow � Caution. There is not sufficient evidence to saywhether these interventions are effective.
Benefits balanced with harms: Interventions for whichclinicians and patients should weigh the beneficialand harmful effects according to individualcircumstances and priorities.● RCTs, meta-analyses, or systematic reviews with
documented adverse effects in certainpopulations.
Effectiveness not established: Interventions for whichinsufficient or conflicting data or data of inadequatequality currently exist, with no clear indication of harm.● Well-conducted case control study or poorly
controlled RCT. Conflicting evidence or statisticallyinsignificant results.
B: Limited supportingresearch evidence.
Fair. These studies are susceptible to somebias, but it is not sufficient to invalidatethe results. They do not meet all thecriteria required for a rating of goodquality because they have somedeficiencies, but no flaw is likely to causemajor bias. The study may be missinginformation, which makes it difficult toassess limitations and potential problems.
Red � Stop. Evidence indicates these interventions eitherare ineffective or may cause harm.
Effectiveness unlikely: Interventions for which insufficientor conflicting data or data of inadequate qualitycurrently exist, with no clear indication of harm.● A single RCT with at least 100 subjects that showed
no benefit. No benefit and unacceptable toxicitiesfound in observational or experimental studies.
Not recommended for practice: Interventions forwhich lack of effectiveness or harmfulness has beendemonstrated by strong evidence from rigorouslyconducted studies, meta-analyses, or systematicreviews, or interventions in which the costs, burden, orharm associated with the intervention exceedanticipated benefit.● No benefit or excess costs or burden from at least
2 multi-site, well-conducted RCTs with at least 100subjects. Discouraged by expert recommendationderived from explicit literature search strategy;includes thorough analysis, quality rating, andsynthesis of evidence.
C: Experiencedcommonjudgment.
Poor (high risk of bias). These studies havesignificant flaws that imply biases ofvarious types that may invalidate theresults. They have serious errors in design,analysis, or reporting; large amounts ofmissing information; or discrepancies inreporting.
PEP � Putting Evidence into Practice; BPD � best practices document; RCT � randomized controlled trial.
*Reprinted with permission from [56-59]
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596 Lasinski et al EVIDENCE FOR COMPLETE DECONGESTIVE THERAPY IN LYMPHEDEMA
[27]. The MLD varied from 30-minute sessions [25] to 45- to60-minute sessions [13,18,20,22,27]. The CDT sessions alsodiffered in whether the compression between sessions wassupplied by bandaging [12-15,22,25,26] or by a CG[16,17,20,21,23]. Sometimes the exercise component ofCDT was included [13-15,21-23]; sometimes it was not [25].
MLD was never conceived to be a stand-alone therapy forLE. The exception to using MLD alone to treat LE wasreported in a 2007 systematic review by Moseley et al [28], inwhich MLD contributed to improvement in self-reportedsymptoms and thus was recommended for symptom man-agement in palliative care [2,6]. In a summary of 3 years oftreatment data collected from patients with LE after breastcancer treatment (n � 168), breast edema showed the mostmprovement when MLD was performed [29]. Other re-searchers have noted that MLD may be the best interventionpossible among the CDT components in cases that involvedhead and neck, genital, or breast swelling, and in palliativecare situations in which compression by bandaging or gar-ments is not well tolerated or possible [2,6].
McCallin et al [30] reviewed an RCT by Johansson et al20] that compared MLD with sequential pneumatic com-ression in 24 women with postmastectomy LE. Both treat-ent modalities reduced swelling significantly, the MLD
roup by 15% (P � .001) and the intermittent pneumaticompression group by 7% (P � .03). The researchers con-
cluded that both interventions were effective, with MLDtending to reduce swelling by a larger amount. McCallin etal [30] noted that the subjects reported decreased subjec-tive feelings of tension and heaviness after MLD, whichwas not the case when sequential pneumatic compressionwas used as a single technique. They concluded thatstudies of MLD, exercise, skin care, and laser were limitedin number, and suggested that individuals with stage II orIII LE may benefit from the addition of MLD to theirtreatment regimen and that larger studies with longerfollow-up are needed [30].
