EFFICIENCY OF TREATMENT OF LYMPHEDEMA OF THE UPPER LIMB BY MULTICOMPARTMENT SEQUENTIAL PNEUMATIC COMPRESSION THERAPY

Translated from the original, Rehabilitacion (Madr) 1998:32:234-250.

AUTHORS
Miguel Angel Gonzalez Viejo (*), M? Jesus Condon Huerta (**), Margarita Lecuona Navea (***), T. Etulain Marticorena (****), M?.A. Ruiz Arzoz (****), M. Arenas Paos (****).

* Hospital Universitari Germans Trias i Pujol. Badalona
** Hospital Virgen del Camino. Pamplona
*** Hospital Ntra. Sra. de Aranzazu. San Sebastian
**** Physical Therapist

Correspondence:
Miguel Angel Gonzalez Viejo. Servicio de Rehabilitacion. Hospital Universitario Germans Trias i Pujol. Carretera Canyet sn. Apartado correos 72. 08916 Badalona. Spain.

ABSTRACT

The study comprised a total of 14 patients, including 13 women and one man, affected by lymphedema of upper limb.

In thirteen cases the lymphedema was secondary to breast cancer. Eight cases were treated by modified Madden radical mastectomy and ganglionic axillary drainage. One case was treated by tumorectomy and radiotherapy, two by quandrantectomy and radiotherapy, one by Halsted radical mastectomy, and one by radiotherapy. Lastly, the only case that was not due to breast cancer involved a lymphedema secondary to an axillary lymphadenectomy owing to ganglionic metastasis of an undifferentiated malignant tumor, whose primary tumor could not be located.

We determined the efficiency of the multicompartment sequential pneumatic compression therapy during two weeks of treatment, in ten sessions of one hour each, by determining the volume in cubic centimeters (cc) of the healthy and affected limbs according to the measurement of the girth, in centimeters, at seven levels along the limbs.

The average volumes showed statistically significant differences on the first day, before and after treatment (p=0.007) and the fourth day (p=0.001), but not on the sixth or the eighth days. However, we did find significant differences between the volumes on the first day before treatment and the last day after treatment (p=0.007).

We consider that multicompartment sequential pneumatic compression therapy has a place in the treatment of lymphedema of the upper limb, which was the subject of our study, always in combination with other physical therapy techniques, such as manual lymphatic drainage.

KEY WORDS: LYMPHEDEMA, COMPRESSION THERAPY.

INTRODUCTION

Lymphedema is an edema of the soft tissues due to an increase in the quantity of lymph resulting from an incapacity of the lymphatic system to clear proteins and macromolecules, and/or to an excess production of lymph caused by obstruction of the lymphatic vessels (1-3).

From the physiopathologic standpoint, the fluid accumulated in the lymphedema is an abnormal collection of proteins in particular, and of water and solutes, in the interstitial space of the subcutaneous cellular tissue (SCT) (4,5). The maintenance of this fluid, and above all of the large quantity of proteins, may promote lymphangitis and, consequently, a fibrous reaction owing to an excessive formation of connective tissue, possibly leading to elephantiasis or sclerotic changes that will have a large influence on the effectiveness of the possible treatments of the lymphedema. Accordingly, a lymphedema following a radical mastectomy and/or radiotherapy may respond to the application of external compression measures but may also be limited by the progression of the fibrotic changes (2,6).

The treatment of lymphedema is well known. It consists of the hygienic care of the limb, manual lymphatic drainage (MLD) (7), and the use of elastic bandages such as compression sleeves and gloves (8) to prevent the accumulation of fluids. This is the so-called complex physical therapy (9). Drugs such as 5,6-Benzo-(alpha)-pyrones are sometimes used (10).

Likewise, external compression devices (11-14) have been used to simplify the mobilization of fluids. This therapeutic technique, called compression therapy, may be applied by means of single- or multicompartment chambers (15). In the single-compartment chambers, the pressure is applied evenly and distributed centripetally and centrifugally under the compression therapy sleeve. In the multicompartment chambers, the pressure is applied by means of several chambers that may be positioned one after the other or be overlapped. By modifying the apparatus to allow the addition of a control mechanism that calibrates the pressure gradient in the various chambers, compression may be applied in cycles and sequences all along the limb, in the distal to proximal direction.

