Application of the L-Dex Score for the Assessment of Bilateral Leg Edema

Abstract

Background:

We evaluated a modified L-Dex score by using the right arm as a reference (LDS_rarm), to determine whether it could be used for the assessment of leg edema in place of the usual L-Dex score calculated by using the contralateral normal leg as a reference (LDS_cont).

Methods:

Bioimpedance analysis was performed in the legs and right arms of 38 patients with unilateral leg edema and in 42 healthy volunteers by using a standard equipotential electrode arrangement.

Results:

The impedance ratio in the right arms of patients (2.6 ± 0.4) was lower than that in their contralateral normal legs (3.0 ± 0.8, p < 0.05), but it was similar to that in the legs (right: 2.4 ± 0.7, left 2.5 ± 0.8) of normal subjects. There was a significant correlation between LDS_cont and LDS_rarm in legs with edema (right: r = 0.80, left: r = 0.93). No such correlation was found in the legs of normal subjects, but the mean ± 2 standard deviation of their LDS_rarm ranged from −3 to 37, which was similar to LDS_rarm values in legs with edema corresponding to the normal range of LDS_cont (−10 to 10), that is, from 1 to 34.

Conclusions:

LDS_rarm could be used as an alternative for LDS_cont in the assessment of leg edema.

Introduction

Bioelectrical impedance spectroscopy (BIS) has been gaining popularity for the early detection and/or assessment of treatment of lymphedema because of its accuracy and noninvasiveness.^1–4 The L-Dex score, which is calculated from the impedance obtained by BIS, is highly sensitive for abnormal local fluid accumulation in the extremities, for example, early stages of lymphedema, when it exceeds +10.^5,6 The basis of the L-Dex measure is to compare the extracellular fluid (ECF) of the affected limb with that of the unaffected control side measured by resistance at zero frequency (R₀) in the affected side against R₀ in the unaffected side, by using the equation ECF affected/ECF unaffected = R₀ unaffected/R₀ affected.⁷ This ratio is then compared with a normal population, and lymphedema is defined as a ratio more than 3 standard deviation (SD) greater than the mean.^5,8 The L-Dex is a “normalized” scale of this (−10 to +10), which is created to facilitate an easy-to-use score for clinical settings. Since the L-Dex score of a limb is determined in reference to the contralateral normal limb (LDS_cont), it is not available for bilateral limb edema. Most postmastectomy lymphedema cases present with unilateral arm swelling, whereas more than half of postsurgery leg lymphedema cases are bilateral,⁹ and they are not suitable for assessment using LDS_cont. Moreover, legs can be affected by various types of edema, including a physiological increase in ECF associated with aging.⁷ In contrast, the arm is not in as dependent a position as the legs and is less affected by other types of edema; therefore, the use of the arm as a reference seems reasonable. It would be useful if an L-Dex score calculated in reference to the right arm (LDS_rarm) could be available for the assessment of bilateral leg edema. Although the original algorithm should not substitute LDS_cont with LDS_rarm, we attempted this substitution and compared the results for clinical convenience.

Patients and Methods

This study was approved by the Institutional Review Board of Yamaguchi University Hospital (Ube, Yamaguchi, Japan). All participants provided signed, informed consent before enrollment. The subjects included in the current study were 38 patients with unilateral leg edema who attended our clinic between April and September 2015, and 42 healthy volunteers. Subject characteristics are summarized in Table 1.

Table 1.

Subject Characteristics

	Normal (N = 42)	Unilateral leg edema (N = 38)	p
Age, years, median (range)	32 (23–59)	64 (31–88)	<0.0001
Height, cm, median (range)	160 (143–180)	156 (140–176)	<0.05
Weight, kg, median (range)	58 (42–105)	57 (45–98)	NS
BMI, kg/m², median (range)	21 (17–34)	23 (19–34)	<0.01
Sex (males:females)	13:29	3:30	NS
Dominant side (right:left)	40:2	35:3	NS
Edema side (right:left)		17:21
Diagnosis
Lymphedema		33
Chronic venous insufficiency		5

BMI, body mass index; NS, not significant.

A bioimpedance spectrometer (U-400; Impedimed Ltd., Brisbane, Australia) was employed to determine impedance. The details of measurement were as described in a previous report.¹⁰ First, the impedance in an edematous leg (the right leg in normal subjects) was normalized to the contralateral normal leg (the left leg in normal subjects), and used to obtain the ratio of ECF resistance (Re), which is equal to R₀ described in introduction, to intracellular fluid resistance (Ri), that is., Ri/Re_cont and LDS_cont by using a standard equipotential electrode arrangement. Next, the impedance in a leg with edema (the right leg in normal subjects) was normalized to the right arm, and Ri/Re_rarm and LDS_rarm were obtained.

