Mixed Arterial and Venous Ulcers

  Abstract: The most common underlying etiologic factors responsible for chronic delayed healing among lower extremity wounds encountered in the outpatient clinic are chronic venous insufficiency (CVI), diabetic neuropathy, and arterial insufficiency (AI). One or more of these factors can be identified in more than 90% of chronic lower extremity ulcers, and treatment protocols have been designed to manage wounds of each type to maximize healing potential. It is important to remember that multiple factors may coexist in any individual patient with a chronic wound, complicating management and hindering the healing process. Recently, it has been reported that the neuroischemic diabetic foot ulcer is now more common than nonischemic neuropathic diabetic foot ulcers, as arterial insufficiency promoted by poorly controlled diabetes complicates already impaired healing present in patients with diabetes. This article will discuss the management of patients with leg ulcers and both arterial and venous insufficiency, including identification, diagnostic methods, and treatment protocols to maximize the potential for wound healing.

Introduction

  Neuroischemic diabetic foot ulcers are now more common than nonischemic neuropathic diabetic foot ulcers, as arterial insufficiency promoted by poorly controlled diabetes complicates already impaired healing present in the diabetic patient.^1,2   Arterial insufficiency complicating a patient with a venous leg ulcer (VLU) leads to difficulties in treatment due to the standard protocols for leg ulcers associated with venous hypertension. Obstruction and/or reflux in the venous system, either from a primary or secondary etiology, results in elevated venous pressures in the lower extremity. This venous hypertension must be addressed to eliminate inflammation and allow wound healing to commence. Two general methods are available to eliminate venous hypertension: correction of the underlying venous dysfunction by endovenous ablation, venous stenting or other interventions, or the application of external compression strong enough to eliminate venous hypertension.   The amount of compression required to eliminate venous hypertension and allow venous ulcers to begin to heal remains debatable, but it appears that higher strength compression is better than lower strength compression. In a review of the available literature on compression for CVI ulcers, the Cochrane review found that evidence clearly favored outcomes for strategies employing higher strength compression, which is typically defined as a minimum of 30 mmHg to 40 mmHg of compression at the ankle.³ In a string of well documented studies, Partsch and colleagues⁴ have reported excellent results with higher applied pressures using inelastic compression systems that have the potential to apply higher pressures to the limb while ambulating and lower resting pressures to avoid patient discomfort or other complications. All treatment guidelines for venous ulcers include the use of high-strength compression therapy as mainstays of treatment. The American Venous Forum rated compression a 1B (strong) recommendation for CVI ulcer healing.⁵ The Wound Healing Society venous ulcer guidelines advised the use of Class 3 high-compression systems with a Level 1 recommendation.⁶   Patients with significant arterial obstruction in the lower extremity vasculature may not be able to tolerate high strength compression as this may reduce forward flow in the arterial system to the point where the patient experiences severe pain or tissue necrosis. A recent Cochrane review on compression for venous ulcers found that an ABPI < 0.8 was considered an exclusion criterion for compression therapy in 23 of 33 reviewed studies.³ The Wound Healing Society guidelines state that the degree of compression must be modified when mixed venous/arterial disease is identified during diagnostic work-up, but the level of arterial disease requiring compression reduction and the amount of modification are not defined.⁶

Epidemiology

  In numerous clinical studies, the reported incidence of arterial insufficiency in patients with VLUs has ranged from 15% to 30%. In a study of 1416 VLUs, Humphreys et al⁷ reported that 13.6% of patients had moderate AI with an ankle brachial index (ABI) of 0.5 to 0.85 and 2.2% of patients were found to have severe AI with an ABI of < 0.5. In the Lothian and Forth Valley leg ulcer study, 21% of 827 limbs with ulceration were found to have an ABI below 0.9.⁸ In a study of 252 VLUs identified at a specialized wound clinic, Marston et al⁹ reported the presence of AI defined as an ABI below 0.8 in 15% of cases. As noted above, AI is generally broken into categories of severe and moderate AI for treatment considerations. Although the exact hemodynamic parameters are not consistently defined, one can consider moderate AI to refer to patients with an ABI between 0.5 and 0.9 or a toe pressure between 50 mmHg and 70 mmHg, and severe AI to refer to patients with critical limb ischemia that is defined by the Trans-Atlantic Inter-Society Consensus Guidelines as an ankle pressure < 70 mmHg or a toe pressure < 50 mmHg.¹⁰

