evidence based review - acc · 2019. 3. 27. · systematic reviews covering ipc devices for lower...

Evidence Based Review:

Intermittent pneumatic compression (IPC) devices in the management of

lower limb lymphoedema

Reviewer Amanda Bowens

Date Report Completed June 2014

Important note:

• The purpose of this evidence based review is to summarise information on the effectiveness of IPC devices and to provide best practice advice

• It is not intended to replace clinical judgement or be used as a clinical protocol

• A reasonable attempt has been made to find and review papers relevant to the focus of this report; however, it does not claim to be exhaustive

• The review has been prepared by the staff of the Evidence Based Healthcare group, ACC Research. The content does not necessarily represent the official view of ACC or represent ACC policy

• This review is based upon information supplied up to May 2014

A c c i d e n t C o m p e n s a t i o n C o r p o r a t i o n

Contents

Abbreviations .............................................................................................................................. 3

Summary ..................................................................................................................................... 3

1. Introduction ......................................................................................................................... 4

What is lymphoedema? ....................................................................................................................... 4

Managing lymphoedema ..................................................................................................................... 4

The role of IPC devices in lymphoedema management ..................................................................... 4

Purpose of this review ......................................................................................................................... 6

2. Methods .............................................................................................................................. 6

Literature search ................................................................................................................................. 6

Selection criteria .................................................................................................................................. 6

Grading the evidence .......................................................................................................................... 7

3. Findings .............................................................................................................................. 7

Effectiveness ....................................................................................................................................... 7

Safety and adverse events .................................................................................................................. 8

4. Additional information ........................................................................................................ 8

Guidelines & consensus statement recommendations on the use of IPC .......................................... 8

US payer policies on IPC devices ....................................................................................................... 9

5. Discussion .......................................................................................................................... 10

Nature and quality of the evidence ................................................................................................... 10

Limitations of the evidence based review ......................................................................................... 10

6. Conclusions & recommendations ....................................................................................... 11

Evidence for IPC devices in lymphoedema management ................................................................ 11

Recommendations for purchasing .................................................................................................... 11

7. Acknowledgements ............................................................................................................ 11

Appendix 1: search strategies ..................................................................................................... 12

Appendix 2: SIGN levels of evidence .......................................................................................... 13

Appendix 3: evidence tables ....................................................................................................... 14

Appendix 4: summary of guideline & consensus statement recommendations .......................... 18

Appendix 5: framework for selecting IPC devices for patients with leg & trunk lymphoedema .. 22

References ................................................................................................................................ 23


Abbreviations

CDT Complete decongestive therapy, also known as decongestive lymphatic therapy (DLT) or complex/combined physical therapy (CPT); generally a combination of skin care, exercise, MLD/ SLD, compression garments/MLLB and possibly IPC; considered to be the gold standard treatment option

CPT See CDT DLT See CDT DVT Deep vein thrombosis IPC Intermittent pneumatic compression ISL staging International Society of Lymphology’s three (I-III) or occasionally four (0-

III) level system for lymphoedema staging1 MLD Manual lymphatic drainage MLLB Multi-layer inelastic lymphoedema bandaging (compression bandaging) mmHg A unit of pressure (millimetres of mercury) RCT Randomised controlled trial SLD Simple lymphatic drainage (self massage)

Summary

IPC devices are sometimes used in the management of lymphoedema as an adjunct to CDT (widely accepted as the gold standard treatment option). A range IPC of devices are currently available, but there are no established guidelines on their use.

ACC Research has been asked to review the evidence on the effectiveness of IPC devices in the management of lower limb lymphoedema in order to develop guidance on purchasing these devices for ACC clients.

The review found limited evidence on IPC devices. It identified only four studies published in the last ten years that met the inclusion criteria: one systematic review, two RCTs and one case series. Overall, the quality and generalisability of the evidence was low.

The review also identified nine guidelines and consensus statements that make relevant recommendations on the use of IPC devices. The majority of these recommendations are based on expert consensus rather than formal reviews of the evidence, and guidelines that do have an evidence based component draw predominantly on studies involving patients with upper limb lymphoedema related to a history of breast cancer.

The small number of studies identified by this review report only minor transient adverse events and suggest that IPC devices are a relatively safe treatment option. However, some of the guidelines and consensus statements identify more serious risks and recommend that IPC devices be used with caution.

In conclusion, the evidence currently available appears insufficient to support purchasing IPC devices for ACC clients with lower limb lymphoedema.


1. Introduction

What is lymphoedema?

Lymphoedema is the accumulation of excess fluid in the body caused by obstruction of lymphatic drainage mechanisms2. It usually occurs in the limbs and is chronic and progressive: affected limbs become swollen and painful, and movement and function may be impaired. Lower limb lymphoedema has a particularly high risk of progression without effective management3. Primary lymphoedema arises from congenital malformation of the lymphatic system whilst secondary lymphoedema is caused by damage to lymph vessels or nodes. In industrialised countries, this damage is most commonly caused by cancer or associated treatments3. In Australia, the most common causes of upper limb lymphoedema are surgery or radiotherapy to the axillary lymph nodes in the treatment of breast cancer and the most common cause of lower limb lymphoedema is surgery to the inguinal or pelvic lymph nodes in the treatment of genitourinary or gynaecological cancers4.

