Clinical Efficacy and Safety of Long-Term Compression in Patients with Mixed Arterial and Venous Etiology Ulcers in the Leg

Abstract

Elastic compressions are standard treatment for leg ulcers of venous etiology. The effect of compressions on ulcers of mixed (arterial or venous) etiology, however, has rarely been studied. The objective of this study was to evaluate the variation in transcutaneous oxygen pressure (TcPO2) in patients with ulcers of mixed arterial or venous etiology treated with 1 month of compression. This prospective cohort study was conducted at a university hospital in France. Patient eligibility was for those attending a consultation of a work-up of a leg ulcer of mixed arterial-venous etiology lasting at least 4 to 6 weeks. Compressions were prescribed according to the hemodynamic status and were evaluated by the ankle-brachial index and toe-brachial index using a decision-making algorithm based on French national guidelines. Quality of life was assessed using the Short-Form 36-Item (SF-36) questionnaire. In total, 32 patients were included between September 30, 2018 and May 31, 2019. A difference was observed between TcPO2 before compression (49.3 ± 13.01 mm Hg) and after 1 month (51.2 ± 15.05 mm Hg), average change 1.9 ± 2.04 mm Hg ( p  = 0.025). The average ulcer size prior to compression was 49 ± 102 cm ² versus 37 ± 94 cm ² after 1 month of effective compression, corresponding to a reduction of 12 ± 8 cm ² ( p  < 0.001). There was a reduction in the bodily pain dimension of the SF-36. Compressions adapted to the hemodynamic status led to an increase in TcPO2, a reduction in wound size, and an improvement to bodily pain in patients with leg ulcers of mixed arterial-venous etiology.

Leg ulcers affect up to 2.0% of the general population ^{1 2} and its frequency increases in line with an aging population, obesity, and sedentary lifestyle. ³ Vascular etiology is most common with around 70% of all leg ulcers of venous origin, ⁴ 15% strictly arterial, ⁵ and 17 to 25% of mixed arterial and venous origin. ^{5 6} Leg ulcer management ranges from 4,000 to 30,000 euro per patient across Europe. ⁷ Most of the cost is accounted for by hospitalizations, nursing care, and wound dressings. In addition to its financial impact, leg ulcers are associated with increased morbidity and mortality, reduced quality of life (QoL), and increased social isolation. ⁸

Elastic compression is the first-line treatment for venous leg ulcers. In patients with ulcers of mixed arterial-venous etiology, compression use requires hemodynamic evaluation ^{9 10 11} and ankle-brachial pressure index (ABI) is the only recommended measure to guide the choice of it. ¹²

There has been some controversy surrounding the ABI, particularly in its use in older patients, those with diabetes, or renal failure. ¹³ It has been shown that other measures, such as transcutaneous oxygen pressure (TcPO2) or the toe-brachial index (TBI), may be reliable indicators of peripheral hemodynamics. ^{14 15 16} One study evaluating the variation in TcPO2 with compression in patients with mixed-etiology ulcers as assessed 10 minutes after the application of inelastic bandages with different pressures, reported a 7% increase in TcPO2 with bandages exerting a pressure of 31 to 40 mm Hg. ¹¹ In this study, we sought to demonstrate that the application of compression when adapted to the patient's hemodynamic status does not lead to a decrease in TcPO2 in patients with leg ulcers. The primary objective was to assess the hemodynamic repercussions of compressions by measuring TcPO2 in patients with leg ulcers of mixed arterial-venous etiology. The secondary objective was to evaluate the tolerance by measuring QoL, compliance with compression therapy, and ulcer size.

Methods

Study Population

A single-center prospective pilot study was performed at the University Hospital of Caen, Normandy, France, from September 30, 2018 to May 31, 2019. Patients who attended a consultation in the vascular surgery department for work-up of a leg ulcer were eligible for inclusion. Inclusion criteria were: (1) adult patients (≥ 18 years of age), (2) mixed arterial-venous etiology, (3) having a leg ulcer ongoing for 4 to 6 weeks, (4) with the presence of both arterial criteria (ABI < 0.9 or TBI < 0.7), and (5) venous criteria (clinical signs of venous insufficiency visible on a Doppler ultrasound). For patients with ulcers on both legs, each leg was included separately. Noninclusion criteria were patients < 18 years of age, ABI < 0.6 or TBI < 0.5, and/or TcPO2 < 30 mm Hg.

