While physicians commonly check pedal pulses and the ankle brachial index to assess vascularity, microvascular testing methods are also key to assessing wound healing potential. Accordingly, these authors offer current insights on the toe brachial index, photoplethysmography, skin perfusion pressure and transcutaneous oxygen pressure.
Chronic or non-healing ulcerations are wounds that have failed to proceed through the repair process and do not demonstrate functional or anatomic integrity within a three-month period.1 Such wounds affect over 6.5 million patients in the United States and cost an excess of $25 billion annually to treat.2-3
Along with increasing healthcare costs, the burden of treating chronic wounds is also due to a population of increasing age, obesity and diabetes. The diabetic foot in particular constitutes a tremendous challenge as up to 25 percent of patients with diabetes will at some point develop a foot ulcer and at least 12 percent of those patients will require some form of lower extremity amputation.4 Even more alarming, 50 percent of patients who undergo limb amputation will die within a five-year period.4 In addition to amputation, failure to manage chronic wounds may lead to other devastating and life-threatening conditions such as cellulitis and sepsis.
The causes of impaired wound healing are diverse and multifactorial, but a common factor in the etiology of most chronic wound cases is extreme hypoxia. Since oxygen is essential for both cellular metabolism and host defense, it is important to maintain normoxic conditions in a healing wound to keep up with energy demands and prevent worsening infection.5 In order to maintain normoxic conditions in the wound bed, there must be an adequate vascular supply to the area.
In patients with diabetes, peripheral arterial disease (PAD), especially atherosclerosis and medial sclerosis, is a common cause of arterial insufficiency that results in decreased distal blood flow and perfusion pressure to the lower extremity.6 In addition to PAD being a risk factor for poor wound healing capacity and limb amputation, diabetic peripheral neuropathy (DPN) is also a risk factor as it further contributes to microvascular disease since the peripheral sympathetic nervous system controls blood flow to the skin. Accordingly, utilizing microvascular assessments in addition to macrovascular testing is necessary to adequately assess the healing potential of diabetic foot ulcerations.
Macrovascular tests such as assessment of pedal pulses, either via palpation or the use of a Doppler, the ankle brachial index (ABI) and pulse volume recording (PVR), are often the first-line tests for vascularity. One can easily conduct these tests in almost any clinic and consensus statements recommend them as an important part of the diabetic foot assessment.7
While these tests are helpful, they do not provide an adequate assessment of microvascularity. Blood flows through microcirculation (capillaries, arterioles and venules) to supply nutrition and oxygen to the skin so utilizing noninvasive modalities to evaluate microvascular disease can be valuable in predicting diabetic foot ulcer healing. Accordingly, let us take a closer look at some of the clinical tools available for microvascular assessment of wound healing such as the toe-brachial index (TBI), photoplethysmography (PPG), skin perfusion pressure (SPP) and transcutaneous oxygen pressure (TcPO2).
What You Should Know About The Role Of The TBI
The ABI has long been established as a useful clinical test to assess blood supply to the foot and is a commonly utilized diagnostic test for PAD. An ABI of ≤ 0.90 mmHg is generally indicative of PAD.8,9 In patients with diabetes, however, the ABI can be associated with some important diagnostic limitations. Ankle brachial index values may be falsely elevated due to calcification of medial arteries, which causes hardening and incompressibility in patients with diabetes, renal failure and rheumatoid arthritis.9 An ABI value of >1.3 usually indicates the presence of incompressible vessels.
One can use the toe brachial index (TBI) as an alternative in such patients because toe vessels are less susceptible to calcification. While TBI is not necessarily a microvascular assessment since it does not directly measure blood circulation into the tissues, it is a simple and quick way to assess blood flow distal to the ankle, which is particularity important in patients who have active foot ulcers.