In patients with leg edema, extremity volume was calculated from tape measurements at 10-cm intervals from the groin to the ankle, as described by Casley-Smith.¹¹

Statistical analysis

The results are expressed as mean ± SD or count, unless otherwise indicated. The Mann–Whitney U test was used to compare subject characteristics based on BIS and leg volume measurements. Simple linear regression analysis was used to study the correlation between LDS_rarm and LDS_rarm, LDS_rarm in the right and left normal legs, LDS_cont and Ri/Re_cont, LDS_cont and leg volume, LDS_cont and the ratio of Ri/Re_cont or leg volume of the legs, LDS_rarm and Ri/Re_rarm, LDS_rarm and leg volume, and LDS_rarm and the ratio of Ri/Re_rarm of the legs. Statistical analyses were performed by using JMP 11.0 (SAS Institute, Cary, NC). A p < 0.05 was considered significant.

Results

The results of bioimpedance and leg volume measurements are summarized in Table 2. In normal subjects, Ri/Re_cont and Ri/Re_rarm were similar in both legs. These values were also similar to Ri/Re in the right arm. In patients with unilateral leg edema, Ri/Re_cont and Ri/Re_rarm were not significantly different between both legs. However, Ri/Re in the right arm was significantly lower than Ri/Re_cont and Ri/Re_rarm in the legs (p < 0.05 each), and it was similar to the value in normal subjects. In contrast to Ri/Re_rarm, mean LDS_rarm was significantly different between the leg with edema and the contralateral normal leg.

Table 2.

Bioimpedance Analysis and Leg Volume Measurements

	Normal (N = 42)		Unilateral leg edema (N = 38)
	Right leg	Left leg	Leg with edema	Contralateral normal leg
Ri/Re_cont (range)	2.4 ± 0.7 (0.4 to 3.5)^a	2.5 ± 0.8 (0.4 to 3.8)	3.3 ± 1.9 (−0.4 to 8.7)	2.9 ± 0.6 (1.7 to 4.6)
Ri/Re_rarm (range)	2.4 ± 0.7 (0.4 to 3.5)^a	2.5 ± 0.8 (0.4 to 3.7)^a	2.9 ± 0.6 (1.9 to 4.8)	3.0 ± 0.8 (1.9 to 6.3)
Ri/Re of the right arm (range)	2.5 ± 0.4 (1.6 to 3.1)		2.6 ± 0.4 (1.9 to 3.3)
LDS_cont (range)	−0.6 ± 2.6 (−5.1 to 8.7)	—	36.9 ± 36.0 (−2.1 to 189.9)^b	—
LDS_rarm (range)	17.4 ± 10.0 (−2.7 to 36.3)	18.1 ± 11.1 (−2.9 to 43.6)	70.5 ± 51.2 (6.9 to 227.2)^a,b	23.6 ± 18.4 (1.6 to 80.7)

Versus contralateral normal leg.

Versus normal right leg.

LDS_cont, L-Dex score calculated by using the contralateral leg as a reference; LDS_rarm, L-Dex score calculated by using the right arm as a reference; Ri, intracellular fluid resistance; Re, extracellular fluid resistance; Ri/Re_cont, Ri/Re measured by using the contralateral leg as a reference; Ri/Re_rarm, Ri/Re measured by using the right arm as a reference.

The correlation between LDS_cont and LDS_rarm for each leg is shown in Figure 1. In a right leg with edema, LDS_cont and LDS_rarm showed a good linear correlation (r = 0.80). Values of LDS_rarm for these legs corresponding to −10 and 10 for LDS_cont, that is, a normal range, calculated from the regression line were ∼1 and 31. LDS_cont and LDS_rarm for the left leg similarly showed a good correlation (r = 0.93). The values of LDS_rarm for the left leg corresponding to a normal range for LDS_cont were ∼9 and 34. In the normal right leg, no significant correlation was found between LDS_rarm and LDS_cont. LDS_rarm for these legs ranged from −3 to 36, and mean ± 2 SD was 17 ± 20 (i.e., −3 to 37). LDS_rarm for the normal left leg was almost the same as that for the normal right leg (Fig. 2).

FIG. 1.

Correlation between LDS_cont and LDS_rarm in legs with edema and right legs in normal subjects. LDS_cont, L-Dex score calculated by using the contralateral leg as a reference; LDS_rarm, L-Dex score calculated by using the right arm as a reference.

FIG. 2.

Correlation between LDS_rarm in right and left legs in normal subjects. LDS_rarm, L-Dex score calculated by using the right arm as a reference.

Discussion

We demonstrated that the use of LDS_rarm might be a feasible alternative to that of LDS_cont.