Data Source

For all eligible patients, age, sex, hemodynamic status as assessed by the ABI measured using continuous Doppler, DIADOP 200 (Diatecnic, Toulouse, France), and TBI (Systoe device, Atys Medical, Soucieu-en-Jarrest, France) were recorded. All patients underwent Doppler ultrasound examination with EPIQ (Philips Medical Systems, Andover, MA), Siemens S2000 (Siemens Medical Solutions, Mountain View, CA), or Hitachi ARIETTA V70 (Hitachi Ltd, Tokyo, Japan) devices. The etiology of the ulcers was determined by the vascular medicine physician in charge of a patient by means of clinical examination and the results of the examinations cited above. Smoking history status, diabetes, and duration of leg ulcers (in months) were also recorded. The size of ulcer was measured during clinical examination (cm ² ).

The primary objective was the variation in TcPO2 between the value measured before and after 1 month of compression therapy in each patient. The aim of this analysis was to measure the hemodynamic variation in microcirculation under compression. TcPO2 was measured in the leg of a patient comprising an ulcer using a Radiometer TCM4 (Radiometer, Copenhagen, Denmark) in the supine position and using a single probe positioned on the dorsum of the foot between the first and second interdigital space.

Decisions for the use of a compression were based on patient data according to a decision tree from the recommendations of the French national health authority ( Haute Autorité de Santé , HAS). ¹⁷ The decision tree used in our center is presented in Fig. 1 .

Fig. 1.

Decision tree for the application of elastic compression.

For patients with an ABI:

• ≥ 0.9, and TBI < 0.7 and a toe pressure ≥ 50 mm Hg, nonelastic compression was prescribed.

• between 0.9 and 0.8, compression at 40 mm Hg was prescribed.

• between 0.8 and 0.6, and a TBI ≥ 0.7, compression at 30 mm Hg was prescribed.

• between 0.8 and 0.6, and a TBI between 0.7 and 0.6, compression at 20 mm Hg was prescribed.

• between 0.8 and 0.6, and a TBI between 0.6 and 0.5, nonelastic compression was prescribed.

• between 0.8 and 0.6 and a TBI < 0.5 were excluded.

Patients were prescribed the appropriate compression therapy based on data recorded (namely a prescription stating the type and degree of compression). All included patients completed the Short-Form 36 (SF-36) QoL questionnaire at the beginning of the study and another one after a 30-day follow-up period. The SF-36 questionnaire comprised of 36 items covering eight domains, namely physical functioning, role limitations due to physical health problems, role limitations due to personal or emotional problems, bodily pain, general health, vitality, social functioning, and mental health. At discharge, all patients were given an adherence notebook for completion either by the home nurse, patient's caregiver, or by the patient themselves. In the notebook, they were requested to note the times when the compression was put in place and when they were removed in the day.

Follow-Up

All patients systematically underwent a follow-up with a consultation after 30 days without compression. During the follow-up consultation, the physician reassessed the clinical status of the ulcer, measured the size of the ulcer, and assessed the hemodynamics (TcPO2). All patients were requested to bring their adherence notebook to the follow-up consultation for review.

Statistical Analysis

Quantitative variables were presented as mean ± standard deviation or median and interquartile range (Q1–Q3) as appropriate. Categorical variables were presented as a number (%). For the primary objective, the change in TcPO2 between the value measured before and after 1 month of compression therapy in each included patient was analyzed. In patients with mixed arterial-venous leg ulcers, average TcPO2 was reported to be 13.9 ± 10.7 mm Hg. ¹⁶ The aim was to show an absolute increase in TcPO2 under compression of at least 20% (2.78 mm Hg). To this end, 234 patients were required at an α risk of 5% and a power of 80%.

Clinical tolerance was evaluated by the size of an ulcer, the SF-36 QoL questionnaire, and adherence. The size of the ulcer in cm ² was calculated by multiplying the width at the widest point by the length at the longest point. The paired samples Wilcoxon test was used for comparisons. All tests were two-sided. Data were analyzed using SPSS version 25.0 (IBM Corp., Armonk, NY).

