ADVERTISEMENT
NPWT In Ischemic Patients: What The Literature Reveals
Negative pressure wound therapy (NPWT) can be a powerful treatment for wounds but does ischemia complicate the use of NPWT? These authors examine the literature and emphasize caution in using NPWT in patients with ischemia on a case-by-case basis.
Negative pressure wound therapy (NPWT) has become another tool in the armamentarium we utilize to treat complex wounds and surgical sites.
In 2017, Liu and colleagues performed a systematic review and meta-analysis of NPWT use in diabetic foot ulcers, and found that NPWT in this population was efficacious, safe and cost-effective.1 The authors noted that in comparison with standard dressing and interval dressing changes, NPWT-treated wounds had a higher rate of complete healing, shorter healing time, and greater reduction in ulcer area and depth, ultimately leading to fewer amputations.
Negative pressure promotes wound healing by removing excess interstitial fluid, increasing blood flow and decreasing bacterial levels and the mechanical deformation of cells.2 Galstyan and coworkers evaluated the intensity of reparative processes in the lower extremity soft tissues of patients with diabetes receiving NPWT.3 The authors found that during NPWT, the area and depth of wound defects decreased by 19.8 percent and 42.8 percent respectively. They compared this to standard wound care, which demonstrated a 17 percent and 16 percent decrease in area and depth respectively. Negative pressure wound therapy facilitates wound healing by decreasing the bacterial burden; promoting granulation tissue formation, capillary blood flow, endothelial proliferation and angiogenesis; and restoring the integrity of the capillary basement membrane.4
How The Presence Of Ischemia Complicates The Use Of NPWT
The decision to use NPWT becomes challenging when one is treating patients who have concomitant limb ischemia. We can define ischemia as any form of inadequate blood supply to an organ or part of the body, causing a shortage of oxygen that is needed for cellular metabolism to keep the tissues alive. There are concerns that patients with ischemic wounds may develop worsening necrosis with NPWT if wounds are not well vascularized but studies have yet to establish this notion of precipitating necrosis with NPWT.2
Necrosis refers to cell and/or tissue death caused by irreversible injury to cells, typically a lack of blood flow and oxygen, although any noxious stimulus to cells can create necrosis. In a setting with easy access to vascular intervention, patients are able to have revascularization and this avoids any concern regarding the use of NPWT.
When patients are not eligible for revascularization or do not have optimal blood flow post-intervention, the decision to use NPWT is not as clear-cut. Although some studies have noted that NPWT significantly decreases tissue oxygenation of the foot, these studies used transcutaneous partial pressure of oxygen (TcPO2) in order to measure tissue oxygenation.5,6 While this may seem like a reliable method of measuring oxygenation to the foot, it is important to note that conditions need to be perfect. The temperature of the room needs to be constant, the temperature of the transducer needs to be consistent, the sensor has to be perfectly adhered with no gaps between the sensor and the patient’s skin and, lastly, the patient cannot move.
These challenges and the time-intensive nature of TcPO2 make interpretations of findings limited, particularly in the setting of microvascular disease, which is common in the diabetic cohort. It is important to note that such studies have not made the claim that NPWT should be contraindicated in those who cannot have revascularization nor do studies imply the worsening of preexisting wounds or surgical sites with NPWT in these patients.
Key Insights On Measuring Perfusion
Few studies use the same criteria and methods to measure perfusion, which makes it very challenging for clinicians to extrapolate meaningful data regarding the use of NPWT in the context of suboptimal perfusion. There are a few papers that utilize the laser Doppler, a newer, more accurate technology to assess tissue perfusion.7,8 Studies using laser Doppler cite increased perfusion to ischemic wound beds using NPWT. For example, a study by Timmers and colleagues looked at negative pressure dressings in healthy volunteers and found a fivefold increase in basal perfusion after application.7 Some of the backlash to this measurement of perfusion comes from the theory that the laser Doppler measures perfusion by multiplying the velocity and concentration of red blood cells. However, during NPWT, these vessels are compressed and narrow. Thus, the Doppler incorrectly records increased perfusion due to tissue compression.9
Kairinos and coworkers used radioisotope perfusion imaging to determine perfusion beneath circumferential NPWT dressings on 20 healthy hands and found that NPWT decreases suction pressure.10 Ichioka and colleagues conducted a study to test microcirculation of the wound bed after NPWT and found a negative pressure of -125 mmHg significantly increased wound bed blood flow immediately after NPWT application.11 The downside to this study was that it was on mice and not humans. Researchers could remove the superficial stratum layer of the mouse’s skin and visualize the microcirculation using a microscope-video-computer system.
