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Edema Management: It’s Not Just for Venous Leg Ulcers
As someone who has been in wound care for 25+ years, I have come to understand a simple truth: any amount of swelling slows down healing. It’s something that intuitively makes sense. In sports medicine, one of the first things you do for an extremity injury is apply compression and elevate the limb. However, in wound care, the only time we consistently think about edema management in is venous leg ulcers and lymphedema.
In my experience, managing the edema associated with any type of wound greatly improves both healing and patient comfort, even (with caution) in arterial wounds. And yet, there is very little discussion (or research) of this in wound care. Much of the research for this article was done in the literature of other disciplines, such as dermatology, endocrinology, vascular surgery, cardiology, pathophysiology, plastic surgery and even orthopedics. Though wound care overlaps with many specialties, it was surprising how little discussion there was about the effects of edema on wound healing in dedicated wound journals. In my review of the most widely accepted guidelines for wound bed preparation and the treatment of chronic wounds, the discussion of edema management is almost entirely limited to the treatment of venous leg ulcers.
What You Should Know About Edema
We will get back to the guidelines later. First, let’s talk about edema.
To understand edema, it is important to understand the factors affecting the balance of fluids in the body. The two main fluid compartments in the body are the vascular system (intravascular) and everything outside the vascular system (extravascular). The extravascular compartment is made up of sub-compartments such as cellular, interstitial, and lymphatic compartments. Fluid exchange between compartments is important for normal function; however, volume between compartments needs to maintain an overall equilibrium for this to happen properly.
The movement of fluid and solutes between compartments is governed by three factors: oncotic pressure, hydrostatic pressure, and permeability of the vessels. Hydrostatic pressure is the effect of gravity on fluid. Oncotic pressure is the attractive force of proteins on fluid. Because plasma proteins in the vascular system are too large to diffuse through vessel walls, the vascular system has both a higher oncotic pressure, which attracts fluid; and a higher hydrostatic pressure, which pushes fluid out. These opposing forces are regulated by the permeability of the vessel walls, which, to a greater or lesser extent, allows fluid and solutes to flow back and forth between compartments.
The opposing forces of hydrostatic pressure and oncotic pressure change as blood flows through the vascular system. As blood makes its way through smaller and smaller vessels, such as capillary to arteriole, hydrostatic pressure increases, forcing fluid into the tissues (a process called filtration). This increases oncotic pressure in the blood because the concentration of protein increases as the vessels lose fluid. As the blood moves from arterioles into the venules, where hydrostatic pressure is less, oncotic pressure draws fluid back into the vessels (reabsorption). Typically, there is about 1% more filtration than reabsorption, which leaves extra fluid in the interstitial tissue; however, equilibrium is restored as the excess is removed by the lymphatic system and returned to the vascular compartment. This fluctuation of opposing forces, as blood moves through the vascular system, is what allows nutrient delivery and removal of cellular debris and waste products from the tissues.
There is an added factor in the extremities: Gravity causes increased venous hydrostatic pressure with sitting and standing, making the venules less efficient at removing fluid from the tissue through resorption. However, this is typically resolved by muscle activity. In the lower legs, this is done through the mechanism of the calf muscle pump. When calf muscles contract with activity or ambulation, the deep veins empty, pushing blood toward the heart, and one-way valves keep it from refluxing back. This decreases hydrostatic pressure in the peripheral veins and venules, allowing increased fluid resorption into the vascular compartment.
The dynamic equilibrium in fluid volume between compartments is regulated closely by a number of endocrine, neurologic, physical, and chemical mechanisms, and disruption to any part can lead to dysfunction. It is easy to see how immobility or dysfunction of the venous and lymphatic systems could predispose a patient to chronic edema; however, a fluid imbalance is seen with other conditions as well. Disruption of normal fluid volume between compartments is one of the key pathological processes in conditions such as congestive heart failure, kidney disease and even diabetes. It is no coincidence that we see such a high prevalence of these comorbidities in wound care.
What Happens During Inflammation?
During acute inflammation following tissue injury, inflammatory mediators cause vessel walls to become more permeable. This increased permeability allows important cells, such as neutrophils and monocytes, to pass through the vessel wall into the area of tissue damage; however, it also has the effect of increasing filtration of fluid from the vessels into the interstitial compartment, resulting in tissue edema. Increased fluid volume in the tissue can quickly overwhelm the lymphatics, decrease perfusion and impair the normal filtration/resorption process necessary for nutrient exchange and removal of waste products from the tissues.1 The high metabolic demand associated with the inflammatory response, and the decrease in microcirculation caused by edema, create a hypoxic wound environment.2 Persistent edema facilitates a prolonged presence of proteases, reactive oxygen species (ROS) and cellular debris in the tissues. This causes increased inflammatory signaling, increased risk of infection and may cause further tissue degradation, creating a self-perpetuating cycle of inflammation and edema.3,4
It is no surprise that chronic wounds are much more prevalent on the lower legs, where hydrostatic pressure is greatest, and that chronic wound fluid has higher levels of ROS, proteases, pro-inflammatory cytokines and senescent cells, and reduced levels of inflammatory inhibitors and growth factors.5–7 It could be argued that a mechanical component often contributes to inflammation in pressure injury or diabetic foot ulcers. What is perhaps more telling is that elevated protease levels are predictive of surgical dehiscence, graft failure and delayed healing, even in acute wounds.7 Wound dehiscence is often thought to be caused by infection, but it can happen just as easily in the presence of edema, which creates tension on approximated wound edges, causes increased drainage and interferes with normal cellular activity. Ironically, even if infection is not the original cause of dehiscence, the inflammatory environment, perpetuated by edema, can make the site more susceptible to a secondary infection.