In another systematic review that examined CDT for LEmanagement, Devoogdt et al [31] reported an RCT by Jo-hansson et al (1999) in which 35 patients wore multilayerbandages for 3 weeks and 1 group (N � 17) also receivedMLD in the third week. After 2 weeks, limb reduction wasequal for both groups. After the third week, the MLD grouphad a significantly higher reduction of LE than the groupwithout MLD (11% versus 4%; P � .040). The reduction insubjective symptoms of tension, heaviness, and pain wassimilar for both groups [31].
A review article by Leal et al [32] reported that MLD is notan effective stand-alone treatment for LE, because compres-sion bandaging is needed in combination with MLD toachieve optimal results [3,16,31,33-35]. However, there arepsychosocial and symptom-reduction benefits not producedby compression or other CDT components [11-13,21,
23,25].
Compression Bandaging (MLLB or CB)Unbundled
Multilayer, short-stretch CBs applied to the LE extremityafter MLD helps maintain edema reduction achieved throughlymphatic drainage [3,4]. In a case-control series of 29 sub-jects, Damstra et al [36] studied the loss of pressure undershort-stretch CBs applied to normal and LE legs over a24-hour period and found that there was a loss up to 48% oforiginal pressure under the bandage due to loss of limbvolume under compression. Damstra and Partsch [37] con-ducted an RCT of 36 patients with moderate-to-severe BCRLwho failed to respond to outpatient treatment. The patientswere randomized into low-pressure bandages (20-30 mmHg) and high-pressure bandages (44-58 mm Hg). There wasno significant difference in edema volume reductions be-tween groups, and low-pressure bandages were better toler-ated. Sub-bandage pressure drops were the same in bothgroups, between 41% and 48% after 2 hours and 55% and63% after 24 hours, which supports daily reapplication ofshort-stretch CBs to provide optimal compression and thatcompression be applied at a level comfortable for the patient,because there was no significant difference in edema volumereduction between the high- and low-pressure groups. Afterthe initial treatment phase of CDT, most individuals are ableto maintain adequate compression on their LE limbs duringthe day with a CG. Studies that examined adherence withnight-time compression bandaging and day-time CG wearsuggest that adherence with compression has a direct corre-lation with maintenance of LE reductions achieved throughCDT [4,11,14,22].
Badger et al [38] conducted an RCT of MLLB, followed byCGs versus CGs alone to treat patients with LE. They fol-lowed up 54 patients with upper extremity and 29 patientswith lower extremity LE over a 24-week period and foundMLLB followed by CGs was twice as effective in reducing LEcompared with use of CGs alone.
CDT and Lymphovenous Disorders
The 2008 consensus statement of Partsch et al [39] and aninternational panel of experts summarized a review of theliterature on the use of compression treatments to managevenous and lymphatic disease. The researchers concludedthat low levels of compression (with stockings 10-30 mm Hg)are effective in prevention of edema and deep venous throm-bosis (DVT) and high levels of compression (30-40 mm Hg)achieved by using CGs or CBs are effective in healing ulcers,preventing postthrombotic syndrome, and managing LE.Bandages and elastic wraps exerting pressure at approxi-mately 30 mm Hg did not reduce arterial flow but diddiminish toe perfusion.
However, they reported that inelastic bandages appliedwith a pressure of 38 mm Hg to normal limbs increased
blood perfusion, whereas inelastic arm sleeves with compres-
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597PM&R Vol. 4, Iss. 8, 2012
sion of 13-23 mm Hg increased blood flow [39]. It is uncer-tain how this evidence would translate to individuals with LEwith subcutaneous tissue fibrosis. The researchers did con-clude that, in the upright position, higher pressures weremore effective with regard to narrowing of leg veins, reducingvenous reflux, and enhancing venous pump function inpatients with chronic venous insufficiency. This informationsupports the application of compression stockings of highercompression class in individuals with lower extremity edemawho have combined venous and lymphatic edema (alsoknown as phlebolymphedema).