Ethical Considerations

This study followed the principles of the Declaration of Helsinki. It was approved by an independent institutional review board according to the national procedure ( Comité De Protection Des Personnes du Sud-ouest et Outre-mer ) on September 28, 2018. The study was registered with ClinicalTrials.gov under the number NCT03725111 (n°2018-A01048–47). All patients provided written informed consent to participate in the study.

Results

Study Population

During the study period, 309 patients attended a vascular medicine consultation for work-up of a leg ulcer; 159 (51.5%) were female and 150 (48.5%) were male. Regarding inclusivity, 48 (15.5%) met the eligibility criteria, of whom 16 were excluded (one died, five required surgery, three did not meet the follow-up criteria, and seven refused to participate). In total therefore, 32 patients were included in the study; 44% female, 56% male; average age was 80 ± 10.5 years, average ABI was 0.86 ± 0.18 mm Hg, and average TBI was 0.54 ± 0.12 mm Hg. Furthermore, 37.5% had diabetes, and 18.7% had incompressible arteries. The flowchart of the study population is given in Fig. 2 .

Fig. 2.

Flowchart of the study.

The characteristics of the study population (both included and not included) are shown in Table 1 . The average duration of ulcers among the patients included in the study was 48 ± 63 months.

Table 1. Characteristics of the 32 patients included in the study, and the 277 patients not eligible for inclusion.

	Not included ( n  = 277)	Included ( n  = 32)
Sex
Female ( n  = 159, 51.5%)	145 (52%)	14 (44%)
Male ( n =150, 48.5%)	132 (48%)	18 (56%)
Type of ulcer
Not documented	80 (29%)	1 (3)
Necrotic angiodermatitis	1 (< 1%)	0
Arterial	93 (33.5%)	0
Lymphoedema	10 (4%)	0
Mixed etiology	17 (6%)	31 (97%)
Trauma	4 (1%)	0
Venous	73 (26%)	0
ABI	0.92 ± 0.29	0.86 ± 0.18
TBI	0.53 ± 0.23	0.54 ± 0.12

Abbreviations: ABI, ankle-brachial index; TBI, toe-brachial index.

Regarding the prescriptions for compression, seven had compression at a pressure of 20 mm Hg, and one at 30 mm Hg. All other patients were prescribed nonelastic compressions.

Primary Objective

Average TcPO2 prior to compression was 49.3 ± 13.01 mm Hg, versus 51.2 ± 15.05 mm Hg 1 month after compression, yielding an average change of 1.9 ± 2.04 mm Hg ( p  = 0.025). The variation percentage ranged from –55.2 to +62.1%, with an average of +5 ± 23.9%. The distribution of TcPO2 values before and after 1 month of compression is presented in Fig. 3 .

Fig. 3.

Transcutaneous oxygen pressure (TcPO2) scores before and after 1 month of elastic compression (TcPO2 is measured in mm Hg).

Secondary Objective

Average ulcer size prior to a compression was 49 ± 102 cm ² versus 37 ± 94 cm ² after 1 month of compression corresponding to a reduction of 12 ± 8 cm ² ( p  < 0.001). Three ulcers completely healed after the 1 month of compression was prescribed, in accordance with the decision-making algorithm. Fig. 4 shows the distribution of the ulcer sizes before and after the compressions (excluding extreme values which were those > 1.5 times the third quartile).

Fig. 4.

Ulcer size before and after 1 month of elastic compression.

There was no significant correlation between the increase in TcPO2 and the reduction in ulcer size ( p  = 0.895). The scores obtained on the QoL questionnaire are detailed in Table 2 . Only the physical pain dimension showed an improvement after compression ( p  < 0.001). Regarding compliance with treatment among the 32 patients included, 6% wore the compression between 0 and 2 days per week, 19% between 3 and 5 days, and 75% reported wearing the compression 6 to 7 days per week.

Table 2. Scores from the SF-36 quality of life (QoL) questionnaire administered before and after the 1 month of compression in 32 patients with leg ulcers.

	Before compression Median (Q1–Q3)	After compression Median (Q1–Q3)	p -Value
General health	16.5 [15; 19.25]	17 [14; 19]	0.509
Vitality	4 [3; 4]	4 [2; 4.5]	0.185
Physical functioning	15 [12; 16.25]	15 [11.5; 17.5]	0.364
Role limitation–physical	4 [4; 6]	5 [4; 7]	0.328
Role limitation–emotional	3 [3; 5]	3 [3; 6]	0.717
Social functioning	6 [6; 6]	6.5 [6; 6.5]	0.360
Bodily pain	9 [7; 11]	7 [5; 7]	< 0.001
Mental health	35 [28.75; 38]	35 [34; 37]	0.154

Abbreviation: SF-36, Short-Form 36.