Treatment of Patients With Mixed Arterial and Venous Ulcers

  Most experts have recommended reducing the strength of compression for treatment of VLUs in patients with significant arterial insufficiency to minimize the risk of compression related complications including pain and compression related necrosis. Tissue necrosis typically occurs over bony prominences including the maleoli and anterior tibia, or over the posterior heel and tendons. Additional padding is recommended to these areas underneath compression to reduce the potential risk of therapy. The exact level of arterial insufficiency that warrants modified compression is debatable, ranging from 0.7 to 0.9 in various publications.^3,7–9 The core consideration pits the perfusion pressure of the capillaries in the tissue of the compressed limb versus the external force of compression. Normal ankle pressures should be above 100 mmHg providing positive perfusion of capillary beds despite externally applied pressures ranging up to 60 mmHg or more. However, as the level of arterial obstruction increases and the ankle pressure drops, there is little information on where capillary bed perfusion is lost when applying high strength compression. In the absence of this specific information, most experts recommend against high strength compression in patients with an ankle pressure below 80 mmHg or ABI below 0.7 to 0.85. If the ankle pressure is below 60 mmHg or the ABI is below 0.5, revascularization is recommended, if possible, to allow safe compression without complications.   Standard high strength compression aims to apply at least 40 mmHg of compression to the ankle area graduated to 30 mmHg at the calf. Protocol for patients with VLUs and moderate AI have recommended 20 mmHg–25 mmHg of compression at the ankle using a variety of techniques. Partsch¹¹ has described the use of inelastic bandages for this purpose using a sub-bandage pressure monitor to identify the actual applied pressure for individual patients.¹¹ Marston et al⁹ reported the use of a 3 layer bandaging system, omitting the third layer from the Profore™ (Smith & Nephew, Largo, FL) 4-layer compression wrap, for patients with an ABI of 0.5–0.8 with a high rate of patient acceptance.

Effect of Arterial Insufficiency on Venous Ulcer Healing Rates

  Humphreys et al reported that moderate and severe arterial insufficiency were associated with significantly lower ulcer healing rates.⁷ Thirty-two of 224 patients with AI (14.3%) eventually required revascularization for poor response to conservative management. Thirty-day mortality after revascularization was 6.5% emphasizing that this is a high-risk population in whom invasive vascular procedures should be avoided if possible. Marston et al⁹ similarly reported a reduced rate of ulcer healing in combined AI/CVI patients (Figure 1), but eventually 85% of wounds were closed at 1 year (mean time to closure 19 weeks).⁹

Effect of Compression Therapy on Arterial Perfusion

  In a recent investigational report, Mosti and associates utilized laser Doppler flowmetry (LDF) and transcutaneous oxygen measurements in patients with AI and venous ulcers before and after application of high strength compression to determine whether compression impedes arterial perfusion.¹¹ In this study of 25 patients, the authors applied inelastic bandaging while measuring sub-bandage pressures ranging from 20 mmHg to 50 mmHg to identify a cutoff point where arterial perfusion decreased. LDF actually increased close to the ulcer (under bandages) applying all pressure ranges, but the amount of increase was greater with bandages applying 20 mmHg–40 mmHg of pressure. At the toe level, a significant decrease in perfusion was noted with bandages applying greater than 41 mmHg. They concluded that for patients with an ABI greater than 0.5 and an ankle pressure > 60, bandages applying up to 40 mmHg did not reduce arterial perfusion, and actually improved LDF at the ulcer level. It is important to note that their data only applies to inelastic bandaging material and elastic systems may not provide a similar compression profile.   A key component of the authors’ treatment protocol for the management of mixed arterial and venous ulcers was the use of a pressure measurement device to measure applied sub-bandage pressures. The use of a device, such as the Picopress (Microlabitalia, Padua, Italy), used in this study is highly recommended for clinicians treating complex mixed ulcers. Despite the cost, the ability to measure the amount of applied pressure in individual patients has the potential to improve results by avoiding excess or inadequate pressure application on individual patients. Customized treatment protocols may improve patient acceptance and compliance as well. Further study on the benefits of sub-bandage pressure measurement is required to confirm these potential benefits.