Based on the cited information, there is currently no widely accepted quantitative standard to measure perfusion. Therefore, there is continued controversy as to whether to use NPWT in ischemic patients. Newer studies have come out with case studies showing benefits of low negative pressure or intermittent negative pressure for wound healing in ischemic patients.2,12 In a study by Kasai and colleagues, the authors applied lower pressures of -50 mmHg to ischemic wounds, and all healed without further necrosis at wound edges.2 The thought behind this was that capillaries at wound edges are believed to occlude at pressures as high as -125 mmHg so ischemic wounds treated with lower pressures would reduce the tissue pressure and promote healing, allowing ischemic patients to reap the benefits of NPWT.
NASA has studied intermittent negative pressure devices and demonstrated that the devices enhance blood perfusion.13 Sundby and colleagues looked at the benefit of intermittent NPWT in four patients with lower extremity ischemia and hard to heal leg ulcers.12 They found that with an eight-week intervention period of -40 mmHg intermittent negative pressure (10 seconds of negative pressure, seven seconds of atmospheric pressure), one ulcer had healed completely and the remaining three were almost completely healed. The authors reported an improvement in rest pain and claudication symptoms in two of four patients with lower foot perfusions. The flow between arteries and veins is comparable to the pressure gradient between arteries and veins. If pressure in the veins abruptly changes with the application of NPWT, the flow will abruptly increase. The preliminary increased flow response to negative pressure should only take place from arteries to veins induced by the vacuum.
How NPWT Devices Have Evolved To Provide Increasing Benefits
The benefits of NPWT have vastly grown and now include many different devices on the market aimed at treating surgical incisions. Physicians do not typically administer these devices in the healthy, well-perfused host. Rather, the intended use is to mitigate the risk of surgical site dehiscence in the complex host. This includes patients with suboptimal tissue perfusion. These incision NPWT vacuums are able to provide an increase in blood perfusion to incision sites.
Ma and colleagues found that NPWT can preferentially enhance vessel maturation and increase the number of pericytes, thus regulating blood flow perfusion.14 This further supports the use of incision NPWT devices in ischemic patients. It is interesting to note, however, that early in the development of such devices, the pressure generated as these devices became smaller was much less than -125 mmHg. As the technologies have improved, several devices on the market do deliver incision pressures at -125 mmHg.
This research provides some benefit to the companies that make smaller, transportable wound vacuums that are unable to reach pressures as high as -125 mmHg due to their size. Although the pressures one utilizes seem to be the only variable in question, there is ample evidence to suggest that NPWT devices can increase tissue perfusion as well as mitigate the risk of postoperative infections and dehiscence. The major discussion and further research emphasis should focus on the pressure and timing of intermittent therapy. There are studies that vary regarding the subatmospheric pressure clinicians would use for the ischemic patient but the anecdotal consensus is it may be safer to use much less pressure than -125 mmHg. The most frequently referenced pressure clinicians utilize in poorly perfused tissue is -75 mmHg.15 It is critical to realize that high negative pressures may actually impair wound healing in the setting of ischemia.
As we noted previously, determination and quantification of degree of tissue ischemia are areas that require further improvement and validation. Unfortunately, there are no current standardized protocols to abide by when deciding to apply NPWT on an ischemic wound. It is needless to say that critical limb ischemia or frank necrosis is an absolute contraindication to NPWT.