Partsch et al [39] suggested that, if pressure of more than0 mm Hg is required, then materials with higher stiffness,uch as inelastic hook and loop closure or short-stretch CBse used. One could also infer that CGs made from fabrics thatave a higher stiffness factor, such as flat-knit fabrics, woulde more effective in controlling LE than higher-elastic fabricsuch as circular-knit fabrics [3].
Shrubb and Mason [40] reviewed evidence in managingVT in the general population to consider its applicability
o the patient population with LE. The researchers re-iewed risk factors for the development of DVT in patientsith LE, which include cancer surgery with disruption ofenous outflow, postradiation fibrosis, treatment with ta-oxifen, abnormal clotting mechanisms, or obstruction
y tumor. They noted that, in non– cancer-related LE,enous outflow may be impaired due to the pathophysiol-gy of LE itself or impaired mobility. According to Shrubbnd Mason [40], traditional practices have recommendedemoving compression to allow the resolution of a DVT inndividuals with LE, fearing that compression might dis-odge the clot. The researchers referenced Partsch et al39] who found that compression bandaging (50 mm Hg)n the bed-bound patient and compression stockings23-32 mm Hg) in the ambulatory patient not only re-uced the incidence of post-thrombotic syndrome but alsoelieved pain and swelling. After review of the studies onVT and LE, Shrubb and Mason [40] concluded thatontinuing compression in patients with LE and DVT wasffective to avoid worsening of LE as well as the associatedhysical and psychological problems. In the bed-boundatient in palliative care, compression may impair bloodow and may be contraindicated, depending on the case.hey further concluded that it might be necessary to applyhigher level of compression in individuals with DVT andE [40].
CDT Effects on QOL
Although there have been a number of studies that haveassessed the effects of CDT on QOL for patients with BCRL[12,13,16,21,23,25], few studies have assessed the effects ofCDT on QOL for patients with lower extremity LE. Kim and
Park [11] conduced a multi-site prospective study of 57
omen with unilateral leg LE after gynecologic cancer toetermine the physical and psychological impacts of CDTreatment and whether limb volume changes were associatedith changes in QOL. At the end of the 2-4–week treatmenthase, excess volume went from 56% � 20% mean SD at
baseline to 32% � 11% at 1 month. The researchers creditthe volume decrease at 1 month to patients’ success in adher-ing to self-bandaging, self-MLD, skin care, and remedialexercises. There was a trend (not statistically significant)toward increases in physical and social functioning, whichthe researchers concluded supports the theory that CDT isbeneficial for lower-extremity LE. Participants self-reportedmore confidence in the use of the affected limb; some re-ported resumption of activities of daily living such as walk-ing, sports, housework, and shopping after the 2- to 4-weekcourse of treatment. The researchers noted that these resultsare inconsistent with some previous reports that did not findimproved QOL scores after CDT. This could be due to theshort 1-month follow-up period, when patients did not yettire of adhering to night-compression bandaging, self-MLD,or exercise [41,42]. Further study with longer follow-up anda focus on adherence is recommended for persons with upperor lower extremity LE.
Special Cases of CDT
LE often involves the truncal quadrant adjacent to the swol-len limb(s), and applying compression to these areas is diffi-cult. There are no studies that examined the role of compres-sion to manage truncal LE, nor are there any standardmeasurement techniques to assess truncal LE. Head andneck, truncal, and genital LE present unique challenges forcompression. Whitaker [43] reviewed the causes, classifica-tions, and clinical presentation of scrotal LE, and madesuggestions on how to manage it in clinical practice. Shereports on a single case of a patient with scrotal LE secondaryto metastatic prostate cancer treated with modified CDT,which consisted of simple, self-MLD techniques, daily self-bandaging with a 4-cm-wide soft-mesh conforming bandage,and a circular-knit support that provided 18-21 mm Hg ofcompression.