Consequently, multicompartment chambers allow sequential application of intermittent pressures with a high pressure gradient. An advance in this field has been the development of multicompartment chambers that are positioned in overlapping arrangement and press the fluid along by a system that may be likened to "milking". These overlapping chambers carry out a centripetal massage, with a higher pressure gradient than can be applied by single-compartment chambers, reaching up to 110 mm Hg in the upper limb and up to 150 mm Hg in the lower limb (16).

The purpose of this study was to make an objective determination of the quantity of transfer of fluids in the lymphedema of upper limb, in short periods and ranges of application, during two weeks of treatment, in order to determine the efficiency of lymphedema treatment by means of the multicompartment intermittent pneumatic compression (MSPC) system, whose use is not widespread in our country.

MATERIAL AND METHOD

Fourteen patients were comprised in the study, including 13 women and one man, who were affected by lymphedema of upper limb and fulfilled the diagnostic criteria of Markowski et al (16) and Clarysse (17). According to these authors, in order to be able to define a lymphedema there must be a difference of 1.5-2 cm between one limb and the other at one or more of the evaluated girth points.

Selection was made at random, including patients in the study who began treatment in a predetermined period of time.

In thirteen cases the lymphedema was secondary to breast cancer. Eight cases were treated by modified Madden radical mastectomy and ganglionic axillary drainage, one by tumorectomy and radiotherapy, two by quadrantectomy and radiotherapy, one by Halsted radical mastectomy, and one by radiotherapy. Lastly, the only case that was not due to breast cancer involved a lymphedema secondary to axillary lymphadenectomy owing to ganglionic metastasis of an undifferentiated malignant tumor, whose primary tumor could not be located.

All the patients received compression therapy by means of a multicompartment device with overlapping chambers, cyclic compression and sequential operation, of the MSPC type (Lympha-Press®).

The treatment was applied at three public hospitals, in three different regions of the country. The length of treatment was one hour per session, after performance of manual lymphatic drainage.

The treatment was administered with the limb elevated and placed in the compression therapy sleeve, which contained 12 overlapping compartments. The compartments were gradually inflated, starting with the most distal one and ending with the most proximal one, so that once all the little compartments had been inflated automatically, they began to deflate, exerting a "milking" action on the limb in the distal to proximal direction. The duration of the cycle was 25 seconds, including 20 seconds in the distal compartment and only 2 seconds in the proximal compartment. This allowed us to achieve pressure figures under 80 mm Hg without causing pain.

Prior to the start of treatment, the pressure was adjusted according to the individual tolerance of each patient. Once the respective pressure had been set, treatment was applied for one hour.

The volume of the healthy and affected limbs was quantified in cubic centimeters (cc), measuring the girth of the limbs in centimeters at seven levels, as specified by Markowski et al (18): palm of the hand, behind the head of the metacarpals (to avoid a bias of measurement due to arthrosis of the metacarpophalangeal joints), wrist, middle third of the forearm, upper third of the forearm, and lower, middle and upper thirds of the arm. The measurements made at the wrist were set a specific distances from the ulnar styloid, which was taken as the reference point.

For the calculation of the volume of each limb, we used the formula proposed by Mortimer (19), which expresses the total volume of the limb as the sum of the volume of each segment and is calculated as follows:

Volume of segment = girth 2 / p. Therefore, the total volume is the sum of the volume of all the segments.

The quality of the lymphedemas was determined by digital pressure, classifying them into one of three groups: soft, when they allowed deformation of the SCT; hard, when did not allow it; and fibrous, when they were of woody consistency.

The girths and, therefore, the volumes, were determined before and after each treatment session.