It becomes important to identify the many factors related to healing wounds, of which blood flow is just one aspect. The benefit of NPWT is that it not only improves blood flow, it creates a barrier from the external environment in the immediate postoperative phase when one places NPWT over incisions. A variety of case studies have shown that improved blood flow decreases infection rates, decreases hematoma/seroma formation and lowers dehiscence rates.16–19
One surrogate marker to measure the effect of NPWT on improved circulation is its indirect effect on edema. Postoperative edema, edema from inflammation and edema are frequently related to immobility of the extremity. There are many studies that have examined the effects of NPWT on both edema and lymphedema in the lower extremity.20 The results of these studies suggest strongly that the intermittent use of NPWT improves microcirculation, which in turn improves edema and lymphedema in patients receiving NPWT. Wrotslavsky looked at the use of negative pressure on surgical incisions and found its use had a dramatic effect on decreasing postoperative edema, decreasing postoperative pain and thus the use of narcotics in the postoperative period.20
In Conclusion
One can argue that any dressing can impart some degree of healing as it is designed to enhance the microenvironment of the wound. Negative pressure wound therapy consists of a complex dressing that has many benefits, which is important from a limb salvage perspective. In the diabetic population, NPWT has been a staple in the treatment of complex lower extremity ulcers, surgical site management and concomitantly with biologics, skin grafts and even free flaps. These patients often have some element of macrovascular disease and microvascular compromise, and yet continue to benefit from the wide use of NPWT. It is important to evaluate each patient carefully. In patients who have been revascularized but may not have complete three vessel runoff to the distal foot, one must consider the angiosome serving the wound site.
At our institution, we have employed NPWT for patients with suboptimal vascular perfusion and utilized -75 mmHg of intermittent therapy. Frequent wound surveillance determines the length of treatment or wheather one should discontinue the treatment. Until further evidence elucidates the use of NPWT in the ischemic limb, evaluate ischemic patients on a case-by-case basis. As with all limb salvage cases, there should be frequent surveillance and prompt changes to treatment modalities. Negative pressure remains an important, viable and common tool, even in patients with suboptimal perfusion.
Although research is limited in the use of NPWT in ischemic patients, the science behind the process supports its use. We must acknowledge that there is no perfect way to measure perfusion to an ischemic wound and until we can do so with consistency, this question shall remain open for debate. The take home message becomes that NPWT can improve wound healing in the ischemic population but one should observe its effects clinically and use NPWT cautiously.
Dr. Bunka is a first-year podiatric surgery resident at MedStar Washington Hospital Center Podiatric Surgery in Washington, DC.
Dr. Saeedi is a third-year podiatric surgery resident at MedStar Washington Hospital Center Podiatric Surgery in Washington, DC.
Dr. Elmarsafi is a podiatric surgery attending physician at MedStar Washington Hospital Center in Washington, DC.
References
1. Liu S, He C, Cai Y, et al. Evaluation of negative pressure wound therapy for patients with diabetic foot uclers: a systematic review and meta-analysis. Ther Clin Risk Manag. 2017; 13:533–44.
2. Kasai Y, Nemoto H, Kimura N, et al. Application of low-pressure negative pressure wound therapy to ischemic wounds. J Plast Reconstr Aesthet Surg. 2012; 65(3):395–8.
3. Galstyan GR, Tokmakova AY et al. 2016. Comparative evaluation of the intensity of reparative processes in the lower extremity soft tissues of diabetic patients receiving local negative pressure wound treatment and standard wound care. Ter Arkh. 2016; 88(10):19–24.
4. Tan KW, Lo ZJ, Chandrasekar S. Use of negative pressure wound therapy for lower limb bypass incisions. Ann Vasc Dis. 2017; 10(4):386–90.
5. Shon YS, Lee YN, Jeong SH, et al. Influence of negative pressure wound therapy on tissue oxygenation of the foot. Arch Plast Surg. 2014; 41(6):668–72.
6. Jung JA, Yoo KH, Han SK, et al. Influence of negative pressure wound therapy on tissue oxygenation in diabetic feet. Adv Skin Wound Care. 2016; 29(8):364–70.
7. Timmers MS, Le Cessie S, Banwell P, Jukema GN. The effects of varying degrees of pressure delivered by negative-pressure wound therapy on skin perfusion. Ann Plast Surg. 2005; 55(6):665–671.