Ri/Re_cont and Ri/Re_rarm reportedly show a very good linear correlation regardless of the presence of edema,¹⁰ and bilateral leg lymphedema can be sensitively discriminated from normal legs using Ri/Re_rarm.⁷ However, it is also known that Ri/Re can be affected by various factors such as systemic disease¹² or aging.⁷ Accordingly, it was not surprising that mean Ri/Re_rarm in legs with edema was not statistically different from Ri/Re_rarm in contralateral normal legs. Since systemic factors affect both legs, it seems reasonable to use the contralateral normal leg to cancel out these factors when calculating a parameter to indicate fluid status in a leg with edema. Although the formula used to calculate L-Dex score is not open, we speculate that this is more or less what is required to obtain the L-Dex score. It is also true that leg edema is more commonly seen in older people; therefore, the contralateral leg may not serve as a good control in this population. However, Ri/Re in the arms of older patients was as low as that in the legs and arms of younger normal subjects. Thus, it seemed reasonable to utilize the arm as a reference to calculate the L-Dex score. Moreover, mean ± 2 SD values for LDS_rarm in normal right legs ranged from −3 to 37, and LDS_rarm values corresponding to the normal range of LDS_cont ranged from 1 to 34. Because these ranges were similar, it was speculated that the normal range of LDS_rarm corresponding to the normal range of LDS_cont might be suitable for use in detection of abnormal fluid status; this was also roughly the case for the contralateral normal legs in the current patients.

Limitations

The number of subjects included in this study might be too small to draw definite conclusions. The confirmation of unilateral nature of the leg edema was very difficult. For instance, the patient with post-thrombotic syndrome in whom the unilateral iliac vein is incompetent should have unilateral edema. However, risk factors such as obesity may cause venous stasis and, therefore, venous edema can occur in the other side. In unilateral lymphedema, the seemingly normal side should have more or less reduced lymphatic transport capacity, and, therefore, may cause minimal edema. Perfect exclusion of these conditions may be impossible as of present. In this study, control subjects were not age-matched with the patients. However, one third of the patients in this study were in their 70s or 80s, and, therefore, it was difficult to find “normal” age-matched controls in the hospital.

Conclusion

The use of LDS_rarm seemed to be suitable as an alternative to that of LDS_cont in the detection of abnormal fluid status in the leg.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

References

DiSipio

, Rye

, Newman

, Hayes

. Incidence of unilateral arm lymphoedema after breast cancer: A systematic review and meta-analysis. Lancet Oncol, 2013; 14:500–515.

Boyages

, Kastanias

, Koelmeyer

, et al. Liposuction for advanced lymphedema: A multidisciplinary approach for complete reduction of arm and leg swelling. Ann Surg Oncol, 2015; 22,Suppl 3:S1263–S1270.

Bundred

, Stockton

, Keeley

, et al. Comparison of multi-frequency bioimpedance with perometry for the early detection and intervention of lymphoedema after axillary node clearance for breast cancer. Breast Cancer Res Treat, 2015; 151:121–129.

Blaney

, McCollum

, Lorimer

, Bradley

, Kennedy

, Rankin

. Prospective surveillance of breast cancer-related lymphoedema in the first-year post-surgery: Feasibility and comparison of screening measures. Support Care Cancer, 2015; 23:1549–1559.

Ward

, Dylke

, Czerniec

, Isenring

, Kilbreath

. Confirmation of the reference impedance ratios used for assessment of breast cancer-related lymphedema by bioelectrical impedance spectroscopy. Lymphat Res Biol, 2011; 9:47–51.

, Cleland

, Guth

, et al. L-dex ratio in detecting breast cancer-related lymphedema: Reliability, sensitivity, and specificity. Lymphology, 2013; 46:85–96.

Ward

, Winall

, Isenring

, et al. Assessment of bilateral limb lymphedema by bioelectrical impedance spectroscopy. Int Journal Gynecol Cancer, 2011; 21:409–418.

Ward

, Dylke

, Czerniec

, Isenring

, Kilbreath

. Reference ranges for assessment of unilateral lymphedema in legs by bioelectrical impedance spectroscopy. Lymphatic Res Biol, 2011; 9:43–46.

Werngren-Elgstrom

, Lidman

. Lymphoedema of the lower extremities after surgery and radiotherapy for cancer of the cervix. Scand J Plast Reconstr Surg Hand Surg, 1994; 28:289–293.

10.

Suehiro

, Morikage

, Yamashita

, et al. Distribution of extracellular fluid in legs with venous edema and lymphedema. Lymphatic Res Biol, 2016; 14:156–161.

11.

Casley-Smith

. Measuring and representing peripheral oedema and its alterations. Lymphology, 1994; 27:56–70.

12.

Haverkort

, Reijven

, Binnekade

, et al. Bioelectrical impedance analysis to estimate body composition in surgical and oncological patients: A systematic review. Eur J Clin Nutr, 2015; 69:3–13.