Fortunately, edema-related inflammation is relatively easy to mitigate. Beidler et al showed that 4 weeks of compression therapy for patients with venous leg ulcers (VLUs) significantly reduced elevated levels of pro-inflammatory cytokines, increased levels of anti-inflammatory cytokines, and improved healing.8,9 The mechanism of action for this is multifactorial. Compression facilitates increased filtration and lymphatic function by increasing interstitial pressure and improving the efficiency of the calf muscle pump. This normalizes microcirculation, increasing perfusion, and allows removal of highly inflammatory proteins by the lymphatics. In addition to this, micro-deformation or cell stretch caused by the mechanical forces of compression results in the release of anti-inflammatory modulators, which further assist in the resolution of inflammation.10,11
There are a variety of methods for managing edema. Multilayer compression systems are a good solution for many patients with leg wounds. Mosti et al showed that short stretch compression therapy can be safely used in patients who have mixed arterial and venous disease or even the combination of diabetes, arterial insufficiency and venous disease.12 Several studies have shown that short-stretch or modified inelastic wraps, in patients with arterial insufficiency and concomitant edema, can improve lower extremity perfusion as well as reduce edema, so long as the amount of compression does not exceed perfusion (systolic) pressure at the ankle.10,12–14 This makes sense, considering the negative effect of edema on microcirculation.
Intermittent pedal compression systems have been shown to reduce edema and increase perfusion, even in patients with severe arterial insufficiency.15 With this modality, a wrap is placed around the foot and short bursts of high compression are used to empty pedal veins. Edema reduction is achieved by decreasing hydrostatic pressure in the venules and allowing increased absorption of fluid from the interstitial tissue into the vascular compartment. The decrease in venous pressure allows easier arterial flow, and short periods of hypoxia with high pump pressure stimulates angiogenesis and formation of collateral vessels.15–17
A trial focusing on edema reduction studied 115 patients with diabetic foot infections requiring incision and debridement (with adequate blood flow).18 Patients were treated with either a functional or a placebo (non-functional) pulsatile pneumatic foot compression system for 12 weeks post-procedure. The functional pump group had a significantly higher healing rate (75% vs 51%) than the placebo group at 12 weeks, and those in the treatment group (n = 11), who were more compliant with using the device (at least 50 hours a week), were all healed at 12 weeks. Considering this, the benefit of edema reduction, seen with total contact casting (TCC), should be explored in DFU treatment.
Through removal of wound fluid and mechanical contraction of the dressing, local edema reduction is seen as one of the key beneficial mechanisms of action of negative pressure wound therapy (NPWT). A dramatic example of this can be found in burns. Thermal injury causes tissue damage in zones. The zone of greatest injury is where there is complete cell death. The zone adjacent to this is where cells are initially viable but can later die, increasing the size and depth of the burn. The extent to which this happens is closely correlated to the degree of edema that develops in this zone. It has been shown that managing edema in burns with negative pressure wound therapy (NPWT) can cause an immediate improvement in perfusion, prevent the progression of tissue damage, and speed healing.19–21
Not surprisingly, a reduction in pro-inflammatory cytokines has been seen with NPWT as well.22 The mechanism of action for this is similar to that of compression; cell stretch causes the release of anti-inflammatory modulators while reduction of edema normalizes microcirculation. NPWT differs from compression, in that edema reduction is only local but it has the added benefit of actively removing inflammatory wound fluid from the wound environment. It is quite possible that local edema reduction plays a larger role than we think, in how modalities such as NPWT, low-frequency ultrasound and shockwave therapy work to facilitate healing.
Closed surgical incisions also benefit from the local edema reduction and contractive forces of NPWT. Studies have shown decreased incidence of infection, sero-hematoma formation, dehiscence and re-operation rates with the use of incisional NPWT.23–27
In wound care, it is standard practice to address underlying factors, such as mechanical trauma, the presence of necrotic tissue, and infection in any wound we treat. We know tissue trauma causes swelling; therefore, edema can be expected to be present, to some extent, with any wound. If edema plays a part in perpetuating the inflammatory response, why are we not assessing and managing it in all wounds we treat, particularly extremity wounds?