Similar to the ABI, the toe brachial index measures the ratio between the systolic pressure of the hallux and the brachial systolic pressure. One can determine the systolic pressure of the hallux using a handheld Doppler or photoplethysmography as the pressure cuff around the toe slowly deflates. Reference ranges vary but a toe brachial index < 0.70 generally indicates arterial insufficiency, and a toe systolic pressure of at least 30 mmHg can be an indicator of healing potential in a foot with ulcers.10,11
The toe brachial index may be completely noninvasive and painless, but there are some disadvantages. Some suggest there is a broad range of error when utilizing a manual sphygmomanometer and handheld Doppler to measure toe systolic pressure.10 More generally, one cannot measure toe systolic pressures in patients who have had hallux amputations, if digital wounds or digital gangrene are present, or in the presence of extensive edema that prevents the clinician from detecting pressure. Under these circumstances, one must employ other noninvasive techniques to determine distal blood flow to the foot.
Exploring The Diagnostic Potential Of Photoplethysmography
Photoplethysmography is an optical technique that can detect blood volume changes in the microvascular tissue bed. The photoplethysmography sensor detects blood volume by emitting non-visible infrared light into the skin and the intensity of light is reflected by cutaneous circulation into the photodetector.12
One can utilize this technique anywhere on the skin surface but clinicians typically use this on distal skin surfaces such as the digits.13 As we mentioned previously, one can often use photoplethysmography to detect toe systolic pressure when measuring TBI by simply placing the photoplethysmography probe on the hallux to obtain an indirect summation of blood in the microcirculation of the toe. When the clinician uses it for this purpose, a value of <30 mmHg for systolic toe pressure is indicative of decreased healing potential and increased amputation risk.10 Photoplethysmography is also one technique available for measuring skin perfusion pressure, which we will discuss in more detail below.
Unlike the use of the handheld Doppler, one can still obtain photoplethysmography waveforms in patients with advanced occlusive disease or when there is calcification of larger arteries such as the posterior tibial artery and dorsalis pedis artery. Still, limitations exist in both the use of the Doppler and photoplethysmography in limbs of obese patients, or limbs with edema in which arteries are incompressible. Another advantage in using photoplethysmography to detect systolic ankle or toe pressure measurements instead of the Doppler is that systolic pressure measurements and pressure index measurements could become less operator dependent by automating the measurement procedure.13 Regardless of which technique one applies for measuring TBI or ABI, a pneumatic pressure cuff is still required, which can be a limitation since some patients may find the inflated cuff to be uncomfortable or even painful.
What You Should Know About Skin Perfusion Pressure
As a noninvasive diagnostic method, skin perfusion pressure is useful as an objective indicator of healing potential, in assessing the severity of PAD and in determining the proper level of amputation when necessary. Similar to TBI, calcified arteries do not adversely affect skin perfusion pressure. However, skin perfusion pressure is a true microvascular assessment as it specifically measures the return of blood flow to capillaries.
Measure skin perfusion pressure at the site of interest by slowly decreasing the inflation of the pressure cuff to allow the return of blood flow to the capillaries. There are several techniques for measuring the pressure at which blood returns to the capillaries. Two common techniques include photoplethysmography and laser Doppler. When using photoplethysmography, the return of pulsatile flow to the area indicates the perfusion pressure whereas laser Doppler detects the movement of red blood cells when there is reperfusion of the skin.14
Several studies have assessed the specific cutoff value for skin perfusion pressure that can predict the healing potential of ulceration. We generally accept that a skin perfusion pressure value <30 mmHg is indicative of critical limb ischemia and unlikely wound healing. A value of 30 to 50 mmHg indicates PAD and the need for additional therapies and close patient monitoring. A skin perfusion pressure value >50 mmHg indicates sufficient perfusion for the healing of wounds.15 When specifically using skin perfusion pressure for testing wound healing potential, one should measure proximal to the wound or as close to the wound as possible in order to determine the local tissue perfusion near the wound. When it comes to assessing PAD, one can take skin perfusion pressure measurements at the hallux, midfoot, ankle region or calf. One advantage of utilizing skin perfusion pressure in the assessment of PAD, as opposed to the TBI, is that if the hallux has been amputated or if gangrene is present, one can easily test other areas.
In addition to its ability to test any region of interest and not being affected by arterial calcification, skin perfusion pressure testing is advantageous because it is portable and relatively quick in comparison to other methods of microvascular assessment. Unlike the other methods discussed thus far, one can also utilize skin perfusion pressure testing in patients with lower extremity edema.