Revascularization and Patient Selection

  Revascularization is recommended for patients with mixed leg ulcers based on an evaluation of their level of symptoms and degree of arterial insufficiency. Patients with leg ulcers and AI may also have claudication or rest pain, as well as ulceration. Compression therapy would not be expected to control these symptoms and may exacerbate rest pain in some situations. Ischemic rest pain may be difficult to separate from ulcer-related wound pain, but typically does not occur in patients without severe AI. Patients believed to have ischemic rest pain or severe limiting claudication should be considered for revascularization as an initial therapeutic step. Patients with no other symptoms of arterial insufficiency should be evaluated for revascularization if they have severe AI. Patients with moderate AI may be initiated with compression therapy using one of the previously discussed protocols but should be followed closely for any complications, increased pain, or lack of improvement. If no improvement occurs within 4 to 8 weeks of therapy, evaluation for revascularization should be considered.

Percutaneous Revascularization in Patients With Mixed Leg Ulcers

  The decision to recommend revascularization in each individual patient depends on the risk/benefit analysis of an invasive procedure in patients who often have numerous serious comorbid conditions. The vascular specialist performs Doppler evaluation of the site of arterial obstruction and the options for revascularization. Most vascular specialists recommend less invasive percutaneous procedures to revascularize the lower extremity as the initial option when possible.¹² Once the arterial supply is improved, standard compression protocols may be utilized to achieve healing of the venous leg ulcer. Given the high risk of surgical bypass in the limb with a mixed ulcer, a percutaneous strategy may theoretically reduce the risk of major morbidity, incisional wound complications, infection, and death. Lantis et al¹³ recently reported the treatment of 27 patients with mixed leg ulcers (defined as ABI < 0.7) using percutaneous revascularization followed by ambulatory compression. Revascularization resulted in an increase in ABI from a baseline mean of 0.56 to 0.97 with no major complications.¹³ Ulcer closure occurred in 75% at 10 weeks after revascularization—a rate that is similar to the healing rates for VLU patients without AI.

Surgical Revascularization for Patients With Mixed Ulcers

  Surgical bypass is typically performed for patients with leg ulceration requiring revascularization that fail percutaneous revascularization or are poor candidates for this less invasive revascularization method. It must be remembered that surgical bypass is associated with a better long-term patency, which should yield a more durable revascularization when compared to percutaneous techniques such as stenting or atherectomy. The price for a better durability is a higher risk of morbidity or mortality at the time of revascularization. Young, active patients with relatively good overall health are good candidates for surgical bypass, but relatively few patients with mixed arterial and venous leg ulcers fit into this category.   Treiman et al¹⁴ reported a series of 59 patients with mixed arterial/venous ulcers, 55 of which were treated with surgical revascularization. The patients were followed after revascularization for a mean of 22 months. In 8 cases, the surgical reconstruction failed and 34 (58%) of the ulcers eventually healed at an average of 7.9 months. Seven patients required below-knee amputation due to a nonhealed, infected ulcer. A prior history of DVT was a significant predictor for poor healing with only 15% of patients in this category achieving a closed wound. This series exemplifies the difficulty of treatment when the arterial component of mixed ulcers is severe. Patients with chronically edematous, lipodermatosclerotic tissue have difficulty with surgical procedures with a high risk of wound complications, exacerbation of limb edema in the postoperative period, and slow wound healing.