Managing lymphoedema

Management aims to decongest impaired lymphatic vessels and reroute fluid though remaining functional vessels in order to improve drainage and reduce swelling. It usually involves a combination of physical interventions. These combined regimes are currently recognised as the gold standard in lymphoedema management5 and go by a number of names including complex or combined physical therapy (CPT), complete decongestive therapy (CDT) and decongestive lymphatic therapy (DLT)6. The components vary, but typically include:

Manual lymphatic drainage (MLD): gentle massage administered by a health care professional

Simple lymphatic drainage (SLD): self-massage (a modified version of MLD)

Compression bandaging (multi-layer inelastic lymphoedema bandaging or MLLB)

Compression garments, e.g. stockings

Exercise, elevation and skin care

IPC devices may be used as an adjunct to CDT regimes.

Management typically takes a two stage approach. The first, or intensive, stage lasts around 2-6 weeks: treatments are given daily, sometimes in a clinical setting. This is followed by a longer term maintenance stage, usually in the patient’s home: the patient’s commitment and compliance is crucial to the success of this stage6. Some guidelines also recommend a transition stage between the two main stages7.

The role of IPC devices in lymphoedema management

IPC devices consist of an air compression pump attached to an inflatable plastic garment resembling a sleeve or stocking. The garment is placed on the affected limb and sequentially inflated and deflated, applying pressure to the limb. The aim is to push excess lymph fluid out of the limb and into the trunk, mimicking the pumping action of muscles in lymph transport. IPC also decreases lymph formation by decreasing capillary filtration8.

IPC devices may be used at home or in clinical settings as an adjunct to CDT regimes. They are often advocated for patients who have difficulty complying with some aspects of CDT or who have limited access to health care facilities.


A wide range of devices are now available with varying designs and degrees of sophistication. There are three main types:

1. Single chamber (nonsegmented) non-programmable models: the most basic devices with a single chamber garment that applies uniform pressure.

2. Multi-chamber (segmented) non-programmable models: the garment has multiple chambers that can be inflated sequentially, producing a massaging effect along the length of the limb back towards the trunk. They may apply the same pressure in each chamber or produce a pressure gradient, e.g. higher near the ankle and lower on the thigh. They may allow manual adjustment (“calibration”) of pressure levels in individual chambers.

3. Advanced compression systems including: (i) programmable pumps that allow digital adjustment of pressure applied in individual chambers (the preferred option for patients with scarring or ulceration) and (ii) two-phase (preparation followed by drainage) pumps that simulate MLD & can treat the trunk as well as the limbs.

Multi-chamber devices have now largely replaced single chamber pumps in lymphoedema management, as the latter have less sophisticated therapeutic capacity9 and tend to move fluid bidirectionally, thus exacerbating fluid build up in already swollen areas8. Fig. 1 below shows an example of a multi-chamber, calibrated gradient pressure IPC device:

Fig 1: typical IPC device - Spectrum Healthcare’s Lympha Press MAX model 201M

There are currently no established guidelines on optimal pressure ranges, inflation/ deflation cycles, or length or frequency of treatment sessions. There is no evidence on the relative effectiveness of different products. Pressure levels and treatment durations need to reach a compromise between efficacy and patient comfort; there is some evidence to support pressures in the range 30 - 60mmHg8 and treatment sessions typically last 30–120 minutes7. Daily treatment is often recommended to maintain benefits in the long term, but patients may have difficulty complying with this10. Compression therapy with garments or bandaging may be required after IPC to prevent rapid rebound swelling.


In addition to lymphoedema, IPC devices are used to treat arterial disease, chronic venous insufficiency and venous ulcers, and to prevent deep vein thrombosis.

Purpose of this review

This ACC review is the second of two reports on the management of lymphoedema that the Clinical Services Directorate has asked Research to produce:

1. A summary of international guidelines and consensus statements on best practice in lymphoedema management (completed, Stephenson 20146).

2. An evidence based review of the effectiveness of IPC devices in the treatment of lower limb lymphoedema.

The intention is to identify and assess the evidence in order to develop guidance on purchasing IPC devices for ACC clients with lower limb lymphoedema.

2. Methods

Literature search

The following databases were searched in March 2014 (see Appendix 2 for information on the search strategies used):

AMED Medline & Pre-Medline

Centre for Reviews & Dissemination databases

National Guideline Clearinghouse

Cochrane Library Ovid Nursing Database

Embase PubMed

Google Scholar TRIP database

Selection criteria

Studies published in English during the last 10 years (i.e. since 2004) and meeting the following criteria were included in the evidence review:

Systematic reviews covering IPC devices for lower limb lymphoedema

Primary research (RCTs and case series) on the effectiveness of IPC devices in the management of lower limb lymphoedema that were not covered by included systematic reviews

The following studies were excluded from the evidence review:

Those available in abstract or summary only, e.g. conference presentations

Trials in progress

Short term experiments carried out to determine optimum device parameters, e.g. pressure levels or inflation/deflation cycles

Studies on IPC devices for indications other than lymphoedema, e.g. venous ulcers.


Grading the evidence

Studies meeting the inclusion criteria were graded using the Scottish Intercollegiate Guideline Network (SIGN) level of evidence system. For information on the SIGN grading system see Appendix 2.

A number of guidelines and consensus statements were also identified and are discussed in Section 4. However, they were not included in the evidence review and were not assigned a SIGN grade.