8. Sundby ØH, Høiseth LØ, Mathiesen I, et al. The acute effects of lower limb intermittent negative pressure on foot macro- and microcirculation in patients with peripheral arterial disease. Plos One. 2017; 12(6):e0179001.
9. Morales F. Improving the clinical applicability of laser Doppler perfusion monitoring. Printpartners Ipskamp, Enschede, 2005. Available at https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.454.8771&rep=rep1&type=pdf .
10. Kairinos N, Voogd AM, Botha PH, et al. Negative-pressure wound therapy II: negative-pressure wound therapy and increased perfusion. Just an illusion? Plast Reconstr Surg. 2009; 123(2):601–612.
11. Ichioka S, Watanabe H, Sekiya N. A technique to visualize wound bed microcirculation and the acute effect of negative pressure. Wound Repair Regen. 2008; 16(3):460–465.
12. Sundby ØH, Høiseth LØ, Mathiesen I, et al. The effects of intermittent negative pressure on the lower extremities’ peripheral circulation and wound healing in four patients with lower limb ischemia and hard-to-heal leg ulcers: a case report. Physiological Reports. 2016; 4(20):e12998.
13. Campisi CC, Ryn M, Campisi CS, Di Summa P, Boccardo F, Campisi C. 2015. Intermittent negative pressure therapy in the combined treatment of peripheral lymphedema. Lymphology. 2015; 48(4):197–204.
14. Ma Z, Li Z, Shou K, et al. Negative pressure wound therapy: Regulating blood flow perfusion and microvessel maturation through microvascular pericytes. Int J Molec Med. 2017; 40(5):1415–1425.
15. Liu Z, Dumville JC, Hinchliffe RJ, et al. Negative pressure wound therapy for treating foot wounds in people with diabetes mellitus. Cochrane Database Syst Rev. 2018 Oct 17;10:CD010318.
16. Wang D, Stockard CR, Siegal GP, et al. Immunohistochemistry in the evaluation of neovascularization in tumor xenografts. Biotech Histochem. 2008; 83(3–4):179–89.
17. Li PY, Yang D, Liu D, Sun SJ, Zhang LY. Reducing surgical site infection with negative- pressure wound therapy after open abdominal surgery: a prospective randomized controlled study. Scand J Surg. 2017;106(3):189-95.
18. Stannard JP, Volgas DA, McGwin G 3rd, et al. Incisional negative pressure wound therapy after high-risk lower extremity fractures. J Orthop Trauma. 2012;26(1):37-42.
19. Yu Y, Song Z, Xu Z, et al. Bilayered negative-pressure wound therapy preventing leg incision morbidity in coronary artery bypass graft patients: a randomized controlled trial. Medicine (Baltimore). 2017;96(3):e5925.
20. Wrotslavsky P. Pain reduction with negative pressure on surgical site incisions. Surg Technol Int. 2018; 33:47–51.
21. Nam D, Sershon RA, Levine BR, Della Valle CJ. The use of closed incision negative-pressure wound therapy in orthopaedic surgery. J Am Acad Orthoped Surg. 2018; 26(9):295–302.
22. Hasan MY, Teo R, Nather A. Negative-pressure wound therapy for management of diabetic foot wounds: a review of the mechanism of action, clinical applications, and recent developments. Diabetic Foot Ankle. 2015;6:27618.
23. Timmers MS, Le Cessie S, Banwell P, Jukema GN. The effects of varying degrees of pressure delivered by negative-pressure wound therapy on skin perfusion. Ann Plast Surg. 2005;55(6):665-671.
24. Vig S, Dowsett C, Berg L, et al. Evidence-based recommendations for the use of negative pressure wound therapy in chronic wounds: steps towards an international consensus. J Tissue Viability. 2011;20(Suppl 1):S1-18.
25. Marston WA, Davies SW, Armstrong B, et al. Natural history of limbs with arterial insufficiency and chronic ulceration treated without revascularization. J Vasc Surg. 2006; 44(1):108–114.e1.