Even though skin perfusion pressure is overall an excellent noninvasive technique to assess microcirculation, it is not without limitations. Patients with a marked tremor such as those with Parkinson’s disease may create noise artifacts in the reading, making skin perfusion pressure determination difficult. Do not place the sensor over bone, large vessels or on non-blanching tissue. Some patients have found the cuff inflation required to occlude capillary flow too painful to tolerate.15
How Accurate Is Transcutaneous Oxygen Pressure Measurement?
Transcutaneous oxygen tension is a noninvasive method to measure tissue perfusion. The transcutaneous monitor measures the partial pressure of oxygen (PO2) and carbon dioxide (PCO2) of the skin surface to provide an estimate of the partial pressure of arterial oxygen and carbon dioxide. The TcPO2 is therefore an indirect measurement of the partial pressure of arterial oxygen (PaO2) and does not reflect oxygen delivery or content.16
The transcutaneous monitor device works by inducing hyperperfusion of the capillaries by increasing local temperature of the skin at the sensor site. The externally applied heat alters the solubility of CO2 in the blood and increases the metabolic rate of the skin by approximately 4 to 5 percent for every degree Celsius. A Clark electrode, which is composed of a platinum cathode and silver anode, measures the PO2. In order to achieve accurate transcutaneous oxygen pressure, the skin probe temperature must be 44°C, which may lead to injury or burning of the skin, particularly in patients with thin or damaged skin. Most transcutaneous monitors, however, do allow the reduction of the probe temperature to minimize the risk of thermal injury.
Unlike the ABI, TcPO2 is not affected by arterial calcification and is useful both as an indicator of healing potential in diabetic foot ulcers and as an indicator of amputation level.17 Generally, a TcPO2 value <40 mmHg is predictive for impaired wound healing and a value <10 mmHg indicates critical limb ischemia.18,19 In comparison to other microvascular assessments, TcPO2 is relatively time consuming. The entire process takes 30 minutes or longer as the electrode requires at least 15 minutes to warm up before one can take any measurements and the sensors require calibration.15,18
Not only is TcPO2 time consuming but the accuracy of the measurements has been questioned as results are often variable. For example, lower extremity edema or increased thickness of the skin and/or subcutaneous tissue can result in falsely decreased TcPO2 values, and increased capillary blood flow induced by patient movement may falsely elevate TcPO2 values. Studies have demonstrated that TcPO2 has a sensitivity of 66 to 85 percent as a predictor of wound healing potential.19,20 It is important to note that TcPO2 measures the oxygen partial pressure in areas adjacent to a wound as opposed to the wound itself and the measurements may not represent the actual partial pressure of oxygen within the wound.20
Transcutaneous oxygen does offer several advantages. One can apply it to any skin area and utilize it in patients with previous toe or midfoot amputations. The measurement does not require a pneumatic cuff, which can sometimes be uncomfortable for patients, and TcPO2 is specifically useful in assessing oxygenation in patients with advanced PAD. While there are no documented absolute contraindications for the use of TcPO2, one may consider alternative assessment tools in patients with poor skin integrity or allergies to adhesives. Moreover, the presence of severe lower extremity edema may limit accuracy of this modality in assessing wound healing potential.
Assessment is the cornerstone of effective care and evaluating the healing potential of an ulcer in a patient with diabetes is essential as it will help influence the direction of treatment. Traditional methods of lower extremity arterial assessment, such as the palpation of pulses and pain history alone, may be insufficient to determine the presence and extent of ischemia. Noninvasive macrovascular as well as microvascular testing are imperative first steps to assess the wound healing capacity in patients with diabetes. Microvascular evaluations have proven to be particularly important when assessing wound healing potential as capillary blood flow specifically provides nutrition to the skin and therefore directly impacts wound healing.
While there are some limitations associated with the currently available tools for microvascular assessments, they do provide clinicians with a measure of wound healing probability and help guide the treatment algorithm. They are valuable tools that one should use in conjunction with other macrovascular and microvascular assessments to ensure the achievement of the most comprehensive evaluation of wound healing potential. It is important to note that one must still consider other factors when assessing wound healing potential. Even if sufficient circulation is present to allow for wound healing, one must also consider properties such as bioburden control, pressure mitigation as well as metabolic and pharmacologic imbalances to assess wound healing potential accurately.