3. Findings

The literature search identified four studies (one systematic review, two RCTs and one case series) that met the inclusion criteria. For more detailed analysis of the included studies, see the evidence tables in Appendix 3.

Effectiveness

The systematic review by Feldman et al (2012)11 focused on peer reviewed, English language studies on IPC therapy in lymphoedema management published between 2004 and 2011. It identified 13 studies including a consensus statement by Partsch et al12 and two controlled trials13 14 on patients with lower limb lymphoedema. The review concluded that, for selected patients (e.g. those with limited access to health care facilities), IPC offers an acceptable home based adjunct to CDT and is well tolerated at low to moderate pressure ranges (30-60mmHg). However, the review had methodological shortcomings and was graded Sign evidence level 1-. In addition, its conclusions were largely based on studies carried out in populations with upper limb lymphoedema related to breast cancer treatment. The two lower limb trials were short term studies carried out to investigate fluid flow dynamics and dose responses at different pressures and both were ranked relatively lowly (Bandolier grade III)15 by the review authors.

The pilot RCT by Wigg (2009, UK)16 compared the effects of IPC versus MLD when used as an adjunct to intensive phase DLT in 12 female patients with arm or leg lymphoedema. IPC was provided by the Flowtron Hydroven 12 device, which offers an advanced LymphAssist mode that aims to mimic MLD. At one month follow up, limb volumes and skin thickening were reduced in both groups, but the small sample size prevented the detection of statistically significant differences. The trial could not establish whether the larger mean volume reduction observed in the IPC group (700ml versus 452ml) showed that IPC was more effective than MLD or was due to the IPC group having larger baseline limb volumes and therefore a greater capacity for reduction. The author concluded that the findings support the use of a LymphAssist mode IPC device in standard lymphoedema management and that it may be as effective as MLD. This RCT had a high risk of bias, mainly due to sample size (the author’s subsequent power calculations indicated that 22 participants would have been required in each study arm), and there were also questions over baseline comparability and the decision not to separate arm and leg lymphoedema patients in the statistical analysis of limb volume reduction. It was therefore graded Sign evidence level 1-.

The RCT by Taradaj et al (2013, Poland)17 examined the effects of adding IPC at two different pressures to standard outpatient management (CDT-type physical therapy plus drug treatment) in 33 menopausal women with bilateral primary lower limb lymphoedema and chronic venous insufficiency. Like the RCT by Wigg above16, this trial used the Flowtron Hydroven 12 device. At four week follow up, limb volume reductions in the


group receiving IPC at 60mmHg were similar to those receiving standard management only (no IPC), but reductions in the group receiving IPC at 120mmHg were significantly greater (approx. 45% versus approx. 19% reduction, p=0.01). The authors concluded that IPC at 120mmHg significantly assists the reduction of venous lymphoedema in menopausal women, but that IPC at a pressure of 60mmHg appears to be ineffective. This reasonably well conducted pilot-level RCT was graded Sign evidence level 1+, but its generalisability (e.g. to patients with secondary lymphoedema) may be limited.

Muluk et al (2013, US)18 reported on a device registry study in which 196 participants with lower limb lymphoedema trialled an advanced programmable Flexitouch IPC device under a pre-purchase arrangement operated by third party payers. Participants were given prescribed protocols for daily home treatment and instructed on device use. After treatment, 88% of participants experienced limb volume reduction (mean reduction 8%, p<.0001); 35% experienced volume reduction >10%. Higher BMI and greater limb volume at baseline were strong predictors of volume reduction. Post-treatment clinician assessments identified decreased skin hardening/fibrosis and improved function and range of motion in a majority of participants. A post-treatment patient survey found that survey responders (50%) reported a high degree of satisfaction with their ability to control their lymphoedema with IPC treatment. The authors noted that this was to date the largest study of IPC treatment outcomes in patients with lower limb lymphoedema. The study appeared to be a reasonably well conducted prospective case series and was graded Sign evidence level 3. However, there were variations in treatment duration and participants’ use of co-treatments (e.g. compression bandaging) was not standardised.

Safety and adverse events

Adverse events reported in the four included studies were minor and temporary. In Muluk’s case series18, four of the 196 participants reported muscle cramps, redness or rash, non-specific allergic reaction or increased fatigue, but all were able to continue treatment. Some participants in a controlled trial14 discussed in Feldman’s review11 reported discomfort at 60mmHg and the trial authors therefore recommended that future research focuses on IPC at 50mmHg. However, pressures of 120mmHg were well tolerated in the RCT by Taradaj et al17.

4. Additional information

Guidelines & consensus statement recommendations on the use of IPC

The literature searches for this review and for ACC Research’s previous report on lymphoedema management6 identified nine relevant guidelines and consensus statements. These documents make recommendations on the use of IPC devices in the management of lymphoedema of the lower or upper and lower limbs; documents dealing solely with upper limb lymphoedema, e.g. following breast cancer treatment, were excluded. However, the actual recommendations of the remaining documents are still largely based on or extrapolated from studies on upper limb lymphoedema. The guidelines and their recommendations are summarised in Appendix 4.