The percentage of reduction of the girths of the lymphedemas was calculated by means of this formula:

sum of pre-treatment girths-sum of post-treatment girths x 100
sum of pre-treatment girths

Likewise, the percentage of reduction of the volumes of the lymphedemas was calculated by means of the following formula:

pre-treatment volume - post-treatment volume x 100
pre-treatment volume

The different variables were entered on an EXCEL 5.0 spreadsheet to calculate the volume of each segment and the total volume of each limb. The statistical analysis was performed with the EPISTAT program, using variance analysis to compare the girths and volumes before and after each treatment session. The statistical significance was determined for a p value under 0.05.

RESULTS

The average age of the patients was 64.5 years (SD 11.1), with a range extending from 49 to 84 years. The time of occurrence of the lymphedema was between 5 and 232 months with respect to the therapy applied. TABLE 1.

TABLE 2 shows the girth and volume results for all the patients, with the girth and volume differences and the percentages of reduction of girths and volumes. The range of percentage differences of the girths before and after treatment varied from -0.14% for a lymphedema of long evolution and fibrous consistency which was the most voluminous of all (case no. 14), located in the arm region, and 6% for a hard edema of short evolution (case no. 5). The range of percentage differences between the volumes before and after treatment was -0.2% to 11.6%, which were likewise the values found in the respective aforementioned cases, of course.

The average values of the girths (TABLE 3) and volumes (TABLE 4) show statistically significant differences on the first day before and after treatment (p=0.007) and the fourth day (p=0.001), but not on the sixth or the eighth day. However, we did find significant differences between the volumes on the first day before treatment and the last day after treatment (p=0.007).

DISCUSSION

After treatment of breast cancer, lymphedema of the upper limb has a substantial incidence and a high prevalence (20). It has long been known (21,22) and Halsted (21), one of the most outstanding figures in the field of breast surgery, described it in 1921. It is now considered a cause of disability (23) and of loss of quality of life (24).

Animal experimentation has allowed determination of the effects associated with chronic lymphedema. In dogs in which the proximal lymphatics were resected (25), a decrease occurred in the phagocytic activity of the leukocytes, with an increase in the number of macrophages and fibrocytes, a reduction in the level of collagenase and other proteolytic enzymes, and a rise in the number of globulins.

The combination of the increase of fibroblasts and globulins, together with the reduction in the activity of the proteolytic enzymes, leads to a situation in which collagen and proteic materials are deposited in the subcutaneous cellular tissue. This situation leads in turn to a deficient oxygenation of the tissues, an increase in the weight of the limb and a decreased articular function, because of the infiltration of proteins of high molecular weight into the capsular-muscular-ligamentous structures, and finally to fibrosis.

It is increasingly clearer in medical literature that lymphedema can only be approached effectively through physical medicine (9, 26) since surgical techniques have had little result, require highly experienced surgeons, and show a hardly favorable cost-benefit ratio.

The purpose of physical therapy is to transfer the lymph accumulated in the SCT. To this end, external compression devices (11-14) have been used, showing themselves be effective in fluid transfer trials since, according to Laplace's law, when a fluid is subjected to a compression, the pressure is distributed in all directions.

These devices may make use of single- or multicompartment chambers (15), exerting an even pressure or a pressure in several places, respectively.

No studies have previously been published in our country on the use of this technique. In our experience, the compression therapy chambers that are most often used as those of the single-compartment type, in which the pressure is distributed centripetally and centrifugally under the compression therapy sleeve, consequently resulting in a partial loss of the hydraulic efficiency of the system since part of the fluid is moved in the proximal direction and part in the distal direction. For this reason, the fluid that is moved distally in the limb does not approach the most important drain of the lymphatic system, the large thoracic duct or large lymphatic vein. Multicompartment compression therapy has been developed to obviate this drawback. The compression therapy sleeve is modified to allow the compartments to be arranged one after the other, while a modification of the compression device allows regulation of the pressure cycles and sequences in the compartments, by means of a control mechanism that calibrates the pressure gradient in the multicompartment chambers.