Ms. Winder is a student at the Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University. She is a NIH T35 funded research scholar and currently serves as an executive board member of the Illinois Podiatric Medical Student Association.
Dr. Wu is the Associate Dean of Research and a Professor of Surgery at the Dr. William M. Scholl College of Podiatric Medicine, and is a Professor of Stem Cell and Regenerative Medicine at the School of Graduate Medical Sciences at the Rosalind Franklin University of Medicine and Science in Chicago. She is also the Director of the Center for Lower Extremity Ambulatory Research (CLEAR) in Chicago.
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- Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med. 1999; 341(10):738-46.
- Brem H, Stojadinovic O, Diegelmann RF, et al. Molecular markers in patients with chronic wounds to guide surgical debridement. Mol Med. 2007; 13(1-2):30-9.
- Sen CK, Gordillo GM, Roy S, et al. Human skin wounds: a major snowballing threat to public health and the economy. Wound Repair Regen. 2009; 17(6): 763-71.
- Sen CK. Wound healing essentials: let there be oxygen. Wound Repair Regen. 2009;17(1): 503-11.
- Schaper NC, Andros G, Apelqvist J, et al. Diagnosis and treatment of peripheral arterial disease in diabetic patients with a foot ulcer. A progress report of the International Working Group on the Diabetic Foot. Diabetes Metab Res Rev. 2012;28(Suppl 1): 218-24.
- Dolan NC, Liu K, Criqui MH, et al. Peripheral arterial disease, diabetes, and reduced lower extremity functioning. Diabetes Care. 2002;25(1):113-20.
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- Khan TH, Farooqui FA, Niaz K. Critical review of the ankle brachial index. Curr Cardiol Rev. 2008; 4(2):101-106.
- Romanos MT, Raspovic A, Perrin BM. The reliability of toe systolic pressure and toe brachial index in patients with diabetes. J Foot Ankle Res. 2010; 3:31.
- Scanlon C, Park K, Mapletoft D, Begg L, Burns J. Interrater and intrarater reliability of photoplethysmography for measuring toe blood pressure and toe-brachial index in people with diabetes mellitus. J Foot Ankle Res. 2012; 5:13.
- Hoyer C, Sandermann J, Peterson LJ. The toe-brachial index in the diagnosis of peripheral arterial disease. J Vasc Surg. 2013; 58(1): 231-8.
- Allen J. Photoplethysmography and its application in clinical physiological measurement. Physiol Meas. 2007; 28(3): R1-39.
- Alnaeb ME, Albaid N, Seifalian AM, Mikhailidis DP, Hamilton G. Optical techniques in the assessment of peripheral arterial disease. Curr Vasc Pharmacol. 2007;5(1):53-9.
- Yamada T, Ohta T, Ishibashi H, et al. Clinical reliability and utility of skin perfusion pressure measurement in ischemic limbs—comparison with other noninvasive diagnostic methods. J Vasc Surg. 2008; 47(2):318-23.
- Restrepo RD, Hirst KR, Wittnebel L, Wettstein R. AARC clinical practice guideline: transcutaneous monitoring of carbon dioxide and oxygen: 2012. Respir Care. 2012; 57(11):1955-62.
- Castronuovo JJ, Adera HM, Smiell JM, Price RM. Skin perfusion pressure measurement is valuable in the diagnosis of critical limb ischemia. J Vasc Surg. 1997; 26(4):629-37.
- Andrews KL, Dib MY, Shives TC, et al. Noninvasive arterial studies including transcutaneous oxygen pressure measurements with the limbs elevated or dependent to predict healing after partial foot amputation. Am J Phys Med Rehabil. 2013; 92(5):385-92.
- Lo T, Sample R, Moore P, Gold P. Prediction of wound healing outcome using skin perfusion pressure and transcutaneous oximetry. Wounds. 2009; 21(11):310-16.
- Fife CE, Smart DR, Sheffield PJ, Hopf HW, Hawkins G, Clarke D. Transcutaneous oximetry in clinical practice: consensus statements from an expert panel based on evidence. Undersea Hyperb Med. 2009; 36(1):43-53.