Discussion

This study showed that compressions, when prescribed according to the patient's hemodynamic status, does not lead to a deterioration of microcirculation in patients with mixed arterial-venous leg ulcers, and is associated with a reduction in the size of an ulcer. Furthermore, it was well tolerated, as shown by the high rate of compliance with the prescribed therapy. The increase observed in TcPO2 in our study may be explained by the effective management of the venous component and reduction in edema.

Regarding epidemiology, the proportion of ulcers of various etiologies in our findings differed from that observed in other studies. In literature, venous etiology is largely predominant, accounting for almost 70% of all ulcers, compared with only 26% of ulcers in our study. ^{4 5 6} This may be due to the low prevalence of venous ulcers in the tertiary care sector. Moreover, reports of compression in literature generally use pressures of 20 to 35 mm Hg, and even up to 50 mm Hg for ulcers of venous etiology. ^{9 10 11} In our study, 75% of patients had nonelastic compressions. This high proportion may be due to, at least partially, patient's satisfactory compliance with therapy. Indeed, nonelastic compression exerts a low level of pressure at rest, and a high level of pressure during movement, and it may be kept in place during the night, or even for several days at a time.

We chose TcPO2 as the primary objective of this study as it is a reliable, reproducible, and a noninvasive measure that can quantify the maximal peripheral oxygen delivery. However, this metric has some limitations. First, it is dependent on systemic parameters and may be altered and provide a false reading in case of inflammation or infection. We did not perform any measure of oxygen saturation in our study as it was not feasible, and moreover, on the assumption that any errors in the measurement of TcPO2 arising from systemic parameters would be constant within each patient.

Our findings showed, albeit with a limited sample size, that 1 month of compression did not change the underlying hemodynamic state. In a study by Mosti et al ¹¹ (in 25 patients with mixed-etiology leg ulcers who received inelastic bandages applied with pressures from 20 to 30, 31 to 40, and 41 to 50 mm Hg), a 7% increase in TcPO2 was observed in the group with compression at 31 to 40 mm Hg for 10 minutes. Our results were in line with these findings with an increase in TcPO2 of 5% with 10 minutes of compression ( p  < 0.05).

In total, seven patients had a deterioration in TcPO2 during the study period. This may have been due to a discrepancy between the compression prescribed and the compression dispensed by the pharmacy. Moreover, it may have been due to poor tolerance, hospitalization for cardiorespiratory decompensation leading to an alteration in the systemic parameters, or an erroneous measurement at inclusion due to substantial drift.

The assessment of QoL in our study used the generic SF-36 health questionnaire which was found difficult to be taken by the elderly population. Nevertheless, an improvement in bodily pain dimension was observed which may have been due to the efficacy of a compression on the venous component of the ulcers and the reduction in ulcer size. ^{10 18} In a cross-sectional study among 530 patients in Germany, Herberger et al ⁸ found that pain, wound size, and time required for dressing changes were predictors of health-related QoL.

In our study, good compliance with treatment was observed in 75% of patients. This was consistent with literature, where an 89% adherence was reported by one study by Stansal et al. ¹⁹ In their study, Stansal et al reported that the main causes of poor adherence were inadequate comprehension of expected benefits (45.5%), pain related to compression (36.4%), difficulty applying the compression system (27.3%), and difficulty putting on footwear (27.3%). It is worth noting that the reasons for noncompliance of prescribed compression were not recorded in our study.

Conclusion

In conclusion, this study showed that compression therapy for 1 month is not associated with the deterioration of microcirculation in patients with leg ulcers of mixed arterial-venous etiology, when compression was prescribed based on hemodynamic status. Furthermore, a reduction in ulcer size and bodily pain dimension of the SF-36 was observed. These findings suggest that measuring ABI and TBI prior to prescribing a compression could be helpful. Furthermore, therapeutic patient education, including the assessment of QoL and a clear explanation of the expected benefits of compression should be implemented regularly to improve compliance with treatment.

Funding Statement

Funding This research received no specific grants from any funding agency in the public, commercial, or not-for-profit sectors.