Differential Impact of Bundled CDT
CDT has been shown to be effective in reducing edema, bothin mild acute cases as well as more severe chronic cases. In aprospective study by Liao et al [24], 30 subjects reduced theirswelling an average of 68% after a median of 10 sessions ofCDT. The amount of initial swelling was correlated withsubjects’ age and LE duration, but the results in volumereduction were independent of these factors. Yamamoto andYamamoto [44] did a retrospective study in Japan of 82 of222 patients with LE but no metastatic disease seen over a
1-year period; this included 27 women with upper extremity
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598 Lasinski et al EVIDENCE FOR COMPLETE DECONGESTIVE THERAPY IN LYMPHEDEMA
LE and 53 women with lower extremity LE treated with CDT.Patients with upper extremity LE achieved an average 59%reduction after a median of 6 treatments, whereas those withlower extremity LE achieved an average 74% reduction aftera median of 10 treatments. There was no correlation betweenLE, duration of CDT treatment, and the rate of edema reduc-tion during the treatment phase. Neither study provided anexplanation of what determined length of treatment; patientswere seen a range of 3-26 times (upper extremity), 2-35 times(lower extremity) [44], or 4-21 times [24]. Also, there was nolong-term follow-up.
In a prospective study, Yamamoto et al [45] examinedthe length of treatment of 31 patients with upper extremityLE and 52 patients with lower extremity LE. This studyfound that the maximum reductions were achieved withinthe first few days of treatment: more than 50% reductionafter 1 day of treatment, then an additional decreasebetween the second and third day, and, after that, continu-ing but very slight reductions. The reductions achieved in7 days of treatment were comparable with reductionsreported in other studies, in which the treatment coursewas longer. As average body mass index of Japanese sub-jects was less than 25 kg/m2, the researchers hypothesizedhat this may have made a difference in the rapidity ofolume reduction.
Pinell et al [46] conducted a retrospective study of 72atients (62 with unilateral and 10 with bilateral swelling; 56ithout tumors and 16 with tumors) to assess the efficacy ofDT in patients with locoregional tumors. They found no
ignificant difference in the amount of reduction achievedith CDT, but more sessions were required to achieve these
esults in the patients with tumors.Knowledge of potential factors that influence CDT out-
omes would help clinicians develop plans of care. Thereave been attempts to predict who will benefit most fromDT. Ramos et al [47] conducted a retrospective study of9 women with BCRL and their response to CDT. Theyound that the most important predictor of outcomes washe amount of swelling at the time of presentation: annitial difference of less than 250 mL between the armsesulted in a mean reduction of 78%, whereas a differencef more than 500 mL led to a less than 56% reduction,hich was in contrast to what Liao et al [24] found in arospective study of 18 patients with upper extremity and2 with lower extremity LE, which was that treatmentffectiveness showed no relationship with the initialmount of swelling or with age, number of treatments, oruration of LE. Vignes et al [26] conducted a prospectivetudy of 357 patients with BCRL and reported that LEuration and/or patient body mass index was associatedith greater swelling, but that all patient subgroups, re-ardless of these factors, had the same percentage ofeduction from CDT. In another prospective study,
wang et al [48] examined the lymphoscintigrams of 20
atients with LE before treatment with CDT and 1 yearater. They found that the patients who had the best resultsith CDT had a baseline lymphoscintigram that showed aominant lymphatic vessel and no collateralization. To-ether, the inconsistency of the findings points to the needor further rigorous research related to CDT.
DISCUSSION
Twenty-six of a total of 99 articles related to LE treatmentmet inclusion criteria for this review. In addition, 1 novelcase study, 14 review articles, and 2 consensus documentswere included in this systematic review. In general, levelsof evidence were of only moderate strength, because therewere few RCTs with control groups, well-controlled inter-ventions, and objective measurements of volume, mobilityand/or function, and QOL. In addition to small samplesizes and limited follow-up, studies reported a variety ofprotocols, LE definitions, and measurements, whichmakes comparisons across groups difficult. Interventionswere often bundled, which makes it difficult to determinethe contribution of each individual CDT component.