Primary Arterial Ulcers and Associated Chronic Venous Insufficiency

  Most patients with leg ulcers primarily due to arterial insufficiency do not present with limb edema in the absence of infection. However, some will develop relative venous and/or lymphatic dysfunction due to prolonged inflammation or infection. Also, operative procedures for revascularization typically cause postoperative edema due to a combination of lymphatic and inflammatory problems that may be severe in occasional cases. Judicious use of compression therapy in these patients is important to prevent incisional breakdown leading to limb threatening surgical wound complications. The incidence of postrevascularization wound breakdown has been reported as 3%–12% in various studies, with wound infection occurring in 27% of cases in a recent study.¹⁵ In rare cases, patients with wound complications may develop infection involving the bypass graft resulting in graft loss and a high risk of limb loss. Limb edema resolves rapidly in some cases, but in others may last for months after limb revascularization.¹⁶ Percutaneous procedures may also result in postrevascularization edema, but this is less frequent and typically less severe than in open surgical bypass cases.   There has long been a concept that compression should not be performed on the limb of a patient who has had a recent lower extremity bypass graft. The methods available to eliminate edema in postrevascularization patients include constant limb elevation, intermittent pneumatic compression, limb bandaging, and compression stockings. There is little data in the literature to guide therapy for postrevascularization edema. From the author’s experience, constant limb elevation is impractical, slows rehabilitation, prolongs hospitalization time, and is associated with limited efficacy. Intermittent pneumatic compression is a useful modality that can be placed only on the foot, on the foot and calf, or on the entire limb. In the author’s practice, for patients with deep-tunneled grafts, intermittent pneumatic compression is used on the foot and calf. For patients with a superficial tunneled graft, the author does not apply compression over the graft for the first 3 days, and then applies the device distal to the graft endpoint. Unfortunately, IPC is not reimbursed in the home setting for most patients after revascularization. At the time of discharge, we recommend limb compression for those with edema from the toes to the knee using a reduced (3-layer) bandaging system designed to apply 20 mmHg–30 mmHg. While the author’s group has not reported the results from this strategy, it is believed that it has allowed a reduction in problematic postrevascularization edema in our patients.

Protocol for Management of Mixed Leg Ulcers

  Based on the above noted information, the author typically evaluates all patients with mixed arterial and venous ulcers with both arterial and venous Doppler studies. This analysis provides information on the severity of arterial insufficiency and the locations of venous disease. At the same time, a general risk assessment is performed to determine the patient’s suitability to tolerate invasive procedures that might be considered to improve the arterial supply or address venous insufficiency. Based on the results of this analysis, the most appropriate treatment plan may be developed. Patients with an ABI between 0.6 and 0.9 or toe pressures between 50 and 80 can generally be treated with compression protocols, but at a slightly reduced amount. Other symptoms, such as severe claudication or rest pain, would indicate a need for arterial revascularization using the percutaneous method whenever possible. If a patient treated conservatively is able to improve with control of edema and ulcer healing, the plan is continued without revascularization. Patients should be followed closely to watch for evidence of complications of compression or for lack of healing. Either would be indications to proceed with revascularization.   In this group with moderate arterial insufficiency, patients may be considered for venous ablative procedures when superficial venous reflux is identified, primarily to prevent ulcer recurrence after healing. There may be a potential improvement in the rate of healing with superficial venous correction, but this has not been supported by the current clinical data.   Patients with mixed ulcers who present with an ABI < .5, an ankle pressure < 70, or a toe pressure < 50 mmHg, should be evaluated for arterial revascularization and compression should be avoided.   Based on the literature, inelastic compression may have significant advantages in the treatment of mixed ulcers, at least up to 40 mmHg of compression.

Conclusion

  Patients with mixed arterial and venous ulcers require careful evaluation and frequent follow-up. Poor response to initial treatment pathways should mandate re-evaluation of the wound and the need for revascularization if this has not been performed. The participation of a vascular specialist is recommended given the rapid need for revascularization in some patients.

References

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