The following recommendations are of particular relevance to the management of lower limb lymphoedema:

IPC is relatively free from complications, but there are concerns that it can worsen truncal or genital lymphoedema and that high pressures may cause peripheral lymphatic damage3 19


Careful observation is needed to avoid displacing oedema more proximally in the limb (i.e. closer to the trunk) or in the genitalia, as this can cause a fibrosclerotic ring to develop at the limb root, further obstructing the lymph flow1

IPC devices are ill suited to palliative care, as at this stage oedema is often present at the limb root and IPC may exacerbate this20

Daily or thrice weekly IPC may be added to modified intensive stage regimes for some patients who (i) cannot tolerate high levels of compression from bandaging etc. (ii) have had DVT or (iii) are at risk of developing leg ulceration7

IPC may be added to transitional regimes for some patients with venous disease, obesity or limited mobility7

IPC may be added to long term management regimes for some less mobile patients7

While some of the recommendations are evidence based, the majority are derived from expert consensus – see Appendix 4 for more details.

The literature search also identified a paper by Maul et al (2009) which proposed frameworks for (i) deciding whether IPC use is appropriate and (ii) selecting a device type for home use, based on patient characteristics and symptom severity21. The frameworks are based on clinical experience and a very small number of case studies involving patients with leg and trunk lymphoedema. They are included for information only, see Appendix 5.

US payer policies on IPC devices

Although the evidence for IPC devices in lymphoedema management is limited, many in the US medical community consider it a safe and effective adjunct to standard treatment regimes. Medicare, Blue Cross Blue Shield, Cigna and Aetna therefore cover home use of IPC devices for members with durable medical equipment (DME) benefits, usually after a four week trial of conservative management (e.g. home exercise, limb elevation and compression garments/bandaging) has failed22 23 24. Standard single or multi-chambered devices are typically offered first, with more advanced pressure gradient or programmable models only available if simpler devices fail to provide relief or there is documented need due to scar tissue or ulcers. Where Cigna or Aetna members do not have DME benefits, coverage may be limited to upper limb lymphoedema following breast cancer treatment.

External peer review feedback

Feedback was received from two external reviewers: a senior lecturer in palliative care at the University of Canterbury and a physiotherapist/lymphoedema specialist based at St. George’s Cancer Centre in Christchurch. The reviewers acknowledged the lack of formal evidence to support the effectiveness of IPC devices and placed emphasis on practice-based experience. The main premise of their opinion was that IPC devices are a useful adjunct to conventional lymphoedema management and that more research is required into the use of IPC devices.


5. Discussion

Nature and quality of the evidence

The evidence base for IPC devices in the management of lower limb lymphoedema is limited. There is a paucity of well conducted published studies and clinician experience has therefore tended to dominate decision making18. Only four studies were identified that met the inclusion criteria for this ACC review; of these, only one was a reasonably well conducted RCT (SIGN grade 1+) and its generalisability is limited due to the fairly specific nature of its study population17 (i.e. menopausal women with bilateral primary lymphoedema and chronic venous insufficiency). What appears to be the largest study to date on IPC devices for people with lower limb lymphoedema (n=196) is at case series level (SIGN grade 3) and as such is not regarded as strong evidence. The three primary studies all involved relatively advanced multi-chamber devices. The majority of clinical guideline and consensus statement recommendations are not based on strong evidence.

To date, most studies on the role of IPC devices in lymphoedema management have been conducted on people with upper limb lymphoedema related to a history of breast cancer and care should be taken in generalising the findings of such studies to people with other conditions18 25. There have been calls for more RCTs on lower limb lymphoedema, given its high incidence related to treatment for genitourinary and gynaecological cancers25. In addition, some authors suggest that reductions in leg volume may have a more significant impact on patients’ quality of life than reductions in arm volume, as the legs sustain balance and mobility18 26 27.

Studies on mixed upper and lower limb lymphoedema populations are problematic. Changes observed in arm and leg volumes should be dealt with separately in the statistical analysis as the percentage volume reductions that can be achieved in arms versus legs are likely to differ due to differences in muscle and bone mass16 18.

There is currently no non-invasive method of measuring acute changes in lymphatic flow and it is therefore difficult to assess in vivo whether any particular model of device, pressure level, inflation/deflation cycle or sleeve design feature is more efficacious28.

With regard to safety, the four included studies reported only minor and temporary adverse events. However, the guidelines and consensus statements draw attention to a number of risks associated with IPC. These include concerns that: (i) high pressures may cause peripheral lymphatic damage; (ii) IPC may cause fibrosclerotic changes at the limb root, further obstructing lymph flow; and (iii) IPC of the lower limbs may exacerbate lymphoedema in the trunk or genitals. One older study has linked IPC use to the development of genital oedema29, but other authors have argued that the risk was overstated as the study in question was retrospective and patients had limited supervision and monitoring. Some authors argue that older, more basic IPC devices were designed primarily to treat chronic venous insufficiency and that the advanced programmable models now available are specifically designed for lymphoedema and the risks are therefore reduced21.

Limitations of the evidence based review

Foreign language material and conference presentations were excluded from the evidence review. Authors of conference presentations and trials in progress were not contacted for data. ACC Research originally intended to review the evidence on IPC devices for both upper and lower limb lymphoedema, but due to decision making priorities and time constraints the decision was taken to focus on lower limb lymphoedema at this stage.


