Transcutaneous oxygen values and associated clinical interpretation
Globally, diabetes mellitus has grown to pandemic proportions, affecting 194 million people worldwide and is expected to increase in prevalence to 344 million by the year 2030 (Wild, et al., 2004). Of these patients, between 2 and 6% will develop a diabetic foot ulcer (DFU) yearly (Ramsey, et al., 1999). The onset of a DFU often precipitates a complex chain of events that may lead to limb loss. Infected DFUs account for 20% of hospital visits for this patient population (Bouter, et al. 1993) and precede roughly 85% of lower extremity amputations in patients with diabetes (Pecoraro, et al. 1990). The long-term outcome for a diabetic patient after a major limb amputation is grave with 50% of these patients deceased at 5 years (Moulik, et al. 2003). Additionally, the cost to treat this disease places a significant strain on the health-care system. The cost to manage these foot disorders is estimated at several billion dollars annually (Wild, et al. 2004), while the individual cost of a major limb amputation is estimated at almost $45,000 (Apelqvist, et al. 1994). With the combination of excessive cost to treat diabetes complications coupled with the major detrimental health effects on individual patients, it is necessary to develop and employ new technological methods to predict healing of diabetic foot ulcers.
Once a diabetic patient develops a pedal ulceration it becomes incumbent on the physician to evaluate the ulcer’s healing potential. Much research has focused on the prediction of diabetic foot ulcer healing. Clinically, it has been shown that a 50% decrease in area over a 4-week period with standard wound care adequately predicts ulcer healing at 12 weeks (Sheehan, et al., 2006). The disadvantage of this method, however, is the delay in treatment that occurs as a result of the natural time deferment in this process. As such, newer technologies have utilized the determination of microcirculation to predict ulcer healing. This chapter focuses on the application of these new technologies to determine microvascular circulation and predict diabetic foot ulcer healing.
Large artery (macrocirculatory) disease has been well documented elsewhere with disease at the infrapopliteal region (Bembi, et al. 2006) causing loss of tissue perfusion and critical limb ischemia and gangrene. Various noninvasive vascular testing modalities exist to determine large vessel luminal disease. These include dual mode ultrasound, segmental leg pressures, ankle brachial indices, pulse volume recordings, toe pressures, and toe brachial indices. The above tests have been found to yield useful clinical data regarding large vessel disease and often function as safe precursors to more advanced imaging techniques such as magnetic resonance arteriography. These methods also assist with surgical revascularization planning. However, the options for assessment of microvascular disease are comparatively sparse. This chapter will focus on the following noninvasive modalities to evaluate microvascular disease and predict ulcer healing: Transcutaneous Oxygen Pressure, Skin Perfusion Pressure, Laser Speckle Perfusion Imaging, and Hyperspectral Imaging.
2. Peripheral arterial disease and the pathophysiology of microvascular disease in diabetes
The pathogenesis of macrocirculatory disease has been discussed in depth elsewhere. Microcirculation includes the capillaries, arterioles, and venules. These microvessels are arranged in two horizontal network patterns with a superficial subpapillary plexus and a deeper cutaneous plexus with capillary blood flow providing nutrition and arteriovenous shunts that serve a thermoregulatory function (Chao & Cheing, 2009). The nutritional capillaries are organized into functional units within the papillary layer of the dermis. A precapillary sphincter is situated just upstream of the capillary which controls vasodilation and constriction (LaFontaine, et al., 2006). Arteriovenous anastomoses exist between the arterioles and venules to allow normal shunting of blood under physiologic conditions. The internal vessel lumen is lined with a single-layer-thick endothelium. This endothelium lies on a basement membrane which is normally thicker in the foot than other body locations due to the increased hydrostatic pressure associated with stance (LaFontaine, et al., 2006). Blood flow to the skin runs through this arteriovenous system supplying nutrition, oxygen, and regulating temperature through an increase or decrease of blood flow to the dermal papilla.
Blood flow to the skin is controlled by the peripheral sympathetic nervous system via vasodilatory cholinergic and vasoconstrictor adrenergic nerve fibers (Chao & Cheing, 2009) as well as vasoactive substances such as nitric oxide. Additionally, the endothelial basement membrane regulates blood flow and the local inflammatory response via vasoactive substances (Guerci, et al. 2001).
The pathogenesis of microvascular disease in diabetics is complex and multifactorial. Hyperglycemia is considered the most important risk factor (LaFontaine, et al., 2006) and is noted to occur in two stages, a reversible functional stage and a structural adaptation and remodeling stage leading to a thickened basement membrane and capillary failure (LaFontaine, et al., 2006). The hemodynamic hypothesis of microangiopathic disease was first described by Parving, et al (Parving, et al. 1983). Blood flow dysregulation, caused by neuropathic changes to the sympathetic nerve fibers, is mediated by hyperglycemia. The resulting stimulation of the polyol pathway decreases nitric oxide production, increasing blood flow and capillary pressure. This increased pressure leads to thickening of the basement membrane which resists vasodilation and increases capillary permeability with ensuing chronic edema.