At least theoretically, these chambers allow application of high intermittent sequential pressures, beginning distally and advancing proximally until the root of the limb is reached. This moves the accumulated lymph to the proximity of the thoracic duct.

The MSPC devices, such as the one used in this study, would appear to represent an advance in this field. These devices have a series of superimposed overlapping chambers that prevent the wave of fluid from backing up, thanks to the tiled arrangement of the chambers, which press the fluid along by a "milking" action. The overlapping chambers perform a centripetal massage with a higher pressure gradient than can be applied by single-compartment chambers, reaching up to 110 mm Hg in the upper limb and 150 mm Hg in the lower limb (16).

The subcutaneous cellular tissue is composed of a solid matrix of macromolecules of proteoglycans and collagen fibers, which represent about 20% of its weight, and by interstitial fluid, which forms the remaining 80%. This fluid is in free form and may be moved between the tissues by the action of the forces applied to it. The pores of the tissues have between 20 and 65A°, so they may be considered a micropous material (27). Under the action of compression forces, the deformation of the solid matrix and the interstitial flow become increasingly larger (12), and this is the mechanism on which the multicompartment chambers are based.

The transfer of fluids under compression differs notably between normal and edematous tissue, and depends on two variables. The first of these is the resistance of the circuit and the second is the quantity of stored liquid. The effectiveness of transfer does not depend so much on the degree of the edema as on the capacity of mobility of the fluid. According to the study by Mridha and ?dman (12), this mobility is greater at distal level than at proximal level, and for this reason, multicompartment systems are theoretically more efficient than single-compartment systems, and the most effective among the latter would be those allowing changes of cycle and pressures.

The resistance of the circuit is another element to be considered. It depends on the viscosity of the fluid and is inversely proportional to the dimensions of the channel through which the fluid flows. The increase of volume of the fluid owing to the edema is accompanied by a reduction in the viscosity of the fluid and a decreased resistance to the interstitial flow, which may express itself as a greater mobility of the fluid that would theoretically enhance its transfer.
In lymphedema, however, histological and biochemical changes also occur, which translate into a hyperkeratosis that may affect the extensibility of the skin since the corneal layer becomes 100-1000 times more rigid than the dermis (28). The degeneration of the elastic fibers which occurs in the lymphedema plays a lesser role in extensibility, and for this reason the modification of the intermolecular septa of the collagen fibers and the change of the architecture of the fibers, together with the thickness of the bundles and the alteration of the wave structures may contribute to the reduction of extensibility. The structural change of the collagen fibers has two consequences that influence the natural evolution of the lymphedema. One is the reduction of the friction between the fibers, and the other, which is very important, is the alteration of the drainage of the interstitial fluid due to the increased width of the mesh of the fibrous network, and this is where external compression systems, such as elastic stockings or sleeves and compression therapy devices, have a role to play, since they modify the natural evolution of the collagen fibers subjected to lymphedema.

There is a difference between the lymph kinematics in a system producing an intermittent pressure throughout the limb without any rise in the pressure wave, and in a system producing an intermittent pressure that rises all along the limb, since the latter has show itself to be more effective and intense in the transport of lymph marked with radioactive isotopes (29).

Statistical analysis has shown that compression therapy pumps with multiple compartments and with pressure gradients are effective in reducing the lymphedema of lower limbs in a short period of time: 48 hours (30). Our results concur with these findings, although our study was conducted on upper limbs. During the first four days we observed a statistically significant difference between the girths and volumes before and after treatment, which is confirmed by a comparison of these values for the first day of treatment and last day of treatment.

The use of compression therapy is also supported by the pletismographic impedance studies, which have demonstrated the reduction of the blood volume and flow by undulating (multicompartment) pneumatic massage, with a reduction of edema in 54% of the cases (15).