6. Conclusions & recommendations

Evidence for IPC devices in lymphoedema management

IPC devices are used as an adjunct to intensive or maintenance CDT regimes for the management of lymphoedema

A wide range of devices are available. Multi-chamber products have now largely replaced more basic single chamber models in lymphoedema management

There is limited evidence on the effectiveness of IPC devices in the management of lower limb lymphoedema; this ACC review identified only one systematic review, two RCTs and one case series published in the last ten years

The overall quality and generalisability of the evidence is low

The majority of guideline recommendations are based on expert consensus rather than evidence based reviews of the literature

Guidelines that do have an evidence based component draw predominantly on studies involving patients with upper limb lymphoedema related to a history of breast cancer

The small number of studies identified by this review report only minor transient adverse events and suggest that IPC devices are a relatively safe treatment option

However, some guidelines and consensus statements recommend that IPC be used with caution to avoid more serious side effects such as exacerbating lymphoedema in other regions or developing a fibrotic cuff at the limb root.

Recommendations for purchasing

The evidence currently available appears insufficient to support purchasing IPC devices for ACC clients with lower limb lymphoedema. The Research team will now present this review to the ACC Purchasing Guidance Advisory Group (PGAG) in order to develop purchasing recommendations and consider whether further advice is needed.

7. Acknowledgements

Thanks to Helen Brodie in ACC Information & Knowledge Services for valuable assistance in obtaining copies of the studies referenced in this review.


Appendix 1: search strategies

Cochrane Library, run on 25 March 2014:

#1 MeSH descriptor: [Intermittent Pneumatic Compression Devices] explode all trees #2 lymphoedema #3 lymphedema #4 #1 and (#2 or #3)

Medline & Embase (on Ovid platform), run on 11 March 2014:

1. covidien.af. 2. 1 and (lymph$ or pump$).mp. 3. Intermittent Pneumatic Compression Devices/ 4. limit 3 to humans 5. Lymphedema/ 6. 4 and 5 7. 2 or 6 8. remove duplicates from 7 9. limit 8 to yr="2004 - 2014"

Free text search of main Ovid databases, run on Medline, Pre-Medline, Medline Daily Update, Embase, AMED & Ovid Nursing Database on 26 March 2014:

1. (compress$ adj2 (pump$ or device$ or intermittent or pneumatic)).mp. 2. (lymphedema or lymphoedema).mp. 3. 1 and 2 4. remove duplicates from 3 5. limit 4 to abstracts 6. limit 5 to english language 7. limit 6 to human 8. limit 7 to yr="2004 - 2014" 9. limit 8 to humans

Trip database, run on 27 March 2014:

""compress* lymph*"~10 (pump* or device* or intermittent or pneumatic) to:2014 from:2004"

Centre for Reviews & Dissemination databases, searched 27 March 2014:

(lymphoedema):TI OR (lymphedema):TI FROM 2004 TO 2014

Google Scholar, searched 27 March 2014:

compression lymphedema OR lymphoedema pump OR device OR intermittent OR pneumatic


Appendix 2: SIGN levels of evidence

SIGN criteria for classifying studies

Score Design

1++ High quality meta-analyses, systematic review of RCTs, or RCTs with a very low risk of bias

1+ Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias

1- Meta-analyses, systematic reviews of RCTs or RCTs with a high risk of bias

2++ High quality systematic reviews of case-control or cohort studies. High quality case-control or cohort studies with a very low risk of confounding, bias or chance and a high probability that the relationship is causal

2+ Well conducted case control or cohort studies with a low risk of confounding, bias or chance and a moderate probability that the relationship is causal

2- Case control or cohort studies with a high risk of confounding, bias or chance and a significant risk that the relationship is not causal.

3 Non-analytic studies

4 Expert opinion

Available from Scottish Intercollegiate Guidelines Network (SIGN) website, see www.sign.ac.uk/


http://www.sign.ac.uk/

Appendix 3: evidence tables

Evidence table 1: Systematic review

Study Inclusions Intervention Outcome measures & results Comments & level of evidence

Systematic review of the evidence for IPC in lymphoedema treatment (Feldman et al. 201211)

Inclusion criteria:

Peer reviewed, English language literature published 2004 – 2011

Included studies:

13 articles (2 systematic reviews, 1 literature review, 2 RCTs, 6 controlled trials & 2 case series) including:

Consensus statement on compression therapy in venous & lymphatic disease12

A report of 2 phase II controlled trials (n=28, venous leg oedema ≥6 weeks); one (n=16) investigated dose responses to differing IPC pressures14

Controlled trial (n=25, obstructive lower limb lymphoedema) exploring tissue fluid pressure & flow under IPC vs. manual massage13

Intervention:

IPC in lymphoedema treatment

Controls:

Controls (where applicable) were mainly conservative treatments e.g. MLD, differing IPC regimes

Outcomes & variables assessed:

Physiological changes, pressure levels, treatment times & frequency, volumetric changes, adverse events

Results (lower limb studies):

Consensus statement12 (Bandolier grade II): identified some lower limb case series, but the recommendation that evidence supports IPC is based on a single RCT on upper limb lymphoedema in breast cancer patients 12

Controlled trial14 (Bandolier grade III): limb volume was most effectively reduced at higher IPC pressures (87ml @ 60mmHg vs. 69ml @50mmHg); some patients reported discomfort at higher pressure & the authors therefore advocated further research on 50mmHg graduated IPC

Controlled trial13 (Bandolier grade III): manual massage caused tissue fluid flow only when tissue was actually pressed, while IPC produced unidirectional flow towards the groin without backflow, displacing up to 100ml per cycle; measured tissue fluid pressures were up to 20% lower than the IPC chamber pressures of 50 -125mmHg

Authors’ conclusions: In selected patients, IPC offers an acceptable home based adjunct to CDT, is well tolerated at low-moderate pressure ranges (30-60mmHg) & may be particularly suitable for to chronic lymphoedema patients with limited access to health care facilities.