A second mechanism that has gained experimental support is the “capillary steal syndrome” (Uccioli, et al. 1992). This is thought to result from sympathetic denervation with chronic vasodilation, resulting in an increased blood flow through the arteriovenous shunt away from the arterioles in the papillary dermis. As blood moves more rapidly toward the postcapillary venule, nutrition, metabolite, and oxygen exchange are significantly reduced (Boulton, et al, 1982).
It is unknown which pathway is dominant or if another mechanism is responsible, though there is most likely a combination of both pathogenic pathways that end with functional ischemia, reduced nutritional capacity, and increased metabolic end products that function together to limit healing capacity in the face of skin ulceration.
3. Current methods to assess healing potential in diabetic foot ulcers
Large vessel disease is evaluated through several noninvasive methods including dual mode ultrasound, segmental leg pressures, ankle brachial indices, pulse volume recordings, toe pressures, toe brachial indices, magnetic resonance angiography, and computed tomographic angiography. However, these modalities only characterize blockages of large arteries and do not assist with prediction of direct wound healing on the lower extremity. Contemporary microvascular technologies utilize the above pathogenic principles to evaluate microangiopathic changes and predict ulcer healing. The following discussion will review the currently available methods to clinically assess microvascular blood flow and predict the healing potential of diabetic foot ulcers.
4. Transcutaneous oxygen pressure
Courtesy of Casa Colina Centers for Rehabilitation Wound Care and Hyperbaric Medicine Program.
|40mmHg||Unimpaired wound healing|
|<30 mmHg||Impaired wound healing|
|20mmHg||Predicted rest pain, ischemic ulceration, gangrene.|
As noted above, TcPO2 measurement is most clinically relevant for assessing oxygenation in patients with more advanced arterial occlusion or performing the test with exercise. Additionally, since the results are not affected by sclerosis of the tunica media of arteries this is a viable test in patients with diabetes and renal disease (Hauser, et al. 1984). TcPO2 may also be used in conjunction with hyperbaric oxygen therapy.
Several limitations exist with the use of TcPO2. TcPO2 cannot be measured under certain physical conditions (edema, dry flaky skin, maceration, callused or plantar skin, cellulitis, or skin over bones and tendons) (Dooley, et al. 1996). These conditions tend to decrease the sensitivity of the probe to detect skin perfusion. Since the electrode probe is placed on intact adjacent skin rather than directly on the wound itself this method does not measure oxygen tension within the wound. The need to warm the extremity causes temperature differences between sites and subjects leading to false readings. TcPO2 is reliable in the normal but not in the low range, resulting in a high false positive rate for critical limb ischemia (Byrne, et al. 1984). Mechanical pressures on the electrode alter the TcPO2 value. Additionally, a significant amount of time is necessary to obtain pressure measurements with calibration, sensor maintenance and skin preparation delaying a reliable reading upwards of 45 minutes. TcPO2 is therefore site restrictive and operator sensitive.
5. Skin perfusion pressure
Method. A laser sensor is placed on the desired location while a pressure cuff is placed at the ankle. The cuff is inflated until occlusion of the arterial flow to the extremity occurs and is then released. As arteriolar flow is restored and the subsequent reactive hyperemia occurs, the laser sensor reads the resulting arteriolar pressures.
The advantages of SPP are the following: it can be used in the presence of edema and in the plantar foot, no calibration is needed, no maintenance is required, no skin warming is necessary, and it is faster than TcPO2 measurement (2-3 minutes per site).
The limitations of SPP are that it provides data regarding the limited area of skin under the sensor. Multiple separate readings are necessary to obtain a global understanding of pedal microvasculature.
6. Hyperspectral Imaging (HSI)
Hyperspectral imaging provides multiple advantages including the lack of contact with skin, global examination of lower extremity microvascular supply, immediate accurate ulcer healing prediction, use on glabrous and nonglabrous skin, and ease of use and interpretation with a healing index.
Disadvantages of HSI are that few studies currently exist to fully validate the use of this modality. A thicker border surrounding the wound decreases the ability of HSI to discriminate well from poorly vascularized tissues. It is currently recommended to use a border thickness of 0.5 to 1 cm (Nouvong, et al., 2009).
7. Future directions for microcirculation testing
The assessment of microangiopathic disease is a new science with early clinical applications. As new technologies are developed physicians will increasingly be able to extract information about the vascular status of potentially ischemic areas while providing a greater understanding of the pathophysiology of the diabetic lower extremity.