Back to wound bed preparation guidelines, the TIME concept of wound bed preparation/ wound healing optimization was developed by an international group of wound experts in 2003.28 Since that time, it has been revised several times, as new understandings and technologies have emerged, but has remained widely regarded as a seminal document in the field of wound care.29 The acronym stands for:
Tissue—assessment and debridement of non-viable or foreign material
Infection/Inflammation—assessment of the need for topical antiseptic and/or systemic antibiotic use to control infection and management of inappropriate inflammation unrelated to infection
Moisture—assessment and management of wound exudate to maintain moist wound healing
Edge of wound—assessment and management of non-advancing or undermined wound edges
Guidelines for infection are exhaustive, while the only guidance for non-infective inflammation is that it could be the result of autoimmune diseases, such as scleroderma or pyoderma gangrenosum. A great deal is said about biofilms, and their presence is put forth as a possible explanation for wounds that are inflamed but don’t otherwise have signs or symptoms of infection. While I’m sure biofilms play a part in inflammation, I have seen the dramatic difference edema management makes, in every type of wound, enough times to be certain it is underrepresented in this section. If biofilm is suspected, perhaps a good test would be to add edema management to your treatment and see if the inflammation persists.
Sibbald et al suggested that oxygen balance be added to this model and cite the previously described fact that a wound in the inflammatory phase is naturally hypoxic. It was also noted that infection and poor blood supply can further worsen hypoxia.30 Infection control, hyperbaric oxygen therapy and topical oxygen therapy were discussed as interventions but, again, there is no mention of the positive effect of edema management on perfusion/oxygenation.
An excellent review by Guo et al2 gives a comprehensive explanation of wound healing and the factors that influence it, down to the cellular level, from oxygenation to sex hormones (for a deep dive into the biology of wound healing, I highly recommend it). Even so, the only mention of inflammation is in the context of infection and biofilm.
The ABCESS model31 addresses edema the most thoroughly of any model reviewed; however, it also does so mainly within the etiological silos of venous insufficiency and lymphedema. The C in ABCESS stands for circulation. In this section, an important point is made that “The circulatory system is not just arterial flow, but venous and lymphatic outflow, too.” and that each part is dependent on the other two to function properly. The lymphedema portion of the circulation section states that “Treatment of lymphatic overload can assist any wound with an edema component …” but in the section where edema and exudate are discussed independently (the E in ABCESS) only exudate is addressed. This would have been the perfect place to detail how edema impairs perfusion and interferes with the resolution of inflammation, and explicitly recommend its assessment and treatment in all wounds, regardless of etiology.
The truth is, soft tissue trauma can cause persistent edema in any dependent tissue, even in the absence of venous insufficiency or true lymphedema. Talking about it only in the context of etiology is inadequate. We are missing a key factor in chronic wounds that is easily treatable, while we apply all manner of expensive products to wounds that are not optimally prepared. Wound bed preparation guidelines should be modified to reflect the effect of edema on healing, the main points being:
1) the presence of persistent edema, alone, can cause a wound to become chronic, particularly in extremity wounds,
2) edema should always be addressed for optimal outcomes, regardless of wound etiology and
3) due to its pro-inflammatory effects, edema should be managed, as part of conservative therapy, prior to initiating expensive cellular and tissue-based products.
In Conclusion
A few practical notes:
It is important for edema management to be consistent. It can take a couple of weeks for inflammation to subside, but one significant episode of uncontrolled edema can restart the inflammatory process and delay healing days or even weeks.
With compression, patients should always be educated about what to do if their wrap starts feeling tight. I typically recommend that patients first try walking around for a bit to engage the calf muscles or elevate their legs above their heart for 20–30 minutes. If this relieves the tightness, it should be incorporated into their daily schedule, if not they should remove the compression and be reevaluated.
If you are treating a DFU with a TCC and the patient is not tolerating the TCC due to fluctuating edema (often described as feeling “claustrophobic” in the cast), the use of a tubular elastic bandage under the cast and/or periodic elevation of the limb can help. If used, the elastic sleeve should be folded over the top edge of the cast and fixed in place, to prevent it from slipping down.
For wounds in places where compression is difficult or not optimal, NPWT is an excellent option for local edema reduction.
Finally, in patients where edema is extensive, persistent, or difficult to manage, consider referring to a lymphedema therapist for evaluation and possible decongestive treatment.
Edema management is accessible and cost-effective, it improves patient comfort, and it increases both the speed and likelihood of healing in all types of wounds. It’s TIMEE for woundology to recognize, edema management is best practice for any wound.
Dr. Blakely is a physical therapist and board certified wound specialist with over 20 years clinical experience, 15 years consulting and speaking in industry and 5 years in medical affairs for both biotech and medical device. Dr. Blakely has served two terms on the Board of Trustees of the American Board of Wound Management Foundation and is a contributing editor for Today's Wound Clinic.
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