Evidence level of each study graded using recog-nised tool (Bandolier)15

Narrative synthesis was used appropriately due to the broad range of study designs, outcomes etc.

Literature search missed several relevant studies & excluded grey literature

Preponderance of lower-ranked studies means that evidence for IPC may be overstated

Due to methodological shortcomings & the resultant risk of bias this systematic review is graded SIGN evidence level 1-

NB: the review included only 2 relatively low ranked studies on lower limb lymphoedema


Evidence table 2: Randomised controlled trials (2)

Study Participants Interventions Outcome measures & results Comments & level of evidence

Pilot randomised feasibility study conducted in a UK lymphoedema service (Wigg 200916)

Inclusion criteria:

Patients aged 18 or over requiring DLT for arm/leg lymphoedema & able to commit to daily treatment and follow up sessions

Participants: 12 patients (all female) aged 36-79 (mean 59) with oedema of 1-50 (mean 14) years’ duration (5 upper limb, 2 lower limb, 4 bilateral, no limit on cause) One patient in the intervention group was unable to comply with treatment & dropped out

Two week intensive phase* DLT consisting of daily MLLB compression bandaging plus either:

Intervention:

Daily 2 x 19 minute IPC session using Flowtron Hydroven 12 device in LymphAssist mode (aims to mimic MLD) at 30-40mmHg

or:

Control:

Daily 45 minute session of MLD (Leduc method) *After two weeks participants entered a maintenance phase with IPC/MLD administered with reducing frequency (3 x weekly for 1 week, twice weekly for 1 week then once weekly for 4 weeks)

Outcomes measured:

Limb volume reduction (primary), skin changes, patient response/ease of use (secondary) measured on days 1, 5, 10 and after 1 month

Results:

Limb volume & skin thickening were reduced in both groups at 1 month, but no statistically significant differences were detected between groups; the IPC group had larger baseline volumes & showed mean reductions of 700ml vs. 452ml in controls, but the results could not establish whether IPC treatment was superior or larger volume limbs had greater capacity for reduction. At 1 month follow up, volumes had not returned to pre-treatment levels in either group. IPC subjects found the device easy to use.

Author’s conclusions: The findings support the use of the LymphAssist mode IPC device in standard lymphoedema management & suggest it may be as effective as MLD. However, they confirm the null hypothesis that patients treated with this type of IPC will experience no greater limb volume reduction than patients treated with standard best practice lymphoedema treatment using MLD and multilayer bandaging.

Sample size too small to provide statistical significance; author aimed for 40 subjects but encountered recruitment & compliance problems; subsequent power calculations indicated 22 subjects would be required in each group

Other issues: groups not comparable at baseline; therapists’ experience of bandaging varied between groups; some participants had compliance problems with the compression bandaging regime

The author recommends statistical analysis of volume changes in upper & lower limbs should in future be separated

RCT with high risk of bias: SIGN evidence level 1-


RCT based in lymphoedema outpatient clinics in Poland (Taradaj et al. 2013)17

Inclusion criteria:

Menopausal women with bilateral primary lower limb lymphoedema & chronic venous insufficiency

Participants:

33 women with signs of menopause for at least 2 years

All participants had 4 weeks of comprehensive outpatient physical therapy (MLD for 50 mins 3 times weekly and MLLB 40-50mmHg) plus standard drug therapy; in addition, they were randomised to:

Interventions:

Group A (n=10): IPC treatment at 120mmHg using Flowtron Hydroven 12 device, 45 mins three times per week

Group B (n=10): as above, but at 60mmHg

Control:

Group C (n=13): physical & drug therapy only, no IPC

Outcomes measured:

Reduction in limb volume

Results:

Limb volume was more significantly reduced in Group A than in Groups B or C. Reductions in Groups B and C were similar:

Small sample size

Groups comparable at baseline

Participants selected from a fairly specific population, so generalisability may be limited

Inclusion of drugs in standard therapy may not reflect typical NZ practice

Reasonably well conducted pilot-level RCT: SIGN evidence level 1+

Group A Group B Group C

Right leg mean % volume reduction

46.2 SD 12.1

20 SD 7

18.5 SD 6.8

Left leg mean % volume reduction

44.6 SD 10.6

19.8 SD 8

17.9 SD 6.9

p(A vs. B) = 0.01; p(A vs. C) = 0.01; p(B vs. C) > 0.05

Authors’ conclusions:

IPC at 120mmHg significantly assists the reduction of venous lymphoedema in menopausal women. This pressure was well tolerated. IPC at 60mmHg appears to be ineffective.