In looking for evidence-based confirmation of out-comes and examining the individual and bundled ele-ments from the composite protocol of CDT, there aredisappointing weaknesses in the evidence. With inconsis-tencies in defining and measuring LE, a lack of blinding ofparticipants and assessors, and small sample sizes that ledto inadequate power and a high likelihood of �-typeerrors, it is not surprising that conclusions are contradic-tory and ambiguous. There also are ethical questions inestablishing a control group when subjects should not bedenied timely treatment [1]. Our clinical knowledge hasadvanced to where clinical equipoise is achievable inwell-planned clinical trials [49], a step that has the poten-tial to elevate our available levels of evidence for bestpractice in LE management. An equivalency trial mightexamine individualized dosing of CDT components forindividuals’ LE stage at diagnosis and response to treat-ment, recognizing each patient’s lymphatic system willvary in its ability to respond to any therapy.
The studies that examined BCRL are more numerousand have various advantages: (1) BCRL is usually unilat-eral, which allows the normal arm to serve as a compari-son; (2) there is a clear etiology, which makes it possible tohave more homogenous study groups; and (3) there is arelatively large pool of subjects. Although many of thestudies are inadequate in rigor for high-level evidence,some patterns have emerged. Both in earlier review articlesand in the current literature, CDT is seen to be effective inreducing LE, although the relative roles of each compo-nent of CDT and the factors that affect its efficacy are stillnot conclusively understood [28,31,32,50-55].
Evidence-based medicine is important to ensure that
patients are receiving safe, effective treatment. Before
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there can be evidence-based medicine, there have to behypotheses based on astute clinical observation and sci-ence-based medicine [49]. The medicine-based evidenceis undeniably strong that CDT is an effective way to treatLE. Clinical equipoise requires that, at the time a clinicaltrial is being initiated, there be a state of genuine scientificuncertainty over which of the treatments being tested ismore efficacious and safer [49]. With this systematic re-iew foundation, we can move to establishing clinicalquipoise in the random assignment of interventions withundled and nonbundled CDT interventions and CDTith and without adjunct therapies, areas ripe for future
esearch.Among patients with LE, there is a wide variety of
tiologies, severity, and comorbidities. The role of pa-ients’ adherence to compression and their exercise and/orelf-care program in the maintenance of CDT outcomeseeds to be studied to provide evidence for the efficacy ofurrent therapeutic recommendations. Additional re-earch is required to understand the effects of body massndex, comorbidities, LE emergence and progression, un-erlying lymphatic function, and patient adherence on theutcomes after CDT. Improved techniques also are neededo examine the following issues: facial, breast, truncal, andenital LE; more effective LE risk-reduction strategies;mproved treatment for radiation fibrosis; the effects ofDT on restoring function and range of motion; the patho-hysiology of the lymphatic system; and standardizationf protocols. Economic data on optimal clinical outcomesn the short and long term are needed to inform healtholicy and reimbursement guidelines. Findings from thisystematic review lay the foundation for guiding researchfforts to elevate the level of evidence for optimal patientare.
CONCLUSION
CDT improves overall QOL and is effective for variousdegrees of LE: mild, moderate, or severe; early or lateonset; recent or chronic; in patients with active cancer;and in palliative care situations. CDT is associated with thegreatest reduction in volumes after the first 5 days oftreatment, with reductions continuing at a slower rate inthe next weeks until progress plateaus. Continued use ofcompression is usually needed to maintain treatment re-sults. MLD enhances the effects of compression and hasbeen shown to improve QOL and symptoms. Longer-termfollow-up studies are needed to determine the optimaltreatment protocols, not only for the best outcomes butalso for the optimal home program required to maintainand/or enhance physical and psychosocial function after
the initial intensive phase.
ACKNOWLEDGMENTS
ALFP staff and reference librarian time were supported byindustry donations to the ALFP.
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