The Food and Drug Administration approved the use of pneumatic compression therapy pumps in 1976. The analysis of the Office of Health Technology Assessment of the Agency for Health Care Policy Research (13), states that all the compression therapy devices seem to have a similar effect and that the cost of the single-compartment devices is US$ 198 while that of the multicompartment systems ranges from US$ 535 in the case of simple devices to US$ 1,437.39 for units with pressure gradients. This analysis seems to recommend the use of single-compartment devices, although its study was based on the results quantified in percentage of improvement of volume and the calculation of volumes in the various publications are not uniform. Moreover, all the physiological analyses of the mechanical effects that we have mentioned were excluded.

We consider that intermittent multicompartment compression therapy has a place in lymphedema treatment. Firstly, it should be used in the most important period of lymphedema in combination with other physical therapy techniques. One such technique is manual lymphatic drainage, since, as mentioned, MSPC is capable of reducing the edema that remains after MLD. Elastic sleeves and gloves should also be used since they prevent alteration of the skin, fibrosis, and destructuring of the collagen fibers, which are partly responsible for lymph drainage difficulties. And secondly, intermittent multicompartment compression therapy is also appropriate as home therapy, since there a small devices that may be used for hours in the home.

BIBLIOGRAPHY
1. Brennan MJ, DePompolo RW, Garden FH. Focused review: postmastectomy lymphedema. Arch phys Med Rehabil 1996;77:S74-S80
2. Mortimer PS. Managing lymphoedema. Clin Exp Dermatol 1995;20:98-108
3. Roddie IC. Lymph transport mechanisms in peripheral lymhatics. News Physiol Sci 1990;5:85-9
4. Drinker CK, Field ME. The protein content of mammalian lymph and the relation of lymph to tissue fluid. Am J Physiol 1931;97:32-9
5. Badger C. Lymphoedema. Prof Nurse 1987;2:100-2
6. Hodkinson M. Lymphoedema: applying physiology to treatment. European J Cancer Care 1992;1:19-22
7. Foldi E, Foldi M, Weissleder H. Conservative treatment of lymphoedema of the limbs. Angiology 1985;36-171-80
8. Swedorg I. Reduction of arm oedema in postmastectomy patients by different methods of physiotherapy. En: Progress in Lymphology. Proceeding of the Xth International Congress of Lymphology. Casley-Smith JR & Casley-Smith JR (eds.) Adelaide University 1985:176-9
9. Casley-Smith JR, Casley-Smith JR. Modern treatment of lymphoedema. Complex physical therapy: the first 200 Australian limbs. Australas J Dermatol 1992;33:61-8
10. Casley-Smith JR, Morgan RG, Piller NB. Treatment of lymphoedema of the arms and legs with 5,6-Bonzo-(alfa)-pyrones. N Engl J Med 1993;329:1158-63
11. Bates DO, Levick JR, Mortimer PS. Starling pressures in the human arm and their alteration in postmastectomy oedema. J Physiol 1991;477:355-63
12. Mridha M, ?dman S. Fluid translocation measurement. A method to study pneumatic compression treatment of postmastectomy lymphoedema. Scand J Rehabil Med 1989;21:63-70
13. Hotta SS, Holohan TV. Lymphedema pumps: pneumatic compression devices. Health Technol Rev 1993;4:1-7
14. Palmer A, Macchiaverna J, Braun A, Hendrix R, Miller A. Compression therapy of limb edema using hydrostatic pressure of mercury. Angiology 1991;41:533-45
15. Yamazaki Z, Idezuki Y, Nemoto T, Togawa T. Clinical experiences using pneumatic massage therapy for edematous limbs over the last ten years. Angiology 1988;2:154-63
16. Zelikovski A, Manoach M, Giler SH, Urca I. Lympha-Press. A new pneumatic device for the treatment of lymphoedema of the limbs. Lymphology 1980;13:68-73
17. Clarysse A. Lymphoedema following breast cancer treatment. Acta Clin Belg 1993;15(Suppl.):47-50
18. Markowski J, Wilcox JP, Helm PA. Lymphoedema incidence after especific postmastectomy therapy. Arch Phys Med Rehabil 1981;62:449-51
19. Mortimer PS. Investigation and management of lymphoedema. Vascular Med Rev 1990;1:1-20
20. Logan V. Incidence and prevalence of lymphoedema. J Clin Nursing 1995;4:213-9
21. Halsted WS. The swelling of the arm after operation for cancer of the breast, elephantiasis chirurgica, its causes and prevention. Bull J Hopk Hosp 1921;32:309-13
22. Watson TA, Boud AF, Phillips AJ. Swelling and dysfunction of the upper limb following radical mastectomy. Surg Gynecol Obstet 1963;108:99-104
23. Maunsell E, Brisson J, Deschenes L. Arm problems and psycological distress after surgery for breast cancer. CJS 1993;4:315-20
24. Tobin MB, Lacey H, Meyer L, Mortimer PS. The psychological morbidity of breast cancer-related arm swelling. Cancer 1993;72:3248-52
25. Knight KR, Collopy PA, McCann JJ. Protein metabolism and fibroid in experimental canine obstructive lymphedema. J Clin Lab Med 1987;110:558-66
26. Bunce IH, Mirolo BR, Hennessy JM, Ward LC, Jones C. Post-mastectomy lymphoedema treatment and measurement. Med J Australia 1994;161:125-8
27. Kwan MK, Lai W, Van Mow C. Fundamentals of fluid transport through cartilage in compression. Ann Biomed Eng 1984;12:537-40
28. Auriol F, Vaillant L, Pelucio-Lopes C et al. Study of cutaneous extensibility in lymphoedema of the lower limbs. Br Med Dermatol 1994;131:265-9
29. Partsh H, Mostbeck A, Leiner G. Experimental investigation of the effect of a pressure wave massage apparatus in lymphedema. Phlebol Proktol 1980;2:120-8
30. Kelin MJ, Alexander MA, Wright JM, Redmon CK, LeGasse AA. Treatment of adult lower extremity lymphoedema with the Wright linear pump: statistical analysis of clinical trial. Arch Phys Med Rehabil 1988;69:202-6