Evidence table 3: Case series

Study Participants Intervention Outcome measures & results Comments & level of evidence

Prospective device registry study by Muluk et al. (2013)18

196 lower extremity US lymphoedema patients (mean age 56 years, 67% female, 80% secondary lymphoedema) who received an IPC device under a trial “rental with reauthorization” process required by their third party payers

Participants were required to have at least stage II lymphoedema

Daily home treatment to a prescribed protocol with an advanced programmable IPC device (Flexitouch, Tactile Systems Technology) designed to mimic MLD

Participants were given prior training on use of the device & advised to re-apply any compression garments or bandaging after IPC treatment

Outcomes:

Primary outcome: limb volume (LV) reduction measured at baseline & approx. 60 ± 27 (median 55) days. Secondary outcomes: post-treatment clinician assessment & patient-reported outcomes

Results:

LV reduction: 88% of participants experienced reduction & 35% experienced reduction >10%; mean reduction was 8% or 1,150ml (p<.0001); greater baseline LV & BMI were strong predictors of LV reduction (p<.0001)

Clinician assessment: skin hardening/fibrosis decreased in 86% of participants; 85% demonstrated improved function in activities of daily living and 77% experienced increased range of motion

Patient-reported outcomes: post-treatment survey completed by 50% of participants showed significant increases in ability to control lymphoedema with subsequent increases in function & decreases in pain; 96% of responders ‘satisfied/very satisfied’ with IPC treatment

Adverse events (AEs):

Four participants reported AEs (muscle cramps, limb redness/rash, non-specific allergic reaction & increased fatigue); all AEs resolved & participants were able to resume IPC treatment

Author’s conclusions: Advanced IPC device use was associated with consistent LV reduction, decreased pain & improved function.

Hard to establish the degree to which registry studies represent the typical population

LV was measured at variable time points after initiation of therapy

Use of other treatment components was not standardised

Authors ruled out survey response bias (non-responders to the patient survey demonstrated similar LV reductions to responders)

The device manufacturer funded the statistical analysis & employs one of the authors

Reasonably well conducted prospective case series: SIGN evidence level 3


Appendix 4: summary of guideline & consensus statement recommendations

Guideline Development methods Recommendations & strength of evidence (where stated)

Clinical Resource Efficiency Support Team (CREST) (2008). Guidelines for the diagnosis, assessment and management of lymphoedema30

Northern Ireland guidelines developed in accordance with recognised tools (e.g. Scottish Intercollegiate Guidelines Network methodology) by a multidisciplinary group with clinician & patient involvement. Development methods are briefly outlined in the document.

IPC must be used in combination with MLD & is not to be used in isolation It requires specific compartmentalised sequential pressure at precise settings It must be used under the guidance of a therapist Comments: Findings from a review of the literature rather than formal recommendations; not graded The authors reported limited high quality research available at the time (consensus and expert

opinion rather than RCTs) & noted that most trials involved breast cancer-related lymphoedema

International Lymphoedema Framework (2010). The management of lymphoedema in advanced cancer and oedema at the end of life: position document20

The Canadian Lymphedema Framework led the development of this position document in partnership with the International Lymphoedema Framework. No further information on development methods is given.

Standard CDT approaches may be adapted to the palliative care content providing there is close collaboration with the palliative team in understanding the aetiology of the oedema & developing a clear picture of the location of the disease and its impact on standard clearance pathways

IPC devices are ill suited to palliative care, as there is usually oedema at the root of the limb which IPC might worsen

Comments: Position statements rather then formal recommendations; not graded

International Society of Lymphology (ISL) (2013). Diagnosis & treatment of peripheral lymph-edema: 2013 Consensus Document of the ISL1

Consensus document developed via a series of international meetings and discussions. Intended as a “living document” that will undergo ongoing revisions and refinement.

Careful observation is needed to avoid displacing oedema more proximally in the limb & genitalia, as this could cause a fibrosclerotic ring to develop at the root of the limb and exacerbate the obstruction of lymph flow

Combining IPC with MLD has been reported but not sufficiently evaluated Design improvements of newer devices may increase patient compliance Comments: Consensus statements rather than formal recommendations; not graded


Kerchner (2008). Lower extremity lymphedema. Update: Patho-physiology, diagnosis, & treat-ment guidelines3

Narrative review aimed at dermatologists who may be unfamiliar with the lymphoedema literature.

IPC has been shown to be a beneficial adjunct in the treatment of lymphoedema When used in conjunction with DLT, IPC enhances the therapeutic response There are no established guidelines on optimal pressure range, inflation/deflation cycles or length or

frequency of IPC sessions Typical recommended pressures are 80-110mmHg pumping 4-8 hours per day; lower pressures may

be used when used in combination with DLT No one device appears to be superior to another IPC is relatively free from complications, but there are concerns that it can worsen truncal/genital

lymphoedema and that high pressures can cause peripheral lymphatic damage Comments: Findings from a narrative review of the literature rather than formal recommendations; not graded Recommendation on effectiveness largely extrapolated from a single 2002 RCT of DLT versus DLT

plus IPC in patients with breast cancer-related lymphoedema31

Kitamura (2011). A practice guideline for the management of lymphoedema32

Development of this guideline was led by the Japan Lymphoedema Study Group using recognised tools (Centre for Evidence Based Medicine & AGREE tools, DELPHI technique to establish consensus). Development methods are well described in the document.

Recommendations for clinical question 6, “Is there a better outcome when IPC is performed?”: There is currently no evidence that IPC decreases the circumferential diameter of limbs with

lymphoedema. Grade of recommendation = D (no evidence of usefulness or lack of clinical agreement; treatment should only be provided if there is both patient request and clinical need)

Comments: The authors note that the efficacy of IPC is unclear, its use is not standardised and there is no

agreement on optimal pressures, treatment regime or post-treatment support

Lymphoedema Framework (2006). Best practice for the management of lymphoedema: international consensus7

Derived from a UK national consensus on lymphoedema care & developed via a robust process including appraising best evidence, grading recommendations & consulting with national groups. The development methods are not described in detail in the document.

Intensive stage, 2-4 weeks: IPC may be used in the following modified, lower pressure intensive stage regimes for people with ISL stage II-III lower limb lymphoedema who can’t commit to standard high pressure (MLLB > 45mmHG) therapy: Modified intensive therapy with reduced pressure: suitable where high levels of compression are

unsafe or hard to tolerate (e.g. due to neurological deficit, cancer requiring palliative care); recommended regime involves skin care, exercise/ movement, elevation, SLD and MLLB (15-25mmHG) ± IPC three times weekly.

Intensive therapy for lymphovenous disease: suitable for people post-DVT/with post-thrombotic syndrome & with or at risk of developing leg ulceration; recommended regime involves skin care, exercise/movement, elevation and MLLB (35-45 or 15-25mmHg) ± IPC either daily or thrice weekly.


Transition stage, 1-3 months: a regime of MLD/SLD and compression garments ± IPC (plus self management, skin care, elevation, exercise etc.) is suitable for patients with upper or lower limb lymphoedema who require transition management and have venous disease, limited mobility or obesity, or soft, pitting oedema (but no truncal oedema). Long term management: a regime of high stiffness elastic/inelastic MLLB ± IPC (plus self management, skin care, elevation, exercise etc.) is suitable for less mobile patients with lower limb lymphoedema, but without severe arterial disease, who are unable to use compression hosiery. Guidelines & good practice points on IPC use: IPC is thought to reduce oedema by decreasing capillary filtration (& therefore lymph formation)

rather than by accelerating lymph return IPC is particularly effective for non-obstructive oedemas (e.g. due to immobility, venous

incompetence, lymphovenous stasis, hypoproteinaemia) In obstructive lymphoedema (e.g. caused by lymph node or vessel damage), SLD or MLD is

recommended before IPC to stimulate lymphatic flow Important to continue compression therapy with garments/bandaging after IPC Adjust pressure according to patient tolerance & treatment response; in general, pressures of 30-

60mmHg are advised (20-30mmHg in palliative care) A duration & frequency of 30 minutes to 2 hours daily is recommended IPC should be prescribed & performed by practitioners with appropriate specialist level training Contraindications & cautions for IPC include DVT, pulmonary embolism, acute skin inflammation,

uncontrolled/severe cardiac failure, pulmonary oedema, severe peripheral neuropathy, oedema at the root of the affected limb or active metastatic disease affecting the limb.

Comments: This consensus document still appears to be highly regarded The recommendations are not graded

National Lymphedema Network (NLN) Medical Advisory Committee (2011). The diagnosis and treatment of

The development methods are not described in the document.

IPC can be a useful adjunct phase I (intensive) CDT in some patients “or a necessary component of a successful home program (phase II CDT)”

Single chamber pumps are no longer used for lymphoedema as they can cause fluid to move in both directions, thus risking fluid build-up in the already swollen area

Recommended pressure range is generally 30-60mmHg; superficial structures can be damaged if the pressure is too high. The length of each treatment is usually one hour


lymphedema: position statement of the NLN33

IPC is not a stand alone treatment; it is to be utilised alongside standard CDT to maintain control of lymphoedema at home in the phase II or maintenance stage

To maintain oedema control, compression garments or short stretch bandages should be worn between IPC treatments and when IPC is discontinued

Comments: Position statements/good practice points rather than formal recommendations (therefore no grading); based on studies on both upper & lower limb lymphoedema

Partsch (2008). Indications for compression therapy in venous and lymphatic disease. Consensus based on experimental data and scientific evidence under the auspices of the IUP12

An international expert group (International Compression Club, ICC) located & appraised RCTs and other experimental studies of compression therapies including IPC. They used recognised tools to grade their recommendations and agreed them by consensus. Development methods are briefly outlined in the document.

Evidence supports the use of IPC in lymphoedema (Grade of recommendation = 1B, i.e. strong recommendation based on moderate evidence)

Comments: The recommendation is based on a single 2002 RCT of DLT versus DLT plus IPC in patients with

breast cancer-related lymphoedema31

Poage (2008). Demystifying lymphedema: development of the lymphedema putting evidence into practice card19

Developed by a project team from the Oncology Nursing Society (ONS) using recognised tools. The development methods are briefly outlined in the document.

IPC may be an effective adjunct to a comprehensive treatment plan when ordered and performed by trained clinicians

It should not be used a stand alone therapy & should be carefully used only in selected patient populations

Some researchers have suggested that IPC may cause harm and actually increase lymphoedema by causing scarring & fibrosis or by damaging remaining functional lymphatic structures

Comments: According the ONS weight of evidence classification scheme34 used for this guideline, the authors

place IPC in the “effectiveness not established” category due to insufficient evidence The evidence the authors did find consisted largely of studies involving breast cancer patients


Appendix 5: framework for selecting IPC devices for patients with leg & trunk lymphoedema

Figure 1. factors to consider when deciding whether to use an IPC device:

Figure 2.”decision tree” for selecting a device type for home use:

PCD = pneumatic compression device; phase II = maintenance stage CDT; LPO = Lympha Press Optimal and FT = Flexitouch (advanced programmable IPC devices); standard PCD = less sophisticated non- programmable device.

Taken from Maul et al (2009), Development of a framework for pneumatic device selection for lymphedema treatment21


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