TABLE 1. Characteristics of the lymphedema cases

CASE AGE SEX TREATMENT LYMPHEDEMA LYMPHEDEMA TYPE DURATION months

1 53 F Quandrantectomy Fibrous 6
2 68 F Radical mast. Fibrous 108
3 78 F Radical mast. Fibrous 48
4 68 F Tumorectomy Soft 34
5 60 F Quandrantectomy Hard 22 6 62 F Radical mast. Fibrous 48 7 49 F Radical mast. Hard 28
8 67 F Radical mast. Soft 216
9 84 F RT+QT Hard 5
10 78 M Axil. lymphadenec.Fibrous 144
11 73 F Radical mast. Soft -
12 53 F Radical mast. Hard 108
13 62 F Radical mast. Hard 43
14 49 F Halsted mast. Fibrous 232


F = Female M = Male

RT = Radiotherapy QT = Chemotherapy

TABLE 2. Differences in absolute and relative values of girths and volumes in affected limbs before and after treatment

CASE DIFFERENCE PERCENTAGE DIFFERENCE PERCENTAGE
GIRTH IMPROVEMENT VOLUMES IMPROVEMENT
START-END GIRTHS START-END VOLUMES
cm cc.

1 4,5 2,3 545 4,9
2 6,4 2,9 879 5,7
3 0,5 0,2 86 0,4
4 8,5 4,46 994 8,6
5 5,5 2,96 641 5,8
6 4,5 2,15 590,5 4,26
7 5 2,64 594 5,22
8 2 1,22 207 2,43
9 12,5 6 1606 11,6
10 5 2,85 549 5,63
11 9,5 5,17 1082 10,08
12 6 2,9 777 5,72
13 1,9 1,37 166 2,73
14 -0,3 -0,14 -38 -0,2

TABLE 3. Limb girths in cm

Girth P

Before treatment 185,61 ± 22,1
Day 1 180,01 ± 29,1 0.007
Day 4 181,87 ± 20,5 0.008
Day 6 181,06 ± 23,9 NS
Day 8 174,80 ± 22,9 NS
Last day 152,70 ± 17,4 0.007